PDA Receptor theory I

pharmacology

study of body’s reaction to drugs

Alters the existing system

What does a drug do?

5 drug action targets

receptors, ion channels, enzyme, carrier molecules, microtubules,

morphine

cell surface receptor on neuro cells that block transmission of pain signa

GABAa receptor

Cl channel that when stimulated, causes chloride influx and results in hyperpolarization to suppress neuronal activity

Aspirin

targets cyclooxygenase, an enzyme through reducing pro-inflammatory factors.

GABA

the major inhibitory neurotransmitter is … 

Cocaine

increase dopamine levels through blocking the carrier molecule uptake, to prevent dopamine from entering the presynaptic nerve terminal.

Taxol

targets microtubule to block mitotic spindles, leading to mitotic arrest and cell death.

receptor

a protein molecule that receives and respond to a neurotransmitter, hormone, drug, or other substances

cell surface receptors

large molecule (peptides), charged, hydrophilic

nuclear receptors

small, non-polar, lipophilic (readily diffuse through the plasma membrane)

agonist

A molecule that binds to a receptor and elicits a biological response

Antagonists

block binding of endogenous ligands to their receptors, resulting in reduced biological responses of their target cells. This property is useful in treating diseases/medical conditions.

Agonists

albuterol, terbutaline, isoproterenol, dobutamine are examples of?

Antagonists

propranolol, metoprolol, atenolol, nadolol are examples of what?

Antagonists

prazosin, phenoxybenzamine, yohimbine are examples of what?

Inverse agonists

an agent that binds to the same receptor-site as an agonist but exerts the opposite pharmacological effect; cause conversion, agitation, irritation

insomnia, agitation, inability to sleep

A drug induces sleep.  What would be the effect of an inverse agonist of the receptor?

Affinity

a measure of how tightly a drug binds to its receptor

lower affinity ligand

The GRN line graph represents what?

higher affinity ligand

The red line graph represents what?

Smaller kd equals higher affinity

What does the graph imply

Kd

the concentration of ligand at which half of the receptor binding sites are occupied

efficacy

intrinsic activity or the ability to produce a therapeutic effect; how well it activities receptor

Full agonists

produce a maximal response (ex. morphine)

Partial agonists

produce submaximal response (ex. buprenorphine)

partial agonists

The bottom graph line describes what?

Full agonists

The top graph line represents what?

potency

measure the drug activity

The smaller the EC50, the better the potency

What does the arrow imply?

EC50

represents the concentration of a compound

where 50% of its effect is observed

IC50

represents the concentration of an inhibitor

that is required for 50% inhibition

spare receptors

a maximal response is elicited without all receptors being

occupied

ED50 < kd

There are spare receptors when …

competitive reversible antagonism

The following graph implies what?

More concentration for NA

Increasing propranolol mean what for the maximal heart rate?

competitive irreversible antagonism

The following graph represents what?

The GRN line cannot reverse due to blood vessel constriction

Increasing PBA implies what?

non-competitive/functional antagonism

The following graph represents what?

lowers the maximal response

Increasing verapamil means what

physiological antagonism

body function regulation

chemical antagonism

drug-drug interactions followed by suppression

chemical antagonism

heparin prevent clog formation (anticoagulant)

chemical antagonism

In the case of digoxin overdosage, an antidote digoxin immune Fab (Digibind) is used. Digibind binds and inactivates digoxin. What type of antagonism is this?

Desensitization

body’s protective mechanism against high concentration and prolonged exposure to hormones, neurotransmitter, and drugs

Desensitization

The loss of responsiveness to the continuing or

increasing dose of a drug

Homologous desensitization

The following graph represents what?