Basic and Essential Pharmacology

LECTURE NOTES
ON
PHARMACOLOGY OF ESSENTIAL DRUGS. (for community health workers).
Lecture Notes on Pharmacology of Essential Drugs. IORJIIM, W.M ( B.pharm)
INTRODUCTORY PHARMACOLOGY. DEFINITION. Pharmacology can be defined as the study of substances that interact with living systems through chemical processes, especially by binding to regulatory molecules and activating or inhibiting normal body processes. These substances may be chemicals administered to achieve a beneficial therapeutic effect on some process within the patient or for their toxic effects on regulatory processes in parasites infecting the patient. Or Pharmacology is the study of drugs. A drug on the other hand is defined as any chemical substance of plant, animal or chemical origin used in the diagnosis, prophylaxis and treatment of diseases in man and other animals. SOURCES OF DRUGS. The range of raw materials used in the manufacture of medicinal products is extremely large. Principally, pharmaceutical raw materials are derived from three sources namely Animal, Plant and Mineral Sources. Plants Based Raw Materials. Plant based drugs are obtained in the form of extract and may further be processed into different form of the drugs as tablets, capsules, tinctures, etc. Drugs Quinine Atropine Reserpine Artesunate source Cinchona bark, Atropa belladonna Rawolfia serpentine Atemisia annua use antimalaria Iritis, Uveitis, Mydriatic Organophosphate Poisoning antihypertensive antimalaria
Animal Based Raw Materials. Animal based drugs may be obtained from organs or glands of animals or they may be obtained from microorganisms. e.g Drug (animals) Adrenaline Thyroxin Insulin Vasopressin Testosterone e.g Drug (microbes) Penicillines Vancomycin Bacitracin Chloramphenicol Tetracyclines source Adrenal cortex Thyroid gland Pancretic cells Hypothalamus Testis source Penicillium notatum Septococcus orientalis Bacillus subtilis Sreptomyces venezuelae use hypersensitivity reaction. thyrotoxicosis Diabetes mellitus Diabetes insipidus. hormonal replacement. use antibiotics antibiotics antibiotics
Streptomyces aureofaciens
Mineral Based Raw Materials. Mineral based drugs may be obtained from single mineral element or a combination of two or more such mineral elements through a process or method known as chemical synthesis. Examples include. Acetylsalicylic acid which entails the bringing together of salicylic Acid and Acetic anhydride in a chemical reaction. Other drugs produced synthetically include: Paracetamol, chloroquine phosphate, Normal Saline, etc. Genetic Pharmacy ( or Recombinant DNA technique) The gene responsible for the production of a complex protein is isolated from human cells and inserted into other vector (carrier ) cells ( e.g E. coli or yeast) which divide rapidly and are manipulated to produce the required protein in large quantities. This method is used for Insulin and Erythropoeitein production.
NAMING OF DRUGS. A drug commonly has three names viz: chemical name, Generic name and Trade name. Generic name of a drug refers to a name assigned to a drug by the World Health organization ( WHO) and is independent of that of the manufacturer. A generic name is also known as non-proprietary name. eg. Paraceamol and Cprofloxacin. Trade name of drug is the name given to a drug by its manufacrurer. A Trade name is also known as brand name or proprietary name. A trade name distinguishes a given drug name by a company from same drug made by another company e.g Panadol is a trade name given to paracetamol by Glaxosmithkline while the same paracetamol made by Dana Pharmaceuticals is known as Danamol. Chemical name of drug is the name given to a drug by virtue of its chemical composition. E.g Paracetamol is called N-acetyl-paraAminophenol. CLASSIFICATION OF DRUGS. Drugs can be classified into many groups using several systems. Some of the systems of classifying drugs include: 1. Classification drugs base of dosage forms. In actual pharmacy practice, pure drugs are rarely administered alone. They are combined with inactive (or inert) materials to produce a pharmaceutical dosage form. The term dosage form refers to the physical form in which the drug product is made available for administration to the patient. in pharmacy practice today includes: 1. SOLID DOSAGE FORMS. Tablets. Capsules. 2. LIQUID DOSAGE FORMS. Solutions, Syrups, Elixirs, Tinctures, Suspensions, Emulsions,Enemas. Enemas are liquid medications introduce into the rectum for local effect: - cleansing the bowel prior to surgery or as stool softeners. e.g soap enemas. 3. SEMI-SOLID OR TOPICAL DOSAGE FORMS. Ointments, Pastes; Creams, Powders, Gels and Jellies.
Some of the common dosage forms used
2. Classification of Drugs According to Pharmacological Actions. Drugs may also be classified according to the known action in the human system. eg. Anti- convulsants. These are drugs used in the treatment of acute fits or convulsions. Examples include Diazepam, paraldehyde and phenobarbitone sodium. Antehelmintics: these are a group of drugs that are effective against worm infestations. Eg. Albendazole, Mebendazole, Levamisole etc Anti-malaria. chloroquine etc Antibacterial drugs. These are drugs that are used in the treatment of bacterial infections. Examples include Ciprofloxacin, Metronidazole, Streptomycin, Tetracycline, etc. 3. Classification Based on Organ or System of Body the Drug works. Drugs may similarly be classified based on the organ or system the drug is known to elicit their pharmacological or therapeutic action. Cardiovascular system drugs: These include all the drugs that are used in the treatment of cardiovascular system disorders eg. Anti-hypertensives ( Propranolol, Atenolol, Nifedipine, Lisinopril, etc), Cardiac glycosides eg. Digoxin, Antiarrhythmic agents ( drugs in the treatment of cardiac arrythmias) eg. Propranolol, Quinidine, Amiaodarone, Acebutolol etc. Drugs used in the treatment of malaria infection. Eg. Artesunate,
Endocrine System Drugs. These are drugs used in the treatment of endocrine system disorders. eg. Antidiabeties ( drugs used in the treatment of diabetes mellitus) e.g Insulin, Metformin (Glucophage), Glibenclaminde ( Daonil), etc. Antithyroid drugs (drugs in the treatment of thyrotoxicosis) e.g Carbimazole, Methimazole, Iodine etc. Central Nervous System (CNS) Drugs: These include drugs used in the management of CNS disorders e.g Antispychotics (Chlopromazine, Haloperidol), Antiepiletics ( Diazepam, Penytoin, Carbamazipine etc), Antiparkinson drugs ( Levodopa, Tolcapone, etc) These are drugs with action on the gastrointestinal tract.
Gastrointestinal drugs: Examples include:
Antiulcer drugs (Cimetidine, Omeprazole, Ransoprazole, Gascol etc),
Antispasmodic drugs ( drugs that reduces the contraction of GIT smooth muscles eg Hyoscin-N-Butylbromiden (Buscopan ), Propantheline etc,
Laxatives eg. Bisacodyl ( Ducolax), Antiemetics eg. Metocloramide ( Plasil). Dermatological drugs. These include topical preparations for skin infections e.g topical antifungal agents ( e.g Clotrimazole cream, Tioconazole cream etc) , topical antibacterial agents ( Ampicillin ointment etc) BASIC PHARMACOLOGICAL CONCEPTS. Pharmacology is the study of drugs. pharmacokinetics and pharmacodynamics. The two main areas of pharmacology are
Pharmacokinetics Pharmacokinetics is the study of the activity of a drug within the body over a period of time is known as pharmacokinetics. It is the actions/effects of the body on the drug. Pharmacokinetic processes govern the absorption, distribution, and elimination of drugs and are of great practical importance in the choice and administration of a particular drug for a particular patient. Drug Absorption. This is the process whereby a drug enters the circulatory system. That is , the chemical constituents of the drug are absorbed into the blood stream. The absorption of a drug molecule depends on its physiochemical properties. To gain access to the site of action, drug molecule must cross one or more barriers- the GIT mucosa, and the membranes that separate the various aqueous compartments of the body. Drug molecules cross cell membranes and become absorbed in the following ways. * Diffusion through lipids. Many drugs are highly soluble in lipids and therefore penetrate cell membranes freely, by diffusion. Lipid solubility is one of the most important pharmacokinetic characteristic of a drugs, which determine it site of action. * Diffusion through aqueous ( i.e water) channels. In most parts of the body there are gaps between the endothelia cells of the capillaries, which are large enough to permit small drugs molecules to cross by aqueous diffusion, but too small to allow protein. * Carrier mediated transport. Many cell membranes posses highly specific transport mechanism (i.e a protein molecule incorporated in the cell membrane) which binds the drug molecule and ships it to other side of the membrane in the manner of a ferry. The carrier mediated drug transport plays an important role in the transfer of drugs at the renal tubules, GIT and blood brain barrier sites. * Endocytosis and Exocytosis.
A few substances are so large that they can enter cells only by endocytosis, the process by which the substance is engulfed by the cell membrane and carried into the cell by pinching off of the newly formed vesicle inside the membrane. The substance can then be released inside the cytosol by breakdown of the vesicle membrane. binding proteins, across the wall of the gut into the blood. many neurotransmitters This process is responsible for the transport of iron and vitamin B12, each complexed with appropriate The reverse process (exocytosis) is responsible for the secretion of many substances from cells. For example, are stored in membrane-bound vesicles in nerve endings to protect them from metabolic destruction in the cytoplasm. Appropriate activation of the nerve ending causes fusion of the storage vesicle with the cell membrane and expulsion of its contents into the extracellular space. Drug Distribution. This is the process by which a drug moves from the blood stream into other body fluids and tissues and ultimately to its sites of action. Blood flow is the most important rate limiting factor for distribution of a drug.. Many drugs are poorly soluble in plasma and are bound to plasma proteins. It is important to know that the free (unbound) fraction of drugs produces the desired pharmacological action or therapeutic effect. Drug metabolism. ( Biotransformation) This is the process in the body by which drugs are converted to other biochemical compounds, and then excreted through metabolic path ways. The liver is the man site of metabolism for most lipid soluble drugs,. These lipid soluble drugs are change in the liver to more water soluble forms ready for excretion via the kidney or skin. A substance into which a drug is converted by metabolism is called metabolite of the drug. Drugs that must be converted to their metabolite before their actions are produced are called produrugs e.g an antiparkinson drug Levodopa to dopamine. Many factors can alter metabolism e.g disease states, age and genetic predisposition all affect the way the body metabolizes drugs. Drug Elimination. The removal of a drug or its metabolites from the body occurs primarily in the kidney ( through urine) and the liver ( through feces). Other routes of excretion include skin ( via
perspiration), saliva, and breast milk. The rate of drug metabolism, it half life and subsequent elimination is useful in predicting its duration of action and frequency of dosing e.g twice a day with elimination half life of about 12 hours. Half life. The elimination half life of a drug is the time taken for the circulating concentration of the drug to fall by half. For most of the drugs, the rate of decline in the plasma concentration is constant and directly proportional to the amount present. PHARMACODYNAMIC. Pharmacodynamcis is the study of pharmacological properties of a drug and its mechanism of action. It is the actions/effects of the drug on the body. Drug effects are the results of physiochemical reactions between the drug and functionally important molecules in the body. actions are: Drug Receptors. The term receptor is used to mean any clearly defined cellular protein to which a drug binds to initiate its effect. The drug is thought to fit onto a receptor rather as a key fits a lock. It may then either stimulate the receptor and producer ifs effect similar to that of a naturally occurring (endogenous) substances and it is called an agonist or it may occupy the receptor without producing any effect and block the effect of an endogenous agonist and is called antagonist. A few drugs have been show to be partial agonists (antagonists at low concentrations and agonist at high concentrations) e.g pindolol Enzyme inhibition Interaction between drug and enzyme is in many respects similar to that between drug and receptor. Many important drugs owe their action due to inhibition of the enzyme activity, because they structurally resemble a natural substrate and hence compete with it for the enzyme. Examples of enzyme inhibition include Angiotensin Converting Enzyme Inhibitors (ACE Inhibitors) ( Lisinopril Captopril etc), Cyco-oxygenase inhibitors ( NSAIDs -Aspirin, Diclofenac), Xanthine oxidase Inhibitor e.g Allopurinol (zyloric) in the treatment of Gout arthritis. They interact with the bodys natural physiological control systems that include receptors, enzymes, etc. some of the known mechanisms of drugs
Chemical Interaction. Drugs extra-cellulary react according to simple chemical equation know as neutralization reactions. e.g ( acid + base Salt + water) as in the use of antacids to neutralize HCl in the treatment of peptic ulcers. For example, the HCl in the stomach can be neutralized by Aluminum hydroxide ( an antacid) as follows. Al (OH)3 agents. Action on cell membranes General and local anaesthetics appear to act on the lipid, protein or water constituents of nerve cell membranes and interfere with the movement of ions and thus, prevent nerve or muscle function. Cytotoxic Effect. Here, a drug kills bacteria or malignant cells without undue change to the patients cells. e.g cancer drugs ROUTES OF DRUG ADMINISTRATION. This is the ways drugs are administered in a patient. There are various routes of drugs administration viz: Enteral route, Parenteral route, and Topical route Enteral Route. This refers to the administration of drugs through the gastro-intestinal tract. The different ways this is done include.
(b) Per Oral Route. This refers to administration of drugs through the mouth.
(base)
+ 3HCl (acid)
AlCl3 (salt) + 3H2O (water)
Other reactions are: acidifying and alkalinizaing agents, oxidizing agents and chelating
Examples of dosage forms suitable for oral route include: Tablets, Capsules, Syrups, Suspensions, etc. Advantages. it is economical i.e cheap to use, Easy to use as the patient can administer the drug by him/herself. In case of accidental overdose, the drug may (where appropriate) be easily removed via gastric larvage. It is the safest i.e has low incidences of fatal side effects.
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Disadvantages. Onset of action is slow therefore unsuitable for emergency cases. Drugs are subjected to first pass effect. Not convenient for unconscious patients Bitter taste may discourage drug use. Absorption is affect by food. Not convenient for treatment of nausea and vomiting. The route requires patients cooperation.
(c) Sublingual/ Buccal Route: this refers to administration of drugs under the
tongue ( i.e sublingual) or between the cheek and gum (i.e buccal cavity). The drug is place under the tongue or at the cheek and it slowly dissolves. An example of sublingual drug is Nitroglycerin tables. advantages of this route are: - Onset of action is fast because the drug bypasses first pass effect. i.e the medication enters the blood stream directly from the richly vascularized mucous membrane of the mouth and produces its effect more quickly than drugs that are swallowed. Other advantages and disadvantages are similar to oral route The major
Parenteral Route. Administration of drugs by injection is referred to as the parenteral route ( meaning outside of the intestines). . Here, drugs are given by injection or by infusion directly into the blood circulation. a muscle - intramuscular ( IM) a vein- intravenous ( IV) the skin- intradermal the tissue beneath the skin- subcutaneous ( SC) the spinal column- intraspinal or intrathecal. There are different ways of administering drugs through the parental route. Drugs may be injected into:
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Advantages Quickest onset of action therefore most useful in emergencies. Parenteral route provide a way of administering drugs that are inactivated by GIT secretions eg. Insulin
Some drugs are inactivated by first-pass metabolism, so they are injected directly into the tissues of the body.
Convenient for treatment of nausea and vomiting. Disadvantages. Injection can be painful. There is a risk of infection at the site of puncture Has highest incidence of side effect. In case of accidental overdose, drug cannot be withdrawn. It is expensive in that the patients pays for syringes/needles besides the real cost of drugs. Ideally, patients require the services of trained personnel to administer their drugs. Topical routes. Topical medications are applied to the surface of the skin or mucous membranes. The desired effect can be local or systemic. Other topical routes are: inhalation, ophthalmic ( the eye) , otic ( the ear) , nasal( the nose) , rectal, and vaginal. Rectal Route: this refers to administration of drugs through the anal cavity or anus. Examples Anusol Suppositories. Advantages. Drugs bypasses first pass effect.
Onset of action if fast.
Convenient for unconscious patients and children. Cheap. Easy to use by patients or relatives.
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Convenient for treatment of nausea and vomiting. Disadvantages. Route may be embarrassing to patient. Presence of fecal matter affect drug absorption. Drugs may irritate anal mucosal. The inhalation route delivers medications to the respiratory system. These
medications are intended for one or more of the following purposes: to alter the condition of the mucous membranes, to alter the character of the secretions in the respiratory system, to treat diseases and infections of the respiratory tract, or to produce general anaesthesia. Medications can be administered via the ophthalmic route by instillation ( administration of medication drop by drop) of a cream, ointment, or drops of a liquid preparation into the conjunctival sack of the eye. Drugs administered by the otic route, into the ear, are used locally to treat inflammation or infection of the external ear canal or to remove excess cerumen ( wax) or foreign objects from the canal. Medications given by the vaginal route can be used to treat a local infection caused by either bacteria or fungi or for systemic effect. BASIC PRINCIPLES OF DRUG ADMINSTRATION. a. Dosage of a drug. The dose of a drug is the quantitative amount administered or taken by a patient for the intended medicinal effect. The dose may be expressed as: 1. A single dose = the amount taken at one time. 2. A daily dose = the amount taken in 24 hours. 3. A total dose = the amount taken during the time-course of therapy. A daily dose may be subdivided and taken in divided doses; 2 or more times per day depending on the characteristics of the drug and the illness. 4. The schedule of the dosing e.g 4 times per day x 10 days is called dosing regiment.
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Dosages are an important aspect of drug use because accurate choice of dosages of drugs determines the final outcome of a disease being treated. There are number of factors that influence choice of dosages of drugs. They include: b. Age. The age of a patient is an important consideration in the choice of dose of a drug. This factor is particularly important for children who need smaller doses of drugs. c. Genetic make-up- patients respond or ract to drugs differently in accordance with how their genes are made. E.g chloroquine ( an antimalaria drug) produces severe itching in some people whereas it is well tolerated by others. Acquired Tolerance- by acquired tolerance is meant tolerance developed from continued use of a drug. In such patients, large doses of a drug which could have caused harmful effect in normal patients, are taken without any harmful effect. Drug that can product tolerance on continued use include drugs of abuse and addiction such as Pentazocine ( i.e Soseqon or Fortwin) , diazepam (valium) etc. d. Route of Administration The rate and degree of absorption of a drug and finally the rapidity with witch its effect is felt or exerted depends on the method of administration. Generally, drugs administered by injection or parenteral route act faster than those given via oral route. This explains why parenteral doses are usually smaller than the oral doses. e. Rate of Elimination of the drug. The rate at which a drug is eliminated from the body determines the dose of such a drug. As mentioned before, the elimination of drugs depends largely on the functional status of the kidneys and the liver. In a condition where any of these organs is diseased, the function of excreting or eliminating drugs have to be reduced. Therefore doses of drugs that are eliminated by these organs should be reduced. f. Drug interactions. Two drugs given at the same time may react together either negatively or positively. In a positive way the effect of one may be enhanced by the other or in a negative way, the other may reduce the effect of one. These effects are therefore employed when two drugs are to be given together. In a case where the negative interaction is known, the drug
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whose effect is diminished has to be removed. To avoid harmful drug interactions, polypharmacy which is the concurrent use of multiple medications, should be avoided. There are two principal types of interactions between drugs pharmacokinetic interactions resulting from alterations in delivery of drugs to their sites of actions and pharmacodynamic interactions which modify the responsiveness of the target organ or system. * Pharmacokinetic interactions that reduce drug delivery include:

