Sympathetic Blocking Agent/Sympatholytic/Anti Adrenergic Agent
The sympathetic blocking agents inhibit the response to sympathetic nerve stimulation & the response to adrenaline, noradrenalin & other sympathomimetic amines.
The sympathetic blocking drugs can be classified as:
- Drugs Acting on Adrenergic Receptors: These drugs blocks the response of effector organs to endogenous & also exogenous adrenaline & noradrenaline:
- α – Adrenergic Receptor Blockers:
- α1 Blocker – Prazosin, terazosin, doxazosin, trimazosin.
- α2 Blocker – Yohimbine
- α1 & α2 Blocker – Phenoxybenzamine, ergotamine, ergotrine, phentolamine, tolazoline.
- β – Adrenergic Receptor Blockers:
- β1 – Blocker – Atenolol, practolol, metoprolol, esmolol, bisoprolol.
- β2 – Blocker – Butoxamine.
- β1 & β2 Blocker – Propranolol, sotalol, pindolol, carvedilol, dilevalol, oxprenolol, alprenolol.
- Both α & β Adrenergic Receptor Blockers: Labetalol
- Adrenergic neuron blockers: Adrenergic neuron blocking agents are the drugs which acts on postganglionic sympathetic nerves, to prevent the ability of nerve impulse to release noradrenalin. E.g. – Guanethidine, bethanethidine.
- Drugs which interfere with the synthesis & release of noradrenaline: α-methyldopa.
α – ADRENERGIC BLOCKING AGENT
These drugs inhibit adrenergic response mediated through α – adrenergic receptors without affecting those mediated through β – receptors.
This drug belongs to the group of β – haloalkylamines.
Mechanism of Action:
It is a non – selective α receptor blocker. It increase release of noradrenaline from sympathetic nerves occurs & reflex tachycardia is prominent. It also inhibits neuronal as well as extra neuronal uptake of noradrenalin, at higher dosage it partial blockade of 5 HT, histaminergic & cholinergic receptors. It produces remarkable fall in blood pressure in patient with hypertension. The drug is also a potent antihistaminic.
Dose: 10 – 80 mg. ¾ times daily.
Miosis, dryness of mouth, sedation, drowsiness.
It is used for the treatment of hypertension, arteriosclerosis, allergy & hyperthyroidism.
The natural ergot alkaloids are ergotamine, ergosine & ergotoxine.
Mechanism of Action:
These are α – adrenergic receptor blocker. But the duration of blockade is short. They also antagonize the action of 5 – hydroxy tryptamine. These alkaloids antagonize the pressor effects of adrenaline. So, they can produce Dale’s vasomotor reversal.
Ergot alkaloids are not completely absorbed through oral route.
Parental Dose: 0.25mg – 0.5mg subcutaneous/ intramuscular route.
Nausea, vomiting, miosis, diarrhoea, confusion, headache, anginal pain.
These are used for the treatment of
- Induction of labour at full term.
- Control of postpartum haemorrhage.
- Abortion after third trimester.
β – ADRENERGIC BLOCKING AGENT
These drugs inhibit adrenergic responses mediated through β – receptors. They have become very important since they are widely used in hypertension, angina pectoris &arrhythmias.
(BETABLOC, BETACAP TR, CORBETA, INDERAL)
It is a β– adrenergic receptor blocker. It blocks both β1&β2 receptor.
Mechanism of Action:
Propranolol decreases heart rate at rest & post exercise period. It also decreases oxygen consumption of heart. Thus it is beneficial in angina pectories & myocardial infarction. It is also decreases the myocardial contractility, automaticity & conduction velocity & prolongs the refractory period. It also decreased renin release from the kidney.
It is used for the treatment hypertension, pheochromocytoma (tumor on adrenal medulla), angina pectoris, cardiac arrhythmias, migraine, and glaucoma.
Dose: 40 – 120 mg daily.
Insomnia, fatigue, dizziness, nausea, constipation, diarrhoea, anorexia, stomach discomfort, impotence, bronchospasm& mood alteration.
Hypersensitivity, heart block, severe hemorrhage, bronchial asthma & pregnancy.
Diabetes, elderly, congestive heart failure, renal or hepatic dysfunction & lactation.
It is a competitive antagonist of both α & β adrenergic receptors.
On oral administration it decreases heart rate, cardiac contractility, A.V conduction, peripheral resistance & blood pressure.
Dose: Oral dose 200 mg / day, for immediate control of serious hypertension 500 mg / min is given to I.V injection.
Gastrointestinal disturbances, dry mouth, fluid retention, bradycardia & orthostatic hypotension, nervousness, muscle cramps, depression & sexual dysfunction.
It is used to treat high blood pressure & hypertensive emergencies.
ADRENERGIC NEURON BLOCKING AGENTS
Adrenergic neuron blocking agents are drugs which act on postganglionic sympathetic nerves to prevent the ability of a nerve impulse to release noradrenalin. These drugs do not affect parasympathetic nervous system & ganglionic transmission. Also they do not affect the response of effector organs to injected noradrenalin. So, their action is selective on postganglionic sympathetic nerves, where they act by preventing the release of noradrenalin. E.g. – Guanethidine, guanoxon, guanachlor, bethanethidine & debrisoquine sulphate.
DRUGS ACTING ON
Drugs can act on sympathetic & parasympathetic ganglia producing either stimulation or blockade. Ganglionic stimulants have limited therapeutic application. But ganglion blocking agents are effective in the treatment of hypertension. E.g. – Ganglionic stimulators – Nicotine, lobeline, tetramethyl ammonium, dimethyl phenyl, piperazinium.
These are drugs which block transmission in both sympathetic and parasympathetic ganglia. These drug do not affect conduction of impulses in the pre ganglionic or post ganglionic nerves. They do not prevent the release of acetylcholine.They produce ganglionic blockade by occupying receptor sites in the ganglion cells. E.g. – Tetramethyl ammonium, pentamethonium, hexamethonium, pentolinium, chlorisondamine, mecamylamine, trimethaphan and pempidine.
postural hypotension, mydriasis, cycloplegia, dry mouth, constipation, urinary retention, depression, mental confusion and mania.
The ganglionic blocking drugs are rarely used as anti-hypertensive agents. Occasionally they are used to control excessive secretion and motility of gastrointestinal tract.