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Adrenoceptor Antagonists
2
TYROSINE METYLDOPA NA NA
1 2 3
Adrenalin
Simpatomimetika
syaraf pasca ganglion
Simpatolitika penghambatan
perangsangan
neurotransmiter sintesa penimbunan penglepasan perombakan reseptor perangsangan perangsangan penghambatan penghambatan penghambatan penghambatan penghambatan
PENGHAMBAT SINTESA
BLOKADE RESEPTOR
Blokade penimbunan
BLOKADE PENGLEPASAN
NT inhibition
On presynaptic ending Drug affecting NT synthesis Drug affecting NT storage Drug affecting NT release
On postsynaptic ending Drug affecting parasympathetic receptors Drug affecting sympathetic receptors
Tyrosine Tyrosine hydroxylase DOPA DOPA carboxylase Dopamine Dopamine - hydroxylase Noradrenaline PNMT Adrenaline
PENGHAMBAT SINTESA NA
PHENYLALANINE
TYROSINE TYROSINE
DOPA
METHYLDOPA
METHYLDOPA
DOPAMINE
METHYLDOPAMINE
NORADRENALINE
METHYLNORADRENALINE
ADRENALINE
SIMPATOLITIKA
PRASINAPS
GUANETHIDINE
PASCASINAPS
BLOKADE PENYIMPANAN NA
PENGHAMBAT PENGELEPASAN NA
GUANETHIDINE
Selectivity of Antagonists
Selective antagonists Nonselective (1/2) antagonists Selective 1 antagonists Uroselective 1A antagonists Selective antagonists Nonselective (2) antagonists Selective 1 antagonists Nonselective adrenergic ( antagonists
Antagonists
Mechanism & Sites of Actions
Cardiovascular - vascular smooth muscle contraction
Reversal adrenaline Prejunctional 2 negative feedback on NE release
Non-cardiovascular sites
Antagonists
Nonselective
Nonselective
Clinical Uses: Limited
Pheochromocytoma Benign prostatic obstruction
Antagonists
Adverse Effects Cardiovascular
Tachycardia (reflex) Orthostatic hypotention Nasal congestion
(Phenoxybenzamine)
Autonomic hyperreflexia Migraine headache (Ergot alkaloids)
Non cardiovascular
GI (Phentolamine) Impotence (Phenoxybenzamine) Potential mutagen (Phenoxybenzamine)
Selective 1 Antagonists
Advantage over non- Uses selective agents Hypertension
lack 2 component
less prejunctional control (less reflex tachycardia) less CNS component of action
Pheochromocytoma
Selective 1 Antagonists
Adverse Effects
Orthostatic hypotension
Usually becomes tolerated Give first dose at night
Nasal congestion
Uroselective 1A Antagonist
Tamsulosin
QD dosage
Clinical Use
Benign Prostatic Hyperplasia
Adverse Effects
Retrograde ejaculation NOTE: Avoids orthostatic hypotension in most
Selective 2 Antagonists
Yohimbine Apparent Mechanism of Action
major mechanism of action appears to be increasing sympathetic outflow from CNS
Antagonists
Response in normal resting person
Few effects in cardiovascular system or lungs
Low tone in heart Lungs no epi being presented Wrong receptors in vasculature
Antagonists
Response in normal person during stress
Short-term effect
Block heart sympathetic response
rate and contraction - decrease CO block of sympathetic control of rhythm & automaticity
Antagonists
In hypertensive (hyperkinetic heart-induced) In heart failure
Decrease blood pressure
Decrease heart work & protect against arrythmias cause bronchoconstriction
Antagonists
Prototype - Propranolol
Pure antagonist, no Intrinsic Sympathomimetic Activity(ISA) (i.e. not a
partial agonist)
Nonselective to subtypes
Uses of Antagonists
Cardiovascular
Hypertension Angina Arrhythmias Myocardial infarction Heart failure
Non-cardiovascular
Glaucoma Somatic symptoms of anxiety (e.g. stage fright) Fine muscle tremors
CV Symptoms of
Hyperthyroidism Pheochromocytoma Aortic aneurysm
Migraine headache
Antagonists
Nonselective
Propranolol Nadolol: long half-life Timolol: use in glaucoma Pindolol: ISA Selective1
Metoprolol Atenolol: limited entry Esmolol: short half-life Acebutolol: ISA Celiprolol: partial 2 agonist thus causing vasodilation
Bisoprolol
Antagonists
Adverse Effects
Cardiovascular
Induce CHF or bradycardial arrhythmia Sudden withdrawal - in anginal patients may cause sudden death (due to receptor supersensitivity)