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Factors modifying drug action

Dr. Datten Bangun , MSc.SpFK Dept.Farmakologi & Therapeutik Fak.Kedokteran U S U MEDAN

Therapeutic Objective of using drugs

To provide:
= maximum benefit = with minimum harm
Factors that determine Intensity of Response

Administration- dosage size and route Pharmacokinetic processes Pharmacodynamics Individual Variations

General Concepts
Drug Dose Administration

Pharmaceutical

Disintegration of Drug Absorption/distribution metabolism/excretion Drug/Receptor Interaction Drug Effect or Response

Pharmacokinetics Pharmacodynamics Pharmacotherapeutics

Factors modifying drug action


A multitude of host and environmental factors influence drug response. These factors influence drug responses either: I. Quantitatively:- plasma concentration/ the action of the drug is either increased or decreased II. Qualitatively : - the type of the responses is altered e.g. drug allergy or idiosincrasy

Factors modifying drug action


I. Physiological Factors. II. Pathological Factors (Diseases). III. Genetic Factors. IV. Environmental Factors. V. Interaction with other drugs.
Route of drug administration Time of administration Environmental factor

I. Physiological Factors
Age Sex Pregnancy Body weight Lactation Food * Route of drug administration * Time of administration * Environmental factor

I. Physiological Factors
1. AGE
Newborn:Decreased gastric acid secretion. liver microsomal enzymes (glucuronyl transferase). Plasma protein binding. GFR & tubular secretion. Immaturity of BBB in neonates.
-GIT

absorption of ampicillin and amoxicillin is greater in neonatesdue to decreased gastric acidity.

Chloramphenicol ---Grey baby syndrome Inadequate glucouronidation of chloramphenicol with drug accumulation). Sulfonamides ------Hyperbilirubinemia & Kernicterus

CHILDREN
Tetracyclines =Permanent teeth staining Corticosteroids =Growth & development retardation Antihistaminics =Hyperactivity.

Considerations for Pediatric Patients


Wide variation between age and degree of organ-system development Reevaluate all doses at regular intervals. Be sure the dosage is appropriate for the child s age. Always double-check all computations.

Considerations for Elderly Patients


Physiologic Function Changes
Optic Auditory Gastrointestinal Pulmonary Cardiovascular Urinary Hormonal Composition of the body

Considerations for Elderly Patients


Altered Drug Responses Adverse Drug Reactions (ADRs) Polypharmacy Noncompliance

Old Age
Liver function. = diazepam, theophylline. Kidney function. =Digoxin, lithium. Plasma protein binding sensitivity to CNS depressants. =diazepam, morphine

2. SEX.
Testosterone

increases the rate of biotransformation

of drugs. Decreased metabolism of some drugs in female (Diazepam). Females are more susceptible to autonomic drugs ( estrogen inhibits choline estrase).

3. Pregnancy
Cardiac output GFR and renal elimination of drugs. Vd Metabolic rate of some drugs. Lipophilic drugs cross placental barrier & slowly excreted.

Developmental factors; during pregnancy, drugs taken during pregnancy pose a risk throughout the pregnancy, but pose the highest risk during the first trimester, due to the formation of vital organs and functions of the fetus during this time. Environment; = for example receiving medication in an environment that lack of oxygen effects drug reaction, also pt who receives pain medication or sedative in a busy, noisy environment may not benefit as fully as if the environment were quiet and peaceful.

1. Administration- dosage size and route Administration- Because of errors in administration routes and dosage and at wrong time there are many discrepancies in what patient gets and could cause more harm than good - Errors could be made by pharmacists, physicians, or nurses - Should give patients complete instruction about their medication and how to take it 1. Oral Medication 2. Sublingual Medication 3. Buccal Medication pertaining to the cheek 4. Parenteral Medication

Time of administration; = the presence of food in the stomach delays the absorption
of oral administration of medication, = some medications should be given with the food to prevent gastric irritation.

Diet;
= nutrients can affect the action of a medication, for example, vitamin K found in green leafy vegetables can counteract the effect of an anticoagulant such as warfarin.

