ADRENERGIC AND ANTI-ADRENERGIC
DRUGS
By Shabib Akhtar
Divisions of human nervous system
Human Nervous system
Central Nervous System Peripheral Nervous System Autonomic Nervous System
NERVOUS SYSTEM
Includes neurons and ganglia outside of the brain and spinal cord
Peripheral Nervous System
*Either fight and flight mode or rest and digest
*Autonomic Nervous System (involuntary)
Somatic Nervous System (voluntary)
With neurotransmitters nor epinephrine and acetylcholine
Sympathetic Nervous System (adrenergic)
Parasympathetic Nervous System (cholinergic)
Adrenergic drugs are also called as sympathomimetic drugs
Sympathomimetic drugs are substances that mimic the effects of the sympathetic nervous system, such as catecholamines, adrenaline (epinephrine), noradrenaline (norepinephrine), dopamine, etc.
CNS (Autonomic) Sympathetic
Synapse Ach (N) NA
Adrenaline
Ach (N) Adrenal medulla AUTONOMIC
Parasympathetic
Synapse
Ach (M) Smooth muscle Cardiac muscle
Ach (N)
These drugs act at the postganglionic sympathetic terminal,
Such drugs are used to treat cardiac arrest and low blood pressure, or even delay premature labor, among other things.
CLASSIFICATION OF SYMPATHOMIMETIC DRUGS
I. a)
Catecholamines Endrogens Epinephrine
III. a)
Selective 1 adrenergic agonist Direct acting Methoxamine
Norepinephrine
b)
Phenylephrine
b)
Dopamine Non- Endrogens (-agonist) Non- selective
Direct and Indirect acting Mephentermine Metaraminol
Isoproterenol Selective 1
Dobutamine
II.
IV. a) b) c)
Selective 2 adrenergic agonist
Clonidine Guanfacine Methyldopa Indirect acting agonist Amphetamine Ephedrine
Selective 2 adrenergic agonist
a)
Metaproterenol
b)
c) d)
Terbutaline
Salbutamol Ritodrine
V. a) b)
MECHANISMS OF ACTION AND EFFECTS OF ADRENERGIC DRUGS
1. Direct adrenergic drug action: Act directly on postsynaptic and receptors on target effector organs, e.g. epinephrine, norepinephrine, Isoprenaline. 2. Indirect adrenergic drug action: o Stimulation of postsynaptic 1 , 1 and 2 receptors. Cause release of norepinephrine into the synapse of nerve endings or prevent reuptake of norepinephrine. e.g. cocaine.
3. Mixed action: Combination of direct and indirect receptor stimulation, e.g. ephedrine and dopamine.
Stimulation of 2 receptors in CNS is useful in decreasing BP Most body tissues have both and receptors Effect occurs secondary to receptor activated and number of receptors in the particular body tissue Some drugs act on both receptorsdopamine
INDICATIONS FOR USE
Emergency drugs in treatment of acute cardiovascular, respiratory and allergic disorders In children, epinephrine may be used to treat bronchospasm due to asthma or allergic reactions Phenylephrine may be used to treat sinus congestion Stokes Adams Shock Inhibition of uterine contractions For vasoconstrictive and hemostatic purposes
CONTRAINDICATIONS TO USE OF ADRENERGICS
Cardiac dysrhythmias, angina pectoris Hypertension Hyperthyroidism Cerebrovascular disease Distal areas with a single blood supply such as fingers, toes, nose and ears Renal impairment use with caution
INDIVIDUAL ADRENERGIC DRUGS
Epinephrine Effects include: increased BP, increased heart rate, relaxation of bronchial smooth muscle, vasoconstriction in peripheral blood vessels Increased glucose, lactate, and fatty acids in the blood due to metabolic effects Increased leukocyte and increased coagulation Inhibition of insulin secretion, affects both and receptors. Drug of choice for bronchospasm and laryngeal edema of anaphylaxis Excellent for cardiac stimulant and vasoconstrictive effects in cardiac arrest May be given IV, inhalation, topically, Not PO
Pseudo Epinephrine
Used for bronchodilating and nasal decongestant effects
Isuprel (Isoproterenol): o Synthetic catecholamine that acts on 1 and 2 receptors o Stimulates heart, dilates blood vessels in skeletal muscle and causes bronchodilation o No alpha stimulation o Used in heart blocks (when pacemaker not available) and as a bronchodilator
TOXICITY OF ADRENERGICS IN CRITICALLY ILL
PATIENTS Affects renal perfusion Can induce cardiac dysrhythmias Increases myocardial oxygen consumption May decrease perfusion of liver Tissue necrosis with extravasation Do not give epinephrine and Isuprel at same time or within 4 hours of each other. Could result in serious dysrhythmias.
