Lecture 10: Adrenergic Antagonists Flashcards
What is the main vital sign affected by α-adrenergic blocking agents?
BP, it is decreased in response to α-adrenergic blocking agents (decreased peripheral vascular resistance).
How do α-adrenergic blocking drugs affect the cardiac system?
They caused vasodilation and thus decreased BP, this leads to a reflex tachycardia to maintain CO.
CO = HR x BP
α1 Antagonists cause vasodilation. What other conditions affect the magnitude of such effect on BP?
- Activity of sympathetic (stronger drop when not functional)
- Lesser drop in supine position than standing
- hypovolemia increases this drop.
what type of receptors are linked to ortho-static hypotension when blocked?
α1 receptors
What reflex system usually antagonises the activity of α blockers, in response to vasodilation and drop in BP?
The baroreceptor reflex.
It maintains CO by increasing HR.
So even if α antagonists are applied are we have vasodilation, this will be ineffective in changing the cardiac output.
Apart from the baroreceptor reflex that kills the effects of α antagonists, Why are α blockers in nature unable to be potent?
non-specific α blockers will act as both α1/2 blockers.
As α1 blockers they’ll induce vasodilation.
As α2 blockers, they’ll block α2 receptor on sympathetic neurons, killing the negative feedback of the neuron and thus allowing MORE NE/E to be released. This will stimulate β1 of the heart and cause tachycardia.
So Tachycardia is accomplished by both baroreceptor reflex and the nature of these blockers’ non-specificity, making them kind of useless.
Clinically speaking, are non-specific α receptor antagonists useful?
Not really, apart if we’re only trying to have vasodilation.
They simply CANNOT maintain a lowered BP (for reasons explained (reflex tachycardia/increased NE/E secretion))
What is “epinephrine reversal”? When does it occur/ explain the mechanism.
Does NE have this same phenomenon?
- It’s a phenomenon where giving Epinephrine causes vasodilation rather than vasoconstriction.
- This occurs in patients having α blockers. Epi acts on α1 & β2 (with α1>β2). If α1 is blocked by antagonist then only β2 will react, causing vasodilation.
NE acts on α1 & α2 –> unachanged
A patient comes with a schock and known to be taking α1 antagonists. We’re trying to raise his BP.
What drug should we AVOID? what could we give him?
Avoid Epinephrine because of “epinephrine reversal” which will cause vasodilation.
we might want to give him β2 Antagonist to make sure endogenous epinephrine doesn’t make things worse.
What is Yohimbine? How does it affect HR?
It’s an α2 blocker. So it doesn’t allow neuronal α2 to inhibit NE/E release. As a result sympathetic stimulation INCREASES in response to Yohimbine, causing an increase in BP (α1 and β1 responding to NE/E).
So this is an adrenergic antagonist that causes stimulation of sympathetic branch…
What is Phenoxybenzamine?
How does it bind (competitive/non-competitive)?
How can cells bypass it?
How long does it last?
Phenoxybenzamine is non-competitive, non-specific α blocker.
Cell can only bypass it by synthesizing new adrenoceptors. This makes it last ~24hrs.
What’s a pheochromocytoma? Where does Phenoxybenzamien intervene in that?
It’s a catecholamines-secreting tumor derived from the adrenal medulla.
Usually Phenoxybenzamine is given prior to removal surgery to avoid catastrophic vasoconstriction that can result from manipulation of the tissue.
What is raynaud’s disease? how can we treat it?
It’s severe vasoconstriction in the hand, can be treated by α-inhibitors such as phenoxybenzamine or phentolamine.
What are the main side effects of α blockers? (5)
- Postural hypotension
- Nasal stuffiness
- Nausea
- Vomiting
- Inhibit ejaculation
Apart from minor side-effects, what patients are contra-indicated to α-blockers?
Patients with decreased coronary perfusion.
They won’t stand the induced reflex tachycardia (administration would trigger anginal pain).
What is phentolamine? What other drug of the same family is it similar to?
It’s a competitive α blocker.
It’s mainly similar to Phenoxybenzamine except that it has a shorter duration (~4hrs) due to its competitive effect.
Drugs ending with -osin are seen as what type of blockers?
α1 blockers (they’re competitive)
Out of the 5 α1 blockers, which are used for treatment of hypertension? Why?
3 are used for hypertension (PRATEDO):
Prazosin, Terazosin & Doxazosin.
They might trigger some tachycardia but they do not inhibit neuronal α2 receptors: Sympathetic remains ineffective in their presence and they manage to maintain lowered BP.
They also cause very little changes in CO, renal flow & GFR…
What 2 drugs are used to treat benign prostatic hypertrophy? To what family do they belong?
Alfuzosin & Tamsulosin.
They’re competitive α1 blockers. They decrease tone in smooth muscles of the bladder neck and prostate, improving urine flow.
What is the “first-dose effect”? What drugs family causes it? How do we deal with it?
It’s caused by α1 blockers upon first few administrations. It’s an exaggerated orthostatic hypotension often leading to syncope (fainting).
We deal with it by giving lower doses and at bedtime.
What are some symptoms specific to α1 blockers?
- Headache (probably increase cerebral flow?)
- Lack of energy & drowsiness