Impaired absorption eg. Antacids form insoluble complexes with Tetracyclines preventing the absorption of the later. Enzyme induction. Many drugs increase the synthesis of microsomal enzyme protein that metabolizes drugs there by reducing drug effect. Eg. Barbiturates ( phenobarbitone), Griseofulvin, are enzyme inducers therefore when taken concomitantly with drugs whose metabolism is significantly affect by enzyme induction ( e.g contraceptives corticosteroids) may have their effect diminished.
* Pharmacokinetic interactions causing increased drug delivery are: Enzyme inhibition. Many drugs have the potential for interfering with the metabolism of other drugs, usually by competing for binding sites on the appropriate enzymes. Inhibition of the metabolism of the affected drug results in higher plasma concentration with risk of toxicity. levels of warfarin ( an anticoagulant) resulting to excessive bleeding.
e.g co-
trimoxazole and Cimetidine are enzyme inhibitors and my increase the Affecting renal excretion: Drugs are eliminated through the kidney both by glomerular filtration and by active tubular secretion. Competition occurs between those which share the same active transport mechanism\ in the proximal tubule. Example, Probenicid delays the excretion of many drugs including Penicillins, some Cephalosporins, indomethacin and Dapsone, which may result to increased concentration and prolonged action of these drugs. Similarly, thiazide diuretics ( e.g hydrochlothiazide) delay the renal excretion of lithium ( use in mania) , which may result in serious lithium toxicity.
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Pharmacodynamic interactions. These are interactions between drugs which have similar or antagonistic pharmacological effects or side effects. They may be due to competition at receptor sites or occur between drugs acting on the same physiological system.
Synergism: Synergism occurs if two drugs with the same effect, when given together produce an effect that is greater in magnitude than the sum of the effect when the drugs are given individually. For example, the effect of a drug depressing the CNS (say Benzodiazepines) will be enhanced by another CNS depressant ( say alcohol). (trimethoprim-sulphamethoxazole) (sulphadoxine- pyrimethamine) synergism of drugs with similar actions and antimalaria effect of Fansidar may be beneficial also as with antibacterial components of Co-trimoxazole
Antagonism: When one drug decreases or inhibits the action of another drug antagonism occurs. E.g Naloxone (narcotic antagonist) decreases the effect of narcotics analgesics like morphine. Another classic example of antagonism is the suppression of the bactericidal activity of penicillin (which acts on divining bacteria) by Tetracycline, a bacteriostatic agent , which reduces bacterial division. This explains why bactericidal antibacterials are not given concurrently with bacteriostatic antibacterials.
PHARMACOLOGY OF ESSENTIAL DRUGS CHEMOTHERAPY

