NEET MDS Lessons
Pharmacology
Drug-Receptor Interactions
Drug Receptor: any functional macromolecule in a cell to which a drug binds to produce its effects. at receptors, drugs mimic or block the action of the body's own regulatory molecules.
Receptors and Selectivity of Drug Action : If a drug interacts with only one kind of receptor, and if that receptor regulates just a few processes, then the effects of the drug will be limited.
Even though a drug is selective for one type of receptor, it can still produce a variety of effects.
Selectivity does not guarantee safety.
Theories of Drug-Receptor Interaction
- Simple Occupancy Theory: Two factors - The intensity of the response to a drug is proportional to the number of receptors occupied by that drug, and the maximal response will occur when all available receptors have been occupied.
- Modified Occupancy Theory: Assumes that all drugs acting at a particular receptor are identical with respect to the ability to bind to the receptor and the ability to influence receptor function once binding has taken place.
• Affinity: The strength of the attraction between a drug and its receptor. Affinity is reflected in potency. (Drugs with high affinity are very potent).
• Intrinsic Activity: The ability of a drug to activate a receptor following binding. Reflected in the maximal efficacy (drugs with high intrinsic activity have high maximal efficacy).
Sympathomimetics
Beta-Adrenergic Agonists
Beta1-adrenergic agonists (dopamine, dobutamine, prenalterol, xamoterol) have been used to treat acute and chronic heart failure, but have limited usefulness in chronic CHF because of their arrhythmogenic effects, short duration of action, the development of tolerance, and necessity of parenteral administration
Dopamine (i.v.) is used in acute heart failure (cardiogenic shock) to increase blood pressure and increase cardiac output
- It has a short half-life (1 min)
- At high doses dopamine has potent peripheral vasoconstrictor effects (alpha-receptor stimulation), in addition to its inotropic effects
- Low dose dopamine has a renal artery dilating effect and may improve sodium and water excretion in patients refractory to loop diuretics
- When systolic pressure is greater than 90 mm Hg, nitroprusside can be added to reduce ventricular filling pressure and reduce afterload
- i.v. furosemide should also be administered to reduce edema
Levodopa and ibopamine, analogs of dopamine that can be administered orally, have been shown to improve symptoms in some patients, but can exhibit arrhythmogenic side-effects and tachyphylaxis
Dobutamine is a somewhat selective beta1-adrenergic agonist that lacks vasoconstrictor activity and causes minimal changes in heart rate
- It is frequently added to nitroprusside when blood pressure is adequate to increase cardiac output
- It is administered as an i.v. infusion to treat acute severe heart failure
- It has a short half-life (2.4 min) and is only used on a short-term basis, although long-term beneficial effects on cardiac function have been noted
- After 72 hours of therapy, tolerance can develop to dobutamine necessitating switch to other inotropic support (e.g. milrinone)
- Dobutamine can enhance AV conduction and worsen atrial tachycardia
Prenalterol and xamoterol are partial beta1-adrenergic agonists that may simultaneously stimulate beta1-receptors and block the receptors from stimulation by endogenous catecholamines, thereby protecting against beta1-receptor down-regulation