Adrenergic Pharmacology II Flashcards
Adrenoreceptor Antagonist Drugs
Effects vary according to drug’s receptor selectivity
Block either alpha or beta receptors
Phentolamine
Reversible alpha receptor antagonist
Competitive antagonist
Nonselective between alpha 1 and 2
Reduces TPR, MAP
Produces reflex tachy (SNS reflex)
Phenoxybenzamine
Irreversible alpha receptor antagonist
Longer duration of action than phentolamine because irreversible
Tx for pheochromocytoma
Predictable side effects of postural hypotension, reflex tachycardia
Somewhat selective for alpha1 receptors but less so than prazosin
Alpha receptor antagonist pharmacologic effects
Alpha1- peripheral vasculature
- Reduce peripheral resistance, and reduce MAP because largely determined by alpha actions of SNS tone
- Reduce blood pressure
- Alpha antagonist can reverse pressor effects (epinephrine)
- May cause postural hypotension and reflex tachycardia
Prazosin and terazosin
Alpha receptor antagonist
Selective alpha1 receptors
-Zosin
all alpha1 selective antagonist
Doxazosin
Alpha 1 antagonist with longer 1/2 life
Htn and bph tx
Tamsulosin, Alfuzosin
Competitive alpha1 ant
Good efficacy in BPH and helps with urinary retention
Yohimbine
Alpha2 selective antagonist
Alpha2 receptors are inhibitor, autoregulatory, and inhibit norepinephrine release
-Can get runaway catecholamine effects
-Can produce htn with this
Reserpine
Indirect sympatholytic agent
- Inhibits VMAT (vesicular monoamine transporter) so that catecholamines are not stored in vesicles, and are sensitive to metabolism by MAO or COMT by adjacent cell
- Overtime catecholamines will be depleted, so even if system is activated, no chemical will be released
- Not therapeutically useful, just experimental to remove SNS
Alpha receptor antagonist- clinical use
Pheochromocytoma, htn emergencies (vasodilators preffered, nitrates), chronic htn (effective, but lots of side effects and heart failure) , urinary obstruction in BPH
Pheochromocytoma
- tumor of adrenal medulla which releases mix of epinephrine and norepinphrine
- symptoms and signs of catecholamine excess (htn, headaches, palpitations, sweating)
- rarely tx with metyrosine but mostly use alpha antagonists to block activation of peripheral receptors
Beta receptor antagonist
- Blocks effects of catecholamines at beta receptors
- Selectivity for beta1 or beta2 have imp clinical implications
- But there is some crossover even with beta1 specific drugs
- Good oral bioavailability, peak effect within 1-3 hrs (major exception is esmolol)
Esmolol
is a beta antagonist
Unlike others, because it has an ester has a half life of 10 minutes because of rapid hydrolysis
Constant infusion in inpatient setting
Propanolol
Nonselective
Extensive first pass (hepatic) metabolism
-Accommodate for in parenteral vs oral
-Individual differences in metabolism
Beta blocker effects on CV
- Lower Bp in pts with htn
- Produce effects on heart, vasc, renin-angio system
- Conventional doses usually doesn’t cause hypotension in normal subjects
- Cardiac- neg inotropic and chronotropic effects
- Slowed atroventricular conduction, increased PR interval
Beta blocker effects on Resp tract
Bronchial smooth muscle- beta2 blockade increases airway resistance (adverse)
- beta1 antagonists can also increase airway resistance in asthmatics
- Nonselective beta blockers should be avoided in pts who are asthmatic
Beta blocker effects on eye
- Secretion of aqueous humor is controlled by beta receptors at ciliary epithelium
- Block beta receptors- reduce secretion of aqueous humor (open angle glaucoma)
- Topical eye drops
Beta blocker effects on metabolism and endocrine
- beta3 mediated effects on liver and adipose tissue- energy usage in fight or flight situation
- move towards energy storage with meds
- Symptoms- plasma VLDL, dec HDL, shifts in blood-glucose regulation
- Should be used with caution in insulin-dep diabetics
Intrinsic sympathomimetic activity
In some beta blocking drugs- partial agonist activity
- By limiting extent of antagonism, can avoid AE: precipitation of asthma, bradycardia, alteration of plasma lipid prolife
- Pindolol
Propranolol
prototypical beta-blocking drug (nonselective)
Beta1 selective drugs
Metoprolol, atenolol- more cardioselective, less effects on lung and liver
Nadolol and timolol
beta blockers with long DOA
timolol used as eye drops in open angle glaucoma
Pindolol, acebutolol, carteolol
partial agonists
Intrinsic sympathomimetic effects
Labetalol
- beta blocker AND alpha1 antagonist
- nonselective beta blocker
- Anti htnsive drug, but less compensatory tachycardia because of beta blocking ability
Butoxamine
- Beta2 antagonist
- Bronchoconstriction, precipitate asthma
- Tox= toxin, no clinical application
Beta blockers, clinical uses
Htn (in combo with diuretics, vasodilators), ischemic herat disease (reduce anginal episodes, improve exercise tolerance, dec cardiac work, reduce myocardial oxygen demand, good evidence that long term use prolongs survival after MI), cardiac arrythmias (slow propogation of electrical signals through electrical pathways within myocardium, increase refractory period at AV node, reduce ventricular ectopic beats), glaucoma (open angle- topical drops to inh sec of aqueous humor), hyperthyroidism (limiting excessive catecholamine activity)
Toxicity of beta receptor antagonist
- well tolerated
- minor: rash, fever, sedation, depression with chronic use
- major: exacerbation of asthma, shifts in metabolic profile
Nonselective alpha antagonist list
phentolamine, phenoxybenzamine, tolazoline
alpha1 selective antagonist list
prazosin, terzosin, doxazosin, tamsulosin, alfuzosin, silodosin, labetalol
alpha2 selective antagonist list
yohimbine
adrenergic neuron blocking drugs list
reserpine, guanadrel
nonselective beta antagonist list
propranolol, nadolol, timolol, [pindolol, cartelolol, penbutolol,-partial agonists], levopunalol, metipranolol, labetalol
beta1 selective antagonist list
metoprolol, esmolol, atenolol, acebutolol, betaxolol, bisoprolol, nebivolol
beta2 selective antagonist list
butoxamine