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Chemotherapy was formerly thought to be the use of synthetic chemicals to destroy infective organisms. However; it now include the use of antibiotics which are substances produced by some microorganisms which kill/inhibit the growth of other microorganisms. Chemotherapeutic agents are supposed to be toxic to the parasite and harmless to the host; hence it is referred to as selective toxicity. This selective toxicity depends on the existence of biochemical differences between the parasite and the host cells. Parasitic cells include bacteria, protozoa, helminthes (or worms), viruses also (but they are not actually cell since they do not have their own synthesis). A virus depends on the host cell and therefore is not selective toxicity in this case. Cancer cell belongs to another category. These are host cells, which have become malignant, i.e they are no longer being controlled by the regulatory devices that control the normal cells of the host. Although the cancer cells can be considered as foreign or parasitic, they also constitute a difficult problem for selective toxicity. The ability of one microorganism to interfere with the growth of another is called antibiosis and is due to specific diffusible metabolic products termed antibiotics. Since the introduction of penicillin in 1940, research has produced a wide range of antibiotics. In addition, a variety of other chemotherapeutic agents such as metronidazole, trimethoprim, ciprofloxacin and isonazid followed the demonstration of the therapeutic effect of sulphonamide in 1935. A general term for all of these substances is antimicrobial agents. Those that kill microorganisms are said to be bactericidal in action while agents that inhibits their growth are said to be bacteriostatic in action . MISUSE OF ANITMICROBIAL AGENTS AND CAUSES OF FAILURE IN THERAPY WITH CHEMOTHERAPEUTIC AGENTS. Factors that contributes to the failure of treatment with chemotherapeutic agents include: Treatment of infection which do not respond to antibiotics eg 1. The treatment of viral infection with antibiotics.
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2. Treatment of fever of undetermined origin with antipyretics masking of infection. 3. Improper dosage; this can be of three types 4. The use of sub-optimal doses. 5. The use of excessive doses 6. Correct doses for too short a period i.e Improper to resistance.
can
lead
to
duration of use can lead
7. The use of wrong antibiotics for a particular condition can also lead to masking of the infection. PROBLEMS OF CHEMOTHERAPY Development of Resistance. One of the most important problem of antimicrobial therapy is the development resistance. This is a situation where the microorganism become resistance to the drug even though the drug maybe present in adequate doses. To minimize /stop the development of resistance, antibiotics should be used when they are absolutely needed and for a sufficient length of time and in adequate doses. Super-infection. Another problem of antibiotic therapy is development of superinfection. In this case, the antimicrobial agent may kill/ suppress part of the normal bacterial flora. This allows the remaining bacterial to proliferate to pathogenic levels thereby causing secondary infection. For example the broadspectrum antibiotic Tetracycline when used (for a long time) for GIT infection can eliminate most of microbes except the fungus Candida. This then proliferates excessively to cause intestinal candidiasis. Super- infection is common with the broad-spectrum antibiotics. FACTORS WHICH DETRMINE THE CHOICE OF ANTIBIOTICS. 1. The choice of antibiotics can follow form clinical diagnosis. This can be done when the causative organism is always the same and is always sensitive to the same antibiotic e.g in the treatment of Malaria, Tuberculosis, Syphilis etc.
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2. It can also be based of sensitivity test where possible. This should be done when the causative organism cannot be detected by clinical diagnosis e.g in Bronchopneumonia, Meningitis and Urinary Tract Infections. ( UTIs) 3. Toxicity or adverse effect. The least toxic antibiotic should be used. Site of infection. Some drugs penetrate body fluids better then others 4. The patients clinical status. A patient with renal failure should not be given antibiotics that are excreted mainly unchanged via urine eg. Aminoglycosides: Gentamicin etc. ANTIBIOTIC POLICES. Many hospitals/clinics limits the antibiotics that may be used to achieve reasonable economy consistent with adequate cover and to reduce the development of resistant organisms. A policy may indicate a range of drugs for general use and permit other drugs only on the advice of physician responsible for the control of infectious diseases. PRECAUTION BEFORE INITIATING CHEMOTHERAPY Before starting therapy with antibiotics, the following should be considered. 1. Viral infections should not be treated with antibiotics. 2. Samples should be taken for culture and sensitivity testing. 3. Knowledge of prevalent organisms and their current sensitivity is of great help in choosing an antibiotic before bacteriological conformation and sensitivity testing is available. 4. Doses of antibiotics. The dose of antibiotic will vary according to a number of factors including. Age, Weight, Renal function and, Severity of infection. NB: The prescribing of the so-called standard dose in serious infections may result in failure of treatment or even death of the patient, therefore it is important to manage all cases at the PHC level by CHO or CHEW in line with the provision of Standing Orders only and refer accordingly to avoid trial and error type of patients management.
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ANTI BACTERALS USED IN CHEMOTHERAPY THE - LACTAM ANTIBIOTICS These are Penicillins and Cephalosporins. Resistance is common due to bacterial enzymes called -lactamase (penicillinase and cephalosporinase), which can destroy and inactivate the antibiotics. The Penicillins The penicillins constitute one of the most important groups of antibiotics with unique advantage they are drugs of choice for large number of infectious diseases. MECHANISM OF ACTION (MAO): They are bactericidal and act by inhibiting bacterial cell wall synthesis. Penicillins distribute well into the body tissues and fluids and are excreted in the urine. Examples of penicillins include: A: PARENTERAL PENICILLINS Benzyl Penicillin (penicillin G, crystalline Penicillin etc) Pharmacology Penicillin G exerts a bactericidal action against penicillin-sensitive microorganisms during the sate of active multiplication. This action is affected (reduced) by the activities of penicillinase ( the enzyme that destroys penicillins) producing bacterials which include many strains of staphylococci. It acts through inhibition of biosynthesis of cell wall. Indications. Pen G is indicated in the treatment of infections caused by susceptible grampositive and gram-negative organisms, including wound infections, abscesses, boils, acute tonsillitis, otitis media, pneumococcal pneumonia, gonorrhoea, syphilis.
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NB: Penicilins are the drug of choice for the treatment of bacterial infection in pregnancy. Side effects. Allergic manifestations are common with all penicillins and may be severe. This is more frequent and severe when given parenterally ( i.e by injection) than by oral route. Haemolytic anaemia Convulsions Dose:- consults the standing orders (or other reference books eg. Emdex). Benzathin penicillin ( Penadur L-A, Reterpen ) Benzathin penicillin is hydrolysed to penicillin G (benzyl penicillin). It is very poorly soluble and thus is slowly released from the intramuscular infection site. The combination of hydrolysis and slow absorption results in low serum levels, much lower but much more prolonged than other parenteral penicillins. As a result, in many indications, injections at intervals of 1-2 weeks are sufficient so that the frequency of administration and the resultant local trauma can be reduced. Indications Treatment of infections due to penicillin G sensitive microorganisms It is used as a single agent in the treatment of acute tonsillitis, wound infections, bite wounds, Syphilis and other treponemal infections. Precautions Patients should be alerted to the potential occurrence of allergic reactions and instructed to report them. Patients should be watched for 30 minutes after drug administration and adrenalin (epinephrine) should be kept ready so that if allergic reaction occurs the drug should be withdrawn and the usual treatment with epinephrine, antihistamine and corticosteriods be instituted. Contraindications Hypersensitivity reaction to any penicillin or related drugs eg. Cepalosporins.
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Procaine penicillin Same as benzathin penicillin except that procaine penicillin is shorter acting and therefore is administered daily. B: ORAL PENICILLINS Penicillins are also active via oral route. include. Ampicillin (aminobenzyl penicillin) Indication Infections sensitive to penicillins . it is contra-indicated in hypersensitive patients. Important points to consider 1. Ask patient about allergy to penicillins 2. Obtain specimen for culture and sensitivity 3. Give orally on an empty stomach (i.e one hour prior to or 2 hours after food.) 4. Administers round the clock 6 hourly( in equal intervals variation in serum level) Dose: give according to standing orders. The cephalosporin Cephalosporin inhibits bacterial cell wall synthesis in a manner similar to that of peniciin. Classification. Cephalosporins may be classified by their chemical structure, clinical pharmacology, resistance to -lactamase, or antimicrobial spectrum, the well accepted system of classification by generations is very useful. 1st Generation cephalosporins. E.g Cephalothin, Cephalexin, Cefazolin, Cepharodine, Cepaprin. 2ND Generation cephalosporins. E.g Cefaclor, Cefuroxime, and Cefoxtin. 3rd Generation cephalosporins. e.g Cefperazone, Moxalactine, Ceftazidine, to promote less Some examples of oral penicillins
Cefotaximine, Ceftriazone.
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4th Generation cephalosporins. e.g. Cefepine. Clinical uses: a. septicemia especially, wen he causative organism is not known or other antibiotics are contraindicated. b. Menigities caused by menigococci or pneumococci or H. influenzae. c. Peritonitis and biliary tract infections. d. Typhoid fever e. Pneumonia of unkown aetiology. f. Acute pyelonephrities or prostates and resistant urinary tract infections.
g. Other infections simiilar to penicillins.
In areas where there are no facilities for estimating the blood levels of antibiotics, cephalosporins are usually preferred due to their lower toxicity. Cephalosporins are also safe in pregnancy. Side effects. Usual doses of cephalosporins are not toxic. Excesses parenteral doses can lead to drowsiness and mental disturbances. Skin rashes may occur due to sensitization to the cephalosporins nucleus as in penicillins. AMINOGLYCOSIDES. This group of antibiotics includes gentamycin, kanamycin, Tobramycin, amikacin, Neomycin, Streptomycin etc. they have a number of common properties. a. They are bacteriocidal
b. They are not orally absorbed
c. They have potential toxicity and nephrotoxicity, especially in elderly and patients with renal failure. Antibacterial spectrum. Aminoglycosides are effective against a wide range of Gram-positive and Gramnegative organisms. MOA: Aminoglycosides inhibit protein biosynthesis.
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Therapeutic uses. Gnetamycin is the drug of choice and used in: a. peritonitis and biliary tract cephalosporin resistant infections. b. Endocarditis ( inflammation of cardiac muscles) c. Meningitis cause by listeria ( in combination with amoxicillin) d. Acute pyelonephritis or prostatitis e. Septicemia community or hospital acquired f. Prulent conductivities ( as gentamycin eye drops) Adverse effects. Aminoglycosides may cause vestibular and auditory damage and nephrotoxicity. These class of antibiotics are contra-indicated in pregnancy. Co-adminstration with Frusemide increases the risk of ototoxicity. TETRACYCLINES Tetracyclines are bacteriostatic agents which for practical purpose, have identical range of activity examples include doxycycline, tetracycline, oxytetracycline, etc. Mechanism of Action. Tetracyclines are broad spectrum antibiotics that inhibit protein synthesis. They are bacteriostatic for many gram-positive and gramnegative bacteria. Indications Tetracyclines are used in chlamydia (lymphogranuloma venerum and nongonococcal urethritis). They are also employed systemically in acne vulgaris and rosaea. Doxycycline is also used in the treatment of plasmodiasis. They are used in combination regimens to treat gastric and duodenal ulcer disease cased by Helicobacter pylori. Dose The oral adult dose is 250 500mg 6 hourly before meals because the absorption of most Tetracyclines is reduced by chelating with heavy metals (eg calcium) or milk. Doxycycline is an exception and also has the advantage that it is given once daily 200mg first day and 100mg thereafter or twice a day i.e 100mg 12 hourly.
24
Side effects Tetracyclines are generally safe antibiotics with few side effects. The commonest is diarrhoea which usually stops when the antibiotic is discontinued. Tetracyclines chelates with calcium and are deposited in developing bone and teeth causing a brown discolouration. They should not therefore be given to children or pregnant women with the exception of doxycycline and minocycline. The tetracyclines can exacerbate renal failure and should not be given to patients with impaired renal function. MACROLIDES These are Erythromycin, clarithromycin, Azithromycin (zithromax) etc Erythromycin has similar though not identical spectrum of activity with penicillins and is commonly used to treat infections caused by gram-positive organisms in penicillin allergic patients. Mechanism of action Erythromycin and other macrolides inhibit protein synthesis in bacterial. Indications It is effective in whooping cough ( as well as other coughs) campylobacter enteritis. It is effective in many acute respiratory infections and other infections where it is found to be sensitive. Dose Erythromycin is prescribed in doses of 250mg-500mg by mouth six (6) hourly. There is a preparation for intravenous injection. Side effects Diarrhoea, vomiting and abdominal pian are principal side effects. Cholestatic jaundice may rarely develop if the course of treatment exceeds ten days. CHLORAMPHENICOL
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Chloramphenicol is a potent broad-spectrum antibiotic similar to tetracyclines with the important addition of salmonella and paratyphoid organisms. The daily oral dose for an adult is 1g-3g given every six hours. The preparation for parenteral administration is also available. Mechanism of Action. Chloramphenicol act as inhibitor of protein synthesis. Indication Chloramphenicol is a drug of choice in meningitis due to H. Influenzae. It is used in typhoid fever and other infections where it is found to be sensitive. Chloramphenicol eye drop and ointment are useful for purulent conjunctivitis. Side effects Chloramphenicol is known to cause bone marrow depression. It should never be given to premature infants or to the newborn because of the risk of the development of the frequently fatal grey baby syndrome. This is a state of acute circulatory failure caused by the very high blood levels of chloramphenicol due to its inadequate metabolism in the liver at this age.
Ciprofloxacin is the most important of the 4-quinolones. QUINOLONES
It has THE 4-
a relatively broad spectrum with particularly high activity against aerobic gramnegative bacilli including salmonellae, shigellae, campylobacter and pseudomonas spices. It is also active against chlamydia but not against anaerobic bacterial. Although many gram-positive organisms are sensitive to ciprofloxacin the activity is only moderate especially against pneumococi. Mechanism of Action. Quinolones block baterial DNA synthesis.( they are commonly called DNA gyrase inhibitors.) Dose: The oral dose is 250mg 750 mg 12 hourly and for intravenous infusion 200 mg 12 hourly.
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Indication Ciprofloxacin has a wade range of indications including gastrointestinal, urinary tract and lower respiratory tract infections (not phneumococcal), septicaemia and gonorrhoea. Other 4-quinolones include Norfloxacin (norbactin), ofloxacin (tarivid), Sparfloxacin, Levofloxacin (levoxin), etc. Side effects The adverse effects encountered with the 4 qunolones include Nausea, vomiting, diarrhoea, rashes insomnia, dizziness, headache and convulsions (especially when combined with NSAIDs).Quinolones may damage growing cartilage and case an arthorpathy. Thus , they are not routinely recommended for use in patients under 12years of age and pregnant women. However, the arthoropathy is reversible METRONIDAZOLE This is an imidazole compound. It has high activity against anaerobic bacteria and interstinal protozoa but none against aerobic bacteria. Mechanism of Action. Within anaerobic bacteria and sensitive protozoal cell, metronidazole is reduced by ferredoxin. The reduction products appear to be esponsible for killing the organisms by reacting with various intracellular molecules. dracunculiasis, its action apparently is anti-inflammatory. Indications Metronidazole is effective against infection due to Trichomonas vaginalis, Giardia lamblia and Entamoeba histolytica and is widely used for treatment and prophylaxis of infections caused by anaerobic bacteria, notably B. fragilis, clostridium tetani and clostridium difficile. In amobiasis, metronidazole kills Entamoeba histolytica trophozoites but not cysts. In
27
Side effects Side effects of metronidazole are usually limited to headache and nausea but it should not be given to women during the first trimester of pregnancy. Alcohol should be avoided during therapy with metronidazole, which has a similar action to disulfiram.
CO-TRIMOXAZOLE This is the combination of Trimethoprim 80mg + Sulphamethoxazole 400mg, which act by inhibiting enzymes at two successive stages in the synthesis of paraaminobenzoic acid to folic acid and DNA. Mechanism of Action. It inhibit the synthesis of DNA. Uses Co-trimoxazole is used in the treatment of exacerbation of chronic bronchitis and urinary tract infections. It is also effective in the treatment of invasive salmonella infections. Double-dose co-trimexazole is used to treat pneumonia caused by pneumocystis carinii commonly prevalence among HIV/AIDS patients. Dose Usually 2 tabs (960mg) 12 hourly but 1440mg (3 tablets) 8 hourly Or 920mg (4 tablets) 12 hourly can be used in pneumocystis carinii common in AIDS patients. Side effects Rash, ( commonly called Seven-Johshons syndrome), jaundice, headache, vomiting and diarrhea.
