Practical pharmacology. Part 3. Drug response

Drug response

Drug reponse

Normal therapeutic response

Side effects

Exaggeration of pharmacological effect

Toxicities

Abnormal response

Tolerance

Drug reponse

Normal therapeutic response

Side effects

Exaggeration of pharmacological effect

Toxicities

Abnormal response

Tolerance

A

Response

Drug reponse

Normal therapeutic response

Side effects

Exaggeration of pharmacological effect

Toxicities

Abnormal response

Tolerance

A

Response

A

A

Side effects

Side effects

Drug reponse

Normal therapeutic response

Side effects

Exaggeration of pharmacological effect

Toxicities

Abnormal response

Tolerance

Intolerance

Exaggerated response
(magnified pharmacological response)
resembling an overdose of a

Causes

Pharmacokinetic

Renal insufficiency patients taking digoxin

Infants due to underdeveloped

Causes

Pharmacodynamic

Thyrotoxic patients, epinephrine

Thyroxine

Toxicity

Drug reponse

Normal therapeutic response

Side effects

Exaggeration of pharmacological effect

Toxicities

Abnormal response

Tolerance

Drug reponse

Normal therapeutic response

Side effects

Exaggeration of pharmacological effect

Toxicities

Abnormal response

Tolerance

Idiosyncrasy

Genetically determined
abnormal response to a drug

Example 1

Succinyl choline in
pseudocholine esterase deficiency subjects

Example 2

Chloroquine, salicylates, sulfa drugs in
glucose 6-phosphate dehydrogenase
deficiency subjects

Glutathione (GSH)

NADP+

NADPH + H+

Glutathione disulfide (GSSG)

The Glutathione Redox System

SH

SH

Glutathione
Reductase

FAD

Glucose-6-P
Dehydrogenase

Glucose- 6-phosphate

6-Phospho gluconolactone

x

x

x

Example 3

Isoniazide in slow, fast acetylators

Isoniazide

Slow acetylator

Fast acetylator

Isoniazide

metabolites

Drug reponse

Normal therapeutic response

Side effects

Exaggeration of pharmacological effect

Toxicities

Abnormal response

Tolerance

Tolerance

Decreased therapeutic efficacy
on repeated administration over
days or months.

Tachyphylaxis (desensitization)

Rapidly developing tolerance

Resistance (Refractoriness)

Loss of therapeutic efficacy

Types of tolerance

Acquired

Congenital

Acquired tolerance

Due to repeated administration of a drug

Pharmacokinetic

Pharmacodynamic

Pharmacokinetic tolerance

barbiturates cause tolerance
of
concomitantly administered drugs

Pharmacodynamic tolerance

Conformational changes in receptor due to long use of

EFFECTOR

RESPONSE

Congenital tolerance

Natural inborn tolerance to certain drug
which has been never

Congenital tolerance

Racial

Ephedrine is not effective mydriatic in
black colored people

Congenital tolerance

Species

Rabbits
tolerate large quantities of
atropine without toxicity

Congenital tolerance

Individual

Kymograph

Drum

Water bath

Organ bath

Conditions
Physiological solution
Temperature
Aeration

Physiological solution

NaCl & KCl

CaCl2

Mg salt

NaHCO3

NaH2PO4

Glucouse

For isotonicity

Physiological solution

NaCl & KCl

CaCl2

Mg salt

NaHCO3

NaH2PO4

Glucouse

Contractility

Physiological solution

NaCl & KCl

CaCl2

Mg salt

NaHCO3

NaH2PO4

Glucouse

Contractility

Physiological solution

NaCl & KCl

CaCl2

Mg salt

NaHCO3

NaH2PO4

Glucouse

Buffering action

Physiological solution

NaCl & KCl

CaCl2

Mg salt

NaHCO3

NaH2PO4

Glucouse

Nutrition

Temperature
36-37˚C

Aeriation

Pure O2

Carbogen (90% O2 + 10% CO2)

Air

Our isolated organ

Rabbit intestine
Tyrode‘s solution
Temperature 37˚C
Aeration by air pump

0.1

0.2

0.3

0.4

Myogenic contraction

wash

Donot forget