ALPHA ADRENERGIC BLOCKERS:
Pharmacological properties Blockade of 1 adrenergic receptors inhibits the vasoconstriction produced by endogenous catecholamines. Blockade of 2 receptor present in the brain increases vasomotor tone. Block pressure action of adrenaline and causes fall in blood pressure. Vasomotor reversal of Dale. Reflex trachycardia and cardiac output. Blockade of 2 receptor- potentiate release of nor-epinephrine from adrenergic nerve ending. Blockade of 1 receptor mediated contraction of other smooth muscle.
CLASSIFICATION OF ANTI-ADRENERGIC DRUGS
A.
Adrenergic receptor blocking drugs
I.
i. ii. a) b) c)
Alpha adrenergic blocking drugs
Non competitive blocker : phenoxybenzamine. Competitive blocker: Non-selective: phentolamine, tolazoline, ergot alkaloids. 1 selective: prazosin, terazosin, doxazosin. 2 selective: yohimbine.
Non-selective - blocker: propranolol, nadolol, timolol, pindolol. Selective 1: metaprolol, atenolol, esmolol, acebutolol. Selective 2: butoxamine + adrenergic receptor blocker: labetalol, carvedilol.
II.
a) b) c)
Beta adrenergic blocking drugs
d)
B.
Adrenergic neuronal blocking drugs
reserpine, guanethidine.
ALPHA ADRENERGIC BLOCKERS- DRUGS
Phenoxybnezamine:
Slow onset of action - ethyleneiumonium intermediate. Also block 5HT, histamine and acetylcholine responses. Action on cardiovascular system: blood pressure: postural hypotension. Heart: reflex trachycardia. Uses: in patient with pheochromacytoma.
Phentolamine and tolazoline:
Short duration of action Activation of cardiac adrenergic receptors. Activation of cholinergic receptors. Histamine like effect. Uses: to control hypertensive crisis, treatment of impotence in males. Tolazoline is used in treatment of presistent hypertension of the newborn.
ALPHA ADRENERGIC BLOCKERS- DRUGS
Prazosin and related drugs:
Vasodilatation. Less tachycardia than non-selective -blocker.
Terazosin:
Less potent then prazosin. Has higher bioavailability. Have longer duration of action.
Uses:
Mild to moderate hypertension. Congestive heart failure. Conservative treatment of benign prostrate hypertrophy. Occasional postural hypotension and syncope.
ERGOT ALKALOIDS
Natural alkaloids
Ergotamine Ergotoxine: ergocristine+ ergocriptine+ ergocornine. Ergometrine (ergonovine)
Dihydrogenated alkaloid:
Dihydroergotamine. Hydergin.
Pharmacological actions:
-adrenergic receptor blockade. Smooth muscle stimulation. CNS excitation/depression.
Hydrogenation of ergot alkaloids increases- -blockade activity. Oxytocic effect : Ergonovine or ergotamine administered at second or third stage of labor. In migraine: ergotamine in combination with caffeine.
BETA-ADRENERGIC BLOCKING DRUGS
Pharmacological Action:
Cardiovascular system: Decreases both the force and rate of myocardial contraction as well as cardiac output. Produces slow developing hypotension. Pindolol with no plasma renin activity but effective antihypertensive. Respiratory tract: Bronchial constriction in asthmatic patient. Eye Decreases aqueous humor secretion. Metabolic effect: Beta-blocker inhibits the lipolytic and glycogenolytic action of catecholamines. Augment hypoglycemic action of oral hypoglycemics.
ADRENERGIC NEURON BLOCKING DRUGS:
Guanethidine: Mechanism of action: taken up by the sympathetic nerve just as NE is taken up to terminate its activity. Pharmacological action:
Cardiovascular system: fall in blood pressure- Fall in blood pressure is usually associated with bradycardia, decreased C.O and decrease pulse pressure.
Onset of action is, delayed for 3-5 days.
Other effects: increases GIT motility, reduces I.O.P in glaucomatous eyes and produces difficulty or prevention of ejaculation. Therapeutic uses: Severe hypertension only after prior or simultaneous initiation of treatment with thiazide diuretics and reserpine.
RESERPINE
Mechanism of action: binds tightly to storage vesicles in adrenergic neurons destroying them and the nerve endings lose their ability to concentrate and store NE and dopamine. pharmacological action: Cardiovascular system: fall in blood pressure, reduces CO and peripheral resistance. Other effects: sedation, extra-pyramidal effects, increases GIT activity and nasal congestion. Therapeutic uses: use in treatment of hypertension.
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