What are some non-selective alpha adrenoceptor blocking agents?
(2)
Phenoxybenzamine
Phentolamine
What are the alpha-one selective adrenergic blocking agents?
(2 bolded, 4 total)
Prazosin
Terazosin
Tamsulosin (a1A)
Doxazosin
What are the non-selective beta blocking agents?
Propranolol (Prototype)
Nadolol
Timolol
*Pindolol
*Carteolol
What are the cardioselective beta blocking agents?
(4 all bolded)
Atenolol
*Acebutolol
Metoprolol
Betaxolol
What is a short acting beta blocking agent? When is it useful?
Esmolol - useful in surgery
What are two drugs that target both alpha and beta blockers?
(2 both bold)
Labetalol
Carvedilol
Describe the binding activity of phenoxybenzamine!
Irreversible to a1 & a2
Desccribe the binding of phentolamine
prototype reversible Alpha 1 and 2 blocker
Characterize the targeting of prazosin?
selective alpha 1 blocker
Characterize tamsulosins targeting!
selective alpha1A blocker
What type of pharmacodynamics does phenoxybenzamene have?
noncompetitive
What kind of pharmacodynamics does phentolamine have?
Competitive, reversible
Alpha blockers are antagonists, describe their intrinsic activity!
They have no intrinsic activity (haha), but do produce pharmacological changes.
Phenoxybenzamine (dibenzyline) binds covalently to alpha 1 and alpha 2 receptors. How is its effect terminated?
By metabolism and new receptor synthesis
What alpha blocker might be shown here?
Phenoxybenzamine
What impact does phenoxybenzamine have on vasculature? What is a related significant side effect?
Dependent on the degree of sympathetic tone. i.e., blocks the effects of endogenous NE. Reduces blood pressure. Significant side effect is Orthostatic hypotension.
What is the effect of phenoxybenzamine on the cardiac system?
Reflex tachycardia from reducing BP, which enhances NE release. Because alpha-2 receptors on adrenergic nerves are also blocked, this further increases NE release at the heart, where it can act on beta-1 receptors.
What is the effect of phenoxy benzamine on the CNS?
lipophilic agent which can cross the blood brain barrier. Nausea, vomiting and weakness may be signs of non-specific effects.
In what cases might one prescribe phenoxybenzamine?
- Pheochromocytoma: Pre-operative management to treat vascular effects of high circulating catecholamines. Always in combination with a beta blocker.
- Peripheral Vascular Disease. Raynaud’s syndrome where sympathetic tone to peripheral vasculature is high. Acrocyanosis from frost bite.
Phentolamine and tolazoline are non-selective for alpha 1 and 2 receptors. What other receptor are they known to activate, causing adverse effects?
Histamine
Name four things phentolamine is used for clinically! (one no longer)
- Pheochromocytoma. Acute hypertensive crisis.
- Clonidine withdrawal
- Treat necrosis due to vasoconstrictors such as NE and phenylephrine.
- For erectile dysfunction (ED) – has been replaced by drugs with less severe side-effects.
What side effects would you expect from phentolamine? (4)
tachycardia
nausea
diarrhea
orthostatic hypotension
Alpha-1 selective blockers cause less reflex tachycardia than non-selectives, and you may see syncope. Agents include prazosin, terazosin, doxazosin. What are 2 uses for these drugs?
Hypertension
benign prostatic hypertrophy
Discuss how tamsulosin binds alpha-1 subtypes.
What are the effects it causes via each?
Competitive alpha blocker; binds alpha1A with little alpha1B binding
alpha1B - Very limited vascular effects, but alpha1A highly efficacious in benign prostatic hyperplasia (BPH).
What is the prototype nonselective beta receptor antagonist?
Propranolol
What are the drugs that are “like” propranolol?
Timolol
Pindolol
Nadolol
What is the prototype cardioselective B blocker?
Atenolol
What are the drugs that are “like” atenolol?
Acebutolol
Metoprolol
Is propranolol lipid soluble?
Highly lipid solubility - will see some drowsiness
What effect does propranolol have on the heart?