CHEMOTHERAPEUTIC AGENTS IN TUBERCULOSIS MYCOBACTERIAL INFECTION: A BRIEF REVIEW
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Tuberculosis
(TB)
is
bacterial
infection.
The
causative
organism,
mycobacterium tuberculosis, thrives best in organs with high oxygen tension e.g lungs. The infection is transmitted by inhalation of infected droplets or by acquired ingestion of milk from infected cattle. The bacterial can enter the body by several routes viz: lungs, and gastrointestinal tract or by direct cutaneous inoculation (vaccination, accident at autopsy)
CLINICAL FEATURES In most clinical cases of TB, the disease is present in the form of postprimary pulmonary TB. The disease is often bilateral, starting in one lung and commonly spread via the bronchi to the other. The clinical findings of TB can be divided into: Systemic symptoms Symptoms due to the systemic effects of the disease include fever, loss of weight, tachycardia (increase heart rate) loss of appetite, anaemia, malaise and sweating especially during sleep. Specific symptoms Cough, Hemoptysis (blood in sputum) and Dyspnea (difficulty in breathing) PHARMACOLOGY OF ANTI-TB DURGS. Chemotherapy is the most important measure taken in the treatment of all forms of tuberculosis and is therefore given to every person with the active disease. Drug therapy has transform TB from a disabling and often fatal disease into one in which almost 100% cure is obtainable. Chemotherapy was formerly protracted but a better understanding of the pharmacology of TB drugs has allowed the development of effective short course regimen. PRINCIPLES OF ANTI-TB THERAPY A large number of actively multiplying bacilli must be killed: Isoniazide achieves this.
29
Treat persisters, i.e semidormant bacilli that metabolize slowly or intermittently: Rifampicin and Pyrazinamide are the most efficacious. Prevent the emergence of drug resistance by multiple therapies to suppress drug-resistance mutants that exist in all large bacteria populations.
Combined formulations are used to ensure that poor compliance does not result in monotherapy with consequent drug resistance.
SPECIFIC ANTI-TB DRUGS Many drugs are available, whose use is primarily limited to the treatment of tuberculosi. ANTI-TB Drusg are classified into: First line drugs: these include Isoniazid ( INH), Pyrazinamide (PZA), Rifampicin, Streptomycin and Ethambutol Second line drugs: these include Ethionamide, cycloserine, ofloxacin, etc. ISONIAZID (INAH, INH, Isonicontinic Acid Hydrazide) MOA: INH prevents the synthesis of mycolic acid, an important constituent of mycobacterium cell wall. It is bacteriocidal against actively multiplying bacilli but it is bacteriostatic against non-multiplying bacilli. It has little or no activity against other bacteria. Dose: In adult the usual adult dose is 5mg/kg Indication: Treatment of TB in combination with other drugs. Side effects: INH is generally well tolerated. The most sever side effect is liver damage. INH causes an increase in metabolism and in urinary excretion of pyridoxine (vitamin B6). The principal result of vitamin B6 deficiency is Peripheral Neuropathy characterized by numbness and tingling of the feet, Neuropathy is more frequent in a person that metabolizes INH slowly, malnourished people, the elderly, those with pre-existing liver disease, Alcoholism, diabetes and HIV infection. Such patients should receive pyridoxine (10mg- 50my) daily by mouth,
30
which prevent neuropathy and does not interact with therapeutic effect; some prefer simply to give pyridoxine to all patients. Other side effects are Mental disturbances, incoordination, nausea and vomiting Patients advice INH should be taken on an empty stomach. If taken with food to reduce GIT irritation, oral absorption and bioavailability may be impaired. RIFAMPICIN Rifampicin has bactericidal activity against the tubercle bacillus, comparable that of INH. Rifampicin is a semi-synthetic from the group of Rifamycine antibiotics. MECHANISM OF ACTION: Rifampicin act by inhibiting RNA synthesis, bacterial being sensitive to this effects at much lower concentration than mammalian cells. It is particularly effective against mycobacterium that lie semi dormant within cells. INDICATION Rifampicin has wide range of antimicrobial activity. Its uses include: Anti TB, Anti leprosy, Chemoprophylaxis of meningicoccal meningities, Staphylococcal endocarditis and osteomylitis. Dose: 10mg/kg daily (usual adult dose = 600mg daily) Side effect: severe GIT disturbances including nausea, vomiting a diarrhoea. Headache, rashes, urine, tears, saliva and sputum colorued orange red. Hepatitis sometimes reported in some selected individuals taking the drug. Patients advice Do not stop taking drug except on medical advice This medicine may colour urine (or other body fluids) or stool. Take half to one hour before food or on an empty stomach
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Observe for signs of liver damage eg fever, loss of appetite, fatigue, jaundice, dark urine, liver enlargement etc. PYRAZINAMIDE (PZA) pyrazinoic acid Amide. Pyrazinamide is the synthetic pyrazine analogue of nicotinamide. It is included in the first choice combination regimen because of its particular ability to kill persisters; i.e mycobacteria that are semi dormant , often within cells. Indication TB in combination with other drugs. Mechanism of action The action of Pyrazinamide is dependent on the activity of intrabacterial enzyme, pyrazinamidase, which converts pyrazinamide to the active pyrazinoic Acid. This enzyme is most effective in an acidic environment such as the interior of cells. This explains why pyrazinamide is very effective in killing the semi-dormant bacterial. DOSE: 25mg/Kg Side effects: The most common and serious unwanted effect of PZA is injury to the liver with jaundice, and often preceded by nausea and vomiting. This is not a problem again with the modern short course schedules. Hyperuricaemia with acute episodes of gout may occur. The use of NSAIDs is sufficient to reduce pains. Patients instruction Observe for signs of liver damage and report it to the health worker Take drugs on an empty stomach. ETHAMBUTOL
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Ethambutol is a synthetic anti-TB drug. It is bacteriostatic therefore must be used only in combination with other anti-TB drugs to delay or prevent the emergence of resistance bacilli. MOA: Its mode of action is unknown. Indication: TB in combination with other drugs. Dose: 15mg/Kg daily Side effects In recommended oral doses (15mg/Kg /day). Ethambutol is re3latively nontoxic. The main problem is opitc neuritis (unilateral or bilateral) with a reduction I visual acuity and loss of ability to perceiver the colour green. Regular ophthalmological tests should be performed during ethambutol therapy. Contraindication: Optic neuritis, Children under 5 years, (these cannot report symptomatic visual disturbances)and in Severe renal impairment Patients advice. Patient to observe visual disturbance and report immediately. Other instructions as applied to other anti-TB STREPTOMYCIN Streptomycin is an aminoglycoside antibiotic obtained from streptomyces griseus. Mode of action: The aminoglycosides (streptomycin, gentamicine etc) are bactericidal. They act inside the cell by inhibiting bacterial protein synthesis. Aminoglycosides are water-soluble and do not readily cross cell membranes. Poor absorption form the intestine necessitates their administration IV or IM for systemic use.
33
Indications Treatment of TB in combination with other drugs. Dose: 15mg/Kg/day Streptomycin is one of the very few drugs that is not only used against mycobacterium but is also active against other bacteria. Side effects 1 Ototoxicity due to damage on eight (8) cranial nerve which result in the progressive destruction of vestibular and auditory cells. The effect is seen as hearing loss , vertigo and tinnitus which may be permanent if not discontinued. Neuromuscular blockade: streptomycin causes acute muscular paralysis and apnea due to inhibition of prejuctional Acetylcholine release. The drug may aggravate myasthenia gravis or cause a transient myasthenia syndrome in patient whose neuromuscular transmission is normal. The most effective treatment of this problem is administration of calcium salt e.g. calcium gluconate THIOCETAZOLE This drug is tuberculostatic and is used with Isoniczid (as in Diateben) to inhibit the emergence of resistance to the later . Dose= 2.5 mg/Kg/day orally only. Side effects. Thiocetazone causes the following Nausea, vomiting, diarrhoea, conjunctivitis, rashes, acute hepatic failure and may increase the ototoxic effect of streptomycin. Indications: TB and Leprosy.
ANTIFUNGAL DRUGS. Fungal infections are generally divided into superficial infections affecting skin, nails hair mucus membranes and systemic infections involving deeper
34
tissues and orgsna.
The increasing use of broad spectrum antibiotics and
immunosuppressant ( e.g glucocorticoids) drugs is one of the reasons for the increased incidence of fungal diseases. The patients with AIDS are potential candidates for fungal infections. Most of antifungal drugs act by inhibiting the synthesis of ergosterol, an essential components of fungal cell remembrance or by binding to the wall of the fungus, disrupting its integrity. Topical antifungal. Nystatin. An antibiotic is fungistatic at low concentrations and fungiscidal at high concentrations. It is not absorbed appreciably from the gut, skn or mucus membranes. It is not used parenterally. Uses. Nystatin is used in candida infections of the skin, mucuous membranes and intestinal tract. Side effects. Occasional nausea, vomiting and diarrhea occur with high oral doss of nysatin. Rash and rarely Stenvens-Johnson syndrome have reported. Clotrimazole and Miconazole are most effective if applied locally as pessareis in the treatment of vaginal canddiasis. They are also effective in ringworm and other fungal skin infections. SYSTEMIC ANTIFUNGALS. These are antifungal agents internally for their antifungal effect. They produces appreciable absorption from the gut and some may be administered parenterally. Griseofulvin-, a fungistatic antibiotic, is effective for widespread or intractable dematophyte (i.e skin) infections but has been superseded by newer antifungal agent particularly for nail infections. It is ineffective in candidiasis. Griseofulvin is well absorbed from the gut, has a particular affinity for keratin and is eliminated unchanged in the feces. Because of its affinity for keratin, it is useful in the treatment of ringworm infections of the kin, hair and nails. Thrush ( oral candidiasis) and vaginitis are treated by topical application, whereas intestinal candidiasis is treated by oral administration.
35
Side effect. Griseofulvin is usually well tolerated. GIT upset and rashes may occur. It is contraindicate in severe liver disease and pregnancy. TERBINAFINE is given orally and is the drug of choice for fungal nail and
ringworm infections. Side effect include GIT upset and rashes. Serious skin reactions and rarely liver toxicity have also been reported KETOCONAZOLE is largely used in severe candidiasis and other systemic fungal infections. It is well absorbed and given orally. The most important side effect is jaundice, when the drug must be stopped. Others include nauseas, drowsiness and rarely adrenal suppression. FLUCONAZOLE can be administered orally or by intravenous infusion. Penetration of the drug into the CSF and other body fluid is very good. It is effective in candidiasis and all other forms of fungi infections. Side effects. Fluconazole does not cause serious side effects, particularly liver damage. GIT distress and rashes are mot common side effects.
CARDIOVASCUALR SYSTEM DRUGS. Cardiovascular system comprises of the heart and blood vessels. The cardiovascular system drugs are therefore drugs in the treatment of disease conditions affecting the heart and or blood vessels. Some of these conditions include. Hypertension, heart failure, angina pectoris, cardiac arrhythmias, myocardial infarction etc. ANTIHYPERTENSIVE DURGS Hypertension is the persistence increase in blood pressure above acceptable range measured over a long period of time.
36
There are two approaches aimed at the reduction of blood pressure. a. Non- pharmacological therapy b. Pharmacological therapy NON-PHARMACOLOGICAL THERAPY OF HYPERTENSION The non-pharmacological approach to the reduction of blood pressure is generally advisable as the initial approach to treatment of patient with diastolic blood pressure in the range of 90-95mmHg. Further, these approaches will augment the effectiveness of pharmacological therapy in patients with higher levels of blood pressure. All drugs have side effects. If minor alterations of normal activity or diets can reduce blood pressure to a satisfactory level, the complications of drug therapy can be avoided. In addition, non-pharmacological methods to lover blood pressure allow the patient to participate actively in management o his or her disease. Some of these non-pharmacological approaches to BP reduction include
1. REDUCTION OF BODY WEIGHT Obesity and hypertension are closely associated and the degree of obesity is positively correlated with the incidence of hypertension. Obese hypertensives may lower their BP by loosing weight regardless of a change in salt consumption. 2. SODIUM RESTRCTION ( SALT RESTRICTION) Sever restriction of salt will lower the blood pressure in most hospitalized hypertensives patients; this treatment method was advocated prior to the development of effective antihypertensive drugs. However, severe salt restriction is not practical forma a standpoint of compliance. Several studies have shown that moderate restriction of salt intake to approximately 5g per day (2g Na+) will on average, lower blood pressure by 12mmHg systole and 6mmHg diastolic . The higher the initial blood pressure, the greater the response. In addition, subject
37
over 40 years of age are more responsive to hypertensive effect of moderate restriction of salt. 3. ALCOHOL RESTRICTION Consumption of alcohol can raise blood pressure but it is unclear how much alcohol must be consumed to observe this effect. Heavy consumption of alcohol increases the risk of cerebrovascular accidents (stroke) 4. PHYSICAL EXCERCISE Increase physical activity lowers rates of cardiovascular disease in men. Lack of physical activity is associated with a higher incidence of hypertension. 5 RELAXATION THERAPY The fact that long term stressful stimuli can cause sustained hypertension in animals has given credence to the possibility that relaxation therapy will lower blood pressure in some hypertensive patients. A few studies have generated positive results but in general relaxation therapy has consistent and modest effects on blood pressure.
6. REDUCTION OF FATTY FOODS. (HIGH CHOLESTEROL) Cholesterol is a fat-like material carried by the blood to every cell in the body. It is important in maintaining the integrity of the cell walls and forms part of some hormones in the body. Our body makes all the cholesterol it requires. Problems begin when the body makes extra cholesterol for the foods we eat especially fatty foods. High cholesterol s a factor that increases your chance of getting heart diseases. This is because, when there is too much cholesterol in the blood, some of it may begin to stick to the wall of the blood vessels. Over time, the blood vessels may clog and slow down the flow of blood or stop the flow entirely. PHARMACOLOGY OF ANTI-HYPERTENSIVE AGENTS. -Diuretics
38
-Beta Generic name: Methyldopa Trade names: Aldomet, Dopamed, Dopatab etc. Methyldopa is a centrally acting antihypertensive agent. It is a prodrug that exerts its antihypertensive action via an active metabolite. Methyldopa metabolises to alpha-methyldopamine , which then is converted to alpha-methylepinephrine.
Mechanism of action Alpha-methylnorephinephrine acts in the brain as alpha 2 receptor agonist to inhibit or attenuate the output of vasoconstrictor adrenergic signals to the peripheral sympathetic nervous system. Because the site of action is mainly in the brain stem where it is metabolized to its active form, methyldopa is commonly referred to as centrally acting antihypertensive agent. Indications 1 It is an effective antihypertensive agent. 2. It is the preferred drug for treatment of hypertension during pregnancy bases on its effectiveness and safety for both mother and foetus. Dose. The usual initial dose of mehtyldopa is 250mg twice daily. Administration of a single daily dose of methyldopa at bed time minimizes sedative effect, but administration twice daily may be required for some patients. Patients instructions. Administer drug before food. Dry mouth can be relieved with chewing gum or ice chips Teach patient not to discontinue medication abruptly as this may cause headache, raise BP, tremors nausea, vomiting Change position slowly as this may cause postural (orthostatic hypotension) Adverse effects
39
Transient sedation, Dry mouth, Reduction in libido ( this may be worrisome in men, Hyperprolactinemia Haemolytic anaemia. causing gynaecomastia and galactorrhea and
NB: the management of Hypertension by a community health worker must base on the provision in the standing orders. CONGESTIVE HEART FAILURE In CHF, the contractibility of the cardiac muscle decrease and the heart is not able to empty itself completely, resulting in a low cardiac output. The pressure in the venous system, filling the heart rises and the neck veins become distended and the hearth dilates. Low cardiac output leads to inadequate bloods supply to various organs in the body. This is particularly important in the kidney as poor renal blood flow activates the angiotensin/renin system, causing the kidney to retain salt and water with resultant oedema of dependent parts and lungs. Angiotensin causes vasoconstriction and increase in peripheral resistance with increases the work of an already failing heart. Drugs used in CHF mainly belong to three groups.
(a) Cardiac Glycosides.
These drugs increase the force of myocardial This is called positive
contraction thereby raising the cardiac output. cardiac muscles. purpurea. Side effects. Undue slowing of the heart.
inotropism (positive inotropic effect) i.e increase in the contraction of the eg Digoxin and digitoxin which are the two principal glycosides obtained from there dried leaves of the foxglove Digitalis ( i.e decrease pulse rate),
nausea, vomiting, visual disturbances, headache etc.

