Sympatholytic pharmacology Flashcards
orthosteric
site where NE binds directly to block the ability of the agonist to bind
allosteric
not binding directly to site where NE binds, but blocks binding at another site
side effects of alpha1 receptor antagonists
orthostatic hypotension, inhibition of ejaculation, nasal stuffiness, tachycardia
What kind of agonist is Phenoxybenzamine (Dibenzyline)?
non-selective alpha receptor antagonist
What else does Phenoxybenzamine block?
acetylcholine, histamine, and serotonin receptors
What kind of antagonist is Phenoxybenzamine?
irreversible antagonist resulting from covalent modification of receptor
When would you use Phenoxybenzamine?
not used anymore
historically was used in HTN crisis and pheochromocytoma
What type of antagonist is Phentolamine (Regitine)
non-selective alpha receptor antagonist
competitive/reversible blocker
muscarinic and histamine receptor agonist
What kind of effects does Phentolamine produce?
potent vasodilation, but induces pronounced reflex tachycardia
What does Phentolamine block?
blocks presynaptive alpha2 receptors (may promote release of NE) and 5-HT receptors
Quinazolines
Prazosin, Terazosin, and Doxazosin
What kind of antagonists are quinazolines?
alpha-1 adrenergic receptor antagonists
What do quinazolines do?
vasodilators, relaxation of smooth muscle in enlarged prostate and in bladder base
How do the three quinazolines vary?
Vary in half-life:
Prazosin - 3 hours
Terazosin - 12 hours
Doxazosin - 20 hours
Describe the “first dose” effect of quinazolines
orthostatic hypotension occurs with the first dose, but you’ll become tolerant over the first 24 hours
What kind of receptor antagonist is Yohimbine (Yocon)?
alpha2-adrenergic receptor antagonist
What does Yohimbine do?
blockade of alpha2 receptors increases sympathetic discharge, off the market, doesn’t really do anything, used in herbal supplements
Aryloxypropanolamines are what kind of drugs?
beta blockers
Propranolol
non-selective beta blocker, lipophilic (CNS penetration), local anesthetic properties (Na+ channel blocker), first gen but still used a lot
Therapeutic uses for beta-adrenergic receptor antagonists
hypertension, angina, cardiac arrhythmias, migraine, stage fright, thyrotoxicosis, glaucoma, congestive heart failure (types II and III)
Pharmacological effects of beta blockers
decreased cardiac output and heart rate, reduced renin release*, increase VLDL, decrease HDL, inhibit lipolysis, increase bronchial airway resistance, inhibit compensatory glycogenolysis and glucose release in response to hypoglycemia
Non-selective beta-adrenergic receptor antagonists
Propranolol, Nadolol, Timolol, (Pindolol, and Carteolol)
Uses of Nadolol
hypertension, angina, migraine
How is Nadolol different from propranolol?
less lipophilic than propranolol
Describe the structure of Timolol
thiadiazole nucleus with morpholine ring
Uses of Timolol
hypertension, angina, migraine, glaucoma
How do beta blockers affect pupil size?
they don’t
What type of antagonist is Pindolol?
partial agonist, possesses “intrinsic sympathomimetic activity”
Uses of Pindolol
hypertension, angina, migraines
Significance of Pindolol and Carteolol being partial agonists
less likely to cause bradycardia and lipid abnormalities
What type of antagonist is Carteolol?
partial agonist, possesses “intrinsic sympathomimetic activity”
Uses of Carteolol
hypertension, glaucoma
What type of antagonist are Metopropol and Bisopropol?
selective beta1-adrenergic receptor antagonists, cardioselective
Consequence of “cardioselective” beta blockers
less bronchoconstriction
Uses of Metoprolol and Bisoprolol
hypertension, angina, antiarrhythmic, congestive heart failure
What type of antagonist is Atenolol?
selective beta1-adrenergic receptor antagonist; cardioselective
What is the lipophilicity of Metoprolol and Bisoprolol?
moderate lipophilicity
What is the lipophilicity of Atenolol?
low lipophilicity
Uses of Atenolol
hypertension, angina
What type of antagonist is Esmolol?
selective beta1-adrenergic receptor antagonist
Uses of Esmolol
supraventricular tachycardia, atrial fibrillation/flutter, perioperative hypertension
How long does it take Esmolol to act?
very short acting
half life is 9 minutes
What kind of antagonist is Nebivolol
3rd generation beta1-adrenergic receptor antagonist
Selectivity of Nebivolol
beta1 selectivity
Effects of Nebivolol
vasodilation due to nitric oxide production
Uses of Nebivolol
hypertension
What type of antagonist is Labetalol
mixed adrenergic receptor antagonist:
non-selective beta receptor antagonist
alpha1 receptor antagonist
What is the significance of Labetalol being a racemic mixture?
(1R, 1’R) isomer is a beta blocker
(1S, 1’R) isomer is an alpha1 blocker
Beta-blocking activity of Labetalol prevents?
prevents reflex tachycardia normally associated with alpha1 receptor antagonists
Uses of Labetalol
hypertension, hypertensive crisis
What kind of antagonist is Carvedilol
mixed adrenergic receptor antagonist:
non-selective beta receptor antagonist
alpha1 receptor antagonist
Significance of Carvedilol having enantiomers
both enantiomers antagonize alpha1 receptors
only (S) enantiomer possesses beta blocking activity
beta blocking activity of Carvedilol prevents
prevents reflex tachycardia normally associated with alpha1 receptor antagonists
Uses of Carvedilol
hypertension, congestive heart failure (II and III), anti-oxidant activity
Side effects of beta blockers
bradycardia, AV block, sedation, mask symptoms of hypoglycemia, withdrawal syndrome (taper doses down)
Withdrawal syndrome with beta blockers
pronounced tachycardia, hypertension
contraindications of beta blockers
Asthma, COPD, congestive heart failure (type IV-final stage)
What kind of drug is Reserpine
Catecholamine depleter
Mechanism of Reserpine
blocks vesicular monoamine transporters, depletes vesicular pool of NE
Use of Reserpine
used in the treatment of hypertension
Side effect of Reserpine
may precipitate depression, lead to the discovery of anti-depressants
Significance of the slow onset of action of Reserpine
doesn’t trigger baroreceptor reflex
