11/2 Adrenergic Antagonists_2/2- Corbett Flashcards
alpha adrenergic antagonists
two general types:
- nonselective: block both alpha1 and alpha2
- alpha1-selective
can be reversible or irreversible
CARDIOVASCULAR EFFECTS
- decr peripheral vascular resistance (alpha1 effect)
- decr bp
- cause orthostatic hypotension and reflex tachycardia
other effects
- miosis, nasal stuffiness
- decr resistance to urinary flow
non-selective alpha antagonists
non-selective alpha antagonists: phenoxybenzamine
route
mech
effect
use
adv effects
PHENOXYBENZAMINE (oral)
- nonselective alpha1 and alpha2 blockade (alpha1>2)
-
irreversible receptor blockade lasting 14-48hr
- only irrev agent among alpha blockers! (also only oral)
- blocks NE reuptake at presyn terminals
effect: blocks catecholamine-mediated vasoconst\
use: tx of pheochromocytoma (tumor of adrenal medulla → excessive catecholamine production), often with paroxysmal HTN
- point of premedication: block the alpha effects to allow actual blood volume to rise to a level where it’s safe to operate
adverse effects: postural hypotension, reflex tachycardia, nasal stuffiness, fatigue, nausea
non-selective alpha antagonists: phentolamine
route
mech
effect
use
adv effects
PHENTOLAMINE (IV or IM)
- nonselective alpha1 and alpha2 blockade (alpha1=2)
- reversible receptor blockade lasting 4hr
effect: decr peripheral resistance, cardiac stimulation
use: tx of pheochromocytoma, in cases of NE extravasation
adverse effects: severe tachycardia, arrhytmias, myocardial ischemia
selective alpha antagonists
4 ex and uses
adverse effects
1. PRAZOSIN
- highly selective alpha1 effects (1000:1 alpha1:2 effect)
- not much effect on heart
- relaxes arterial and venous smooth muscle
- relaxes smooth muscle in prostate
metabolized in liver w/ 3hr half-life
uses: HTN (not first line) and BPH
2. TERAZOSIN: HTN and BPH
3. DOXAZOSIN: HTN and BPH (22h half-life)
4. TAMULOSIN: “uroselective”
- blocks alpha1A and 1D receptors in prostate → selective for BPH
adverse effects
- orthostatic hypotension (esp with first dose)
- dizziness, headache
- drowsiness
- ejaculation issues
selective alpha2 antagonists
yohimbine
- used for ED (largely displaced by sudenefil - Viagra)
- works in CNS to increase SNS outflow to periphery
- contraindicated in CVD
mirtazapine
- antidepressant
- central presyn alpha2 antagonist effects → stimulate NE and 5HT release
beta-adrenergic antagonists
- nonselective
- beta1-selective antagonists: cardio selective
- antagonists with action against beta1, beta2, alpha1
PK of beta blockers
absorption
distribution
excretion
-
limited bioavailability when taken orally
- implications for IV admin (much higher availability!)
- large volume of distribution
- most metabolized in liver (except nadolol)
esmolol
v v v short acting!
10 min metabolism
only given parenterally
quick metabolism distinguishes it from others
CV effects of beta blockers
lowers high blood pressure
- suppression of renin release
- effective ONLY if you have high bp!
negative chronotrope (slowed AV conduction, incr PR interval)
negative inotrope (decr CO, workload, VO2)
beta2 blockade in periphery → acutely increased PVR
other effects of beta blockers
respiratory system
- bronchoconstriction (even with beta1 selective drugs)
- contraindicated with severe obstructive disease (FEV1 <50% PV)
metabolic/endocrine effects
- lipolysis blocked → incr VLDL, decr HDL
- impaired glucose tolerance
effects on eye
- reduce intraocular pressure
therapeutic effects of beta blockers
- hypertension (not first line!)
- lowers bp in pt with HTN
- decr CO, renin, systemic vasc resistance over time
- not recommended as 1st line tx
- myocardial infarction
* WHY CARDIOPROTECTIVE IN THIS SETTING? reduces myocardial oxygen consumption!!! - heart failure
- metoprolol in symptomatic heart failure (reduced EF) - has to be stable!
- same reason as above: decreases oxygen consumption
- hyperthyroidism
* high SNS tone of hyperthyroidism can be blocked by beta blockers - glaucoma
- migraine
beta blockers: adverse CARDIAC events
- drug rebound
- can precipitate acute MI in pt with CAD
- ventricular tachyarrhythmia
- CHF exacerbation (if pt in acute decomp heart failure)
- bradyarrythmia (pt has AV conduction defect →→→ serious bradyarrhythmia!)
beta blockers: adverse NONCARDIAC events
- bronchoconstriction
- worse glycemic control in DM2
- depression, fatigue, sexual dysfx (low risk)
- affects lipid metabolism
- weight gain
beta-adrenergic antagonists
non-selective drugs and hallmarks
NONSELECTIVE BETA ANTAGONISTS
- propranolol - prototypical beta blocker
- pindolol - partial agonist activity
- nadolol - v LONG duration action
- timolol - opthalmic, along with betaxolol, carteolol
summary table
