PHARMACOKINETICS

Study of the time course of drug absorption, distribution, metabolism and

excretion

ADME PROCESS

ABSORPTION

process by which drug molecules move from their site of admin to blood; determines
onset of drug action; more rapid absorption, faster onset of drug

Numerous sites for systemic absorption-> GI tract, lungs, mucous membranes, eyes,
skin muscles and subcutaneous tissues

FACTORS AFFECTING
ABSORPTION
1.SURFACE AREA

larger surface area= better rate of absorption

2.BLOOD FLOW

blood must be flowing to the absorbing surface during absorptive process to allow entry
during systemic circulation

3. CONCENTRATION
Passive diffusion- common means by which drugs traverse cellular membrane
The concentration of drug at the administration site will influence both rate and extent of
absorption

FACTORS AFFECTING ABSORPTION

Exception to this rule includes active transport system to facilitate movement across
membranes e.g. (ferrous ions)

Contains a carrier protein to which drug attaches ->moves the drug across the membrane ->
release it to the post absorptive side (low-high concentration)
4. ACID- BASE PROPERTIES

Most drugs are either weak acid or weak bases

Non ionized in acidic medium and ionized when in alkaline media

Weak acid crosses best when in an acid medium

e.g. ASPIRIN (Acetylsalicylic Acid)

ASPIRIN -> Enters stomach (gastric juice have a PH of 1.0 to 2.0/ACIDIC ENVIRONMENT

making aspirin nonionized -> creates easier pathway through the membrane for the drug
to enter the blood

FACTORS AFFECTING ABSORPTION

5.LIPHOPHILICITY

Refers to the ability of a chemical compound to dissolve in fats, oils, lipids, and non-polar
solvents such as hexane or toluene.

Drugs with good lipid solubility will cross lipid-layered membranes readily

6. COMPATIBILITY
Some drugs may interact with other chemicals to form insoluble precipitates, when such
interaction occurs, absorption is significantly decreased.
e.g. Barium -> extremely toxic when given intravenously
-> does not cross GI membranes because it forms an insoluble complex in
medium -> safe to use as an oral GI radiopaque agent

that

DISTRIBUTION

Defined as the transport of a drug in body fluids from the bloodstream to various tissues
of the body and ultimately to its site of action

Several factors affect distribution

1.Cardiac output- amount of blood pumped by the heart per minute
2. Regional Blood Flow- amount of blood supplied to a specific organ or tissue
3. Drug Reservoir- drug accumulations that are bound to specific sites such as plasma, fat
tissue and bone tissue

BARRIERS

Blood-brain barrier- a highly selective permeability barrier that separates the

circulating blood from the brain extracellular fluid in the central nervous system (CNS).

Plasma barrier-composed of structures that separate the maternal and the fetal blood

Example situation
CNS infection-> antibiotic should cross blood-brain barrier, with an expectant mother who
did not know she was pregnant, however, it would be undesirable for certain drugs to
cross the placental barrier and affect unborn child.

METABOLISM

Also called biotransformation chemically changes a drug into a metabolite that can be
excreted to the body

LIVER- primary responsible for metabolism

TYPES of chemical reaction in the liver
1.Oxidation, Hydrolysis or reduction
-gaining an electron to decrease positive valence
2. Conjugation
- transforms a drug from a lipid-soluble substance to that can cross-biologic
membranes to a water-soluble substance that can be excreted through the biliary tract

SEVERAL FACTORS CONTRIBUTE TO

PROLONGED DRUG METABOLISM

Liver disease

Immature metabolizing enzyme system

Degenerating enzyme function

Severe cardiovascular dysfunction

Renal problems

SEVERAL FACTORS CONTRIBUTE TO

PROLONGED DRUG METABOLISM

IF DRUG METABOLISM IS DELAYED, CUMULATIVE DRUG EFECT MAY APPEAR AS

SYMPTOMS OF AN OVERDOSE. EVEN THOUGH A USUAL DOSE WAS
ADMINISTERED

*Drugs administered orally normally travels to liver first before entering the general circulation

