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
