drug receptors

ISHIK UNIVERSITYFACULTY OF DENTISTRY

Pharmacology

Dr. Esra Tariq Bayrakdar

Pharmacist (M.Sc.)

Drug Receptors

The drug receptors are macromolecular sites which are situated on the surface or inside the effector cells with which specific agonist combines to produce its response.
Antagonist prevents the action of an agonist on a receptor, but does not have any effect of its own

Drug-receptor interaction

Each drug requires a target within the body called a receptor.
Binding of drugs to receptor is:
Reversible : Effect for short time (reversible bonding forces)…most drugs
Irreversible: Effect is prolonged (Covalent bonding forces) : aspirin cause irreversible inhibition of PG synthesis.

Drugs act by antagonize or inhibit:

Cell surface Receptors
Ion Channels
Enzyme Inhibition
Transport Inhibitors
Nuclear Receptors


1)Action of a receptor :
A spesific macromolecule, usually a protein to which a specific group of drugs or naturally occurring subtances (neurotransmitters or hormones) can bind.
The biochemical evets that result from a dru-receptor interaction and which produce effect, are complex.
The binding of drug to receptor result formation of : Drug-Receptor Complex…Then the effect.
Drug + Receptor  Drug-receptor complex  effect

Receptor

Subtype
Main Actions of Naturale agonist
Agonist Drug
Antagonist Drug
Adrenoceptor
• α1
• α2
β1
• β2
Vasoconstruction
Hypotension
Sedation
Increase HR
Bronchodilation
Noradrenaline
Clonidine
Dopamine
Salbutamol
Prazosin
Atenolol
Cholinergic
Muscarinic
Heart rate


Atropine
Histamine
H1
H2
Bronchoconstruction
Increase gastric acidity

Chlorpheniramine

Ranitidine
Types and subtypes of receptors
Are Drugs That Anatgonize Cell Surface Receptors Clinically Useful?
• Angiotensin receptor blockers (losartan, valsartan) for high blood pressure, HF
• Beta-adrenoceptor Blockers (propranolol, Atenolol) for angina, MI, HF, HBP

Functions of a receptor may be briefly summarized as follows:

• Receptors largely determine the quantitative relations between dose or concentration of drug and pharmacologic effects.
• Receptors are responsible for selectivity of drug action.
• Receptors mediate the actions of both pharmacologic agonists and antagonists.
•

2) Action on an enzyme

Enzymes, like receptors; are protein macromolecules which subtrates interact to produce activation or inhibition
Examples: Enalapril (inhibits ACE-Anti-HTN)
3) Transport Inhibitors: Sodium pump inhibitors . Such as:
Digoxin inhibits the membrane bound Na+/K+ATPase (Used in HF)
Diuretics (Loop DU) inhibit the Na+/Cl- co-tranporter in the kidney

4) Actions on membrane ion channels

The conduction of impulses in nerve tissues and electromechanical coupling in muscle depend on the movement of ions particularly sodium, calcium, and potassium, through membrane channels.
Several groups of drugs interfere with these processes:
Antiarrythmic drugs (Quanidine: Na Channel blockers)
Local anesthetics as (Lidocaine: Sodium channel Blocker)
Anti-HTN: amlodipine (Ca channel blockers)
Oral Anti-DM: Sulphonylureas block ATP-sensitive potassium channels in pancreatic B-cells

5) Drugs work by antagonizing Nuclear receptors:

Lipid soluble ligand can easily diffuse across cell membrane and move to the nucleus of the cell where it binds to nuclear receptors (DNA) and then activate the transcription of spesific gene.
Estrogen receptor antagonists for the prevention and treatment of breast canser (Tamoxifen)


Agonists: Drugs that binds to receptor and stimulates or activates the receptor to produce an effect (salbutamol at beta-1 receptor).
Antagonists are drug that binds to receptors and prevents the action of an agonist but does not have any effect itself (losartan at the angiotensin II receptor)
Have only the affinity but no intrinsic activity.

Drug Tolerance is seen when the same dose of drug given repeatedly loses its effect or when greater doses are required to obtain previous effect.
Eg. Tolerance of Glyceryl trinitrate occurs in treatment of angina pectoris when given repeatedly so a drug free time of 8-12 h is advised.

Up-Regulation : Continouse or repeated exposure to antagonists initially can increase the receptors and with chronic exposure to antagonist, the number of receptors on cell membrane surface increase.
Eg. Β-blockers (propranolol) should not be stopped promptly in people with ischemic heart disease (IHD) because it presipitates unstable angina or mycardial infarction ( avoid sudden withdrawal)

Combined effect of drugs

SYNERGISM
When two drugs are given simultaneously, and the action of one drug is increased by the other, they are treated as synergistic. In the synergism, the drugs can have action in the same direction or when given alone, one may be inactive. Synergism can be additive or supradditive in nature.

Drug Antagonism

COMPETITIVE ANTAGONISM
In competitive antagonism, the antagonist binds with the same receptor as agonist. If the log dose response curve with agonist is obtained in the presence of antagonist, it will be found that antagonist has no effect of its own and there is parallel rightward shift in the dose response curve of agonist with no change in shape, slope or maximum response.
Eg. Acetylcholine (as agonist) – atropine (as antagonist).






Antagonist binds to another site or receptor. The antagonist is not displaced by a high concentration of the agonist on the same receptor and the dose-response curve is flattened and its slope and maximum response will be decreased.
Eg. Noradrenaline--- Phenoxybenzamine

NON-COMPETITIVE ANTAGONISM