FIRST PASS METABOLISM- may cause significant deterioration on the drug-> making
drug INACTIVE

* Some drugs need to be administered to alternative route to ensure proper action

EXCRETION
KIDNEYS

Primary organ responsible

Filters blood and remove unbound, water-soluble compounds

E.g. Drug testing often done in URINE

INTESTINES

After metabolism by the liver, a metabolite can be secreted into the bile, passed into the
duodenum and eliminated in the feces

RESPIRATORY SYSTEM

Gases or volatile liquids that are administered through RS usually are eliminated in the
same route

(BREAST MILK, SALIVA AND SWEAT-contains drug compound but are not the bodys
predominant mechanism for elimination)

PHARMACODYNAMICS

the study of the biochemical and physiologic effects of drugs and their
mechanisms of action on the body or on microorganisms and other
parasites within or on the body.

MECHANISM OF ACTION

method by which drug elicits effect. Drug produce effects through drug-receptors
interaction, drug-enzyme interaction and nonspecific drug interaction

1.Drug-Receptors interaction
Most drugs create their effects in the body by attaching to special sites called,
RECEPTORS

can be thought as a keyholes into which specific keys(drugs) may fit

*Strong Affinity (attraction) for a receptor allows a drug to elicit an agonist, antagonist, or
mixed agonist/antagonist interaction

DRUG- RECEPTOR INTERACTIONS

TARGET ORGAN

Organ or in which desired effect occurs

AGONIST

Is a drug or natural substance with an affinity for a specific receptor sites produces a
physiologic response

Stimulates or enhances bodys natural response to stimulation

DRUG- RECEPTOR INTERACTIONS

ANTAGONIST

Blocks the action of agonist

No increase in response

E.g
Patient with severe anaphylaxis may have worsening respiratory distress if given propranolol
Propranolol is a non selective beta blocker which blocks the action of epinephrine and
norepinephrine

DRUG- RECEPTOR INTERACTIONS

AFFINITY
Propensity of a drug to bind or attach itself to a given receptor site
EFFICACY
Drugs ability to initiate biologic activity as a result of such binding
COMPETITIVE ANTAGONIST
An agent with an affinity for same receptor site as an agonist; competition with the agonist for
the site inhibits action of the agonist; increasing concentration of the agonist tends to
overcome the inhibition
NONCOMPETITIVE ANTAGONIST
Agent that combines with different parts of the receptor mechanism and inactivates receptor
so the agonist cannot be effective regardless of its concentration
PARTIAL AGONIST
Agent hhas affinity and some efficacy but that may antagonize action of other drugs that have
greater efficacy

MECHANISM OF ACTION
2. Drug-Enzyme Interaction
Enzymes- considered catalysts responsible for initiating biochemical reactions
E,g.
ACETHYCOLINESTERASE ENZYME metabolized acetylcholine
responsible for nerve stimulation
Toxic levels in nervous system
acetylcholine to accumulate

Neurotransmitter

Inhibition of AE allows

MECHANISM OF ACTION
3. Nonspecific Drug Interaction
Drugs that affect various sites and have properties of nonspecificity
Drugs that evoke a variety of responses throughout the body
E.g
Radiopaque Contrast Media elicits desired effect through the radiopaque iodine
contained within their structure

DRUG RESPONSE RELATIONSHIP

EFFICACY
Degree to which a drug is able to produce desired effect(how great the effect will be)
POTENCY
Relative concentration required to produce the effect(how much the drug is needed)
E.G
If Drug A produces reduction of pain from severe to mild and if Drug B reduces pain from
severe to none at all= DRUG B IS MORE EFFICACIOUS
If Drug C and Drug D both provde total pain relief, but you must take 5000mg of Drug C and
only 200mg of Drug D= DRUG D IS MORE POTENT

HALF-LIFE

Time required for the current serum drug concentration to decline by 50%
Remains stable for each particular drug, unless metabolism and excretion is altered( SEPTIC
SHOCK)
Drug Dosage does not generally alter half-life of elimination. However, few drugs such as
PENYTOIN, ASPIRIN AND ALCOHOL may have alteration in their respective half-lives of
elimination when dosages overwhelm the biologic capacity for metabolism

