Transcript Antiadrenergic Drugs

Adrenergic Receptor Antagonists
 These are drugs which antagonize α or β or both α and
β adrenergic receptors
 Adrenergic neurone blocking agents (Sympatholytic)
act by interfering with the release of adrenergic
transmitter on nerve stimulation.
Differences between antiadrenergic and adrenergic neurone blocking drugs
Antiadrenergic drugs
Adrenergic neurone
blocking drugs
Locus of action
Adrenergic receptors
on neuronal membrane
or neurones contents
Effects of adrenergic
nerve stimulation
Blocked (less completely)
Blocked (more
completely)
Effect of injected Adr
Blocked
Not blocked (may be
potentiated)
Examples
α—Phentolamine
β—Propranolol
Reserpine, Guanethidine,
Bretylium
α ADRENERGIC BLOCKING DRUGS
A. Nonselective
 Hydrogenated ergot alkaloids—Dihydroergotamine
(DHE), Dihydroergotoxine, Nicergoline
 Phentolamine
 Phenoxybenzamine
B. α1 selective— Prazosin, Terazosin, Doxazosin, Alfuzosin
— Tamsulosin (α1A)
C. α2 selective —Yohimbine
EFFECTS OF α1α2-BLOCKERS
1. Blockade of vasoconstrictor α1 (also α2) receptors →
vasodilation → fall in BP→ marked postural hypotension →
dizziness and syncope.
2. Reflex tachycardia
3. Nasal stuffiness (blockade of α receptors in nasal blood vessels)
4. Miosis (blockade of α receptors in radial muscles of iris)
5. Intestinal motility is increased
6. Tone of smooth muscle in bladder trigone, sphincter and
prostate is reduced by blockade of α1 receptors (mostly of the
α1A subtype) → urine flow in patients with benign hypertrophy
of prostate (BHP) is improved.
7. Contractions of vas deferens and related organs which result in
ejaculation are coordinated through α receptors—α blockers
can inhibit ejaculation; this may manifest as impotence.
Hydrogenated ergot alkaloids
 Ergot alkaloids are partial agonists and antagonists at α
adrenergic receptors.
 The natural ergot alkaloids produce
long lasting vasoconstriction → peripheral
vascular insufficiency and gangrene
of toes and fingers occurs in ergotism.
 Hydrogenation reduces vasoconstrictor and increases α
blocking activity.
Treatment of- acute migraine headache!
-dementia or problems with memory
Phenoxybenzamine
 is a non-selective, irreversible α -blocker → blockade
lasts for 3–4 days till fresh receptors are synthesized.
 It is used in the treatment of:
 Hypertension
 Pheochromocytoma (to control blood
pressure and reduce sweating)
ADR:
 Postural hypotension
 Tachycardia
 Inhibition of ejaculation
 Nasal congestion
 Miosis
 Drowsiness and fatigue
 Dizziness
Pheochromocytoma
 A pheochromocytoma is a tumor of the medulla of the
adrenal glands (originating in the chromaffin cells)
that secretes high amounts of norepinephrine and
epinephrine.
Symptoms :
 Malignant hypertension / Hypertensive emergency
 Tachycardia
 Headaches
 Profuse sweating
Phentolamine
 a reversible nonselective α-adrenergic antagonist
It is used as:
 a quick and short acting α blocker for diagnosis and
intraoperative management of pheochromocytoma
 for control hypertensive emergencies
ADR:
 Postural hypotension
 Tachycardia
 Inhibition of ejaculation
 Nasal congestion
 Miosis
 Drowsiness and fatigue
 Dizziness
Prazosin
 It is first of the highly selective α1-blockers.
 ‘First dose effect’-Postural hypotension
occurs especially in the beginning. This can
be minimized by starting with a low dose and
taking it at bedtime.
The treatment of :
 Hypertension
 Raynaud’s disease
 benign hypertrophy of prostate (BHP).
Tamsulosin (Omnic)
 Selective α1A-blocker
 α1A subtype predominate in
the bladder base and prostate
Indication:
 Benign prostatic hyperplasia/
difficult urination
ADR:
 Dizziness
 Retrograde ejaculation (the
fluid is redirected to the
urinary bladder)
 Postural hypotension (rare)
Yohimbine
 An alkaloid from the West African plant Yohimbehe.
 It is a selective α2 -blocker .
Effects :
 Heart rate and BP are elevated
 Excitation
 Tremor
 Nausea and vomiting.
