sympatholytics Flashcards
side effects of alpha 1 receptor antagonist
Orthostatic hypotension, inhibition of ejaculation, nasal stuffiness, tachycardia
beta-haloalkylamines
-Non-selective a receptor
antagonist
-Also blocks acetylcholine,
histamine, and serotonin
receptors
-irreversible antagonist
resulting from covalent
modification of receptor
imidazolines
-Non-selective a receptor
antagonist
-Competitive (reversible)
blocker
-Potent vasodilator, but
induces pronounced reflex
tachycardia
-Block of presynaptic a2
receptors may promote
release of NE
-Also blocks 5-HT receptors,
and is a muscarinic and
histamine receptor agonist
action of phenoxybenzamine
-noncomptetive (irreversible) antagonist at a1 and a2 receptors
-new receptors must be synthesized in order to restore receptor function leading
to a long drug effect
action of phentolamine
competitive (reversible) antagonist at a1 and a2 receptors
clinical use of phenoxybenzamine and phentolamine
Perioperative management of patients with pheochromocytoma (tumor of
adrenal medulla that results in excessive epinephrine and norepinephrine
synthesis and release)
problems of phenoxybenzamine and phentolamine
Not useful in treatment of hypertension due to a2 effects
by blocking alpha 2 receptors, we get a greater release of _____ at the ______ and increased ___
NE, Heart, HR
alpha 1 antagonist
- Vary in half-life:
- Prazosin 3 hrs
- Terazosin 12 hrs
- Doxazosin 20 hrs
- Undergo extensive metabolism, excreted
mainly in the bile - Vasodilators
- Relaxation of smooth muscle in enlarged
prostate and in bladder base - Quinazolines produce peripheral
vasodilation without causing reflex
tachycardia or increased cardiac output
(a presynaptic a 2 -antagonist effect)
prazosin
decrease TPR via a1 antagonism -> activate baroreceptor reflex -> increase NE release into myocardium -> increase heart rate via b1 receptors -> negative feedback via a2 receptors in myocardium mitigates NE release
phentolamine
decrease TPR via a1 antagonism -> activate baroreceptor reflex -> increase NE release into myocardium -> increase heart rate via b1 receptors -> antagonism of a2 receptors in myocardium blocks negative feedback -> cardiac overstimulation
tamsulosin (flomax)
-alpha 1 antagonist
-very selective to prostate urethra as this is rich in a1 a receptors
-less prone to induce fall in BP as compared to classical a1 blockers such as Prazosin
**Benign Prostatic Hyperplasia (BPH)
-BPH is problem with voiding may lead to overactive bladder.
-Stimulation of a1 a receptors in the trigone muscle of the bladder & urethra contract, contributing
to the resistance to outflow of urine. a1 blockers antagonize this effect
Beta 1 signal through Gs
-Activate adenylyl cyclase
-increase cAMP leading to protein kinase activation,
-Results in phosphorylation of ion channels and other proteins
yohimbine (yocon) alpha 2 adrenergic receptor antagonist
-Indole alkaloid
-Found in Rubaceae and
related trees. Also in
Rauwolfia Serpentina.
-Blockade of a2 receptors
increases sympathetic
discharge
-Folklore suggests use in
the treatment of male
impotence
beta blockers cardiovasular indications
angina, cardiac arrhythmia, post myocardial infraction, hypertension, congestive heart failure
cardiac arrhythmia
Slow AV nodal conduction
angina
Reduction in myocardial oxygen demand due to decreased heart rate and contractility
post myocardial infarction
Reduction in myocardial oxygen demand
Slow AV nodal conduction
hypertension
Decrease cardiac output
Inhibition of renin secretion
congestive heart failure
Decreases chronic overstimulation/toxicity of compensatory catecholamines
propranolol
-Non-selective beta antagonist
-Lipophilic
-Extensive hepatic metabolism, “first-pass”
-Local anesthetic properties
-Blockade is activity- dependent
pindolol (visken)
-non selective beta antagonsit
-Possesses “Intrinsic sympathomimetic activity (ISA)
-Partial agonist
-Less likely to cause bradycardia and lipid abnormalities
-Good for patients who have severe bradycardia or little cardiac reserve
-Administered: Oral
-Uses: Hypertension, angina,
migraine
propranolol pharmacologic effect
-Decreased cardiac output and heart rate
-Reduced renin release
-increase VLDL, Decrease HDL
-Inhibit lipolysis
