Practical Pharmacology

Dr.Gulala

Practical Pharmacology

Dr.Gulala

Pharmacological dosage forms 1-Internal preparation : (solid,liquid,powder,drop for infant ,aerosol ,implant, parenteral) 2-External preparation : (suppository,ointment,cream,drop,liniment.) 1-Internal preparations: z Solid preparation(Tablet Pill - Capsule): 1- Tablet: a) Ordinary compressed tablet: is producing by forcing the powdered form of drug which either contain the drug alone or with diluents(pharmacologically inert substance to make compression of the tablet easier )into solid mass using mechanical machine with optimal degree of compression, the tablet is converted into small masses in the stomach (disintegration)after that it will dissolve in gastric content(dissolution).e.g : paracetamol. b) Coated tablet: this is ordinary compressed tablet coated with sugar for the following purpose: to avoid bitter taste of drug. to prevent oxidation of drug. to facilitate swallowing of drug. e.g : profine,flu out,ferrosan. c) Enteric coated tablet: this is ordinary compressed tablet coated by acid resistance material to allow the drug to pass the stomach unchanged but it dissolves in alkaline media of intestine, e.g: enteric coated Aspirin and Salazopyrin. Advantage: To avoid irritation of stomach, e.g: Indomethacin. Prevent destruction of the drug by the acid, e.g: digestive enzymes. To get local action in the intestine, e.g: Duogastrone. d) Triturated tablet : this type is prepared by mixing the drug with a suitable diluents the mixture moistened with alcohol and the mass is pressed and let to dry form a disc shaped. e.g: Vitamin E tablet. e) Sustained release tablet : compressed tablet coated with many coat each with different disintegration and dissolving rate, this modified manufacture prolong the duration of action and decrease frequency of administration and also called retard, e.g: Glucophage, phyllocotin.

Practical Pharmacology

Dr.Gulala

f) Sublingual tablet: it is usually uncoated specially produced to de suitable for absorption from sublingual mucosa to get rapid action and avoid destruction by first pass metabolism, e.g: Angised. g) Effervescent tablet: this is relatively large tablet containing large dose of the drug , it is producing by mixing the drug with citric acid and sodium bicarbonate to form granules these granules are compressed to form the tablet, this type of tablet appear to have rapid action, disintegration and dissolution occur in water inside the glass , e,g: Vitamin C tablet. h) Chewable tablet: this is ordinary uncoated tablet specially manufactured to be sucked or chewed usually have a good taste, e.g: Antacid. i) Lozenges tablet: this is a sugar flavoured tablet with different shape and attractive color it is usually sucked to treat simple tonsillitis and relief cough, it is usually contain volatile oil, antiseptic, antibiotics, e.g: Vicks. 2- Pill: Is the spherical body containing the drug in a solid or liquid form given by mouth, a pill should not weight more than (0.3 gm), it is sometime coated when the drug has a bitter taste or liable to oxidation, e.g: Contraceptive pill. 3- Capsule (ordinary capsule, spansule capsule, and capsule for inhalation): a) Ordinary capsule: it is a small oval or rounded shape made of gelatine, it is either: v Hard containing powdered drug, e.g: Tetracycline. v Soft contain liquid form of drug, e.g: Adalat. The capsule shell will dissolve in stomach used for the following purpose: to mask the bad taste of drug. prevent oxidation of drug. to get accurate dose of drug. b) Spansule capsule: containing different granule each with different disintegration and dissolution rate , this will prolong duration of action and decrease frequency of administration, e,g: Stelazine. c) Capsule for inhalation: it is ordinary capsule which contain a drug which is usually unabsorbed from the bowel,it is intended to be inhaled to get local action in the lung using certain instrument manufactured for that purpose, e,g: Cromoglycate.

