Flashcards in Alpha Blockers Deck (38)
What do alpha receptors do?
receptors in the vasculature that activate smooth muscle, thereby producing vasoconstriction both in skeletal muscle and in skin and splanchnic vessels.
What are some alpha blockers that have a much higher specificity for a1 than a2?
What are some alpha blockers that have relatively equal specificity for a1 and a2?
-Phenoxybenzamine (slightly more from a1)
What is yohimbine?
an alpha-2 antagonist used in treatment of erectile dysfunction
What are the types of alpha-1 receptors?
a, b, and d
What are alpha-1 receptors involved in?
smooth muscle contraction
Where are the subtypes of alpha-1 receptors located in the body?
b and d- vasculature
a- prostate mostly
Blockade of alpha-1a receptors in the bladder neck and prostate can do what?
improve urine flow rate and reduce symptoms of benign prostatic hypertrophy (BPH)
What is Alfuzosin?
more specific drug for alpha-1a receptors than other alpha-1 antagonists used for BPH
Where are alpha-1 and alpha-2 receptors located in relation to muscular junctions?
alpha-1 receptor on the post-synaptic
membrane where it mediates downstream events, and the alpha-2 receptor on the
presynaptic terminal, where it functions as an auto-receptor to terminate further
release of endogenous NE
What do alpha-1 receptors do?
activation of the receptor decreases production go cAMP leading to an inhibition of further release of norepinephrine from the neuron
What do alpha-2 receptors do?
activation of the receptor increases production go DAG and IP3, leading to an increase of intracellular calcium
Side effects of alpa-2 stimulation?
-bradycardia and hypotension (due to stimulation of vagal activity.)
-reduced anesthetic requirements
What does block of alpha-1 receptors result in?
leads to hypotension, by preventing NE-stimulated
smooth muscle contraction in the vasculature.
Norepinephrine is an agonist for which receptors?
a1, a2, B1
Epinephrine is an agonist for which receptors?
a1, a2, B1, B2
Isoproterenol is an agonist for which receptors?
What does Isoproterenol do to BP?
decreases via beta receptor stimulation
What do Norepinephrine and Epinephrine do to BP?
increases via primarily alpha receptor stimulation
What would pre-treatment someone with an a-blocker and giving epi result in?
the a-blockers would block the alpha receptors so the major effect would be a decrease in BP even though if given alone the epinephrine would raise BP
this is called epinephrine reversal
How would the a-blocker/epi combo affect CV?
- increase in HR and renal blood flow - `decrease in total
peripheral resistance (TPR), BP and effective refractory period (ERP) in the heart
What would pre-treatment someone with a nonspecific b-blocker and giving epi result in?
Blocking the b-receptors would leave only a receptors and that would manifest in a spike in BP and there would be no CV effects upon the heart
What are the side effects of alpha-blockers?
-first dose orthostatic hypotension (most common in prazosin)
-sinus tach (angina, palpitations)
T or F. Non-specific alpha-blockers like phentolamine are more likely than the alpha- 1 selective agents to produce tachycardia.
T, by virtue of the action augmenting the release of endogenous NE
What does NE cause?
Although one thinks of NE as acting predominantly on
alpha-adrenergic receptors to produce constriction of resistance and capacitance
vessels, NE also acts on beta1-receptors, although quantitatively less than either
epinephrine or isoproterenol. In relatively lower doses, the cardiac-stimulant effect of norepinephrine is predominant; with larger doses, the vasoconstrictor effect
How does Phenoxybenzamine work?
it is a non-specific (1 and 2) alpha blocker that binds covalently (LONG LASTING) to both receptors where it produces a reduction of BP via vasodilation that is less intense than for alpha-1 specific blockers
Why are the vaso-dilatative effects of non-specific alpha blockers less intense than specific ones?
because of the mitigating action of increased CO.
What is Phenoxybenzamine approved to treat?
pheochromocytoma, a rare adrenal gland
tumor that produces excessive circulating levels of catecholamines and lifethreatening
Off label uses of Phenoxybenzamine.
The drug is also used “off label” for conditions
involving poor perfusion of peripheral tissue like the fingers and toes- For example,
Raynaud’s syndrome, which is a condition found predominantly in women who have
vasospasm of the smaller arteries that supply blood to the skin, fingers and toes.
Is Phenoxybenzamine fast acting?
No, slow onset but long lasting
What else does Phenoxybenzamine do?
minor action of blocking serotonin, histamine, and acetylcholine
What does the minor blocking of serotonin, histamine, and acetylcholine result in?
-sinus tach, nasal congestion
- drowsiness, fatigue, weakness, headache
What is Phentolamine?
a short acting non-specific alpha blocker
What is Phentolamine used for?
hypertensive emergency and Pheochromocytoma
not for regular HTN
What are the side effects of Phentolamine?
antagonizing alpha-2 receptors increases circulating nor due to loss of negative feedback
What are the effects of small doses of Phentolamine?
positive inotropic effect dominates and BP increases via increased nor levels
What are the effects of large doses of Phentolamine?
peripheral vasodilation predominates and BP decreases