GENERAL CONCEPTS IN

PHARMACOTHERAPY

Dr. Bindira Maharjan

Resident, Department of Clinical Pharmacology
OBJECTIVES

 To define Pharmacotherapy
 To enlist and describe briefly on various concepts
in pharmacotherapy
 To summarize the topic
PHARMACOTHERAPY: DEFINITION

 Use of drugs for therapeutic purpose or

alleviating any illness or condition with good
understanding of the drug, the disease, the patient
and the conditions under which it taken.
 “Drug therapy involves a great deal more than
matching the name of the drug to the name of a
disease; it requires knowledge, judgement, skill
and wisdom, but above all a sense of
responsibility “
DRUG

 WHO Scientific group has defined drug as “ any

substance or product that is intended to be used to
modify or explore physiological systems or
pathological states for the benefit of the
recipient.” WHO 1966 TRS no. 341:7
 The Therapeutic
Situation

Pharmacoeconomics Prescribing, drug

consumption

PHARMACOTHERAPY

Compliance

Essential
Medicines
Placebo Medicines
THE THERAPEUTIC SITUATION

 Factors affecting Drug response

 Patient-related factors : Genetic
 Environmental: Non- Genetic
 These factors modify drug action either
qualitatively or quantitatively
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FACTORS MODIFYING DRUG ACTION

 Qualitatively – Change in drug response

 eg: drug allergy , Idiosyncracy. Often involves precluding
further use of drug

 Quantitatively –Plasma concentration is increased or

decreased thus action of drug. Can be adjusted by
modifying dosage regimen.

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FACTORS MODIFYING DRUG ACTION

Age
 Physiological differences between different age groups.
 For eg: newborn has low GFR and tubular transport is
immature. Thus, the t 1/2 (half-life) of drugs excreted
by glomerular filtration and tubular secretion is
prolonged by 3-5 times.

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FACTORS MODIFYING DRUG ACTION

Age
 After first year, higher metabolism rate than
adults
 Elderly- renal function declines, cumulative
toxicity, slower absorption, drug-drug
interactions
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FACTORS MODIFYING DRUG ACTION

Body size:
 Affects the concentration of drug reached at the site of action.
 Dose of drug is calculated on the basis of body weight.
 For extremely lean or obese , body surface area is considered
for accuracy

Individual dose = BSA (m2)/ 1.7 X average adult dose

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FACTORS MODIFYING DRUG ACTION

 Body surface area is calculated using given

formula
BSA (m2) = BW (kg)0.425 × Height (cm)0.725 × 0.007184

 Charts and slide-rule nomograms

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FACTORS MODIFYING DRUG ACTION

Gender: Body size, distribution and physiological

state differs between male and female

Pregnancy, menstruation and lactation

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FACTORS MODIFYING DRUG ACTION

 Physiological changes during pregnancy that can

alter drug response:
 Gastrointestinal motility is reduced → delayed
absorption of orally administered drug.
 Plasma and extracellular fluid volume expands—
volume of drug distribution increases

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FACTORS MODIFYING DRUG ACTION

Race/ ethnicity
 For eg. blacks require higher and mongols require
lower concentrations of atropine and ephedrine to
dilate their pupil.

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FACTORS MODIFYING DRUG ACTION

Genetics: Individual variations in drug response.

 Key determinants of drug response: metabolizing
enzymes, transporters, receptor function, etc
controlled genetically.

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PHARMACOGENETICS

 The study of genetic basis for variability in drug

response
 deals with genetic influences on drug action as
well as on drug handling by the body.
PHARMACOGENOMICS

Use of genetic information to guide the choice of

drug and dose on an individual basis.
 Applied largely to patients with known genetic
 abnormalities, but the goal is ‘personalized
 medicine’ on a wide scale
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FACTORS MODIFYING DRUG ACTION

 Route of administration
 speed and intensity of drug response
 Different uses through different routes

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FACTORS MODIFYING DRUG ACTION

 Environmental factors:
 Time of administration, Exposure to insecticides,
carcinogens, tobacco smoke, type of diet

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FACTORS MODIFYING DRUG ACTION

 Psychological factors
 Drug efficacy influenced by patient’s beliefs,
attitudes and expectations.
 Specially for centrally acting drugs.
 Placebo and nocebo effect.