Practical Pharmacology

Dr.Gulala

z Liquid preparations : 1. Syrup: the drug is water soluble usually dissolved in already prepared simple syrup with good taste particularly for children, e.g: Samilin ,Ampicillin. The antibiotic syrup usually supplied by pharmaceutical company as a powder mixed with sugar and prepared by adding sufficient quantity of water before use because antibiotics hydrolysis in the aqueous solution to other compound which has no antibacterial activity or causing allergic reaction. 2. Aqua: it is a watery solution contain volatile substance used as flavoured (flavored) vehicle,e.g: Chloroform water. 3. Elixir: it is syrup containing 25% alcohol, e.g: hypnoral. 4. Suspension: a solution contain indiffusibe solid which does not distributed evenly to get a uniform mixture so, it should be shacked before use, e.g: Methoprim. 5. Extract: the solid or semisolid preparation of active principle obtained from plant by mixing with a suitable solvent, after evaporation we get the extract. different solvent are used such as ( water, alcohol, ether and chloroform ).it is named according to the solvent, e.g: watery extract of Cascara, Alcoholic extract of Belladonna. The evaporation done under low pressure otherwise it will destroy the active drug. 6. Liquor: it is a solution containing chemical substance dissolved in water if it is for internal use and alcohol if it is for external use. 7. Emulsion: is a mixture of two immiscible liquid such as water and oil in which one of the liquid is broken up and surrounded by a film emulsifying agent to be dispersed through the other liquid. 8. Mixture: is a combination of drug in liquid form , e.g: white mixture of Magnesium sulphate (which is used as purgative). 9. Decoction: solution of drug obtained from plant by boiling for 10 min, and then strained. 10. Infusion: a dilute solution of active principle obtained from plant by adding hot or cold water shacked from time to time and then strained. z Powder preparation: 1. Ordinary powder: contain the drug as a fine powder in which specific quantity of the powder is mixed with sufficient water before use, e.g: Gastrogel (used for heart burning) 2. Effervescent powder: it is an ordinary powder mixed with sodium bicarbonate and citric acid to de prepared by mixing with sufficient water before use, e.g: Citrogran powder.

Practical Pharmacology

Dr.Gulala

z Drop for internal use: This type of preparation is most convenient for infant, in which the drug is concentrated into
a few drops to facilitate swallowing and minimize the loss of drug, e.g: paracetamol, Digoxin.

z Aerosol: A pressurized liquid form of the drug intended to be inhaled by puff each puff contain a specific dose, e.g: Ventolin (sulbutamol). z Implant: A minute disc preparation inserted under the skin which is usually contain hormone, it is slowly metabolized or absorbed to give a prolonged duration of action, e.g: Stilbestrol. z Parenteral: a. Ampoule: is a thin glass container for single injection,it is usually sterile to be injected (IV, IM, SC) e.g: Buscopan. The ampoule which contains hormone usually mixed with oil and should not be used IV because of fat embolism sometime put in separate ampoule (the solvent and the drug ) ,e.g; Pregnyl. b. Vial: a thick container with a rubber cap contains powder or solution for single or multiple injection , e.g: Procaine Penicillin (for 1 injection ) , Xylocaine (for multiple injection ) .

