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Pharmacodynamics

u the study of the biochemical and physiological

Principles of effects of drugs and their mechanisms of action.
u Simply stated, pharmacodynamics refers to the
Pharmacodynamics effects of a drug on the body.

“ W hat a drug does to the body” à Mechanism of Action

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Site of Drug Action Types of Drug Action

1. Extracellular Effect (Type of Responses)

2. Cellular 1. Stimulation
3. Intracellular 2. Inhibition/Depression
3. Replacement
4. Irritation
5. Cytotoxic

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Mechanism of Action of Drugs Receptor Mediated Action

u Drug act either by receptor or by non receptor or by targeting specific genetic
changes.

u Drug produce their effect through interacting with some

chemical compartment of living organism c/s Receptor.
u Receptors are macromolecules
MOA u Most are proteins
u Present either on the cell surface, cytoplasm or in the
nucleus
Non-receptor
Receptor mediated
mediated

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Drug (D) + Receptor ® ßà Drug-Receptor Complex à Response

Drug receptor interaction:

Ligand binding domain
1. Selectivity: Degree of complimentary co relation between drug and receptor.

Ex:- Adrenaline Selectivity for α, ß Receptor

Receptor Functions : Two 2. Affinity: Ability of drug to get bound to the receptor.
essential functions
1. Recognition of specific ligand 3. Intrinsic activity (IA) or Efficacy: Ability of drug to produce a pharmacological
molecule (Ligand binding response after making the drug receptor complex regardless of the dose of the
domain)
Transduction of signal into 2. Transduction of signal into drug.
response response (Effector domain)

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Agonist
• Drugs that bind to physiological
receptors and mimic the regulatory
effects of the endogenous signaling
compounds are termed agonists.
• If the drug binds to the same recognition
site as the endogenous agonist (the
primary or orthosteric site on the
receptor) the drug is said to be a
primary agonist.
• Allosteric agonists bind to a different
Respons No region on the receptor referred to as an
Response allosteric site.
e
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Pharmacodynamic Activity Antagonist

u Additive – combine effect of two drugs acting by same mechanism.
1+1=2 • Drugs that block or reduce the
u Synergism (Supra additive) (1+1=3)
action of an agonist are termed
antagonists.
u The combine effect of two drug effect is higher than either
individual effect. • Antagonism most commonly results
Example: 1. Sulfamethaxazole + Trimethoprim; 2. Levodopa + from competition with an agonist for
Carbidopa the same or overlapping site on the
u Antagonism (1+1=0) receptor (a syntopic interaction)
u Effect of two drugs is less than the sum of the effect of the
individual drugs.
Example: Warfarin + Phenobarbitone = ↑ Metabolism, ↓ effect

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• Physical antagonist binds to the drug and prevents its Reversible antagonism
absorption like charcoal binds to alkaloids and prevents their
absorption.
(Competitive antagonism)
• Chemical antagonist combines with a substance chemically
like chelating agents binds with the metals.
• Physiological antagonist produces an action opposite to a u These inhibition is commonly
substance but by binding to the different receptors e.g. adrenaline observed with antagonists that
is a physiological antagonist of histamine because adrenaline bind reversibly to the same
causes bronchodilatation by binding to β2 receptors, which is receptor site as that of an agonist.
opposite to bronchoconstriction caused by histamine through H1 u These type inhibition can be
receptors. overcome increasing the
concentration of agonist
• Pharmacological antagonists produce no effect , shows no
intrinsic activity. u Ex:- Atropine

u Competitive (reversible)
u Non competitive (Irreversible)

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Irreversible Antagonism POTENCY

u It occurs when the antagonist
dissociates very slow or not u The amount of the drug needed to produce a given
at all from the receptors effect.
result that no change when u potency is determined by the affinity of the
the agonist applied. receptor for the drug.
u Antagonist effect cannot be u The dose causing 50% from the maximal effect
overcome even after (EC50) can be obtained from graded dose-
increasing the concentration response curve.
of agonist u In quantal dose response curve, ED50, TD50 and
LD50 are potency variables.

