| How is classification of adrenergic receptors antagonists? | . |
| How do adrenergic receptor antagonists act? | The adrenergic antagonists or blockers or sympatholytic agents:
bind to adrenoceptors
act by either reversibly or irreversibly attaching to the receptor, thus preventing its activation by endogenous catecholamines.
are classified according to their relative affinities for α or β receptors in the peripheral nervous system. |
| What are alpha adrenergic blocking agents? | Phenoxybenzamine (non selective)
Phentolamine (non selective)
Prazocin, doxazocin, alfuzocin, tamsulosin (α1 selective)
Yohimbine (α2 selective)
drugs that block α-adrenoceptors profoundly affect blood pressure
blockade of these receptors reduces the sympathetic tone of the blood vessels, resulting in decreased peripheral vascular resistance.
this induces a reflex tachycardia resulting from the lowered blood pressure
phenoxybenzamine and phentolamine have limited clinical applications |
| How is action of phenoxybenzamine? | nonselective, linking covalently to both α1-postsynaptic and α2-presynaptic receptors
the block is irreversible and noncompetitive,
the only mechanism the body has for overcoming the block is to synthesize new adrenoceptors, which requires a day or more |
| What are cardiovascular effects of phenoxybenzamine? | By blocking α receptors, phenoxybenzamine prevents vasoconstriction of peripheral blood vessels by endogenous catecholamines.
the decreased peripheral resistance provokes a reflex tachycardia.
the ability to block presynaptic inhibitory α2 receptors can contribute to an increased cardiac output. (Beta1 stimulation)
Thus, the drug has been unsuccessful in maintaining lowered blood pressure in hypertension, and it is no longer used for this purpose. |
| How is epinephrine reversal action of phenoxybenzamine? | All α-adrenergic blockers reverse the α-agonist actions of epinephrine.
For example, the vasoconstrictive action of epinephrine is interrupted, but vasodilation of other vascular beds caused by stimulation of β receptors is not blocked
Therefore, the systemic blood pressure decreases in response to epinephrine given in the presence of phenoxybenzamine |
| What are therapeutic uses and adverse effects of phenoxybenzamine? | Therapeutic uses
used in the treatment of pheochromocytoma, (a catecholamine-secreting tumor of cells derived from the adrenal medulla).
sometimes effective in treating Raynaud’s disease
Adverse effects:
postural hypotension
nausea, and vomiting
can inhibit ejaculation
reflex tachycardia mediated by the baroreceptor reflex |
| What are actions of phentolamine? | in contrast to phenoxybenzamine, phentolamine produces a competitive block of α1 and α2 receptors.
Phentolamine is a reversible, non-selective alpha-adrenergic blocker that induces vasodilation.
the drug’s action lasts for approximately 4 hours after a single administration
used for the short-term management of pheochromocytoma
used locally to prevent dermal necrosis following extravasation of norepinephrine.
produces postural hypotension and causes epinephrine reversal.
induced reflex cardiac stimulation and tachycardia mediated by the baroreceptor reflex and by blocking the α2 receptors of the cardiac sympathetic nerves.
can trigger arrhythmias (Beta1 stimulation)
contraindicated in patients with decreased coronary perfusion |
| What are prazosin, doxazosin, alfuzosin and tamulosin? | are selective competitive blockers of the α1 receptor.
In contrast to phenoxybenzamine and phentolamine, the first 2 drugs (Prazosin, doxazosin) are useful in the treatment of hypertension.
Tamsulosin (OMNIC) and Alfuzosin (XATRAL) are indicated for the treatment of benign prostatic hypertrophy (also known as benign prostatic hyperplasia or BPH)
Metabolism leads to inactive products that are excreted in the urine except for those of doxazosin, which appear in the feces.
Doxazosin is the longest acting of these drugs. |
| What are cardiovascular effects of prazosin, doxazosin, alfuzosin and tamulosin? | All of these agents decrease peripheral vascular resistance and lower arterial blood pressure by causing the relaxation of both arterial and venous smooth muscle.
These drugs, unlike phenoxybenzamine and phentolamine, cause minimal changes in cardiac output. |
| What are therapeutic uses of prazosin, doxazosin, alfuzosin and tamulosin? | treat elevated blood pressure
Tamsulosin has the least effect on blood pressure because it is less selective for α1B receptors found in the blood vessels and more selective for α1A receptors in the prostate and bladder.
Blockade of the α1A receptors decreases tone in the smooth muscle of the bladder neck and prostate and improves urine flow |
| What are adverse effects of Prazosin, doxazosin, alfuzosin, and tamsulosin? | dizziness,
a lack of energy,
headache,
drowsiness,
nasal congestion
orthostatic hypotension
By blocking α receptors in the ejaculatory ducts and impairing smooth muscle contraction, inhibition of ejaculation and retrograde ejaculation have been reported |
| What is Yohimbine? | is a selective competitive α2 blocker.
works at the level of the CNS to increase sympathetic outflow to the periphery.
Contraindicated in cardiovascular conditions because it is a cardiovascular stimulant |
| What are beta adrenergic blocking agents? | All the clinically available β-blockers are competitive antagonists.
1- Non-selective β-blockers act at both β1 and β2 receptors,(Propranolol)
2- Cardioselective β antagonists primarily block β1 receptors
(Acebutolol, Atenolol)
3- Antagonists with partial agonist activity (Pindolol)
These drugs also have the ability to weakly stimulate both β1 and β2 receptors and are said to have intrinsic sympathomimetic activity (ISA)
4- Antagonists of both alpha and beta adrenoceptors (Labetalol, Carvedilol) |
| What are effects of beta blockers? | All β-blockers lower blood pressure in hypertension
do not induce postural hypotension, because the α-adrenoceptors remain functional.
normal sympathetic control of the vasculature is maintained.
β-Blockers are also effective in treating:
angina, cardiac arrhythmias,myocardial infarction, congestive heart failure, hyperthyroidism, glaucoma, prophylaxis of migraine headaches.
The names of all β-blockers end in “-olol” except for labetalol and carvedilol. |
| What are drugs affecting neurotransmitter release/uptake? | Some agents act on the adrenergic neuron, either to:
- interfere with neurotransmitter release or
- To alter the uptake of the neurotransmitter into the adrenergic nerve.
these agents are rarely used therapeutically. |
| What is Reserpine? | A plant alkaloid,
blocks the transport of biogenic amines from the cytoplasm into storage vesicles in the adrenergic nerves of all body tissues.
This causes the ultimate depletion of biogenic amines
Sympathetic function, in general, is impaired because of decreased release of norepinephrine
The drug has a slow onset, a long duration of action, and effects that persist for many days after discontinuation.
Reserpine is a drug that is used for the treatment of high blood pressure, usually in combination with a thiazide diuretic or vasodilator. |
| What is Guanethidine? | blocks the release of stored norepinephrine from storage vesicles
leads to gradual depletion of norepinephrine in nerve endings
causes orthostatic hypotension
It is no longer used due to lack of availability.
It is still licensed in some countries, e.g., UK, for the rapid control of blood pressure in a hypertensive emergency. |