Practical Pharmacology

Dr.Gulala

External preparations

1) Suppository: a. Rectal: is conical or turbido shaped preparation inserted into the rectum for local (e.g : Antihemorrhoid) or systemic action (e.g:Aminophylline). The active drug is mixed with a fatty base which is melt at body temperature and should not exceed (4 gm) to facilitate the entry and prevent proctitis, the reason of manufacturing of this preparation : to avoid irritation of stomach , e.g: Indomethacin. to get local action in the intestine, e.g: Laxative (Bisacodyl). in uncooparable patient (children, unconscious coma case patient ). e.g: Revanin. in patient with repeated vomiting (pregnant women), e.g: Plasil. to get full dose during night, e.g: Aminophylline. b. Vaginal: it is called ovule or pessary due to its shape, the active drug is mixed with a fatty base melt at vaginal temperature and its miscible in vaginal secretion, inserted into the vagina by a certain applicator. e.g: Mycostatine (antifungal drug), Flagyl. 2) Ointment: The semisolid preparation consist of a fatty base, e.g: Paraffin, Ovile, Wax, and Vaseline. Containing the active drug and the base is immiscible with water therefore it is suitable to be applied on dry surface. 3) Cream: It is a semisolid preparation containing the drug mixed with the fatty base which is miscible with water applied to wet surface, e.g: Nystacort, Clotrymazole ( vaginal cream), Estrogen. 4) Liniment: It is a semisolid or liquid preparation containing irritant substance applied to the skin by friction . e.g: Rheumalgin. 5) Lotion: Is a liquid preparation applied to the skin without friction , it usually containing cooling substance , e.g: Calamine. sometime contain drug like steroid or antiseptic. 6) Enema: It is a solution intended to be injected into the rectum for local (e.g: watery solution of soap as a laxative) or systemic (e.g: Prednisolone Predsol Retention Enema for the treatment of ulcerative colitis).

Practical Pharmacology

Dr.Gulala

7) Drop: Eye: watery sterile isotonic solution instilled into the eye by a dropper, it contains one of the following: 1. Antiseptic, e.g: Boric acid. 2. Antibiotic, e.g: Chloramphenicol. 3. Decongestant, e.g: phenylephrine. 4. Antihistamine, e.g; Mepyramine. 5. Steroid, e.g: Betamethasone. 6. Mydriatic, e.g: Atropine. Miotic, e.g: Pilocarpine. Ear: is a watery solution instill into the ear contain antihistamine, steroid, substance that solubilise the wax. Nasal: is a watery solution instill into the nose contains decongestant, antihistamine, steroid.

Practical Pharmacology

Dr.Gulala

Prescription writing It is a term applied to the formula written by the physician to the pharmacist for preparing medication and to the patient for the use of the drug, it consists of : 1) Superscription: consists of:
a) Name, address, and telephone No. of the physician. written a at t the upper right hand corner.

b) Name, age, and sex (gender) of the patient. written at the left hand corner. c) Date of prescription and registration. d) Diagnosis. e) Symbol (R). 2) Inscription: consists of : a) Name of the drug. b) Strength of the drug. c) Amount of the drug. d) Pharmaceutical form. 3) Subscription: it comprises the direction to the pharmacist for preparation of the drug. It is usually applied when there is compound prescription. 4) Transcription: include direction to the patient for the use of the drug, consist of frequency of administration and time around meal and amount to be used. Compound prescription: it is a type of prescription, include preparation of drug by the pharmacist at the time of dispensing by mixing tow or more drugs in a various dosage form.

The reason of compound prescription:

1) To mask a well known drug from the patient. 2) In case of unavailability of small doses, e.g:Phenobarbital. 3) When the combination of drug are not available as whole drug. 4) In case of unavailability of certain ingredient.

Practical Pharmacology

Dr.Gulala

Prescription Abbreviations bbreviations

Practical Pharmacology

Dr.Gulala

Drug Elimination (excretion) Drugs are eliminated from the body after being partly or wholly converted to water soluble metabolites or in some case without being metabolised. Renal elimination : The following mechanisms are involved : 1. Glomerular filtration : the rate at which a drug enters the glomerulus filtrate depend on the concentration of free drug in the plasma and on its molecular weight .substances that have molecular weight in excess 50,000 are excluded from the glomerular filtrate, while those of M.W less than 10,000 pass easily through the pores of the glomerular membrane. 2. Active tubular secretion: cells of the proximal tubules activily secrete acid and base by tow transport systems.thus acid like Penicillin, Salicylic acid, Probenecid, Frusemidand base like amphetamine and histamine are so secreted. Drugs may compete for the same transport system resulting in prolongation of action of each other, eg: Penicillin and Probenecid. 3. Passive tubular reabsorption : passive diffusion of drug molecule can occur in either direction in the renal tubules depending on the drug concentration, lipid solubility and Ph. As highly lipid soluble drugs are largely reabsorbed, there excretion is slow. acidic drug get ionised in alkaline urine and are easily excreted while base are excreted faster in acidic urine .This property is useful in the treatment of poisoning .
In the poisoning with acidic drugs forced alkaline dieresis is employed to hasten drug excretion