(b) ACE Inhibitors.
These drugs inhibit the overactive angiotensin/rennin
mechanism, thereby cause a reduction in the retention of salt and water and more importantly by dilating arterioles lower the resistance to blood flow from the heart . eg. Lisinopril, Captopril, enalapril.
40
Side effects. ACE inhibitors may cause dry cough, abdominal pain, renal failure and pregnancy.
(c) Diuretics. These drugs causes
abnormal foetal growth.
ACE inhibitors are contraindicated in
the kidney to excrete excess salt and
water thereby relieve the oedema. E.g Furosemide, Hydrochlorthiazide etc. Side effects. These include biochemical disorder such as hypokalaemia, hyperuricaemia, gout, hyperlipidaemia and hypomagnesaemia, hyperglycaemia. CNS DRUGS. The Central Nervous System comprises of the brain and the spinal cord. The CNS drugs are the drugs that produces their effect via the actions on the CNS. Examples of CNS drugs include: ANTIPSYCHOTIC DRUGS Antipsychotics are the drugs that quiten disturbed patients with psychotic disorders irrespective of psychopathology. Psychosis can be divided into schizophrenia and affective disorders. Facets of schizophrenia indicates that it is a complex set of entities rather than a single disorder. In actual clinical settings, schizophrenia of the undifferentiated type is most often seen. Schizophrenia syndrome share similar symptoms that can be alleviated with the use of antipsychotic agents. Schizophrenia has a profound effect on the total personal it, mod , behaviour and thinking. The symptoms include inappropriate behaviour, delusions, hallucination, loose associations, social withdrawal, disorder of affect, bizarre thinking, confusion, mental blocking, personal neglect and excitement. ETIOLOGY The etiology is unknown but the current understanding of schizophrenia suggests that it has metabolic, genetic and psychosocial components. However; it is currently believe that amines (Dopamine and norepinephrine in particular) are
41
involved in the schizophrenic process and that an imbalance between the two is associated with the disease. BASIC PHARMACOLOGY OF ANTIPSYCHOTIC DURGS Several classes of drugs are effective in the symptomatic treatment of psychiatric disorders. Antipsychotic drugs share many pharmacological effects and therapeutic applications. They are classified into the following classes: -Phenothiazines eg Chlorpromazine (largactil), Fluphenazine (Modecate) etc -Butyrophenones eg. Haloperidol (Haldol, Serenace) Thioxantines eg Flupenthixol (depixol) etc Chlorpromazine (CPZ) is commonly taken as prototype for The older antipsychotics. CHLORPROMAZINE (CPZ, Largactil etc) Chlorpromazine is a Phenothiazine antipsychotic agent. It brings about its action by inhibiting (or blocking) dopamine receptors. It is therefore commonly referred to as dompamine receptor antagonist. This is the mechanism by which all antipsychotics produces their therapeutic effects. INDICATION CPZ is a representative antipsychotic agent used in the management of schizophrenia and other psychotic disorders. It is also used as an antiemetic and intractable hiccup. SIDE EFFECTS CPZ causes extrapyramidal symptoms, and on prolonged administration, occasionally tardive dyskinesia occurs. Components of extrapyramidal symptoms include Acute dystonia = spasms of muscles of tongue, face, neck and back. Akathisia = motor restlessness. It is a strong felling of distress or discomfort. Parkinsonism = slowing of movement, rigidity and tremor at rest especially the upper extremities.
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Tardive dyskinesia- this is a late appearing neurological syndrome characterized by painless, involuntary movement of the face, eyelids (blinks and spasms) mouth (grimaces), tongue, extremities (especially the upper extremities). These movements all disappear in sleep Other side effects include: Nightmares, depression convulsions, nasal congestions, dry mouth, blurred vision Dosage forms available: tablets, oral solutions, injectables, suppositories, syrup and suspensions. NB: Owing to the risk of contact sensitization, Health workers should avoid direct contact with CPZ. Tablets should not be crushed and solutions should be handled with care.
HYPNOTICS AND SEDATIVES A sedative drug decreases activity, moderate excitement and calms the recipient while a Hypnotic drug produces drowsiness and facilitate the onset and maintenance of a state of sleep that resembles natural sleep form which that recipient (i.e the patient ) can be aroused easily. Hypnotics-Sedatives depresses the CNS in a dose dependent fashion i.e a drug may be a sedative at small dose; at higher doses; the drug may produce hypnosis in e same individual. The commonly use sedative hypnotics are Benzodiazepines and Barbiturates. BENZODIAZEPINES Examples of benzodiazepine include Diazepam (valium), chlordiazepoxide (Librium) , Bromazepam ( Lexotan) etc. PHARMACOLOGY OF BENZODIAZEPINES All effects of Benzodiazepines result from their activity on the CNS. The most prominent of these effects are:
43
Sedation, Hypnosis, Decreased anxiety, Muscle relaxation and Anticonvulsants activities All Benzodiazepines share similar pharmacological profile as their doses increases, sedation increases to hypnosis. They do not cause true anesthesia, since awareness usually persists and relaxation sufficient to allow surgery cannot be achieved.
MECHANISM OF ACTION Benzodiazepines act directly on Gama Aminobutyric Acid (GABA) receptors. They directly activate GABA receptors which leads to proofed CNS depression. GABA is an inhibitory neurotransmitter in the CNS. INDICATIONS Diazepam (valium) is used in Anxiety disorders, Status epilepticus, Skeletal muscle relaxant Anesthetic premeditation (to improve muscle relaxation and alley fear of surgical procedures) and Management of alcohol withdrawal. Side effects Benzodiazepines share many common side effects and these include: Light headaches, Motor incoordination, Confusion, Weakness, Blurred vision, Nausea and vomiting, Rebound insomnia upon discontinuance. BARBITUREATES Examples of barbiturates include Phenobarbitone, Thiopental etc. The barbiturates enjoy a long period of extensive use as sedative hypnotic drugs; however; except for a few specialized uses, they have been largely replaced by the much safer benzodiazepines.
44
MECHANISM OF ACTION The barbiturates reversibly depresses the activity of all excitable tissues. Enhancement of inhibition occurs primarily at synapses where neurotrasmission is mediated by GABA. Barbiturates also inhibits glutamate induced action potentials. Glutamic acid is an excitatory neurotransmitter in the CNS. INDICATIONS The uses of barbiturates has reduced drastically due to their low therapeutic index. They are commonly use as Sedative in insomnia Anticonvulsants such that occurs in Tetanus, Eclampsia, Status epilepticus, Cerebral hemorrhage and Poisoning with convulsant drugs. Anesthetic agents. (intravenous) Benzodiazepines are however superior for these uses due to their high therapeutic index and low incidences of drug interactions. Side effect Drowsiness, Distortion of mood, Impaired judgment, Vertigo Nausea and vomiting. Drug interaction Barbiturates taken concomitantly with alcohol causes severe CNS depression. Barbiturates inhibit the metabolism of other drugs eg vitamin D and K. NB: The Benzodiazepines and Barbiturates have been termed minor tranquilizers. This term is misleading because not only do they differ markedly from psychotic drugs ( the so called major tranquillizers) but their use is by no means minor. Antipsychotic in low doses are also sometimes used in severe anxiety for their sedative action but long term use is discouraged in view of a risk of Tardive dyskinesia.
45
ANALGESICS REVIEW OF PAIN MANAGEMENT Pain is the activation of electrical activity in afferent neurons with sensory endings in puerperal tissues that have a higher firing threshold than those of temperature or touch. These neurons are activated by stimulation sufficient to cause tissue damage. Pain is primarily a protective signal to warn of damage or the presence of disease. It is also part of the normal healing process. This process involves inflammation, in which protective cells move into the injured area and release chemical mediators that causes fluids and plasma proteins to leak into the surrounding tissue. The result is repair and healing, but also stimulation of pain nerve endings. Pain is classified as acute, chronic nonmalignant chronic malignant.
Acute. This type of pain is associated with trauma or surgery. Acute pain is usually easier to manage by identifying and treating the cause, and it disappears when the body heals.
Chronic Nonmalignant. This type of pain may have a diagnosed or an undiagnosed cause, such as a nonmalignant disease. The pain last for more than three months and may respond poorly to treatment. Chronic nonmalignant pain may have signs and symptoms of depression in patients
46
with a high tolerance of pain. transmission are the same
The neurotransmitters involved in pain as those involved with depression
(norepinephrine, dopamine, and serotonin). In this syndrome, pain lasts longer than three months, may or may not have an identifiable physical or chemical basis, creates an overwhelming lifestyle burden for the patient, and does not respond to medication.
Chronic malignant. This type of pain accompanies malignant disease ( eg. Cancer pain) and often increases in severity as the disease progresses. Acute and chronic pain differs in one important way. Whereas acute pan
has a beginning and an end and warns of a problem, chronic pain does not cease when an illness or injury is cured or healed. Total pain has physical, psychological, social and spiritual components. Adequate sleep, mood elevation, diversion, sympathy, and understanding all can raise an individuals pain threshold. Alternatively, fatigue, anxiety, fear, anger, sadness, depression, and isolation can lower the pain threshold. Analgesics. Analgesics are drugs that relieve pain without loss of consciousness. They are usually classified into narcotics and non-narcotics analgesics. The narcotics analgesics are also called opioid analgesic a name coined after the opium poppy, papaver somniferum from which they are derived. Conversely, the non-narcotics are also called non-opiates. OPIATES ANALGESICS These drugs act on pain perception within the central nervous system. At the PHC level, the naturally occurring opiate in the standing order is Codeine phosphate. Other examples relating to codeine are morphine, Heroine and cocaine. A synthetic opiate in the standing order is pethidine. Other examples relating to pethidine include Pentazocine (sosegon , Fortwin ) Tramadol (Tramal) Opiates work because they are agonists of opioid receptors sites having their main effects on the CNS, GI tract, and, to a lesser extent, peripheral tissues. The body (especially the brain) products three distinct types of natural opiods
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endorphins, enkephalins, and dynorphins in response to pain stimuli. As pain increases, the levels of these chemicals also increase. When opioid receptors are activated, nerve transmission to CNS centres for pain processing is decreased, so the sensation of pan is diminished. Narcotics bind to the same receptors as these natural substances, causing activation ( agonist effect). Narcotics have the following effect. Analgesia i.e they reduce pain Sedation i.e they allay anxiety and cause drowsiness. Euphoria and dysphoria i.e they induce feelings of well-being or feelings of disquiet, restlessness, or malaise, respectively. All narcotics have the potential to induce tolerance and dependence. Narcotics also reduce the cough reflex and respiratory drive; increase mental clouding; and can cause nausea, vomiting, and constipation. Persistent pain should be treated in a stepwise fashion: first acetaminophen, then Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), and then the opiods. A simple scheme for analgesic selection is known as the analgesic ladder, which is illustrated below. The WHO analgesic ladder for pain relief.
Opioid for moderate to sever pain Non-Opioid, Adjuvant

