Adrenergic antagonists Flashcards
What is a reversible alpha antagonist?
Competitively inhibits the binding of physiological agonist; example: phentolamine
Graph –causes more NE needs to be added to get the same effect
What is an irreversible alpa antagonist
Covalently binds to the receptor; example: phenoxybenzamine
Inactivates the R and only way to get more R is to make new
Graph- causes a reduced max response– no matter how much NE added
What are the cardiovascular effects of alpha antagonists?
Hypotension; can cause orthostatic hypotension and reflex tachycardia. Nonspecific agents (alpha 1 and 2) are more likely to cause tachycardia
What happens with a high dose of epi
Alpha response predominates; resulting in increased blood pressure.
If you give an alpha antagonist prior to epinepherine
The effect of epinephrine at beta receptors will prevail and blood pressure will fall.
Why do we get rebound hypertension due to abrupt withdrawal on alpha antagonists
Due to upregulation of receptors, during continued administration of drug
What is the action of alpha-1 receptor antagonists at urethral sphincters and prostate?
These receptors cause contraction, so blockade can facilitate flow in patients with urinary retention.
Additional effects of alpha antagonists; eye
particularly alpha-1 (allowing parasympathetic to predominate) effects the radial muscle produces miosis
Additional effect of alpha antagonists; GI
Blockade of these receptors removes the relaxing influence of alpha receptors; causing hypermotility
Phenoxybenzamine
Non-selective, irreversible alpha blocker
- used for hypertension resulting from Pheochromocytoma -Raynaud’s
- adverse - tachy
Phentolamine
Non-selective alpha blocker used in hypertensive emergencies, has a short half-life
-adverse- tachy
Prazosin
Selective alpha 1 blocker
- used in mild hypertension
- less likely to cause tachy than phentolamine
Doxazosin
Alternatives to prazosin (alpha 1 antag) with longer half-lives
- used in BPH and mild hypertension
Tamsulosin
Selective alpha-1 blocker in prostate
-used in BPH
Yohimbine
Selective alpha-2 blocker
-used for postural hypotension and occasionally impotence
Pharmacokinetics of B blockers
Low bioavailability due to significant first pass metabolism; requiring dose titration per patient.
- Possible high clearance due to extensive metabolism in the liver
- polymorphisms cause some patients to be poor metabolizers leading to elevated concentrations.
What are the cardiovascular effects of B blockers? What happens with abrupt withdrawal
Bradycardia
- decreased contractility and excitability
- Abrupt withdrawal can cause rebound hypertension or myocardial infarction (possibly due to upregulation of receptors).
Renin release
Beta-1 stimulation causes this, therefore beta-1 blockers will suppress leading to a decrease in angiotensin; this may lower blood pressure in patients with hypertension
What are the cardiovascular effects of blocking B-2
Early rise in blood pressure (due to unopposed alpha-1 mediated vasoconstriction); can cause cold extremities (not good for Raynaud’s)
Contraindications: B2 and bronchoconstriction
Particularly in patients with asthma, contraindicated
- beta-1 antagonist should be chosen, however receptor specificity is not complete
- class of drugs should be avoided
Which class of drugs should we use for glaucoma?
Beta blockers are among the most widely used; decrease production of aqueous humor
What happens when we block B2 receptors?
Inhibits epinephrine mediated stimulation of glycogenolysis; may cause bronchospasm, blocks tremor
What masks the symptoms of hypoglycemia in diabetes?
Beta blockade may block tachycardia and inhibit tremors; the primary reason these drugs are problematic in diabetic patients
What do unopposed alpha-2 stimulation with non-specific beta blockers do on lipids?
Inhibit the hormone sensitive lipase; increase VLDL and decrease HDL; altering HDL/LDL ratio
Beta blockers and membrane stabilization
May significantly contribute to toxicity by prolonging QRS duration and impair cardiac conduction; blocks myocyte sodium channels
Pindolol & Acebutelol
Have beta agonist properties (partial agonist); weaker than catecholamines, demonstrate less bradycardia, slight vasodiation and minimal change in lipids: intrinsic sympathomimetic activity
-treats hypertension
What are the CNS effects of B blockers?
Cause dizziness, fatigue, depression and sexual dysfunction; more hydrophilic drugs such as atenolol have fewer effects
Nadolol
Non-selective, long lasting (24 hr) beta blocker used in hypertension and angina
Metoprolol
Beta-1 selective blocker with high lipid solubility; membrane stabilizer, used widely for hypertension, angina and MI
Esmolol
Very short acting beta blocker (beta-1) used for intraoperative and postoperative hypertension, arrythmias
-good for critically ill
Labetolol
Non-selective for beta
- also blocks alpha-1
- used in severe hypertension
Carvedilol
Non-selective for beta blockade; mild alpha-1 block, used in CHF and hypertension
Guanethidine
Rarely used now, was used for hypertension
- acute effect is to release NE, chronic effect is to deplete NE from nerve terminals
Resperine
Inhibits vesicular transport (indirect acting adrenergic antagonist) so NE cannot be taken up into vesicles
- also rarely used, causes depletion of dopamine and seratonin in the CNS leading to depression
What are the clinical uses of B antagonists
Ischemic heart disease, arrhythmias, heart failure, glaucoma, hyperthyroidism, migraine, tremors; performance anxiety
What does the B-1 blockade cause?
Causes decreased heart rate, stroke volume and cardiac output
- decreased renin release
- decreased aqueous humor production
A BEAM
Beta-1 blockers: Acebutalol, Betaxolol, Esmolol, Atenolol, Metoprolol
Please Try Not being Picky (non-selective beta blockers)
Propranolol, Timolol, Nadolol, Pindolol
PAPA
Partial Agonist Pindolol Acebutolol
Clinical uses for alpha blockers for urinary obstruction
-BPH treated with alpha 1 antag (opens up the urethra)
alpha blockers treatment for peripheral vascular disease
- Sometimes prazosin or phenoxybenzamine used to treat vasospasm in peripheral circulation (Raynauds)
- Ca channel blockers preferred
- Behavioral modifications preferred. Like wearing gloves outside
Which alpha blockers would you use for chronic hypertension and what are the adverse effects?
- use alpha 1 blocker (like prazosin) but usually not used alone
- major adverse effect: orthostatic hypotension and palpitations
What alpha blockers would you give for pheochromocytoma?
- phenoxybenzamine mostly used– for several weeks before surgery to reverse chronic changes (from having incr NE circulating)
- May need to give B blocker also– but should ONLY be given AFTER alpha block to avoid alpha-1 vasoconstriction
What happens when you stim alpha-2 presynaptically?
Inh NE release
NE effect with alpha B blocker pretreats (bp)
NE doesn’t stim B-2 so no vasodilation
alpha block- lowers bp
Epi response with alpha and beta block pretreats (bp)
alpha- decr bp
beta- incr bp
Isoproterenol effect with alpha and beta block pretreats (bp)
- isoproterenol is beta agonist
- alpha- no effect
- beta- less of a decr in bp
Terazosin
Alternatives to prazosin (alpha 1 antag) with longer half-lives
- used in BPH and mild hypertension
