Clinical application of Pharmacodynamic(24/10/2018)

a)can be harmful/ beneficial effect

Stimulation -caffeine on brain

-adrenaline on heart
-Ach on GIT
Inhibition -CNS depressant e.g barbiturates
Irritation -Aspirin irritates mucosa→ ulcer

b)target for drug action with examples:

receptor -cholinomimetic drug: bind to cholinergic receptors

-serotonin: physiological receptor
Ion channel Drug bind to channel→ channel open→ transfer of ion
i. mouth ulcer: -local anaesthetic→ block Na+ ion
-cause temporary pain relieved, numbness
ii. antiarrhythmic drug: Na+ ion & Ca2+ ion channel blockers
enzyme i. NSAIDS: inhibit COX 1 & COX 2
ii. Ach-esterase: prevent degradation of Ach
Protein i. NE transporter: amphetamine (indirect sympathomimetic) affecting NE
transporter transporter→ more amount of transporter blocked
ii. dopamine transport: cocaine affect the transporter

c) Affinity: tendency of drug to bind to receptor

d)Intrinsic activity/efficacy: ability if drug to show effect/response

e)Agonist: -mimic the action of endogenous substance/ stimulate receptor of endogenous ligand

-Carbachol an example agonist(cholinergic) -affinity & efficacy(IA) ↑ = 1

f)antagonis: - drugs that antagonise physiological signal/ligand molecule

-prevent action of agonist , affinity high, efficacy(IA) ↓ / = 0

-e.g atropine is antagonist of Ach at muscarinic receptors

g)Partial agonist:- elicits some activities, submaximal effect,

-affinity ↑, 0 < IA< 1

h) receptor: -macromolecule present on the cell surface or intracellular (cytoplasm/nucleus)

-recognition of signal, amplification of signal (↑↑ magnitude of action)

i) Drug interaction :

Synergism i. addition/summation: A+B= effect of A+B

e.g; aspirin & paracetamol: for analgesia
ii. potentiation: - 1+1 =3, drug react by increasing effect of each other.
-e.g: levodopa + carbidopa for Parkinson’s disease
ii. significance: can reduce dose
Antagonism i. chemical: antacid neutralize gastric acid, isoniazid and pyridoxine for TB treatment
ii. physiological: - histamine: bronchoconstrictor
 -adrenaline: bronchodilator
-Ach: stimulate GIT, inhibit SA node
iii. pharmacological: adrenaline + propranolol → antagonism

j) Various types of receptors with examples

Ligand-gated ion i. very fast impulse, e.g: pain signal

channel ii.binding of Ach at nicotinc receptor at motor end plate→ activate Na+
ion channel→ influx of Na+→ depolarization
GPCR i. smooth muscle, vital organ: M1 – M5 rc
ii. NMJ & gaglion: NM & NG rc
Enzyme linked rc i. Insulin + Insulind Rc → phosphorylation forms dimers → downstream
effect
Intracelluar/Nuclear i.steroid hormone/drug -cytoplasmic
recptor iithryoid hormone - nuclear

k) Dose response curve (more to clinical response)

-potency: maximum effect of drug can produce

-efficacy: ability of drug to produce a therapeutic effect with minimal dose, less side effects, reduce
symptoms
-compare and justify which drug is more important medically

10 mg Drug A vs 10 mg drug B, drug A is more potent

Nvtheless, for tx, efficacy is more important not potency

B
A

𝐿𝐷50
A is more potent, B is less potent TI= 𝐼𝐷50

↑ TI Drug A, e.g; warfarin, digoxin

↓ TI Drug B, e.g; paracetamol, penincilin