Faecal and Biliary elimination : unabsorbed portion of the orally administered drugs are eliminated through the faeces. Liver transfer acids, base and unionized molecule into bile by specific acid &base transport system. Large water soluble conjugates are excreted in the bile. Some drugs may get reabsorbed in lower portion of the gut and carried back to the liver. Such recycling is called (enterohepatic circulation) it prolong the duration of action of the drug, e.g: Chloramphenicol, tetracycline, oral contraceptive and erythromycin.

Practical Pharmacology

Dr.Gulala

Pulmonary excretion: The lungs are the main route of elimination for gases and volatile liquids (anasthetics) and alcohol, and has legal implication in medico medico-legal practice. Other routes: small amount of some drugs are eliminated through the sweat and saliva .Excretion in saliva may result in a unique taste of some drug like Phenytoin, clarithromycin, metallic taste with metronidazole. The excretion of drugs in the milk is in small amount an and d is of no significances to the mother , but for the sucking infant it may be important especially because of the infants immature metabolic excretory mechanisms.

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Practical Pharmacology

Dr.Gulala

Histamine and antihistamine drugs (Lippincott :Page 520-524 and 330-332) I.Histamine Histamine is a chemical messenger that mediates a wide range of cellular responses, including allergic and inflammatory reactions, gastric acid secretion, and neurotransmission in parts of the brain. Histamine has no clinical applications, but agents that interfere with the action of histamine (antihistamines) have important therapeutic applications. A. Location, synthesis, and release z Location: Histamine occurs in practically all tissues, but it is unevenly distributed, with high amounts found in lung, skin, and the gastrointestinal tract (sites where the inside of the body meets the outside). It is found at high concentration in mast cells or basophils. Histamine also occurs as a component of venoms and in secretions from insect stings. z Synthesis: Histamine is an amine formed by the decarboxylation of the amino acid histidine by histidine decarboxylase,2 an enzyme that is expressed in cells throughout the body, including central nervous system (CNS) neurons, gastric mucosa parietal cells, mast cells, and basophils. In mast cells, histamine is stored in granules as an inactive complex composed of histamine and the polysulfated anion, heparin, along with an anionic protein. If histamine is not stored, it is rapidly inactivated by amine oxidase enzymes.
z Release of histamine: The release of histamine may be the primary response to some

stimuli, but most often, histamine is just one of several chemical mediators released. Stimuli causing the release of histamine from tissues include the destruction of cells as a result of cold, bacterial toxins, bee sting venoms, or trauma. Allergies and anaphylaxis can also trigger release of histamine. B. Mechanism of action Histamine released in response to various stimuli exerts its effects by binding to one or more of four types of histamine receptorsH1, H2, H3, and H4 receptors. H1 and H2 receptors are widely expressed and are the targets of clinically useful drugs. H3 and H4 receptors are expressed in only a few cell types, and their roles in drug action are unclear. All types of histamine receptors have seven transmembrane helical domains and transduce extracellular signals by way of G protein mediated second-messenger systems. Some of histamine's wide range of pharmacologic effects are mediated by both H1 and H2 receptors, whereas others are mediated by only one class. For example, the H1 receptors are important in producing smooth muscle contraction and increasing capillary permeability. Histamine promotes vasodilation by causing vascular endothelium to release nitric oxide.3 This chemical signal diffuses to the vascular smooth muscle, where it stimulates cyclic guanosine monophosphate production, causing vasodilation. Histamine H2 receptors mediate gastric acid secretion. The two most common histamine receptors exert their effects by different