THERAPEUTIC INDEX
Measure of relative safety of a drug

LD 50

Ration between Lethal Dose and effective Dose

TI = ----------

ED50
Lethal Dose: dose at which a drug is lethal to 50% of the
Population
Effective Dose: dose required to produce a therapeutic effect in the 50% of the population

ADVERSE EFFECTS

SIDE EFFECT

Generally considered a predictable pharmacologic action on body systems other than the
action intended
Can be either good or bad depending on the situation
ADVERSE EFFECT
Unwanted effect
E.G
HYDROXIZINE-a strong anti histamine that can be used to prevent itching
SE: antiemetic and anxiety relief- may be considered good but not the primary function
MEPERIDINE(DEMEROL)- AE:causes frequent nausea and vomiting
*ALL ADVERSE EFFECT NEED TO BE CONSIDERED AND AN ACCEPTABLE RATION
BETWEEN THE GOOD AND ADVERSE EFFECT SHOULD BE SOUGHT FOR ALL DRUG
THERAPY

ADVERSE EFFECTS

TOXICITY

Extension of pharmacologic action and is directly related to dose

Higher the dose, the greater the toxic effects
*Normal Dose may become toxic if metabolism or elimination is impaired
ALLERGIC REACTION
Results from an immune-mediated response by the bodyagainst the drug and is not
necessarily related to the dose.
ABSOLUTELY NO DRUGS ARE COMPLETELY SAFE
*PATIENTS SHOULD NEVER BE GIVEN A MEDICATION WITHOUT PROPER,
SYSTEMATIC AND CRITICAL THOUGHT

PHARMACODYNAMICS
4. DRUG-DRUG INTERACTIONS
Occurs when two or more drugs act in unison to produce additive agonist, synergistic or
antagonist response
E.G Sedative-hypnotics
SYNERGISM- two drugs that act together to give a pharmacologic response that is greater
than the additive response expected
CHEMICAL INCOMPATIBILITY- When two drugs with different chemical composition are
placed together, they may precipitate to an insoluble complex or may chemically destroy their
activity

DRUG CLASSIFICATIONS

CARDIAC MEDICATIONS

ANTIARRHYTMIC/ ANTIDYSRHYTMIC

Drugs that affect electrical conduction system of myocardium

Blocks sinoatrial node, atrioventricular node, His-Purkinje system or the electrical membrane
current within the myocardial cell(sodium, calcium and potassium) or by blocking the beta
receptors located within myocardium
GOAL: Suppress excess electrical conduction within cardiac system and thus decrease
arrhytmia production
-Lidocaine, procainamide, amiodarone, atenolol, metropolol, verapamil, adenosine, digoxin

CARDIAC MEDICATIONS

ANTIHYPERTENSIVE

Assist in lowering blood pressure to safe, long-term goals

Also affects heart failure in a positive way by decreasing pressure against which the heart
must pump
Causes vasodilation, decreased heart rate, decreased sympathetic nerve outflow or inhibtion
of Renin-Angiotensin-Aldosterone System
-Terazosin, minoxidil, nicardipine, amlodipine, nifedipine, bumetanide, enalopril

CARDIAC MEDICATIONS

HEART FAILURE MEDICATIONS

DIGOXIN- Positive inotropic effect(increased force of contraction)

- used to block AV node in the heart so that patients with atrial fibrillation do not
experience too many adverse beats from atrium to the ventricle
DOBUTAMINE, MILRINONE, DOPAMINE, NOREPINEPHRINE AND EPINEPHRINE
- IV MEDS that can be used to increase the force of contraction in a failing heart

LIPID LOWERING MEDICATIONS

Lowers serum cholesterol levels and assist in long term life enhancement for patients with
coronary syndromes
LOVASTATIN, SIMVASTATIN,PRAVASTATIN