Pain persisting or increasing
e.g morphine, oxycodone, fentanyl Adjuvant. e.g Codeine, Pentazocin.
Opioid for moderate to sever pain Non-opiod, Adjuvant

Pain persisting or increasing.
Non-opioid Adjuvant
e.g aspirin, acetaminophen or an NSAID
Pain Pharmacology of Narcotic analgesic
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Opioid (or narcotic) analgesic provide relieve of pain, but the underlying disease remains. The health worker should weigh the benefit of the relief against any potential risk to the patient, which may be quite different in an acute compared with a chronic disease. CODEINE Codeine is an opioid analgesic. Its use has been restricted as a prescription only drug due to its highly addictive property. When taken codeine is converted to morphine in the body . it is available both as oral and parenteral formulation respectively. Indications Codeine is indicated in mild to moderate pain. It is also used as an antitussive (cough suppressant) examples of cough preparations containing codeine include Benylin and Phensydyl linctus. Side effect Severe constipation, Nausea and vomiting, Drowsiness and urinary retention. MEPERIDINE (PETHIDINE, Demerol) meperidine produces a pattern of effect similar but not identical to tat described for codeine. Meperidine is a synthetic opioid. It is less potent and short acting analgesic. It has no effect on cough centers. It is less depressant to respiratory center and does not cause constipation. Indication Meperidine is indicated in moderate to sever pain. It is not suitable for severe continuing pain. It is used for analgesic in Labour and in neonate is associated with less respiratory depression, (probably because its action is weaker). Other uses of opioids are: Treatment of diarrhoeas and Anaesthesia
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NON-OPIOIDS ANALGESICS These include paracetamol, and other general class known as Non-Steroidal Antiinflammatory Drugs (NSAIDs). NSAIDs are very useful in the control of painful inflammatory conditions in general
NSAIDs: Pharmacological properties. These drugs, besides analgesia, have Antipyretic property and Anti-inflammatory property. They do not affect temperature when it is elevated by factors like exercise and ambient temperature. Aspirin) Mechanism of actions. All NSAIDs acts by inhibiting the enzyme cyclo-ogygenase thereby preventing the conversion of arachidonic acid to prostaglandins as shown in the schematic pain pathway below. The prototype of NSAIDs is Acetylsalicylic Acid (ASA,
Pain pathway in tissue injury Tissue injury Arachidonic acid (-) NSAIDs
Cyclooxygenase
Inflammation. * Oedema * Pain * Fever Prostaglandins
ASPRIN
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This is the oldest and cheapest NSAID typically taken as the prototype. Its pharmacological action include: Antipyretic action. Aspirin is rapidly effective in febrile patients. It has no effect on normal body temperature. The antipyretic effect is believed to be due to inhibition of prostaglandin synthesis. Anti-inflammatory action. The anti-inflammatory activity is responsible for the use of aspirin in musculoskeletal disorders such as rheumatoid arthritis.
Analgesic action Aspirin is effective against pain of low intensity through peripheral and central mechanism. It inhibits the synthesis of prostagaladins peripherally in inflamed tissues and centrally in hypothalamus. Respiration Aspirin stimulates respiration directly and indirectly. High doses results in medullary stimulation leading to hyperventilation and respiratory alkalosis. Toxic doses can depress the medulla resulting in metabolic acidosis. Gastrointestinal tract Aspirin can cause dyspepsia, nausea and vomiting by irritating the gastric mucosa and stimulating chemoreceptor Triger Zone (CTZ) in the central nervous system (CNS). It may lead to a dose dependent gastric ulcer and bleeding . Liver close proximity to the antipyretic region in the
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Hepatotoxicity associated with encephalopathy (Reyes syndrome) can occur in children. Therefore, it is contraindicated in children below 12 years of age. Blood Aspirin , by inhibiting cyclo-oxygenase irreversibly inhibits thromboxane ( the prostaglandin produced by platelets) which is responsible for platelet aggregation . The net result is inhibition of platelet stickiness. Therapeutic uses Analgesia. ASA in low doses ( 300-600mg) is effective in conditions such as headache, musculoskeletal pain, dysmenorrheoea etc. Anti-inflammatory agent: High doses (3.6-4.2g a day) are required to achieve a clinical anti-inflammatory effect in rheumatoid arthritis and acute rheumatic fever. However; other NSAIDS may be better tolerated and preferred over ASA for inflammatory conditions. Eg Diclofenac, Ibuprofen etc Antiplatelet: Aspirin in low doses (75-100mg daily) inhibits platelet aggregation and has important therapeutic benefit in angina pectoris, myocardial infarction, and heart failure. Side effect In large doses when given over a prolonged period, aspiring causes dyspepsis, ( nausea, vomiting and epigastric pains) dizziness, tinnitus (ringing in the ear) and deafness. Hepatotoxicity and hypersensitity may also occur. Aspirin is contraindicated for fever myalgia and malaise in children aged under 12 years as it may precipitate hepatotoxicity associated with encephalopathy (Reyes syndrome) Other NSAIDs Examples of other non-sterioidal anti-inflammatory drugs include: Ibuprofen ( Brustane-N), Diclofenac (cataflam, voltaren etc,) Piroxicam (Feldene), Tenoxicam, Celecoxib (celebrex) etc.
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PARACETAMOL Paracetamol is a widely used minor analgesic and antipyretic. It has practically no anti-inflammatory action. It is believed to act as analgesic by raising the threshold to pain perception in the CNS. Unlike Aspirin, paracetamol has no effect on other body systems. It is less irritant to stomach and for this reason, it is generally preferred to aspirin as an analgesic for many type of pains. Paracetamol is the drug of choice for mild pain and fever in children as it does not cause Reyes syndrome seen with aspirin.
RESPIRATORY SYSTEM DRUGS. The pulmonary disease include asthma, chronic obstructive pulmonary disease (COPD). COPD is irreversible. Asthma, a reversible syndrome, obstructs inspiration, whereas Emphesema, and chronic bronchitis obstruct expiration. Related diseases, also obstructive include pneumonia, respiratory distress syndrome, tuberculosis, and histoplamosis. In addition, the lungs are frequently attacked by less severe upper respiratory tract infections including the common cold. DRUGS USED IN THE MANAGEMENT OF ASTHMA Asthma is a chronic disease characterized by inflammation of the airways and reversible bronchoconstriction resulting in wheezing, coughing, shortness of breath, and exercise intolerance. particularly in young people. PATHOPHYSIOLOGY The prevalence of asthma is increasing,
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In 1997, the National Heart, Lung, and Blood institute release an updated set of guidelines for the diagnosis and management of asthma. In their treatment guidelines, asthma is described as a chronic inflammatory disorder in which mast cells, eosinophils, T-lymphocytes, and other cellular elements contribute to ongoing inflammation. These inflammatory cells secrete mediators that affect airway function either directly or thorough neural mechanisms. Inflammatory mediators can cause airway injury through increased smooth muscle responsiveness, mucus hypersecretion, altered vascular permeability, aberrations in control of autonomic neurons, and alterations in mucociliary function. Theses mediators also cause proliferation of epithelia cells and myofibroblasts that deposit collagen beneath basement membrane. This can cause subendothelial thickening, leading to possibly irreversible airway changes. Asthma is also associated with an exaggerated bronchoconstrictor response to various stimuli, which is mediated through the beta2 receptors on the airway. This hyperresponsiveness is correlated with airway inflammation which ma be controlled with anti-inflammatory therapy but not completely eradicated by it. Changes in the airway associated with the activation of inflammatory mediators include acute bronchoconstriction, airway edema, and chronic mucus plug formation, and airway remodeling (i.e irreversible thickening of the basement membrane). These changes lead to bronchial obstruction, resulting in limited airflow. Thus, inflammation contributes to airway hperresponsiveness, respiratory symptoms, limited airflow, and a chronic disease process.
DIAGNOSIS To make a diagnosis of asthma, a physical examination is performed as well as an evaluation of patients medical and family history. Findings may include a history of cough, recurrent wheezing, difficulty breathing, tightness of the chest, and exercise intolerance. Symptoms often worsen at night. Patients often complain of sleep disturbance with asthma symptoms, and frequently wake in the
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morning with a feeling of chest tightness or wheezing worsening of symptoms usually occurs in the presence of viral infection, dust mites, animal dander, feathers, mold, smoke, pollen, chemicals or dust in the air, or during weather changes, exercise, menstrual cycles or stressful emotions. While all of these factors support the diagnosis of asthma, pulmonary function testing (Spirometry) is also required to demonstrate reversibility of airway obstruction.
CLASSIFICATION OF ASTHMA Asthma severity is classified into one of the following four categories: Mild intermittent Symptoms occur less or up to two times per week Exacerbations are brief, ranging from a from hours to a few days. Nighttime symptoms occur less than two times perk month Mild Persistent Symptoms occur more than two times per week Exacerbations can affect patients activity. Nighttime symptoms occur more than two times perk month Moderate Persistent Symptoms occur daily Exacerbations affects patients activity. Nighttime symptoms more than one time a week Severe Persistent Symptoms are continuous Physical activity is constricted Exacerbations occurs frequently Nighttime symptoms occur frequently Management The principal goals of asthma management are:
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To prevent the occurrence of symptoms that are chronic or troublesome ( such as coughing or breathlessness after exercise) in the night or in the morning. To maintain near normal pulmonary function; To sustain normal levels of physical activity, including exercise; To prevent the recurrence of asthma exacerbations; To provide optimal pharmactherapy with minimal adverse effects To provide asthma care that meets the needs and expectations and their families. Care of these patients by health workers well versed in the underlying pathophysiology of asthma as well as current available comprehensive pharmacotherapeutic agents can achieve these goals. Asthma therapies are sometimes divided into two categories A: Short-term relievers and B: Long-term controllers. SHORT-TERM RELIEVERS Short-term relief is most effectively achieved with broncodilators, agents that increase airway caliber by relaxing airway smooth muscle and of these the beta 2 adrenoceptor stimulants (eg Salbutamol) are the most widely used. Theophylline, a methylxanthine drug is also used for reversal of airway constriction. LONG-TERM CONTROLLERS The long-term control is moat often achieved with anti-inflammatory agents such as corticosteriod (eg methylprednesolone etc). The distinction between shortterm relievers and long-term controllers has become blurred. Salbutamol (Ventolin) This is a beta2 adrenoceptor agonist these group of drugs have several pharmacological actions that are important in the treatment of asthma i.e they relax airway smooth muscle and inhibit release of some bronchoconstricting
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substances from mast cells. The beta2 adrenoceptor agonist drugs are the most widely used sympatomimetcis for the management of asthma at the present time. Indications Salbutamol is indicated in Asthma and other conditions associated with reversible airway obstructions. Uncomplicated premature labour because stimulation of uterine smooth muscles via beta2 results to uterine relaxation. Mechanism of action Salbutamol acts by stimulating beta2 ( 2) in bronchial airway smooth muscle resulting to the dilation of the airways. Side effects. Salbutamol causes fine tremors (usually hands), headache, palpitations, slight pain on intramuscular injection, hypokalaemia after high doses. Dose: adult by moth 4mg (elderly and sensitive patients initially 2mg) 6-8 hourly. Maximum single dose 8mg (but unlikely to provide much extra benefit).
Children Under 2 years 100mcg/kg 6 hourly 2-6 years 1-2mg 6 hourly 6-12 years 2mg 6 hourly By parenteral route 250-500mcg PRN By aerosol inhalations 1-2 puffs 6-8 hourly. An important method of administering asthama medications is by a metered dose inhaler ( MDI). The following are the steps involved in using an MDI
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1. Remove cap and shake inhaler 2. Breathe out all the way 3. Place mouthpiece between lips 4. press down on inhaler, hold for a few seconds, then breathe in slowly 5. Hold breath and count to 10 6. Breathe out slowly. Always clean the mouthpiece after each use and rinse the mouth if a corticosteroid is used.
METHYLXANTHINE DRUGS The three important methylxanthines are theophylline, theobromine and caffeine. Their major source is of course beverages (tea, coca and coffee respectively). Of the xanthines, theophyline is most effective bronchodilator and it has been shown repeatedly both to relieve airflow obstruction in acute asthma and to reduce severity of symptoms in chronic asthma. Mechanism of action The methylxanthine inhibits the enzyme phosphodiesterase. Since phosphodiesterase hydrolyzes cyclic Adenosine Monophosphate (cAMP) this inhibition results in higher concentrations of intracellular cAMP. cAMP is a potent smooth muscle relaxant. Theophylline also has an anti-inflammatory property, which makes it very popular in the management of asthma. AMINOPHYLLINE This is a stable mixture or combination of theophylline and ethylenediamine, which is 20 times more soluble than theophylline alone. The ethylenediamine confers greater solubility in water. Aminophylline must be given by very slow intravenous injection over 20 minutes; It is too irritant for intramuscular use. Dose: 100-300mg 6-8hourly after food. Children 1mg/kg.
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Mechanism of action Bronchodilator- via inhibition of phosphodiesterase enzyme resulting to relaxation of airway smooth muscle. Side effects Methylxanthies causes insomnia, tachycardia, palpitations, nausea, gastrointestinal disturbances, headache, arrthymias and convulsions especially if given too rapidly by intravenous injections. NB: in acute over dosage, the side effect could be life threatening and treatment include emptying the stomach (gastric larvage) if the patient is presented within two hours followed by administration of activated charcoal (a universal antidote). It is not recommended by exacerbations. Combination therapies 1. Generic name: Aminophylline/Salbutamol Trade name: Franol
Route of administration: oral 2. Generic name: Sameterol/Fluticasone Trade name Advir
Route of administration: inhalation Chronic Obstructive Pulmonary Disease ( COPD) COPD encompasses emphysema and chronic bronchitis. Emphysema Emphysema is characterized by destruction of the tiny alveoli, or air sacs, of the lungs. As a result, air accumulates in the tissues and organs. Typically, air spaces distal ( farther away from) the terminal bronchioles are enlarged.
Inflammation destroys these air sacs, which ten lose their ability to expand and contact and their ability to pass oxygen into the blood and remove carbon dioxide. In the early stages, shortness of breath occurs only after heavy exercise. As the disease progresses, walking even a short distance can make the patient gasp for air. Patients with emphysema have tachypnea ( very rapid respiration), which
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gives them a flushed appearance.
Major risk factors are cigarette smoking
( which destroys the wall of the lungs), occupational exposure ( as in cement factory) air pollution, and genetic factors. Bronchitis Bronchitis is a condition which the lining of the bronchial airways becomes inflamed, causing the patient to experience obstruction of air flow on expiration. This disease is characterized by a cough that produces sputum that may be purulent (containing pus) , green, or blood streak. Acute bronchitis is caused by an infection especially viral of chronic bronchitis. infection. Drugs Treatment of COPD To understand the treatment for emphysema and chronic bronchitis, you must also understand the lungs natural defense system. when this system is functioning properly, the host defense of the respiratory tract provide good protection against pathogen invasion and remove potentially infectious agents from the lungs. The lungs are normally sterile below the first bench. It is when organisms breach this region that infection and inflammation are initiated. The bodys defense includes a number of cells. The ciliary carpet consists of minute hairlike process, called cilia, that beat rhythmically to propel fluid or mucus, and any inhaled particles that have become trapped in the fluid, over the inner surface of the airway; upward and out. Goblet cells secrete mucus. Clara cells, unciliated cells at the branching of the alveolar duct into the bronchioles, secrete enzymes that break down airborne toxins. Epithelia cells produce a protein-rich exudates in the small bronchi and bronchioles.
and is corrected by the use of antibiotics to prevent
secondary bacterial infection. Several factors can contribute to the development The most prominent of these include cigarette smoke; exposure to occupational dusts, fumes, and environmental pollution; and bacterial
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Type I pneumocytes in the alverolar membranes act as the phagocytes of the lungs. They clear trash and organisms from the lungs,. Type II pneumocytes synthesize and secrete surfactant. Emphysema and chronic bronchitis sometimes occur together, and their pharmacologic treatment is similar. The pharmacologic management of emphysema and bronchitis is still largely empirical, with methylxanthines, corticosteriods, beta agonists and ipratropium forming the foundation of therapy as in Asthma. fever is present. In both emphysema and chronic bronchitis, antibiotic therapy is sometimes needed if either sputum changes from yellow to green or Expectorants and mucolytics are sometimes used to stimulate respiratory secretion and counter dryness which stimulates irritation and coughing. Drinking large amounts of water helps to break up mucus hand enables the patient to cough up secretions; DRUGS FOR GIT DISEASES. The gastrointestinal (GI) tract is a continuous tube that begins in the mouth, extends through the pharynx, esophagus, stomach, small intestine, and large intestine, and ends a the anus. A wide variety of diseases can affect the gi tract. Although gastroesophageal reflux disease (GERD, or heartburn) and the various conditions known collectively as peptic diseases may be the most common, several other diseases, including gastritis and inflammatory bowl disease, are also important. GERD This is a common problem. Symptoms include radiating burning or pain in the chest and an acid taste. GERD patients also have recurrent abdominal pain, They may have nonspecific which may move about n the epigastric area. form sleep. The primary mechanism responsible for meal related symptoms of esophagitis ( irritation of the esophagus) is the reflux ( backflow) of acidic stomach
epigastric discomfort that is worse before measles and may awaken the patient
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contents through an incompetent lower esophageal sphincter. This sphincter is normally in a state of relative contraction. During swallowing, it relaxed enough to allow the forward passage of food and drink into the stomach. Then it contracts again preventing the reflux of the stomach contents. Heartburn occur when the spinster becomes incompetent ( unable to keep itself sufficiently contracted). Even with competent sphincter, the likelihood of reflux increases during pregnancy as the uterus exerts upward pressure on abdominal organs, including the stomach; the gastric contents a are pushed toward the lower esophageal sphincter and up into the esophagus. Factors that may contribute to the malfunctioning of the lower esophageal sphincter include overeating, eating on the run, eating late at night, drinking alcohol, smoking cigarettes, and consuming \various foods. Pharmacologic Treatment of GERD The treatment of GERD is categorized as phase I and phase II treatments. Phase I include lifestyle modifications and or use of an antacid. Antacids neutralize the acidic stomach contents so that if reflux does occur, the content will be less irritating to the esophageal lining. Phase II treatment employ medications to try to improve gastric motility and decrease acid production in the stomach. Examples of phase II drugs include Proton Antacids. Antacid therapy has several shortcomings, including the need for frequency of dosing and patient compliance. For patients with an active bleeding, antacid must be given every hour between meals for 6 to 8 weeks. Magnesium hydroxide ( Phillips milk of Magnesia), Aluminum hydroxide H2 Receptor Antagonist. Gastric acid secretion and pepsin secretion occur in response to histamine , gastrin, foods, distention, or caffeine stimulation. When these processes result from histamine, they can be blocked by an H2 histamine receptor antagonist. The mechanism of action is competitive inhibition of histamine at H2 receptor on the stomach gastric secreting cells which inhibits gastric acid secretion. E.g Eg
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Cimetidine ( Tagament etc) , Ranitidine ( Zantac etc) , Famotidine pepcid etc). Side effects:
(Famodar,
H2 Receptor Antagonists may cause diarrhea, dizziness, rahs tiredness. Gynacomastia (breast enlargement), reduced libido in men. occasional reversible liver damage and confusion has been reported. Proton pump Inhibitors. Acidity in gastric secretion is maintained by an enzyme known as the parietal cell H K-ATPase pump . this term indicates that this enzyme pumps acidic hydrogen ions ( H+) or protons, into the stomach; pumps nonacidic potassium (K+) ions out; and uses up energy ( ATP) to do so a proton pump inhibitor a drug that blocks this enzyme reduces stomach acidity. They must be taken on daily basis and not when needed. Eg. Omeprazole ( Meprasil), Lansoprazole ( Lansogard), Rabepraxole, Pantoprazole etc. Side effects: Generally, proton pump inhibitors are very safe. In high doses, the common side effect reported include diarrhea, nausea, abdominal pain, headache and skin rashes Peptic Disease. The term is used to refere to a broad spectrum of disorders of the upper GI tract caused by the action of acid and pepsin, a stomach enzyme that assist in degrading food proteins. An ulcer is a local defect or excavation of the surface of an organ or tissue. A peptic ulcer is an ulcer formed along any part of the GIT tract exposed to acid and the enzyme pepsin. There are three common types of peptic ulcers: gastric, duodenal and stress ulcers. Many factors, including bacterial infections and sever physiological stress, can contribute to the development of ulcers. Medications can also cause ulcers.
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Gastric Ulcers. . A gastric ulcer is a local excavation in the gastric mucosa. These lesions have malignant potential, occur more often n men than women, and become more frequently with aging. They are prevalent in smokers. A contributing factor for may patients is the bacterium Helicobacter pylori. Duodenal Ulcers. A duodenal ulcer is a peptic lesion situated in the duodenum. Duodenal ulcers occur more in hypersecretors and are more difficult to treat than gas tic ulcers because of the difficulty of getting medication into the duodenum. Stress Ulcers. A stress ulcer is a peptic ulcer, usually gastric, that occur in the clinical setting in patients who are under severe physiological stress form serious illness, such as sepsis, burns, major surgery, chronic disease or chronic infection. Drug induced Ulcers. Several drugs can cause ulcers eg. NSAIDs Pharmacologic Treatment of H. Pylori Research has shown that Helicobacter pylori is responsible is responsible for the majority of peptic ulcers. It also plays a role in chronic active gastritis and gastric cancer. Therefore, treatment regiments aim at eradication of the bacterium. The main\stay of therapy for ulcers include antacids, H2 receptor antagonists, and proton pump inhibitors. Once a positive diagnosis has been made, H. pylori is eradicated using the following triple eradication regiment on the basis of efficacy and simplicity Antibiotics + H2 receptor antagonist + Pronto pump inhibitors for I week. The decision on choosing an eradication regiment for a particular patient should take into account local resistance to antibacterial , cost and availability of the necessary drugs. Egs of a triple therapy of H. pyroli eradication are:
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Omeprazole 40mg od Metronidazole 400mg tid Amoxicillin 500mg tid Or Omeprazole 20mg bd Clarithromycin 500mg bd Amoxicillin 1g bd The most commonly used agents for H. pylori are Antibiotics: Amoxicillin, Clarithromycin, , Metronidazole and Tetracycline H2 receptor antagonists: Cimetidine, Ranitidine Pronton pump inhibitors : Omeprazole, Ransoprazole, Labeprazole x
1 5 2
1 52
ENDOCRINE SYSEM DRUGS. The endocrine system consists of glands and other structures that elaborate, or produce secretions called hormones and release them directly into the circulatory system. The various hormones are responsible for the specific
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regulatory effects on organs and other tissues of the body. Through the work of hormones, the endocrine system maintains homeostasis of the body by regulating the physiologic functions involved in normal daily living and in stress. Diabetes Mellitus. Diabetes Mellitus is not one disease but rather is a heterogenous group of syndrome characterized by an elevation of fasting blood glucose caused by a relative or absolute deficiency in insulin. If left untreated, diabetes can cause a range of serious conditions and eventually death. The pancreas contains specialized cells, called the islets of Langerhans that produce insulin. Insulin helps cell burn glucose for energy, combines with membrane receptors to allow glucose uptake, enhances transport and incorporation of amino acids into protein, increase ion transport into tissues, and inhibits fats breakdown. Thus, insulin is critical in maintaining blood glucose levels, as well as having other metabolic roles. In persons with diabetes, either the secretion or the utilization of insulin is inadequate, which leads to excessive blood glucose levels. The normal glucose level is around 100mg/dL. At elevated levels the kidneys will not be able to reabsorb the excess, and glucose will spill into the urine. elevated blood sugar level is known as hyperglycemia. Diabetes is a devastating disorder that can damage all major organ systems. circulation. Types of Diabetes. Diabetes mellitus can be separated into two groups Insulin-Dependent Diabetes Mellitus (IDDM) and Non-insulin-Dependent Diabetes mellitus ( NIDDM) based on their requirement for insulin. Type I Diabetes (Insulin Dependent Diabetes Mellitus) Over time, diabetes can destroy eyesight, kidneys, and peripheral Level consistently An above 140 -160mg/dL are associated with long term effect of diabetes.
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Type I diabetes occurs most commonly in children and young adults, but it may occur at any age. The average age of diagnosis is 11-12 years. These patients are insulin dependent; that is they have no ability to produce insulin. This group comprises 5-10% of diabetic population. insulin t avoid life-threatening ketoacidosis. Many patients show a honeymoon period following initial treatment when the symptoms transiently disappear and little or no insulin is required. This remission results from a temporary return of insulin secretion which may last for weeks or moths. The metabolic changes in IDDM are mainly hyperglycemia and ketoacidosis is left untreated. Hyperglycaemia is caused by increased hepatic production of glucose combined with diminished peripheral utilization. Ketosis results from increased mobilization of fatty acids form adipose tissues combined with accelerated hepatic synthesis of ketone bodies viz: 3-hydroxybutyrate, acetoacetate and acetone from ketogenic amino acids eg. Leucine and Lysine Individuals with IDDM require
Diagnosis of IDDM Patients with IDDM can usually be recognized by the abrupt appearance of polyuria ( frequent urinating), polydipsia ( excessive thirst) and polyphagia ( excessive hunger) often triggered by stress or an illness. The symptoms are usually accompanied by fatigue, weight loss, and weakness. The diagnosis is confirmed by a fasting blood glucose greater then 140mg/Dl (7.8mmol/L) commonly accompanied by ketoacidosis which can be life-threatening. Type II Diabetes (Insulin Non-Dependent Diabetes Mellitus) Type II comprises 80-90% of diabetic cases. Most patients are over 40 years of age, with the majority being female. Patients with type II diabetes may have relative insulin insufficiency (impaired insulin secretion); however, insulin receptor resistance on cells may be the primary culprit. The peripheral target tissues are resistant to insulin produced. Glucose is not absorbed because the cells do not respond to insulin. The blood glucose concentration is raised with
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glycosuria ( glucose in urine) but ketoacidosis is not common and the symptoms are often those of late complications of diabetes. overweight, and the best treatment is to lose weight. Comparism of Type I and Type II Diabetes Mellitus. Synonym Age Nutritional status Prevalence Genetic predisposition. Defect IDDM Type I juvenile NIDDM onset Type II adult onset. Frequently after 35yrs Obesity usually present 80-90%` Very strong. cell Inability of -pancreatic cell to produce insulin, insulin resistance Rare Hyper-osmolar coma Responsive Usually not required. Most type II diabetics are
diabetes Childhood or puberty Frequently undernourished 10-20% Moderate -pancreatic destroyed
Ketosis Acute complication. Oral hypoglycemia Insulin therapy
Common Ketoacidosis Unresponsive Always necessary
Gestational diabetes Gestational diabetes occurs during pregnancy and increases the risk of fetal morbidity and death. The onset occurs during the second and third trimesters. Gestational diabetes can be treated with diet, exercise, and insulin. Usually, it disappears after the birth of the baby, but 30 40% of women who have gestational diabetes will develop type II diabetes in 5 10 years. they should use this type of birth control is debatable. Secondary diabetes Secondary diabetes is caused by drugs. Among these drugs are oral contraceptives, beta blockers ( e.g propranolol), diuretics ( eg furosemide) , calcium channel blockers ( e.g Nifedipine) , glucocorditcoids ( e.g Prednesolone),
Oral
contraceptives raise blood glucose levels, especially in these women, so whether
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and phenytoin.
Secondary diabetes may return to normal when the drug is
disconteined. The use of these drugs in diabetes should be done with caution. Long term Complications of untreated DM include: Retinopathy here the vessels become damaged, resulting in insufficient blood supply; rupture causes loss of sight. Neuropathy is the result of a lack of blood flow to nerves, leaving them unable to function,. Symptoms are dull aching to sharp stabbing pains. Vascular problems lead to atherosclerosis of peripheral coronary and cerebrovascular vessels. The decrease blood flow causes neuropathy and slows healing, especially in the feet and legs. Wounds that fail to heal can lead to amputation. Dematologic involvement is often expressed as boils, acne, or fungal infections. Nephropathy, or kidney damage, occurs n 10-21% of diabetics and is primary cause of end-state renal disease.
Treatment of Diabetes Mellitus. The goal of treatment of diabetes is to approximate non-diabetic physiology as closely as possible. The treatment consists of diet, exercise, and medications. Blood glucose monitoring is very important to prevent both acute and log-term complications and to guide treatment for reaching target fasting blood glucose goals. To avoid long term complications, diabetes should be controlled to maintain fasting blood glucose levels between 80-120mg/dL. Patients with Type I diabetes must receive insulin. Those with Type Ii diabetes may be able to control the disease through diet and exercise alone, but commonly they have to add a drug and eventually may need insulin. ANTI DIABETIC DRUGS. Insulin. Mechanism of action.
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Insulin lowers the concentration of glucose in the blood mainly by: a. b. c. Facilitating glucose transport across cell membrane resulting in increase uptake of glucose by the tissues. Facilitating glycogen synthesis from glucose in liver muscles and fat Inhibit gluconeogensis.
Sources of insulin. There are three sources of insulin, bovine (extracted insulin from beef pancreas), porcine (extracted insulin from pork pancreas and is very similar to human insulin), and human. Human insulin is prepared semi-synthetically by enzymatic modification of porcine insulin or biosynthetically by recombinant DNA technology using Escherichia coli or yeast. Method of Insulin Administration: Insulin is usually administered subcutaneously, however, IM or IV administration is possible e.g in diabetic emergencies such as ketoacidosis or surgery if a more rapid effect is wanted.
Injection Technique. A volume of air corresponding to the prescribed dose of insulin is injected into the vial. Turn vial and syringe upside down and draw up the prescribed dose of insulin. Remove syringe from vial and expel any air from syringe. Lift up a skin fold and inject the insulin under the skin. Keep the needle under the skin for a few seconds to make sure that all insulin has been injected. If blood appears after withdrawing the needle, press the injected site lightly with a finger. Subcutaneous injection into the abdominal wall ensures a faster absorption tan from other regions of the body. An injection should be followed by a meal or snack containing carbohydrate within 30 minutes to avoid hypoglycaemia. Insulin preparations.
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For clinical use insulin have been classified traditionally into short, intermediate and long acting insulin. Short acting, soluble, regular or neutral insulin. These are human or purified animal insulins and have the advantage of being administered by intravenous, intramuscular as well as subcutaneous routes. Following subcutaneous injection, soluble insulin has a rapid onset of action (after 30 60 minutes).
They are used in diabetic emergencies ( e.g
diabetic coma) and at the time of surgery. Soluble insulins include. Pork Actrapid , Human Actrapid, Humilin S etc. Intermediate acting insulins. These insulins act for a varying periods depending on the mix of rapid and slow acting components. They have an onset of action of approximately 1-2 hours, a peak action of 3-12 hours, and duration of action of 16-24 hours. E.g Isophane and biphasic insulins. Long acting insulin. Protamin Zinc Insulin (PZI) is an example of a long acting insulin. Its action is prolonged. Starting after 4hours lasting for 24-36hours. Human insulin zinc suspension is the choice of preparation when long action is desires. Human insulin does not contain impurities and is preferred in pregnancy because impurities in insulin from animal sources can cross the placenta and damage the islet tissues of the fetus.
Insulin Dosing. The dose, frequency of administration and type of insulin type to use depends on numerous factors which vary greatly between individuals. Blood glucose monitoring is recommended.
71
Total daily dose of insulin is 0.6-1 mcg/Kg body weight. 2/3 of total insulin dose is usually given in the morning before breakfast and the 1/3 in the evening before supper. response. Storage conditions. Insulin preparations not in use should be stored in a refrigerator, between 2oC to 8oc at which temperature they will retain the biological and antimicrobial effect until the date of expiry printed on the pack. Insulin should not be frozen and frozen insulin must not be used. Insulin vials may be stored at room temperature ( up to 25 oC) for up to six weeks after first use but should be protected from excessive heat or direct sunlight. Insulin vials should be stored horizontally. This is because the insulin in certain preparations e.g suspensions can settle during storage. If this should occur while the bottles are stored in an upright position, it can be difficult to redisperse the insulin uniformly in the liquid. Moreover, insulin suspension should not be shaken to re-disperse it but gently swirls between the palms Adverse effects
1. Hypoglycaemia ( which is the most dangerous side effect in DM treatment)
The overall dose is usually adjusted according to
2. Local reaction irritation t the site of injection