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Dr.Gulala

second-messenger pathways. The actions of H1 antihistamines occur through at least two mechanisms. Antiallergic activities of H1 antihistamines, such as inhibition of the release of mediators from mast cells and basophils, involves stimulation of the intracellular activity of the polyphosphatidylinositol pathway.4 Other actions of H1 antihistamines involve the down-regulation of nuclear transcription factors that regulate the production of proinflammatory cytokines and adhesion proteins. In contrast, stimulation of H2 receptors enhances the production of cyclic adenosine monophosphate (cAMP) by adenylyl cyclase. C. Role in allergy and anaphylaxis The symptoms resulting from intravenous injection of histamine are similar to those associated with anaphylactic shock and allergic reactions. These include contraction of smooth muscle, stimulation of secretions, dilation and increased permeability of the capillaries, and stimulation of sensory nerve endings. z Role of mediators: Symptoms associated with allergy and anaphylactic shock result from the release of certain mediators from their storage sites. Such mediators include histamine, serotonin, leukotrienes, and the eosinophil chemotactic factor of anaphylaxis. In some cases, these cause a localized allergic reaction, producing, for example, actions on the skin or respiratory tract. Under other conditions, these mediators may cause a fullblown anaphylactic response. It is thought that the difference between these two situations results from differences in the sites from which mediators are released and in their rates of release. For example, if the release of histamine is slow enough to permit its inactivation before it enters the bloodstream, a local allergic reaction results. However, if histamine release is too fast for inactivation to be efficient, a full-blown anaphylactic reaction occurs. II. H1 Antihistamines The term antihistamine, without a modifying adjective, refers to the classic H1-receptor blockers. These compounds do not influence the formation or release of histamine; rather, they block the receptor-mediated response of a target tissue. [Note: This contrasts with the action of cromolyn and nedocromil, which inhibit the release of histamine from mast cells and are useful in the treatment of asthma.] The H1-receptor blockers can be divided into first- and second-generation drugs. The older first-generation drugs are still widely used because they are effective and inexpensive. However, most of these drugs penetrate the CNS and cause sedation. Furthermore, they tend to interact with other receptors, producing a variety of unwanted adverse effects. By contrast, the second-generation agents are specific for H1 receptors, and because they do not penetrate the blood-brain barrier, they show less CNS toxicity than the first-generation drugs. Among these agents desloratadine , fexofenadine, and loratadine show the least sedation. [Note: The histamine receptors are distinct from those that bind serotonin, acetylcholine, and the catecholamines.]

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A. Actions The action of all the H1-receptor blockers is qualitatively similar. However, most of these blockers have additional effects unrelated to their blocking of H1 receptors; these effects probably reflect binding of the H1 antagonists to cholinergic, adrenergic, or serotonin receptors. B. Therapeutic uses z Allergic and inflammatory conditions: H1-receptor blockers are useful in treating allergies caused by antigens acting on immunoglobulin E antibodysensitized mast cells. For example, antihistamines are the drugs of choice in controlling the symptoms of allergic rhinitis and urticaria, because histamine is the principal mediator. However, the H1-receptor blockers are ineffective in treating bronchial asthma, because histamine is only one of several mediators of that condition. [Note: Epinephrine has actions on smooth muscle that are opposite to those of histamine, and it acts at different receptors. Therefore, epinephrine is the drug of choice in treating systemic anaphylaxis and other conditions that involve massive release of histamine.] Glucocorticoids show greater antiinflammatory effects than the H1 antihistamines. z Motion sickness and nausea: Along with the antimuscarinic agent scopolamine, certain H1-receptor blockers, such as diphenhydramine, dimenhydrinate , cyclizine , meclizine , and hydroxyzine, are the most effective agents for prevention of the symptoms of motion sickness. The antihistamines prevent or diminish vomiting and nausea mediated by both the chemoreceptor and vestibular pathways. The antiemetic action of these medications seems to be due to their blockade of central H1 and muscarinic receptors. z Somnifacients: Although they are not the medication of choice, many first-generation antihistamines, such as diphenhydramine and doxylamine, have strong sedative properties and are used in the treatment of insomnia. The use of first-generation H1 antihistamines is contraindicated in the treatment of individuals working in jobs where wakefulness is critical. C. Pharmacokinetics H1-receptor blockers are well absorbed after oral administration, with maximum serum levels occurring at 1 to 2 hours. The average plasma half-life is 4 to 6 hours except for meclizine, which has a half-life of 12 to 24 hours. H1-receptor blockers have high bioavailability and are distributed in all tissues, including the CNS. All first-generation H1 antihistamines and some second-generation H1 antihistamines, such as desloratadine and loratadine, are metabolized by the hepatic cytochrome P450 system. Cetirizine is excreted largely unchanged in the urine, and fexofenadine is excreted largely unchanged in the feces. After a single oral dose, the onset of action occurs within 1 to 3 hours. The duration of action for many oral H1 antihistamines is at least 24 hours, facilitating once-daily dosing.

