Adrenergic Antagonists Flashcards
What are adrenergic antagonists also called?
Sympatholytics or adrenergic blockers
Why are alpha-antagonists generally unsuccessful at sustained reduction in blood pressure?
Although they block the peripheral vasoconstriction, this causes a reflex tachycardia which cannot be stopped via presynaptic alpha-2 binding (this is also blocked)
What is the mechanism of phenoxybenzamine?
irreversible, nonselective covalent binding to alpha1 and alpha2 receptors, leading to a blockade for about 24 hours
What does epinephrine do when administered with phenoxybenzamine? What about isoproterenol + phenoxybenzamine?
Causes a decrease in blood pressure -> all the alpha effects are blocked, but beta-2 remains.
Isoproterenol -> no change (beta agonist only)
norepinerphine -> decreased action (alpha agonist only + b1)
What is phenoxybenzamine used for?
Pheochromocytoma to prevent hypertensive crisis, or treatment of Raynaud’s disease (blood vesse necrosis due to sympathetic overaction)?
What are the major side effects of phenoxybenzamine?
Orthostatic hypertension (due to loss of venous tone), reflex tachycardia (be cautious with cardiovascular disease patients), and sexual dysfunction
What drug is the REVERSIBLE brother of phenoxybenzamine?
Phentolamine -> competitive antagonist of alpha1 and alpha2
Give three clinical uses of phentolamine?
- Short-term management of pheochromocytoma
- Prevention of dermal necrosis at norepinephrine injection site
- Treatment of hypertensive crisis from clonidine withdrawal or tyramine-foods + MAOI+ cocaine
In what patients are phentolamine + phenoxybenzamine contraindicated in why?
Patients with arrythmias and anginal chest pain, or coronary artery disease -> reflex tachycardia may cause MI
List the clinically important alpha1 blockers.
Prazosin (think of praying opera singer)
Terazosin
Doxazosin
Tamsulosin - the special one
Osin = think of opera singer
What are prazosin, terazosin, and doxazosin used to treat and why?
Hypertension -> work better than the nonselective alpha agonists because they do not increase cardiac output or decrease renal blood flow.
What is tamsulosin primarily used to treat and why?
Used to improve urine flow in benign prostatic hypertrophy (BPH) because it selectively blocks smooth muscle receptors in bladder neck and prostate, relaxing them and allowing urine flow.
Receptors in the bladde (targeted by tasmsulosin)r: Alpha-1-A.
Receptors in blood vessels (not targeted by tamsulosin): Alpha-1-B.
What effect do we worry about in patients taking alpha-blockers for the first time?
The “first-dose” effect which can cause severe orthostatic hypotension -> give less of a dose and adjust later on.
What are other adverse effects of alpha-blockers? Can they be used as monotherapy?
Lethargy, headache, sexual dysfunction (alpha blockade), tachycardia possible (less than phentolamine or phenoxybenzamine)
Should not be used as a monotherapy for hypertension
What is the mechanism of action of yohimbine, and what was it previously used for?
Alpha-2 antagonist
Previously used to increase sympathetic effects -> sexual stimulant, treatment of erectile dysfunction
Not used anymore due to cardiovascular effects
Why are beta-blockers typically preferred over alpha-blockers for treatment of hypertension?
They do not induce postural / orthostatic hypotension because they do not block the alpha receptors
What is the mechanism of action of propanolol?
Beta-adrenergic antagonist, blocking beta1 and beta2 with equal affinity (exact opposite of isoproterenol)
What are the cardiovascular actions of propanolol?
Negative inotropic and chronotropic effects, with depression of SA and AV node activity. During exercise, the heart rate will not increase as expected, so the patient will become fatiguable
Why does propanolol initially cause peripheral vasoconstriction?
- Blocks the beta-2 mediated vasodilation in skeletal muscles
- Reduction in cardiac output leads to decreased blood pressure and subsequent peripheral vasoconstriction
This goes away with long-term use and TPR will drop, causing a general drop in BP
What patient population is propanolol absolutely contraindicated in?
COPD and asthma -> blocking beta-2 can cause bronchospasm
What is the metabolic worry with propanolol?
Since it blocks the beta-2 glucagon action, as well as glycogenolysis, it can lead to hypoglycemia. Patients on insulin must be especially careful with their dosing because it will potentiate the effects of insulin
What is the primary mechanism by which resting BP is dropped by propanolol?
Decreased TPR in long-term use is one, but another big one = decreased renin release from kidney (beta-1 receptor is responsible for increasing renin, alpha-1 decreases)
Why is propanolol good for angina pectoris?