-Inhibit compensatory glycogenolysis and glucose release in response to hypoglycemia
-Increase bronchial airway
resistance
-uses Hypertension, angina, cardiac arrhythmias, migraine, stage fright,
thyrotoxicosis, glaucoma, congestive heart failure (types II and III)
nadolol (corgard)
-non-selective beta adrenergic antagonist
-Less lipophilic than propranolol
-Long half-life: ~20 hours
-Mostly excreted unchanged in
urine
-Administered: Oral
-Uses: Hypertension, angina,
migraine
timolol (timoptic, blocadren)
-non selective beta antagonist
-Thiadiazole nucleus with
morpholine ring
-Administered: Oral, Ophthalmic
-Uses: glaucoma, hypertension,
angina, migraine,
carteolol (cartrol, ocupress)
-nonselective beta antagonist
-Possesses “Intrinsic
sympathomimetic activity (ISA)
-Partial agonist
-Less likely to cause bradycardia
and lipid abnormalities
-Administered: Oral, Opththalmic
-Uses: Hypertension, glaucoma
esmolol (brevibloc)
-selective beta 1 antagonist
-Very short acting
-Half-life: 9 minutes
-Rapid hydrolysis by esterases found in red blood cells
-Administered: Parenteral
Note: incompatible with sodium bicarbonate
-Uses: Supraventricular tachycardia, atrial
fibrillation/flutter, perioperative hypertension
para-substituted phenyl derivatives
-selective beta 1 antagonist
-“Cardioselective”
-Less bronchconstriction
-Moderate lipophilicity
-Half-life: 3-4 hours
-Significant first-pass metabolism
-Administered: Oral, parenteral
-Uses: Hypertension, angina, antiarrhythmic, congestive heart failure
atenolol (tenormin)
-selective beta 1 antagonist
-“Cardioselective”
-Less bronchconstriction
-Low lipophilicity, “Water-soluble Metoprolol”
-Half-life: 6-9 hours
-Administered: Oral, parenteral
-Uses: Hypertension, angina
side effects of beta blockers
Bradycardia, AV block, sedation, mask symptoms
of hypoglycemia, withdrawal syndrome
contraindications of beta blockers
Asthma, COPD, congestive heart failure (Type IV)
lavetalol (normodyne, trandate)
-mixed adrenergic receptor antagonist
-Phenylethanolamine derivative
-Two asymmetric carbons (1 and 1’)
-Racemic mixture used clinically
-(1R, 1’R)-isomer Non-selective b
receptor antagonist
-(1S, 1’R)-isomer a1 antagonist
-(Administered: Oral, parenteral
-Uses: Hypertension, hypertensive
crisis
-b-blocking activity prevents reflex tachycardia normally associated with a1 receptor antagonists
-vasodilation via a1-blockade prevents bradycardia associated with b-blockade
carvedilol (coreg)
-Non-selective b receptor antagonist
-a1 receptor antagonist
-Both enantiomers antagonize a1 receptors
-Only (S)-enantiomer possesses b-blocking activity
-b-blocking activity prevents reflex tachycardia normally associated with a1 receptor antagonists
-Administered: Oral
-Uses: Hypertension, congestive
heart failure
actions of catecholamine synthetic path: inhibiting with metyrosine
- Inhibits tyrosine hydroxylase
- Depletes catecholamines everywhere
clinical use of catecholamine synthetic path: inhibiting with metyrosine
- Perioperative management of
pheochromocytoma (tumor of adrenal
medulla that results in excessive
epinephrine and norepinephrine synthesis
and release)
problems of catecholamine synthetic path: inhibiting with metyrosine
Depletes catecholamines everywhere
bretylium tosylate (bretylol)
-drugs that reduce storage or release of NE
-Aromatic quaternary ammonium
-Precise mechanism unknown
-Displace and release NE and prevent further release (depletion)
-Local anesthetic
-Administered: Parenteral
-Uses: Antiarrhythmic (ventricular fibrillation)
reserpine (serpasil)
-catecholamine depleters
-Indole alkaloid obtained from the
root of Rauwolfia serpentina
-Block vesicular monoamine
transporters
-Deplete vesicular pool of NE
-Slow onset of action
-Sustained effect (weeks)
-Used in the treatment of hypertension (rarely because of adverse effects)
-May precipitate depression
actions of VMAT inhibitor reserpine
-Nonselective, irreversible inhibitor of Vesicular
Monoamine Transporter (VMAT)
-Depletes stored NE
clinical use of VMAT inhibitor reserpine
Hypertension but rarely used because of adverse effects
problems of VMAT inhibitor reserpine
-Expected peripheral adverse effects (orthostatic hypotension, increased GI activity)
-CNS effects such as sedation, severe depression and suicide in susceptible individuals
