Pheochromocytoma :It is a tumour of adrenal medullary cells. Excess CAs are secreted which can cause intermittent or persistent hypertension. Estimation of urinary CA metabolites (VMA, normetanephrine) is diagnostic. In addition, pharmacological tests can be performed.
USES OF Α
BLOCKERS
It is a tumour of adrenal
medullary cells. Excess CAs are secreted which can cause intermittent or persistent
hypertension. Estimation of urinary CA metabolites (VMA, normetanephrine) is
diagnostic. In addition, pharmacological tests can be performed.
Phentolamine test Inject phentolamine 5
mg i.v. over 1 min in recumbent
subject. A fall in BP > 35 Hg systolic and/or > 25 mm Hg diastolic is
indicative of pheochromocytoma. However, it is not very reliable and both false
positive and false negative results are obtained.
Provocative tests have
been performed by injecting histamine, methacholine or glucagon—which provoke
release of CAs and cause marked rise in BP if pheochromocytoma is present.
These tests are dangerous; phentolamine must be available to counteract
excessive rise in BP.
Therapeutic Phenoxybenzamine can
be used as definitive therapy for inoperable
and malignant tumours. When surgical removal of the tumour is contemplated, it
is desirable to give phenoxybenzamine orally for 1–2 weeks preoperatively and
infuse it i.v. during surgery because:
·
Due to excess circulating CAs blood volume is
low (they shift fluid from vascular to extravascular compartment). Treatment
with α blocker normalizes
blood volume and distribution of body water.
·
Handling of the tumour during surgery may
cause outpouring of CAs in blood → marked rise in BP. This is prevented by
phenoxybenzamine given pre and intraoperatively. Alternatively, phentolamine
drip can be instituted during the operation.
·
Removal of the tumour is often attended by
marked fall in BP as blood vessels dilate and the blood volume is low. This
does not happen if volume has been restored before hand with the aid of an α blocker.
α blockers other than
those selective for α1 like prazosin have
been a failure in the management of essential hypertension, because
vasodilatation is compensated by cardiac stimulation. Moreover, postural
hypotension, impotence, nasal blockage and other side effects produced by
nonselective α blockers are unacceptable.
However, phentolamine/phenoxybenzamine are of great value in controlling
episodes of rise in BP during clonidine withdrawal and cheese reaction in
patients on MAO inhibitors.
The urinary obstruction
caused by BHP has a static component due to increased size of prostate and a
dynamic component due to increased tone of bladder neck/prostate smooth muscle.
Two classes of drugs are available:
·
α1 adrenergic blockers
(prazosin like): decrease tone of prostatic/bladder neck muscles.
·
5α reductase inhibitor (finasteride): arrest
growth/reduce size of prostate.
Since activation of α1 adrenoceptors in
bladder trigone, prostate and prostatic urethra increases smooth muscle tone,
their blockade relaxes these structures, reducing dynamic obstruction,
increasing urinary flow rate and causing more complete emptying of bladder in
many patients of BHP.
Voiding
symptoms (hesitancy, narrowing of stream, dribbling and increased residual
urine) are relieved better than irritative symptoms like urgency, frequency and
nocturia. The α1 blockers afford
faster (within 2 weeks) and greater symptomatic relief than finasteride which
primarily affects static component of obstruction and has a delayed onset
taking nearly six months for clinical improvement. The α 1 blockers
do not affect prostate size, but are more commonly used. However, effects last
only till the drug is given. Even with continued therapy, benefit may decline
after several years due to disease progression. They may be used concurrently
with finasteride.
Terazosin,
doxazosin and tamsulosin are the peferred α1 blockers because of
once daily dosing. There is some evidence that terazosin and doxazosin promote
apoptosis in prostate. Tamsulosin appears to cause fewer vascular side effects
because of relative α1A /α1D selectivity.
Shock due to blood or
fluid loss is accompanied by reflex vasoconstriction. If volume replacement
fails to reverse this (extremities remain pale and cold, pulse pressure does
not improve), therapy with an α blocker (phenoxybenzamine i.v.) can help by:
·
Counteracting vasoconstriction.
·
Shifting blood from pulmonary to systemic
circuit.
· Returning fluid from extravascular to the
vascular compartment so that cardiac output improves.
5.
Peripheral Vascular Diseases
α blockers do increase skin and to some
extent muscle blood flow in normal individuals, but these drugs are largely
disappointing in peripheral vascular diseases when obstruction is organic
(Buerger’s disease). However, when vasoconstriction is a prominent feature
(Raynaud’s phenomenon, acrocyanosis), good symptomatic relief is afforded by
prazosin or phenoxybenzamine.
6.
Congestive Heart Failure (CHF)
The
vasodilator action of prazosin can afford symptomatic relief in CHF in the
shortterm, but longterm prognosis is not improved.
7.
Papaverine/Phentolamine Induced
Penile Erection (PIPE)
Therapy For Impotence
In
patients unable to achieve erection, injection of
papaverine (3–20 mg) with or without phentolamine (0.5–1 mg) in the corpus
cavernosum has been found to produce penile tumescence to permit intercourse. However,
the procedure requires skill and training. Priapism occurs in 2–15% cases,
which if not promptly treated leads to permanent damage. This is reversed by
aspirating blood from the corpus cavernosum or by injecting phenylephrine
locally. Repeated injections can cause penile fibrosis. Other complications
are—local haematoma, infection, paresthesia and penile deviation. This therapy
should therefore be reserved for selected situations with proper facilities.
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