Lecture 14 (EXAM 3) Flashcards
How Alpha-1 Agonists work
Direct and indirect NE-release
Alpha-1 is vasoconstrictive
Blocking of Alpha-1 receptors - Antagonist
blood pressure -> decreases bc it blocks vasoconstriction
heart rate -> goes up
nose -> nasal congestion
Bladder -> bladder emptying
Eye (hint: dilator mm of the iris) - Miosis - smaller pupils
Phenoxybenzamine: Alpha-1-Antagonist
-Long-acting, non-competitive blocker (covalent) (α1 > α2)
-used to lower BP in pheochromocytoma (epinephrine-producing tumor -> causing very high BP)
-Adverse effects: Reflex tach (baroreceptor increase HR); increase in sympathetic to the heart, nasal congestion, decrease in ejaculation, miosis, orthostatic hypotension, urinary emptying
Phentolamine: Alpha-1 Antagonist
competitive α1+α2 Antagonist
less radical treatment of pheochromocytoma
-Adverse effects:
blocks peripheral α1 receptors -> lowers BP -> ++ Reflex tach (HR goes up) -> sends sympathetic impulses to the heart to release more NE -> NE binds to ß1 on the heart -> increasing HR!!
increase sympathetic tone by blocking α2 (α2 Antagonist)
nasal congestion, headache, decreased ejaculation, orthostatic hypotension, miosis, urinary incontinence
Why is the effect of reflex Tach bigger with Phentolamine?
Because it blocks α1: causing more NE release on the heart (ß1)
and it blocks α2 (α2 limits NE - so more NE when α2 is blocked) -> more NE
-overall more NE release from neurons in the heart (ß1)-> leading to higher HR -> leading to a greater Reflex Tach
Specific Alpha-1 Antagonists
Prazosin (Minipress, et al), Doxazosin (Cardura), Terazosin
(Hytrin), Tamsulosin (Flomax)
(α1 specificity»_space;>α2 specifity) competitive, vasodilators
Used for BP, Raynaud’s disease (an increase of the sympathetic tone -> vasoconstriction in the extremities), BPH (increase urine flow)
Adv effects: orthostatic hypotension, reflex tach, nasal congestion, headache, decrease in ejaculation, miosis, incontinence
What is retrograde ejaculation?
Semen moves into the urine bladder instead of going down the urethra -> caused by improper closing of the sphincter due to Alpha-1 blocker
-often caused by anti-depressants, anxiety, Tamsulosin (for BPH)
Examples pf Alpha-2 Antagonists
Yohimbine
Used for sexual dysfunction disorders
-erectogenic, stimulates libido
Example of ß2-Antagonists
Butoxamine
-No clinical value, used in labs to study ß2-receptors
Effects of ß1-Antagonists
ß1 would stimulate the heart; SO..
the ANTAGONIST is Antihypertensive bc it will decrease heart rate (1st line in heart failure - less work for the heart and time to heal)
-Antihypertensive (no longer 1st choice)
-Migraine headaches: decrease vasodilation
-Glaucoma: reduces aqueous humor
-Reduce the sense of situational stress bc the area of alertness is activated by ß1-receptors
-reduce symptoms of thyrotoxicosis (too much Thyroid will cause increased ß-receptors formation on the heart -> too sensitive -> high BP)
Adverse effects of ß-blockers
-Bronchoconstriction (CAUTION: asthma)
-reduce cardiac output - heart can’t work as much
-Depression and sluggishness
BP: Hypotension, dizziness, syncope
Risk rebound hypertension when abruptly stopping ß-blockers -> the heart compensates for low BP with more ß-receptors -> sensitive reaction to NT when stopping the drug -> MI
Diabetics:
-reduced gluconeogenesis, lipolysis, AND glycogenolysis
-lose the sense of hypoglycemia bc the Warning signal of high BP is not there due to ß-blockers
Why is a non-selective ß-blocker bad for patients with asthma and COPD?
Because it also blocks ß2
ß2 is needed for Bronchodilation
Example of a cardioselective ß-blocker
Metoprolol
selective for ß1 -> on the heart: Cardio
What does ISA intrinsic sympathomimetic activity mean?
Pindolol
block ß-receptor and thereby also partially stimulate
them (Partially Agonist)
-for patients that are too sensitive to ß-blockers (HR too low) -> with Pindolol the HR is decreased but it stimulates the heart to an extent that the HR is not too low and not too high
What is MSA Membrane stabilizing activity?
Acebutolol
helps with membranes that depolarize inappropriately and cause cardiac arrhythmia
