PPT 10 Adrenergic Antagonists Flashcards
What are the effects of alpha(α) blockers on blood pressure and heart rate
alpha-blockers inhibit the α1 receptors on blood vessels, causing vasodilation and reduced BP
No direct effects on HR but Reflex Tachycardia can occur by body trying to compensate
What effect will occur if alpha-blocker given in absence of an agonist?
Without an agonist to block, an α-blocker will have little to no immediate effect on blood pressure or heart rate because it is not counteracting the activation of α-adrenergic receptors
What effect will occur if alpha-blocker given in presence of an agonist?
Normally, an agonist like norepinephrine would bind to α1 receptors on blood vessels, causing vasoconstriction, which raises blood pressure. An α-blocker prevents this binding, leading to vasodilation and a reduction in blood pressure
What is the mechanism of action of alpha antagonists?
bind to alpha receptors and block the normal endogenous ligand
What are the two types of alpha antagonists?
Reversible - competitive, safer
Irreversible - non-competitive, form covalent bonds; recovery requires new receptors
What are the examples of reversible alpha antagonists?
Phentolamine, Tolazoline, Prazosin, and Labetalol
What is an example of an irreversible alpha antagonist?
Phenoxybenzamine
Non-selective α antagonists are useful in the treatment of _______
pheochromocytoma (tumor that results in over-production of epinephrine)
Drugs that end in -osin are used to treat _______ and ______
Hypertension and benign prosthetic hyperplasia
Alpha 2 antagonists have _______ effect clinically
little - Ergotamine and Yohimbine
How do primary dopamine receptor antagonists work? Name the 2 examples given in lecture
decrease dopamine in CNS, reduce delusions/anxiety
Chlorpromazine and Haloperidol
How will alpha selectivity affect HR in alpha antagonists?
Mixed antagonist - increase HR
Alpha 1 selective - no affect on HR
What are the different types of competitive antagonism for beta blockers?
- Most are pure antagonist
- Some partial agonists
- Some inverse agonists
ADME of beta blockers
- A: well absorbed orally; peak 1-3 hours
- D: rapid; most half-lives 3-10 hours
- M: major first-pass metabolism – low bioavailability
- E: varied mechanisms depending on the agent
Change in FORCE of muscular contractions
Inotropic
Change in RATE of muscular contractions
Chronotropic
Pressors vs depressors
- Pressors – vasoconstriction (raise BP)
- Depressors – vasodilation (lower BP)
What effect can B-blockers have on respiratory system?
Increased airway resistance, inhibits B2 vasodilation
What effect can B-blockers have on the eye?
decrease IOP by decreasing production of aqueous humor
what effect can B-blockers have on metabolism?
inhibits lipolysis
inhibits glycogenolysis
chronic use inc VLDL, dec. HDL
Which Beta-blockers are best for patients with COPD and/or diabetes? why?
metoprolol (Lopressor) and atenolol (tenormin)
Mainly B1 specific, no effect on B3
What are the clinical indications from lecture that B-blockers are used for?
HTN, ischemic heart disease, cardiac arrhythmia, obstructive cardiomyopathy, dissecting aortic aneurysm
Which B-blocker are all B-blockers compared to?
Propanolol
What effect can B-blockers have on the heart?
negative inotropic and negative chronotropic
What effect can B-blockers have on skeletal blood vessels?
opposes B2 mediated vasodilation, increasing peripheral resistance acutely, and decreases peripheral resistance chronically
What effect can B-blockers have on the kidneys?
Suppression of renin-angiotensin (beta receptors in the kidney)
List the mechanism of action and clinical uses of phentolamine
Alpha blocker
Competitive antagonist of α1 and α2, reduction in peripheral resistance and causes cardiac stimulation
Treatment of HTN linked to pheochromocytoma and for male erectile dysfunction
List the mechanism of action and clinical uses of phenoxybenzamine
Alpha blocker
Treatment for pheochromocytoma, marked effect on orthostatic BP
Covalently bound (irreversible), somewhat selective for α1, inhibits NE reuptake
List the mechanism of action and clinical uses of labetolol
mixed alpha and beta blocker, used to treat HTN
List the mechanism of action and clinical uses of drugs that end in -osin
Alpha blocker
Prazosin, Terazosin, Doxazosin, Alfuzosin, Tamulosin (Flowmax)
Treatment of HTN and BPH, α1 selective so no tachycardia
What are alpha 2 selective blockers used for?
Yohimbine and Ergotamine - little use clinically, possible future drug target
What is the mechanism of action of propanolol?
mixed beta antagonist, extensive first-pass metabolism
How is the makeup of labetalol different?
racemic mixture, 2 centers of asymmetry = 4 different isomers - 2 are completely inactive, 1 is alpha blocker, 1 is beta blocker
Which beta blocker is good for intraoperative tachycardia?
Esmolol. - ultra short-acting and beta 1 selective
What are the partial beta agonists?
- Nebivolol - selective β1 antagonism
- Nadolol - long duration of action, nonselective
- Pindolol, Acebutolol, Carteolol, Penbutolol - treat HTN and angina; less likely to cause bradycardia and cholesterol abnormalities
What are the clinical indications for alpha blockers?
HTN, treatment of pheochromocytoma (tumor that results in over-production of epinephrine)
What are the adverse effects of alpha blockers?
- Cardiac stimulation
- Abdominal pain, N/V/D
- Postural hypotension
What are the adverse effects of beta blockers?
- Bradycardia
- Rash, fever, other allergies in susceptible
- CNS effects - sedation, sleep disturbances, depression
- Worsening of asthma
- Hypoglycemia in diabetics
- Discontinue use gradually
Explain the following sentence: Phentolamine converts a pressor (epinephrine) into a depressor. Describe the effects of phentolamine by itself vs with epinephrine
Phentolamine is a competitive antagonist - not much change by itself
Epinephrine before phentolamine - presser effects
Epinephrine after phentolamine - depressor effects