3. Immunogenic response. Non human insulin can stimulate the production of
anti-insulin antibodies which may lead to hypersensitivity reaction and to insulin resistance. 4. Weight gain. Every diabetic should be aware of the risk of hypoglycemia ( blood glucose <70mg/dL or <2.5mmol/dL. Hypoglycemia can be caused by any of several factors skipping of meals too much exercise a poorly adjusted medication regiment
72
concurrent use of alcohol and or other drugs Symptoms of Hypoglycaemia. The symptoms of hypoglycaemia, usually considered as blood glucose concentration of < 45mg/dL (i.e <2.5mmol/L) can be divided into two categories. Adrenergic symptoms. Anxiety, palpitation, tremor, and sweating are mediated by epinephrine (Adrenaline) release regulated by the hypothalamus in response to hypoglycaemia. Usually Adrenergic symptoms occur when glucose levels fall abruptly. Neuroglycopenic Symptoms Neuroglycopenia ( the impaired delivery of glucose to the brain) results in impairment of brain function causing headache, confusion, slurred speech, blurred vision, seizure, coma, and death. Neuroglycopenic symptoms often results from gradual decline in blood glucose often to the levels below 400mg/dL. The slow decline in glucose deprives the of fuel but fails to trigger on epinephrine response. Types of Hypoglycaemia
1. Postprandial Hypoglycaemia.
It is cause by an exaggerated insulin release following a meal prompting a transient hypoglycaemia with mild adrenergic symptoms. The plasma glucose levels return to normal even if the patient is not feed. The only treatment usually required is that the patient ea\t frequently small meals rather than the usual three large meals. 2. Fasting hypoglycaemia. Low blood glucose occurring during fasting is rare but is more likely to present a serious medical problem. Fasting hypoglycaemia tend to produce
73
neuroglycopenic symptoms and which may be due to an increased rate of glucose utilizations by the peripheral tissues due to oral hypoglycemic agents eg. Biguanides and Sulfonylureas. Behaviours associated with alcohol intoxication - agitation, and impaired judgment are also common. Treatment of Hypoglycaemia. Treatment of hypoglycaemia necessitates giving the patient additional sugars. Milk or sugars in any form (fruit juices, soft drinks, or candy) are highly effective. Glucose tablets are available and type I diabetics should have then on hand. Oral Hypoglycemic Agents. Oral hypoglycemic agents cause the pancreas to release stored insulin. Thy are not effective in type I diabetes because there is no insulin available for the body to release. Oral hypoglycemic agents are divided into Sulfonylureas. . Sulfonylurea drugs increase insulin release These are subdivided into first generation sulfonylureas and second generation syulfonylureas. Examples of first generation sulfonylureas are: Tolbutamide and Chorpropamide ( diabenese Examples of second generation sulfonylures are: Glipizide, Glyburide, Glimepiride ( Amaryl), Glibenclamide ( Daonil, gliben-J etc) Side effects. Hypoglycaemia, headache Biguanides. Biguanides decreases intestinal absorption of glucose and improves insulin sensitivity. One of these compounds Metformin (Glucophage) rarely causes hypoglycemia and has a favorable effect on serum lipids. Others include phenformin, and Bufomin. Only Metformin is on essential drugs list.
74
Side effects. Lactic acidosis, ( especially in patients with renal impairment), Thiazolidinediones. Thiazolidinediones ( or Glitazones) lower blood glucose by improving cellular response to insulin. Examples include Piloglitazone , Rosiglitazone MOA: Glitazones reduces blood glucose concentrations by increasing insulin sensitivity in muscles and adipose tissues, and inhibiting hepatic gluconeogensis. Side effects. Headache, pharyngitis, hypoglycaemia and upper respiratory tract infection have been reported. Inhibitors of GIT glucose absorption. Acarbose lowers blood glucose by delaying the hydrolysis of ingested complex carbohydrates and disaccharides and the absorption on of glucose.
REFERENCES. Agarwal S.L and Agaral Sunil ( 2002). Pharmacology for Undergraduates. Kumar jain new Dehil India. Don A. B and Mary M. L (2010). Pharmacology for Technicians. Paradigm Publishing. St. Paul. Los Angeles USA. Pever, J. T (2003). Fundamentals of Pharmacology for Health Workers. Publishers, Mkd Nigera. Hardman J. G etal (ed) ( 2001). Goodman & Gilmans The Pharmacological Basis of Therapeutics 10th edition. McGraw Hill. USA Selfers Satish
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Basic and Essential Pharmacology