Decreases HR, cardiac output, and pacemaker activity
What does propranolol do to the blood vessels?
Slow developing decrease in peripheral resistance. Possibly due to: central reduction in sympathetic tone and reduction in renin release (beta-1 effect)
What does propranolol do in the lungs? Any problems here?
Bronchial Smooth Muscle
- Block sympathomimetic bronchodilation
- precaution or contraindication in asthma & COPD
What are the metabolic effects of propranolol? Anything to keep in mind here?
- Blocks beta receptor effects on lipolysis and glycogenolysis.
- May mask signs of hypoglycemia, e.g., tachycardia, BP changes. May potentiate insulin-induced hypoglycemia.
Propranolol has a quinidine-like effect, what is it?
“Membrane stabilizing activity”, decreased cardiac excitability
Propranolol is well absorbed on oral admin. to what degree is it impacted by first pass metabolism?
75% may be inactivated. (highly variable), must titrate the dose upward for each individual.
Name 9 clinical applications of B blockers!
- Angina pectoris
- HTN
- Migraine headache
- Arrhytmias
- pheochromocytoma
- thyrotoxicosis
- adjuctive treatment for anxiety (panic) attacks
- MI and post MI phrophylaxis
- CHF
Why do B blockers help with angina pectoris?
decrease cardiac work and O2 consumption
What do B blockers do to help with HTN?
Decrease CO
Slow decrease in peripheral resistance due to blockade of renin release.
What are some arrythmias that B blockers are used for?
Sinus tachycardia and supraventricular ectopic beat.
Why are beta blockers used in thyrotoxicosis?
Hyperthyroid patients have increased B receptor sensitivity
How do beta blockers help with MI and post-MI prophylaxis?
protects against arrhythmias & limits infarct size
5-12 days after MI, reduces O2 demand & spread of infarct zone
Beta blockers have been shown to have dramatic results in CHF patients, with mortality reductions of 65%, 34% and 33% for carvedilol, metoprolol and bisoprolol, respectively. Prevent heart failure in 50% and decrease risk of stroke by 38%. What do they do to make this possible?
Beta blockers increase LVEF,
cause beneficial remodeling of heart
What are side effects associated with propranolol?
(7 common, plus 3 severe)
Common:
- dizziness
- fatigue
- diarrhea
- constipation
- nausea
- depression
- bizarre dreams
Severe
- purpura
- rash
- fever
Propranolol interferes with SGOT and BUN tests, and chronic use for HTN can lead to what?
Increased VLDL & HDL
Why must you use caution in providing B blockers to diabetics?
Ininhibits compensatory response to hypoglycemia (glycogenolysis with glucose release) masks signs of hypoglycemia (tachycardia) that are important “clues” to diabetic patient
Why are B blockers contraindicated in patients with most asthmatics and COPD
Blocks B2 bronchodilation
What can happen if a patient abruptly discontinues B blockers? Explain why this happens.
rebound hypertension, anginal attack & possibly MI if drug suddenly withdrawn after chronic therapy.
Because Beta receptor synthesis is increased by beta blocker use. Example of receptor up-regulation.
What are some noteable contraindications for B blockers?
Acute treatment of decompensated heart failure
2nd and 3rd degree heart block
cardiogenic shock
As you’ve seen mentioned a couple times, B blockers can be used for glaucoma, which one would be best? How does it do this?
Timolol
reduces aqueous humor production
What is metoprolol selective for?
B1 receptors. At high dose can block B2 though
What are two common uses for metoprolol?
HTN and CHF
Are B1 selective blockers contraindicated in asthmatics?
Yes, d/t potential at higher doses to block B2
Esmolol is selective for what?
B1
Under what circumstances is Esmolol useful?
- Used as IV infusion for peri-operative tachycardia and hypertension, arrhythmias
- Used in electroconvulsive therapy
What receptors does labetolol target?
Selective a 1 blocker
Nonselective b1 & b2 blocker
Carvedilol is a blocker of?
Nonselective b-blocker and a-blocker
Is carvedilol lipid soluble?
Yes