 It may cause congestion in genitals and has been
considered to be an aphrodisiac. This effect is only
psychological, but can overcome psychogenic impotence
in some patients.
 Potential treatment for erectile dysfunction but there is
insufficient evidence to rate its effectiveness
β ADRENERGIC BLOCKERS
Nonselective (β1 and β2)
a. Without intrinsic sympathomimetic activity:
 Propranolol
 Sotalol
 Timolol
b. With intrinsic sympathomimetic activity:
 Pindolol
Cardioselective (β1):
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Metoprolol
Atenolol
Acebutolol
Bisoprolol
Esmolol
Betaxolol
Nebivolol
α and β blockers (with additional vasodilator property):
 Labetalol
 Carvedilol
Cardioselective drugs are more potent in blocking cardiac
(β1) than bronchial (β2) receptors. However, selectivity is
only relative and is lost at high doses( Lower ability to
cause ADR)
Intrinsic sympathomimetic activity (in pindolol, celiprolol,
acebutolol)- ability to activate β1 and/or β2 receptors
submaximally. The benefits of this property are
controversial.
 1. Bradycardia and depression of contractility at rest are
not prominent, but exercise tachycardia is blocked; may
be preferred in those prone to severe bradycardia (elderly
patients; sick sinus) or with low cardiac reserve.
 2. Not suitable for secondary prophylaxis of MI.
PHARMACOLOGICAL ACTIONS
 Heart:
Decreasing of heart rate
Retarding of force of contraction
A-V conduction is delayed.
 Blood vessels
Blockade of β2-mediated vasodilatation → peripheral
vasospasms
• BP
Both systolic and diastolic BP fall (on prolonged
administration)
 Respiratory tract
Bronchospasm (increasing of bronchial resistance by
blocking dilator β2 receptors)
PHARMACOLOGICAL ACTIONS
CNS
 Sleep disturbances (increased dreaming and
nightmares)
 Sexual and erectile dysfunctions
 Depression
Eye
 β blockers reduces secretion of aqueous humor.
Uterus
 Constriction of uterus
Indications
Hypertension
 They are one of the first choice drugs because of good patient
acceptability and cardioprotective potential
Angina pectoris (stenocardia)
 All β blockers benefit angina of effort.
 β blockers are not suitable for variant (vasospastic) angina.
Cardiac arrhythmias
 β blockers suppress extrasystoles and supraventricular
tachycardias.
Myocardial infarction (MI)
CHF
Thyrotoxicosis
Glaucoma (Timolol(β1 + β2), Betaxolol (β1))
Metoprolol
 It is the prototype of cardioselective (β1) blockers.
 Metoprolol was first made in 1969. It is on the WHO
Essential Medicines(the most important medications
needed in a basic health system).
 Use:
 Hypertension
 Angina Pectoris
 Myocardial Infarction
• t½ is 3-4 hours.
Atenolol
 A selective β1 blocker.
 It is one of the most commonly used β blockers for
hypertension and angina.
 Atenolol does not pass through the blood–brain barrier
thus decreasing the side effects related to CNS.
 Antihypertensive effects persist for at least 24 hours.
Uses:
 Hypertension
 Angina
 Long QT syndrome
 Acute myocardial infarction
 Supraventricular tachycardia
 Ventricular tachycardia.
Nebivolol
 a β1 receptor blocker with nitric oxide → potentiating
vasodilatory effect.
 Along with labetalol and carvedilol, it is one of b
blockers to cause dilation of blood vessels in addition
to effects on the heart
 Uses:
 in treatment of hypertension
 for left ventricular failure (in Europe)
Labetalol
 A nonselective b blocker/a-1 blocker
To treat:
 chronic and acute hypertension
 pheochromocytoma
Side effects :
 Orthostatic hypotension (due to a receptor blockade)
 Drowsiness
 Fatigue
 Weakness
 Difficulty sleeping
 Diminished sexual function
Carvedilol
 It is a β1 + β2 + α1 adrenoceptor blocker.
 Producing vasodilatation due to α1 blockade and has
antioxidant property.
 Use:
Angina Pectoris
Congestive Heart Failure
Hypertension
Left Ventricular Dysfunction.
 t½ - 6–8 hrs.
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Side effects
Dizziness
Drowsiness (sleepiness)
Depression
Sexual dysfunction (impotence)
Peripheral vasospasms → bluish discoloration of the
fingers and toes, numbness/tingling/swelling of the
hands or feet
Bradycardia
↓BP
Symptoms of Congestive Heart Failure (CHF)
Bronchospasm
Allergic reaction