4. Plasma Protein Binding


Malnutrition.----- plasma protein decrease--

free drug concentration increases---intoxication---- Mentawai victims Drug Interaction: 1. drug-drug interaction: = synergism = potentiation = summation/addism = antagonism 2. food- drug interaction

II. Pathological Factors

Illness and disease;


The presence of a disease affect the action of drugs. For example, aspirin can reduce the body temperature of a feverish client but has no effect on the body temperature of a client without fever. The liver is the primary organ for drug breakdown and the pathologic conditions that involve the liver may slow down metabolism

II. Pathological Factors


Diseases cause individual variation in drug response (A) Liver Disease Prolong duration of action = (t1/2). Plasma protein binding for warfarin, tolbutamideadverse effects. Hepatic blood flow clearance of morphinepropanolol. Impaired liver microsomal enzymes Diazepam-rifampicin-theophylline

(B) Renal Disease


GFR. tubular function. Plasma albumin digoxin-lithium-gentamycin-penicillin.

(C) Malnutrition
plasma protein binding of drugs. amount of microsomal enzymes. ------ Increases portion of free, unbound drugwarfarin

III.Genetic Factors
Pharmacogenetics
is the study of the relationship b/w genetic factors and drug response.

Idiosyncrasy;abnormal drug reaction due to genetic


disorder . Acetylation. Oxidation. Succinylcholine apnea. Glucose 6-phosphate dehydrogenase deficiency.

III. Genetic Factors


GENETIC POLYMORPHISM The existence in a population of two or more phenotype with respect to the effect of a drug. Acetylation enzymes deficiency acetyl transferase (non-microsomal). Isoniazid, sulphonamides, etc. Slowacetylator phenotype --- peripheral neuropathy . Rapidacetylator phenotype --- hepatitis.

Pseudocholinesterase deficiency. Succinyl choline ( Sk.muscle relaxant ) ---------Succinylcholine apnea due to paralysis of respiratory muscles. Malignant hyperthermia By succinyl choline due to inherited inability to chelate calcium by sarcoplasmic reticulum. Carelease, muscle spasm, Temp.

Oxidation Polymorphism
Debrisoquine. Extensive metabolizers (EM) need larger dose. poor metabolizers (PM) need smaller dose. Porphyria Deficiency of Glucose6 phosphate dehydrogenase (G-6-PD). G-6-PD Deficiency in RBCs -------- hemolytic anemia upon exposure to some oxidizing drugs. Antimalarial drug, primaquine. Long acting sulphonamides. Fava beans ( favism).

IV. Environmental Factors: Microsomal Enzyme Inducers


Tobacco Smoke Smokers metabolize drugs more rapidly than non smoker.

Adverse drug effects:


Undesirable or harmful effects which can occur at therapeutic doses and need a reduction of dose or drug withdrawal . Nausea and vomiting Deafness with gentamycin Death with penicillin

Types of adverse drug reactions: =A, B, C, D and E etc -------- prior lectures

Drug dependence
State in which use of drugs for personal satisfaction is accorded a higher priorit than other basic needs,often when the risks to health are known Drugs capable of altering mood & feelings are liable to repetitive use to derive euphoria, withdrawal from reality, social adjustment, etc
Psychological dependence

Drug dependence Physical dependence

Drug tolerance
Requirement of higher dose of a drug to produce a given response Its an adaptive biological phenomenon Drug tolerance may be: Natural or Acquired Natural the individual is inherently less sensitive to the drug. E.g. black races are tolerant to mydriatics

Acquired developed by repeated use of a drug in


an individual who was initially responsive

Cross tolerance
It is the development of tolerance to pharmacologically related drugs E.g. alcoholics are relatively tolerant to barbiturates & general anaesthetics

Tachyphylaxis
rapid development of tolerance ( as in doses repeated at quick successions)

Drug resistance:
Refers to tolerance of microorganisms to inhibitory action of antimicrobials e.g. P.falciparum shows resistance to Chloroquin at certain geographical areas

Drug resistance:
Refers to tolerance of microorganisms to inhibitory action of antimicrobials e.g. P.falciparum shows resistance to Chloroquin at certain geographical areas

Key Points
The most important properties of an ideal drug are: effectiveness, safety, and selectivity. If the drug is not effective, it should not be used. There is no such drug as safe drug: all drugs can cause harm. There is no such thing as selective drug: all drugs can cause side effects. The objective of drug therapy is to provide maximum benefit within minimum harm. Because all patients are unique, drug therapy must be tailored to each individual.