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Dr.Gulala

They are most effective when used prophylactically before allergen exposure rather than as needed. Tolerance to the action of H1 antihistamines has not been observed. D. Adverse effects First-generation H1-receptor blockers have a low specificity; that is, they interact not only with histamine receptors but also with muscarinic cholinergic receptors, -adrenergic receptors, and serotonin receptors. The extent of interaction with these receptors and, as a result, the nature of the side effects vary with the structure of the drug. Some side effects may be undesirable, and others may have therapeutic value. Furthermore, the incidence and severity of adverse reactions for a given drug varies between individual subjects. 1) Sedation: First-generation H1 antihistamines, such as chlorpheniramine, diphenhydramine, hydroxyzine, and promethazine, bind to H1 receptors and block the neurotransmitter effect of histamine in the CNS. The most frequently observed adverse reaction is sedation. Other central actions include tinnitus, fatigue, dizziness, lassitude (a sense of weariness), uncoordination, blurred vision, and tremors. Sedation is less common with the second-generation drugs, which do not readily enter the CNS. Secondgeneration H1 antihistamines are specific for H1 receptors and penetrate the CNS poorly. They show less sedation and other CNS effects. 2) Dry mouth: Oral antihistamines also exert weak anticholinergic effects, leading not only to a drying of the nasal passage but also to a tendency to dry the oral cavity. Blurred vision can occur as well with some drugs. 3) Drug interactions: Interaction of H1-receptor blockers with other drugs can cause serious consequences, such as potentiation of the effects of all other CNS depressants, including alcohol. Persons taking monoamine oxidase (MAO) inhibitors should not take antihistamines, because the MAO inhibitors can exacerbate the anticholinergic effects of the antihistamines. In addition, the first-generation antihistamines (diphenhydramine and others) have considerable anticholinergic (antimuscarinic) actions. These actions would decrease the effectiveness of cholinesterase inhibitors (donepezil, rivastigmine, and galantamine) in the treatment of Alzheimer's disease. 4) Overdoses: Although the margin of safety of H1-receptor blockers is relatively high and chronic toxicity is rare, acute poisoning is relatively common, especially in young children. The most common and dangerous effects of acute poisoning are those on the CNS, including hallucinations, excitement, ataxia, and convulsions. If untreated, the patient may experience a deepening coma and collapse of the cardiorespiratory system.

