Question

2. Compare and contrast the general sites and mechanisms of action of reserpine, clonidine, and methyldopa with those of drugs that block adrenergic receptors (for example, propranolol and phentolamine).

3. Explain the factors that lead to and the characteristics of the “rebound” phenomenon associated with sudden discontinuation of clonidine.

4. How responses to the main classes of adrenergic agonists would be affected.

Answer 1

1.Clonidine

it is a drug used in child psychiatry.

Mechanism of action

• Alpha2-adrenergic receptor antagonist.
• The agonist effects of clonidine on presynaptic alpha2-adrenergic receptors result in a decrease in the amount of neurotransmitter released from the presynaptic nerve terminal .This decrease serves generally to reset the sympathetic tone at a lower level and to decrease arousal.

Reserpine

Reserpines mechanism of action is through inhibition of the ATP/Mg2+ pump responsible for the sequestering of neurotransmitters into storage vesicles located in the presynaptic neuron. The neurotrandmitters that are not sequestered in the storage vesicle are readily metabolized by monoamineoxidase causing a reduction in catecholamines.

Methydopa

It leads to a reduction in sympathetic tone ,total peripheral resistance and blood pressure, as it gets converted into the metabolite, alpha methylnirepinephrine ,in the CNS and stimulates the central inhibitory alpha-adrenergic receptors, leading to a reduction in sympathetic tone ,total peripheral resistance and blood pressure. Reduction in plasma renin activity, as well as the inhibition of both central and peripheral nor epinephrine and serotonin production may also contribute to the drugs anti hypertensive effect, although this not a major mechanism of action. This is done through the inhibition of the decarboxylation of dihydroxyphenylanine- the precursor of nor epinephrine and of 5- hydroxytryptophan-the precursor of serotonin- in the CNS and in most peripheral tissues.

Mechanism of action of Adrenergic Receptors

There are two main groups of adrenergic receptors, alpha and Beta, with several subtypes.

Alpha receptors have the subtypes a1 and a2. Beta receptors have the subtypes Beta1, Beta2 and Beta 3.All three are linked to G proteins ,which in turn are linked to adenylate cyclase. Agonist binding thus causes a rise in the intracellular concentration of the second messenger cAMP. Downstream effects of cAMP include cAMP- dependent protein kinase, which mediates some of the intracellular events following hormone binding

3.if the patient stop taking drugs abtuptly, your blood pressure might go very high. Rebound hypertension is a potential adverse effect of clonidine. Patients should be warned against abrupt withdrawal It can cause drowsiness and usually is taken at night. Clonidine is not recommended for pregnant ladies.