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Characteristics of Receptor Families

Drug Receptors
Four types of receptor families:
1. Ligand-gated ion channels (inotropic receptors)
2. G-protien coupled receptor (Metabotropic
receptors)
3. Enzymatic receptors (tyrosinekinase)
4. Receptor regulating gene expression (transcription
factors/ Steroid )

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Non receptor Mediated Action

All drugs action are not mediated by receptors. Some of drugs may u END
act through chemical action or physical action or other modes.

u Chemical action
u Physical action (Astringents, sucralfate)
u False incorporation (PABA)
u Being protoplasmic action (antiseptics)
u Formation of antibody (Vaccines)
u Targeting specific genetic changes.

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DOSES
Total dose: It is the maximum quantity of the drug that is
needed the complete course of the therapy.
Single dose: Ex:- procaine penicillin àearly syphilis is 6 million unit à
u 1.Piperazine (4-5g) is sufficient to eradicate round worm. given as 0.6 million units per day for 10days.
u 2.Single IM dose of 250mg of ceftriaxone to treat gonorrhea. Loading dose:- It is the large dose of drug to be given initially
Daily dose: to provide the effective plasma concentration rapidly. The
u It is the quantity of a drug to be administered in 24hr, all at once drugs having high Vd (volume of distribution).
or equally divided dose.
u Chloroquine in Malaria –
u 1.10mg of cetrizine (all at once) is sufficient to relive allergic u 600 mg Stat
reactions.
u 300mg after 8 hours
u 2.Erythromycin is 1g per day to be given in 4 equally divided u 300 mg after 2 days.
dose (i.e., 250mg every 6 hr)

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Therapeutic Index

Maintenance dose:- Loading dose normally followed by u Margin of safety

maintenance dose.
u Depend upon factor of dose producing desirable effect à
u Needed to maintain the steady state plasma concentration dose eliciting toxic effect.
attained after giving the loading dose.

u TI àshould be more than one

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Therapeutic window:
u Optimal therapeutic range of plasma concentrations at which most of the
patients experience the desired effect. • Cyclosporine – 100-400ng/ml
u Therapeutic rangeà Therapeutic window • Carbamazepine- 4-10μg/ml
• Digoxin- 0.8-2ng/ml
• Lithium- 0.8-1.4 mEq/L
• Phenytoin – 10-20μg/ml
• Quinidine- 2-6μg/ml

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Tolerance: Types of Tolerances

u Increased amount of drug required to produce initial u Innate tolerance: Genetically lack of sensitivity to a drug.
pharmacological response.
u Usually seen with alcohol, morphine, barbiturates, CNS
active drugs Ex:
• Rabbits tolerate to atropine large doses
• Chineseà Castor oil
u Reverse tolerance:- Same amount drug produces inc • Negros à Mydriatic action of sympathomimetics
pharmacological response.
• Eskimosà high fatty diets
u Cocaine, amphetamine à rats- inc. Motor activity

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u Acquired tolerances: Pharmacodynamic tolerance

u Occurs due to repeated use of drug u Down regulation of receptors
– Pharmacokinetic tolerances
u Impairment in signal transduction
– Pharmacodynamic tolerance
– Acute tolerance
Ex: Morphine, caffeine, nicotine.

u Pharmacokinetic tolerances: Repetitive administration causes Acute tolerance: Tachyphylaxis Acute development of
decrease their absorption or inc. its own metabolism tolerance after a rapid and repeated administration of a drug
Ex: Alcohol à dec. absorption in shorter intervals
Barbituratesà Inc. own metabolism Ex; Ephedrine, tyramine

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u Ex: Monday disease.

u Nitroglycerine – Monday , Tuesday workers get headache,
after they get tolerances.
u After holiday (Sunday) they get again headache .

u Cross tolerances: Cross tolerance among drugs belonging

to same category.
u •MORPHINE à HEROIN à NARCOTIC

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