CARDIAC MEDICATIONS

DIURETICS

Referred as water pills

Designed to eliminate excess fluid and sodium from the bloodstream, thus decreasing overall
pressure within the vessels
OVERUSE CAN LEAD TO DEHYDRATION AND KDNEY FAILURE

ANTICOAGULANT, ANTIPLATELET AND

THROMBOLYTIC MEDICATIONS

ANTICOAGULANT

Frequently used in patients who have either hstory of blood clot formation or potential develop
clots
WARFARIN-oral medication to prevent absorption of Vit. K from intestinal tract->prevents
formation of blood clotting factors
HEPARIN, ENOXAPARIN, DELTAPARIN, FUNDOPARINOX- medications that affect the
activity of thrombin in various ways to inhibit clot formation

ANTIPLATELET

Used in patients who have experienced an acute ischemic event to either the heart or brain
ASPIRIN, CLOPIDROGEL AND DIPYRIDAMOLE- ORAL
EPTIFIBATIDE, ABCIXIMAB AND TIROFIBAN- IV

ANTICOAGULANT, ANTIPLATELET AND

THROMBOLYTIC MEDICATIONS

THROMBOLYTIC

Medications use to actively break up newly formed clot such as found in patients with acute
myocardial infarction(heart attack), acute stroke secondary to blood clot or lower leg ischemia
ALTEPLASE, RETAPLASE, STREPTOKINASE AND UROKINASE
*HIGH RISK FOR BLEEDING
*DO NOT START IV LINE WITHOUT PHYSICIAN ORDERS AND CLOSE SUPERVISION

ANALGESIC MEDICATIONS

ANALGESICS

Medications that are used to treat both acute and chronic pain syndromes such as arthritis,
headache, muscle sprains, cancer pain, surgical and traumatic pain,nerve pain and some
cases, anxiety

NARCOTICS

Medications that stimulate central nervous system receptors known as OPIOD RECEPTORS
and cause a decrease in the perception of pain
MORPHINE, MEPERIDINE, FENTANYL, OXYCODONE, CODEINE, TRAMADOL
*IF RESPIRATORY ARREST OCCURS-> NALOXONE given via IV, IM or Endotracheally

ANALGESIC MEDICATIONS

NSAIDs (NON STEROIDAL ANTIIINFLAMMATORY DRUGS)

Used to treat pain associated with inflammation such as arthritis, vasculitis, muscle tears,
broken bones and surgical incision or trauma wounds
Inhibits production and release of various chemical mediators responsible for stimulating
nociceptor(pain receptor)
*SOME NSAIDs can also cause platelet dysfunction and thus place the patient at risk for
bleeding
*Ulceration of stomach and kidney failure are common adverse effect
IBUPROFEN, NAPROXEN, KETOROLAC, CELECOXIB

ANALGESIC MEDICATIONS

MUSCLE RELAXANTS

Used to treat pain associated with muscle spasm

May affect the way the patient breathes simply by decreasing the strngth of the external
muscles of respiration
DIAZEPAM, LORAZEPAM, CLONAZEPAM
ACETAMINOPHEN- INHIBITS PROSTAGLANDIN IN THE CNS THAT ARE RESPONSIBLE
FOR PAIN PRODUCTION
Long term used may cause renal and cardiac damage

ANTIHYSTAMINE MEDICATIONS

ANTIHYSTAMINE MEDICATIONS

Used to block histamine receptors from producing adverse effects such as itching,
inflammation, respiratory distress and overall allergic reactions.
HYDROXIZINE(VISTARIL, ATARAX) AND DIPHENHYDRAMINE(BENADRYL)
LORATADINE, CETIRIZINE AND FEXOFONADINE
*GENERALLY QUITE SEDATING AND MAY LEAD TO RESPIRATORY DEPRESSION
WHEN USED IN COMBINATION WITH ANALGESIC MEDICATIONS