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PLACEBO

 Inert substance which is given in the garb of a

medicine. Works by psychodynamic rather than
pharmacodynamic
 means
 Produces responses equivalent to the active drug.
 Variable response among individuals
NOCEBO

 Refers to negative psychodynamic effect evoked

by the pessimistic attitude of the patient, or by loss
of faith in the medication and/or
 the physician.
 Nocebo effect can oppose the therapeutic effect
 of active medication.
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FACTORS MODIFYING DRUG ACTION

Pathological state:
 Various diseased states modify drug disposition
and responses
 GI diseases, liver diseases, Kidney diseases

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FACTORS MODIFYING DRUG ACTION

Liver disease:
Alternative drugs that do not depend on hepatic
 metabolism for elimination and/or have shorter
 t½ should be preferred, e.g. oxazepam or
 lorazepam in place of diazepam

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FACTORS MODIFYING DRUG ACTION

Concomitant use of Other drugs:

 Drugs can modify the response to each other by
pharmacokinetic or pharmacodynamic interaction
between them. Desirable or undesirable effects

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FACTORS MODIFYING DRUG ACTION

 In patients with cardiovascular disease, kidney

disease, and/or diabetes, renin-angiotensin
system blockers, non-steroidal anti-inflammatory
drugs, diuretics, and metformin can increase the
risk of CI-AKI ( contrast induced acute kidney
injury) when undergoing contrast imaging.
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FACTORS MODIFYING DRUG ACTION

Drug combinations
 Desirable: Synergistic or additive effect. Or
complementary. Eg. Antimicrobials
 Non-desirable: Fatal, adverse reactions. For eg.
Drugs with narrow therapeutic margin, closely
related function, highly plasma protein bound drugs,
etc. 28
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FACTORS MODIFYING DRUG ACTION

Dosage

With increased dose and rate will cause cumulation of drug

in the body.
 Slowly eliminated drugs also cause cumulative toxicity.
Eg. Chloroquine
 Tolerance: Loss of therapeutic efficacy of drug. Natural or
acquired.
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FACTORS MODIFYING DRUG ACTION

Tachyphylaxis: Rapid development of tolerance when

doses of a drug repeated in quick succession result in

marked reduction in response. Eg. Ephedrine.
 Drug resistance: Tolerance of microorganisms to
inhibitory action of antimicrobials,
 e.g. Staphylococci to penicillin
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PHYSICIAN INDUCED DISEASE (IATROGENIC)

 Disease Induced on following medical advice or

intervention by physician.
RATIONAL PRESCRIBING
 Appropriate indication
 Appropriate drug in efficacy, tolerability, safety,
 and suitability for the patient.
 Appropriate dose, route and duration according
 to specific features of the patient.
RATIONAL PRESCRIBING

 Appropriate patient: no contraindications exist; drug

acceptable to the patient; likelihood of adverse effect is
minimal and less than the expected benefit.
 Correct dispensing with appropriate information/
 instruction to the patient.
RATIONAL PRESCRIBING

 Adequate monitoring of patient’s adherence to

medication, as well as of anticipated beneficial and
untoward effects of the medication
ESSENTIAL DRUGS

 Drugs (or representatives of classes of drugs)

‘that satisfy the health care needs of the majority
of the population; they should therefore be
available at all times in adequate amounts and in
the appropriate dosage forms’.

ESSENTIAL DRUGS

 Countries can use the list as a basis for their own

choices (the WHO also publishes model
prescribing information)
 The list, updated regularly, contains about 300
items.
PHARMACOECONOMICS

 The description and analysis of the costs of drug

therapy to health care systems and society
 It identifies, measures, and compares the costs
and consequences of pharmaceutical products
and services.
PHARMACOECONOMICS
4 economic analysis.
 Cost-effectiveness analysis
 Cost-benefit analysis
 Cost- minimization analysis
 Cost- utility analysis
 Measures qualitative and quantitative aspect.
GUIDE TO FURTHER READING

1. Brown M, Sharma P, Mir FA, Bennett PN. Clinical Pharmacology. 12th

ed. China: Elsevier; 2019.
2. Hiremath, S., Kayibanda, J.F., Chow, B.J.W. et al. Drug discontinuation
before contrast procedures and the effect on acute kidney injury and
other clinical outcomes: a systematic review protocol. Syst Rev 7, 34
(2018). https://doi.org/10.1186/s13643-018-0701-1
3. Tripathi KD. Essentials of medical pharmacology. 8th ed. New Delhi.;
2019
THANK YOU FOR LISTENING 