4 Adrenergic Blocking Agents Flashcards
What do we mean when we say that the effect of an adrenergic blockade depends on the prevailing tone?
An antagonist won’t have an effect unless there is an agonist present (b/c there has to be something to block)
Things that help predict the effect of adrenergic antagonists?
Effect of blockade will depend on selectivity for alpha and beta receptors
Will depend on degree to which a particular tissue is innervated by alpha and beta
If alpha blocked, beta will dominate
If beta blocked, alpha will dominate
Are most alpha antagonists reversible or irreversible?
Reversible! • Phentolamine •Prazosin, terazosin, doxazosin • Tamsulosin • Labetalol, carvedilol
The only irreversible one? Phenyoxybenzamine
For the most part, an alpha blockade will cause …
Decreased vasoconstriction in arteries and veins, lowering peripheral vascular resistance, especially when standing
Reflex tachycardia common (decreased BP —> baroreflex —> decreased vagal input)
_____________ is common with an alpha blockade because alpha1 receptors in veins are antagonized —> low pressure
Postural hypotension
Compensatory vasoconstriction upon standing is blocked
Epinephrine reversal of an alpha blockade
Blocking alpha receptors exposes effect of beta stimulation —> dilation of blood vessels in skeletal muscle causes drop in BP and heart rate increases
Other alpha block effects
Miosis (radial muscles relax)
Nasal stuffiness (vasodilation in nasal mucosa)
Decreased resistance to urine flow (widely used for the treatment of BPH)
Phentolamine is a competitive _____________
A1 and a2 antagonist
Decreases peripheral resistance and BP, esp diastolic
Tachycardia likely (b/c baroreceptors reflex)
Other side effects: arrhythmia, myocardial ischemia, hypotension
Used rarely due to poor pharmacokinetics
IS used in HTN crises due to pheochromocytoma or MAO inhibitors, or to prevent necrosis after local infusion of alpha agonist (ie infiltrated pic lines)
Treatment for pheochromocytoma
Pheos get phenos
Either Phenoxybenzamine (or Phentolamine - but poor pharmacokinetics)
Phenoxybenzamine is a very long acting, irreversible _________
Non-specific alpha blocker
Tachycardia likely
Sympathetic tone determines effect
Used in PHEOCHROMOCYTOMA
Side effects: postural hypotension, tachycardia, nasal congestion, inhibition of ejaculation, hypotension
Prazosin (minidress) is a ___________ blocker
A1 selective
Lack of a2 block means less reflex tachycardia
Beneficial effects on lipids
Must be given twice daily (terazosin/doxazosin have better pharmacokinetics and can be taken 1/day)
First dose phenomenon with Prazosin
Postural hypotension and syncope 30-90 min after 1st dose
Have patient take 1st dose at bedtime, so lying down for some hours
May also happen when dose increased or second drug added
Can also have orthostatic hypotension (don’t get out of bed too quickly), dizziness, nasal stuffiness
If you have a dude with HTN and BPH, what should you give him?
Prazosin! Or another zosin
A good option for men who have had postural hypotension with other alpha blockers?
Tamsulosin
A1a selective (important for prostate) while A1b is the blood vessels - so Tamsulosin has little effect on BP
Main side effect is difficulty ejaculating
What herbal supplement that men with limp dicks try is likely to interfere with the effect of clonidine?
Yohimbine
Blocks alpha2, increases NE release, increases BP and HR
Can be dangerous in men with untreated or uncontrolled HTN
Beta blockade work by
Decreasing HR and contractability —> decreased o2 demand and CO and decreased renin release from kidney
Lowers BP when used chronically, greatest effect when sympathetic tone high
Short term use of beta blocker for BP reduces CO but…
Long term administration actually decreases BP as peripheral resistance returns to pre-drug value
Beta blockers can be fatal in patients with …
Severe asthma/COPD (though a B1 selective drug may be tolerated)
Effect of beta blockade on the eyes
Lowers intraocular pressure by decreasing formation of aqueous humor
Topical use in glaucoma
How do beta blockers affect the liver?
Inhibits glycogenolysis - masks symptoms of hypoglycemia in insulin-dependent diabetics and makes it harder to recover from hypoglycemia (b1 selective antagonists have less effect on glucose)
Inhibits lipolysis in fat cells
Increases VLDL and decreases HDL
K+ uptake into muscle blocked
Beta blockers can have “membrane stabilizing” effect, meaning,
Sodium channel blockade (true of several of them)
Some are used as anti-arrhythmic agents
Propranolol is a competitive antagonist of ___________
B1 and B2 receptors
Decreases HR, contractility, renin, lipolysis, glycogenolysis
Can also be used as a local anesthetic
Oral, low bioavailability so dose varies, can enter CNS (sedation likely)
Why isn’t propranolol a first line treatment for HTN anymore?
Decreases BP with chronic use - better drugs now
But it DOES decrease mortality following MI and improves symptoms of angina (because decreases O2 demand)
Can also be used as an antiarrhythmic in obstructive CM and early CHF
Other weird things about propranolol
Decreases HR in hyperthyroidism
Prevents migraines
Decreases portal vein pressure, reduced bleeding in cirrhosis
Used to decrease sympathetic symptoms of stage fright
Used in familial tremor
Weird, huh?
Major side effect of propranolol
BRONCHOCONSTRICTION - don’t use in asthmatics or COPD patients
Can also exacerbate late CHF
Sedation, fatigue, depression common
Caution in insulin-dependent DM
Lipids
Abrupt d/c of propranolol can cause …
Arrhythmia
___________ have an additive effect with propranolol in terms of AV block
Calcium channel blockers
Timolol is a non-selective B blocker used in…
The eye tor treat glaucoma
Caution in asthmatics! May be absorbed systemically and that’s bad
Nadolol is …
Long acting, doesn’t get into the CNS
Sotalol is an
Antiarrhythmic
Meds that cause a B1 selective blockade?
Metoprolol, Atenolol, Bisoprolol
Effects primarily on the heart (decreased HR, contractility, o2 demand) but also decreases renin
Overall, will decrease BP, used for treatment of HTN
Increased life expectancy with use after MI
Can also be used for migraine prophylaxis
Better exercise tolerance and safer in DM
Nebivolol (Bystolic)
Highly B1 selective
Produces vasodilation due to NO release
Better effect on BP, fewer side effects
Less effect on lipids, glucose than other beta blockers
Esmolol (Brevibloc)
VERY short acting beta1 blocker - rapidly degraded by esterases in RBCs
Given IV when you want a short effect - onset rapid and terminates quickly
Infusion may be continued as long as necessary
Med used in CHF/post MI that blocks both B and A receptors
Carvedilol
It’s sister drug Labetalol used IV for HTN emergency but can cause hepatic problems