Decreases oxygen demands of myocardium, thus reducing chest pain -> drug of choice in stable angina
Why should propanolol be given post-MI?
Reduces effects of circulating catecholamines, preventing increased oxygen demand on an already ischemic heart -> reduces mortality.
Should also be used prophylactically post MI -> proven to prolong life post-MI
Why is propanolol good for headaches?
Very lipophilic, penetrates CNS well, reduces hypertension in the CNS
Other beta blockers can be used for these migraines as well
What is one last metabolic condition which propanolol can be used for?
Hyperthyroidism -> prevents widespread sympathetic stimulation which occurs in it, can has been shown to protect against cardiac arrythmias
What must you keep in mind when stopping a patient who has been using propanolol?
It must be tapered -> never stopped quickly
Stopping abruptly can cause cardiac arrhythmias which may be severe
Do Beta-blockers cause sexual dysfunction? Why?
Yes, and we don’t know why!
What happens to the lipid profiles of patients on propanolol and why?
Beta-3 receptors are also blocked, so patient’s lipids get messed up. LDL goes up, HDL goes down, and triglycerides go up
-> much less pronounced effect with selective B1-antagonists like metoproll
What are the CNS effects of propanolol? How can this be decreased?
Exercise intolerance (decreased exercised reflex), lethargy, weakness, short-term memory loss, vivid dreams
Decreased by beta-blockers which are less lipophilic -> i.e. atenolol
What drugs are known to inhibit the metabolism of propanolol and thus increase its effects?
SSRIs and cimetidine (antihistamine)
Aside from acute glaucoma episode, why are beta-blockers preferred for long-term management of glaucoma?
They do not affect the ability of the eye to focus for near vision (accommodation) and do not change pupil size (cholinergic agonists like pilocarpine cause miosis)
What is the name of the non-selective beta-antagonist of choice for the eye?
Timolol - long-lasting (12-24 hours)
Blocks beta1 and beta2 receptors
What is Nadolol used for?
It is a nonselective beta agonist but very very long-lasting. Used for hypertension in some cases (like propanolol)
What are the cardioselective beta-blockers and how do they work? List 5.
Block beta1 receptors at therapeutic concentrations, without blocking beta2 until much higher concentrations
A-Beam
- Atenolol
- Betaxolol / Bisprolol
- Esmolol
- Acebutolol
- Metoprolol
What is esmolol primarily used for?
To control blood pressure or heart rhythm during diagnostic procedures, due to its short half-life
Why is metoprolol preferable to propanolol in long-term hypertension management?
Does not interfere with pulmonary function, peripheral resistance, and carbohydrate metabolism (all beta-2 mediated)
What special population are cardioselective beta-blockers used to treat hypertension in?
Those with compromised pulmonary function -> COPD / Asthma
What two other major conditions are cardioselective beta-blockers used for?
Chronic stable angina (1st line), and management of chronic heart failure (reduction of oxygen demand)
Also post-MI (like propanolol)
What are the mechanisms of action of acebutolol and pindolol (they are related)?
Acebutolol -> cardioselective B1 antagonist
Think of plastic bugle
Pindolol -> nonselective Beta bl
ocker
Think of pin poking heart blood
They are both partial agonists of Beta1 and Beta2 and are said to have intrinsic sympathomimetic activity (ISA)
Why might partial agonist blockers (beta blockers with ISA) be useful?
- Decreased reduction in cardiac rate and cardiac output
- Decreased metabolic effects (do not decrease plasma HDL levels or carb metabolism)
-> typically used in hypertensive patients with moderate bradycardia (less pronounced drop in HR with these drugs)
When are Beta-blockers with ISA not used?
Those with stable angina or arrhythmias (due to partial agonist effect)
What two drugs stop supraventricular tachycardias by slowing AV conduction velocity?
Esmolol and Propanolol
What are the beta-blockers that are also alpha-1 blockers and why is this desirable?
Labetalol and carvedilol
Desirable because there is no initially peripheral vasoconstriction like the other beta-blockers
What is the primary indication of lebatolol?
Pregnancy-induced hypertension (eclampsia) and hypertensive emergencies
What is carvedilol used for and with what other drugs?
Stable chronic heart failure, in combination with metoprolol and bisoprolol
What is the side effect of concern with labatolol and carvedilol?
Like the alpha-blockers, orthostatic hypotension
Where are pretty much all the beta-blockers metabolized?
The liver -> pretty lipophilic
