Anti-Adrenergics Flashcards
What kind of drugs are drugs ending in -olol
beta blocker
Phenoxybenzamine: alpha or beta blocker?
alpha blocker somewhat selective for A1 over A2 irreversible
Phentolamine: alpha or beta blocker?
alpha blocker non-selective: so A1 and A2 reversible
Atenolol: alpha or beta blocker?
selective B1 blocker
Esmolol: alpha or beta blocker?
selective B1 blocker
Prazosin: alpha or beta blocker?
selective A1 blocker reversible
What are Clonidine and Methyldopa?
A2 agonist acts as anti-adrenergic
physiological effect of prazosin
A1 blockade dec BP get reflex tachycardia
Why do you get reflex tachycardia with prazosin and phentolamine?
prazosin blocks A1 receptors/phentolamine blocks A1 receptors…get vasodilation…dec BP…baroreceptors activate vasomotor center…inc output signaling from vasomotor center…NE released…already got A1 receptors blocked from prazosin so NE acts only on heart…get tachycardia *remember phentolamine non-selective alpha blocker so also blocks A2 which will give you even greater tachycardia
Why is the duration of action longer for phenoxybenzamine?
irreversible alpha blocker duration of action 24 hours B/c must synthesize new receptor to recover A1 effect
physiological effect of phentolamine
reversible, non-selective alpha blocker A1 blockade…dec BP…reflex tachycardia A2 blockade…prevents feedback inhibition by released NE…causes more NE to be released onto B1 receptors in heart…even GREATER tachycardia than with selective blocker
So difference between selective (prazosin) and non-selective (phentolamine) alpha blocker?
tachycardia is WORSE with a non-selective alpha blocker than with a selective A1 blocker
Why even use non-selective alpha blocker (phentolamine) when get worse/double bad tachycardia?
phentolamine and phenoxybenzamine are used in combo with propranolol for pheochromocytoma (which is a tumor that dumps Epi and NE into system) management
What is prazosin used for?
HTN
What can be used for benign prostatic hypertrophy?
phenoxybenzamine, prazosin, and terazosin relax smooth muscle in bladder, prostate capsule, and prostatic urethra which improves urinary flow
Toxicity and side effects of alpha blockers
reflex tachycardia in both selective (prazosin) and non-selective (phentolamine) alpha blockers but worse with non-selective
postural hypotension is caused by A1 blockade
nasal stuffiness
inhibition of ejaculation
What is Epi reversal?
as concentration of Epi goes up at first BP is dec due to Epi’s effects on B2 but as inc Epi concentration more BP inc due to Epi’s effects on A1 (bi-phasic effect)
What happens when Epi is administered in the presence of an alpha blocker?
no pressor response of BP, don’t get bi-phasic effect, just get depressor response of BP, just get dec in BP due to effects on B2
Where are B1 receptors located?
heart
Where are B2 receptors located?
lungs
blood vessels
Do you ever want to be selective and block only for B2?
NO, causes bronchoconstriction and possible bronchospasm no particular reasons to want to antagonize B2 receptors
Since don’t want to be selective for only B2 when say selective for B1 only relatively so
the best selectivity achieved is about 100 fold see picture
What is Propranolol?
non-selective beta blocker both B1 and B2
cardiac effects of non-selective beta blockers (propranolol)
cardiac effects due to blockage of B1
dec HR
dec cardiac output ( more pronounced during exercise)
dec conduction velocity
dec myocardial oxygen demand
dec spontaneous rate of depolarization
vascular and BP effects of non-selective beta blockers (propranolol)
B2 block may inc TPR slightly
B1 block dec in plasma renin…so dec BP
net effect is dec in BP
MECHANISM: dec cardiac output…dec in plasma renin…dec in sympathetic tone via effects in CNS
metabolic effects of non-selective beta blockers (propranolol)
no effect on plasma glucose levels in normal person
does slow recovery from hypoglycemia in diabetics (less of a problem with B1 selective)
inc plasma concentration of triglycerides and VLDL
dec plasma concentrations of HDL
respiratory tract effects of non-selective beta blockers (propranolol)
blocks B2 so airway resistance increased can be life threatening to asthmatics
What is Timolol?
non-selective beta blocker used in glaucoma
although non-selective used for B1 actions in the eye
Drug of choice to treat glaucoma?
Timolol
How does Timolol treat glaucoma?
dec aqueous humor produciton b/c B1 is responsible for production of aqueous humor in the eye
Atenolol and Esmolol are both selective B1 blockers. When do you use Esmolol over Atenolol?
in emergency procedures because Esmolol has 8 min half-life
cardiac effects of selective B1 blockers (Atenolol)
same as non-selective beta blockers:
cardiac effects due to blockage of B1
dec HR
dec cardiac output ( more pronounced during exercise)
dec conduction velocity
dec myocardial oxygen demand
dec spontaneous rate of depolarization
Is there more or less danger of respirator side effects with selective B1 or non-selective beta blockers?
less danger with selective B1 blockers
Are beta blockers really “selective” at high doses?
NO
Remember card with picture where when 100% B1 blockage saw 50% B2 blockage
what do mixed alpha and beta blockers end with?
-alol or -ilol just not -olol (that’s beta blockers)
What are therapeutic uses of beta blockers?
*recent reports suggest B blockers may inhibit cancer progression*
HTN (usually with diuretics and vasodilators)
Cardiac arrhythmias
Angina
Prophylaxis of migraine
Early in MI reduces high sympathetic tone
Prophylaxis to dec mortality after MI
Glaucoma
Performance anxiety
Pheochromocytoma (with alpha blocker)
Heart failure (carvedilol)
Side effects and toxicity of beta blockers
B1 block= dec cardiac output, heart block, bradycardia
B2 block= bronchoconstriction
CNS: depression and lethargy
Give example of a drug that works at presynapse
Guanethidine and Reserpine
How does Guanethidine work?
enters via the NET (revolving hotel door) and concentrates in vesicles and depletes NE over time
Therapeutic uses of Guanethidine
historically but not any more as antihypertensive used therapeutically as a BOARD QUESTION
side effects of Guanethidine
postural hypotension
diarrhea
impaired sexual function
(all related to peripheral antiadrenergic actions)
How does Reserpine work?
enters terminal, blocks VMAT, causing depletion of NE over time
Therapeutic uses of Reserpine
historically used for hypertension
Side effects of Reserpine
CNS: depression
Peripheral: orthostatic hypotension
Mechanism of action of A2 agonists
A2 receptors at pre and post synaptic sites in the brain and block sympathetic outflow (A2 agonists acting on the presynaptic A2 receptors to inhibit NE release)
increases neg feedback = less NE released
functionally working as anti-adrenergic
Give two examples of A2 agonists
Clonidine and alpa-methyl-dopa and dexmedetomide
EXAM QUESTION: What is the difference between the two A2 agonists Clonidine and alpha-methyl-dopa?
Cloninine works directly at A2 receptors
alpha-methyl-dopa must be metabolized to alpha-methly-NE
Therapeutic uses of Clonidine
essential HTN
reduction of unpleasant side effects associated with opioid withdrawal
ADHD
open angle glaucoma (apraclonidine: also dec production of aqueous humor)
Therapeutic uses of alpha-methyl-dopa
essential HTN
safe in pregnancy
toxicities and side effects of A2 agonists (Clonidine and alpa-methly-dopa)
dry mouth
sedation
hypertensive crisis may occur upon abrupt withdrawal from Clonidine
high incidence of autoimmune response with alpha-methly-dopa (positive Coombs test/antiglobulin test)