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III. Histamine H2-Receptor Blockers Although antagonists of the histamine H2 receptor block the actions of histamine at all H2 receptors, their chief clinical use is to inhibit gastric acid secretion, being particularly effective against nocturnal acid secretion. By competitively blocking the binding of histamine to H2 receptors, these agents reduce the intracellular concentrations of cyclic adenosine monophosphate and, thereby, secretion of gastric acid. The four drugs used in the United Statescimetidine, ranitidine, famotidine, and nizatidine potently inhibit (greater than 90 percent) basal, food-stimulated, and nocturnal secretion of gastric acid after a singledose. Cimetidine is the prototype histamine H2-receptor antagonist; however, its utility is limited by its adverse effect profile and drug interactions. z Actions: The histamine H2-receptor antagonists cimetidine, ranitidine, famotidine, and nizatidine act selectively on H2 receptors in the stomach, blood vessels, and other sites, but they have no effect on H1 receptors. They are competitive antagonists of histamine and are fully reversible. These agents completely inhibit gastric acid secretion induced by histamine or gastrin. However, they only partially inhibit gastric acid secretion induced by acetylcholine or bethanechol. z Therapeutic uses: The use of these agents has decreased with the advent of the PPIs. Peptic ulcers: All four agents are equally effective in promoting healing of duodenal and gastric ulcers. However, recurrence is common after treatment with H2 antagonists is stopped (60-100 percent per year). Patients with NSAID-induced ulcers should be treated with PPIs, because these agents heal and prevent future ulcers better than H2 antagonists. Acute stress ulcers: These drugs are useful in managing acute stress ulcers associated with major physical trauma in high-risk patients in intensive care units. They are usually injected intravenously. Gastroesophageal reflux disease: Low doses of H2 antagonists, recently released for over-the-counter sale, appear to be effective for prevention and treatment of heartburn (gastroesophageal reflux). However, about 50 percent of patients do not find benefit, and PPIs are now used preferentially in the treatment of this disorder. Because H2-receptor antagonists act by stopping acid secretion, they may not relieve symptoms for at least 45 minutes. Antacids more efficiently, but temporarily, neutralize secreted acid already in the stomach. Finally, tolerance to the effects of H2 antagonists can be seen within 2 weeks of therapy.

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z Pharmacokinetics: Cimetidine: Cimetidine and the other H2 antagonists are given orally, distribute widely throughout the body (including into breast milk and across the placenta), and are excreted mainly in the urine. Cimetidine normally has a short serum half-life, which is increased in renal failure. Approximately 30 percent of a dose of cimetidine is slowly inactivated by the liver's microsomal mixed-function oxygenase system and can interfere in the metabolism of many other drugs; the other 70 percent is excreted unchanged in the urine. The dosage of all these drugs must be decreased in patients with hepatic or renal failure. Cimetidine inhibits cytochrome P450 and can slow metabolism (and, thus, potentiate the action) of several drugs (for example, warfarin, diazepam, phenytoin, quinidine, carbamazepine, theophylline, and imipramine;), sometimes resulting in serious adverse clinical effects. Ranitidine: Compared to cimetidine, ranitidine is longer acting and is five- to tenfold more potent. Ranitidine has minimal side effects and does not produce the antiandrogenic or prolactin-stimulating effects of cimetidine. Unlike cimetidine, it does not inhibit the mixed-function oxygenase system in the liver and, thus, does not affect the concentrations of other drugs. Famotidine: Famotidine is similar to ranitidine in its pharmacologic action, but it is 20 to 50 times more potent than cimetidine, and 3 to 20 times more potent than ranitidine. Nizatidine: Nizatidine is similar to ranitidine in its pharmacologic action and potency. In contrast to cimetidine, ranitidine, and famotidine, which are metabolized by the liver, nizatidine is eliminated principally by the kidney. Because little firstpass metabolism occurs with nizatidine, its bioavailability is nearly 100 percent. No intravenous preparation is available. z Adverse effects: The adverse effects of cimetidine are usually minor and are associated mainly with the major pharmacologic activity of the drug namely, reduced gastric acid production. Side effects occur only in a small number of patients and generally do not require discontinuation of the drug. The most common side effects are headache, dizziness, diarrhea, and muscular pain. Other central nervous system effects (confusion, hallucinations) occur primarily in elderly patients or after intravenous administration. Cimetidine can also have endocrine effects, because it acts as a nonsteroidal antiandrogen. These effects include gynecomastia, galactorrhea (continuous release/discharge of milk), and reduced sperm count. Except for famotidine, all these agents inhibit the gastric first-pass metabolism of ethanol. Drugs such as ketoconazole, which depend on an acidic medium for gastric absorption, may not be efficiently absorbed if taken with one of these antagonists.

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