Receptor Theory

How can drugs be classified

Similar chemical structure, same mechanism of action, similar therapeutic use

What is pharmacodynamics

What medication does to the body

What is pharmacokinetics

What does the body do to the medication

What does ADME stand for

Absorption, Distribution, metabolism, excretion

What is a biological receptor

Macromolecular protein that bind to ligand

What are the 4 types of receptors

Ligand gated, G coupled protein, enzyme linked, intracellular

What are ligand gated channels

Extracellular receptors that need ligand to bind to open; example: Nicotinic acetylcholine receptors

How do G coupled protein receptors work

Ligand bind to r → GDP release + GTP binding to G protein → alpha subunit dissociate and activate cAMP or PLC

What does Gq activate

PLC → Activate both IP3 and DAG pathways to increase Ca and PKC respectively

What does Gs and Gi do

Gs act to increase cAMP and PKA; Gi inhibit this

How do enzyme linked receptors work (insulin)

Insulin bind to r → Autophosphorylation of tyrosine kinase receptor → Phosphorylation of other pathways → Action of insulin

How do intracellular receptors work (steroid)

Steroid diffuse across membrane → Bind to receptor INSIDE cell → Leads to transcription of genes

Rank the different types of receptors based on the time of response from shortest to longest

Ligand gated (milliseconds) → Enzyme linked (minute to hours) → Intracellular (hours to days)

What is receptor affinity

Strength of attraction; low = less attraction, drug pops off receptor; high = higher potency

What is potency

The amount of drug needed to produce a cellular effect; higher affinity = higher potency = lower dose

What is selectivity

Degree that a drug can bind to a single receptor

How does Kd relate to affinity

Kd = degree of dissociation; lower Kd = higher affinity

How is receptor occupancy calculated

f = [ligand-receptor complex]/[total receptors]

Does increasing the amount of drug always indicate higher action

No → The number of receptors are finite, if all are occupied higher concentrations do not produce effect

What is Emax

The greatest effect that agonist can produce if taken at highest tolerated level

What is EC50

Amount of drug (concentration) needed to produce 50% of Emax

Based on figure B, which drug is more potent

Drug A, since the EC50 is smaller → Means that a smaller concentration is needed to produce 50% of Emax than Drug B

Interpret this graph

The curve of the graph shows that drug A and B have the same efficacy (Emax) but drug A is more potent because the EC50 is lower; C is the worst of the three

What are the types of agonists

Full, partial and inverse

How does an inverse agonist differ from an antagonist

Inverse agonist brings effect BELOW baseline; antagonist never goes below baseline

What is the difference between full and partial agonists

Full produces complete receptor activation; partial produces <100% of binding

What are the types of antagonists

Competitive, non competitive (irreversible) and other

What is the difference between competitive and non-competitive antagonist

Competitive antagonists fight with normal ligand to bind to receptor; non-competitive alters receptors so that only it can bind to it

What is the effect of Ki on inhibition

Lower Ki = higher inhibitory effect

What are functional/physiological antagonist

Two drugs act on two receptors that have opposite action (eg: Histamine bind to H1 to bronchoconstrict, EP bind to beta 2 to bronchodilate)

What are chemical antagonists

Drug counters the effect of another by chemical reaction (eg: protamine sulfate is positive and binds to heparin that is negative charge)

What is pharmacokinetic antagonist

One drug accelerate metabolism of another (eg: phenobarbital induced enzyme induction increase warfarin metabolism

What is desensitization

Repeated exposure leads to lower effect to prevent cell damage; agonist → down regulate, antagonist → up regulation