Clinical Pharmacology Principles

Question 1

Affinity
Shape of linear [drug] proportion of receptor bound graph
Shape of semilog graph [drug] proportion of receptors bound graph
What happens when you add a competitive antagonist

Answer 1

Measure of how well a drug binds to the receptor
Bind at a rate proportional to the [drug]
Unbind at a rate that depends on the chemical properties of the drug-receptor complex

Linear - rapid increase which plateaus
Semilog - sigmoid
Right shift

Question 2

Agonists and antagonists
-how do they work

Types of antagonists

Answer 2

Agonists - binds to target to increase activity
Antagonists - opposes action of another chemical
-cannot act without an agonist (can vary with physiological states

Competitive - prevents direct binding of agonist => right shift
Non-competitive - indirectly prevents binding of agonist

Question 3

Affinity vs efficacy
-how do they affect the dose?

Answer 3

Affinity - tendency for molecule to bind to receptor
Efficacy - how well an agonist achieves a response

Different drugs acting at the same targets can have different efficacies
Different doses needed to achieve same effect

With non-competitive antagonists, affinity of agonist does not change but efficacy does

Question 4

Potency of a drug
Shape of graph with
-full agonists
-partial agonists

Answer 4

EC50 - [drug] that elicits 50% of the maximal response

Lower EC50 = higher potency at lower conc

Have the same shape (linear andc log) but partial agonists do not reach the full effect of 1 (Emax)

Question 5

Allosteric modulators
-how do they work

Answer 5

Bind to a site that is not the primary binding site to
-alter affinity of binding site to agonist
-change efficacy of response when agonist binds
This change can be positive or negative

Question 6

Desensitisation

Answer 6

Continued use => reduced number of receptors
-development of tolerance

Question 7

Nicotinic receptor
-location

Answer 7

Skeletal muscle
Autonomic neurones in CNS
-presynaptic nerve terminals
-postganglionic sympathetic neurones

Question 8

How do [drug] differ in different body compartments
-how does this affect their effects

Answer 8

Lipophilic
Hydrophilic

These properties depends on the chemical structure
Affect metabolism, excretion

Question 9

Monoamines
-what are they
-how is their action terminated, and the clinical relevance of this

Answer 9

NA, D, 5HT (seretonin)

Reuptake through presynaptic nerve terminal
-SSRI, SNRI, TCAs, COC, AMP, MDMA affects reuptake

Antidepressants have a smaller potential for abuse because of the limited affect on D reuptake receptors

Question 10

Enzyme drug interactions
-types of inhibition

Answer 10

Competitive
Non competitive

Reversible
Irreversible - causing permanent loss of function until more enzyme is synthesised