ENDOCRINE MEDICATIONS

ANTIDIABETIC

Medications required for patients who have difficulty maintaining proper balance between
blood sugar and tissue sugar
Insulin Dependent: DM TYPE 1
They have little or no circulating endogenous insulin
Non Insulin Dependent: DM TYPE 2
Patients who have sufficient circulating endogenous insulin but poor receptor sensitivity
INSULIN Ultrashort acting, short acting, long acting and ultralong acting
*MEALS TO BE TAKEN AT REGULAR RATE- Low values can lead to seizure and comatose
state
NID(TYPE 2): GLIMEPRIMIDE, GLIPIZIDE, METFORMIN

ENDOCRINE MEDICATIONS

METFORMIN- SHOULD BE HELD FOR AT LEAST 48 HOURS AFTER RECEIVING A

RADIOPAQUE CONTRAST AGENT

If not held, the patient is put at risk for severe metabolic acidosis secondary to
metformin accumulation, in the event renal dysfunction is caused by the radiopaque
contrast agent

THYROID MEDICATION

Used to treat hypothyroidism

Thyroid hormone: basic regulator of many metabolic processes in the body

LEVOTHYROXINE, THYROXINE, LIOTHYRONINE- block or inhibti thyroid function

CENTRAL NERVOUS SYSTEM MEDICATIONS

ANTISEIZURE (ANTICONVULSANT)

Used to prevent and to treat seizure disorders

GOAL: stop seizure activity and prolong the interval between each seizure event
PHENYTOIN,DIAZEPAM, SECOBARBITAL, CLONAZEPAM,LORAZEPAM, GABAPENTIN
ANTIPSYCHOTIC
used to treat antipsychotic episodes ans disorders such as schizophrenia, paranoid
behaviors, hallucinations, delusions, bipolar affective disorder, acute agitation and mania.
HALOPERIDOL, VALPROIC ACID, CLOZAPINE, OLANZAPINE, RISPERIDONE

ANTIDEPRESSANT

Used to treat clinical depression that result from neurotransmitter deficiencies

Usually enhance the CNS levels of serotonin and norepinephrine-elevates depressed mood
AMITRIPTYLINE, AMOXAPINE, DESIPRAMINE, NEFAZODONE

CENTRAL NERVOUS SYSTEM MEDICATIONS

ANTIANXIETY

Used to treating acute or chronic anxiety states

Generally acts on the limbic system in the brain by enhancing effect of the sedative
neurotransmitter gamma-amnibutyric acid(GABA) in some cases serotonin
MIDAZOLAM, DIAZEPAM, CLONAZEPAM
Radiologic technologists frequently encounters this class because patients requires sedatives
to alleviate anxiety when undergoing CT SCAN and MRI scans

ANTIINFECTIVE AGENTS

ANTIBIOTICS

Used to kill or supress pathologic microorganisms responsible for causing infectious disease
PENICILLINS, CEPHALOSPORINS, TETRACYCLINES, NITROMIDAZOELS

ANTIFUNGALS-agents used to kill mycotic fungal microorganisms

AMPHOTERICIN B, FLUCONAZOLE, KETOCONAZOLE, CLOTRIMAZOLE

ANTIVIRALS-used to suppress and limit the spread or shedding or viruses that invade
human body

ACYCLOVIR, RIBAVIRIN, RIMANTIDINE, INTERFERON, FAMCICLOVIR

CHEMOTHERAPY AGENTS

Extremely toxic compounds designed to kill off rapidly growing cells of the human body by
altering or destroying the various stages in cellular division

SPECIAL PRECAUTIONS SHOULD BE TAKEN WITH ALL CHEMOTHERAPY PATIENTS SO

THAT NO MEDICATION TOUCHES THE UNEXPOSED SKIN OF A HEALTHCARE WORKER
BODILY FLUIDS INTO WHICH CHEMOTHERAPY IS EXCRETED SUCH AS URINE-POSE A
THREAT TO CLINICIANS
UNIVERSAL PRECAUTIONS AND SPECIAL GOWNS;GLOVES SHOULD BE WORN
ADRIAMYCIN, ETOPOSIDE, PACLITAXEL, METHOTREXATE, NITROGEN MUSTAR,
BLEOMYCIN