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Basic and Essential Pharmacology

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LECTURE NOTES

PHARMACOLOGY OF ESSENTIAL DRUGS. (for community health workers).

Lecture Notes on Pharmacology of Essential Drugs. IORJIIM, W.M ( B.pharm)

Lecture Notes on Pharmacology of Essential Drugs. IORJIIM, W.M ( B.pharm)

Lecture Notes on Pharmacology of Essential Drugs. IORJIIM, W.M ( B.pharm)

Some of the common dosage forms used

Lecture Notes on Pharmacology of Essential Drugs. IORJIIM, W.M ( B.pharm)

Gastrointestinal drugs: Examples include:

Antiulcer drugs (Cimetidine, Omeprazole, Ransoprazole, Gascol etc),

Lecture Notes on Pharmacology of Essential Drugs. IORJIIM, W.M ( B.pharm)

Lecture Notes on Pharmacology of Essential Drugs. IORJIIM, W.M ( B.pharm)

Lecture Notes on Pharmacology of Essential Drugs. IORJIIM, W.M ( B.pharm)

AlCl3 (salt) + 3H2O (water)

Lecture Notes on Pharmacology of Essential Drugs. IORJIIM, W.M ( B.pharm)

Onset of action if fast.

PHARMACOLOGY OF ESSENTIAL DRUGS CHEMOTHERAPY

Lecture Notes on Pharmacology of Essential Drugs. IORJIIM, W.M ( B.pharm)

duration of use can lead

Lecture Notes on Pharmacology of Essential Drugs. IORJIIM, W.M ( B.pharm)

Lecture Notes on Pharmacology of Essential Drugs. IORJIIM, W.M ( B.pharm)

Lecture Notes on Pharmacology of Essential Drugs. IORJIIM, W.M ( B.pharm)

Lecture Notes on Pharmacology of Essential Drugs. IORJIIM, W.M ( B.pharm)

Lecture Notes on Pharmacology of Essential Drugs. IORJIIM, W.M ( B.pharm)

Lecture Notes on Pharmacology of Essential Drugs. IORJIIM, W.M ( B.pharm)

Lecture Notes on Pharmacology of Essential Drugs. IORJIIM, W.M ( B.pharm)

Lecture Notes on Pharmacology of Essential Drugs. IORJIIM, W.M ( B.pharm)

Ciprofloxacin is the most important of the 4-quinolones. QUINOLONES

Lecture Notes on Pharmacology of Essential Drugs. IORJIIM, W.M ( B.pharm)

Lecture Notes on Pharmacology of Essential Drugs. IORJIIM, W.M ( B.pharm)

CHEMOTHERAPEUTIC AGENTS IN TUBERCULOSIS MYCOBACTERIAL INFECTION: A BRIEF REVIEW

Lecture Notes on Pharmacology of Essential Drugs. IORJIIM, W.M ( B.pharm)

Lecture Notes on Pharmacology of Essential Drugs. IORJIIM, W.M ( B.pharm)

Lecture Notes on Pharmacology of Essential Drugs. IORJIIM, W.M ( B.pharm)

Lecture Notes on Pharmacology of Essential Drugs. IORJIIM, W.M ( B.pharm)

Lecture Notes on Pharmacology of Essential Drugs. IORJIIM, W.M ( B.pharm)

Lecture Notes on Pharmacology of Essential Drugs. IORJIIM, W.M ( B.pharm)

Lecture Notes on Pharmacology of Essential Drugs. IORJIIM, W.M ( B.pharm)

tissues and orgsna.

The increasing use of broad spectrum antibiotics and

Lecture Notes on Pharmacology of Essential Drugs. IORJIIM, W.M ( B.pharm)

Lecture Notes on Pharmacology of Essential Drugs. IORJIIM, W.M ( B.pharm)

Lecture Notes on Pharmacology of Essential Drugs. IORJIIM, W.M ( B.pharm)

Lecture Notes on Pharmacology of Essential Drugs. IORJIIM, W.M ( B.pharm)

Lecture Notes on Pharmacology of Essential Drugs. IORJIIM, W.M ( B.pharm)

These drugs increase the force of myocardial This is called positive

nausea, vomiting, visual disturbances, headache etc.

These drugs inhibit the overactive angiotensin/rennin

Lecture Notes on Pharmacology of Essential Drugs. IORJIIM, W.M ( B.pharm)

abnormal foetal growth.

ACE inhibitors are contraindicated in

the kidney to excrete excess salt and

Lecture Notes on Pharmacology of Essential Drugs. IORJIIM, W.M ( B.pharm)

Lecture Notes on Pharmacology of Essential Drugs. IORJIIM, W.M ( B.pharm)

Lecture Notes on Pharmacology of Essential Drugs. IORJIIM, W.M ( B.pharm)

Lecture Notes on Pharmacology of Essential Drugs. IORJIIM, W.M ( B.pharm)

Lecture Notes on Pharmacology of Essential Drugs. IORJIIM, W.M ( B.pharm)

Lecture Notes on Pharmacology of Essential Drugs. IORJIIM, W.M ( B.pharm)

with a high tolerance of pain. transmission are the same

The neurotransmitters involved in pain as those involved with depression

Lecture Notes on Pharmacology of Essential Drugs. IORJIIM, W.M ( B.pharm)

Opioid for moderate to sever pain Non-Opioid, Adjuvant

e.g morphine, oxycodone, fentanyl Adjuvant. e.g Codeine, Pentazocin.

Opioid for moderate to sever pain Non-opiod, Adjuvant