Symptoms are of excessive secretion of
catecholamines (norepinephrine, epinephrine, or dopamine) into the circulation.
Severe hypertension, often refractory to conventional treatment.
Response
of receptors to catecholamines
·
Alpha 1 receptors cause vascular
constriction
·
Alpha 2 receptors mediate the
presynaptic feedback inhibition of norepinephrine.
·
Beta 1 receptors increase cardiac rate
and contractility
·
Beta 2 receptors lead to arteriolar and
venous dilation and relaxation of tracheobronchial smooth muscle
Alpha
blockers
Patients of Pheochromocytoma are hypertensive and
volume depleted
To control blood pressure in patients of
Pheochromocytoma alpha blocker are drug of choice. Some institutions use Phenoxybenzamine, which
is long acting drug so need to be stopped at least one day before surgery and
replaced with short acting alpha -1 blockers prazosin, terazosin, and doxazosin
Some advice to give alpha blockers for at least for
15 days before the surgery, so blood pressure stabilizes.
Intravenous Phenoxybenzamine can be given for 5days
before surgery and replaced with short acting alpha-1 blockers a day before
surgery.
Phenoxybenzamine is expensive drug, so many continue
to use short acting alpha-1 blockers instead of Phenoxybenzamine.
In volume depleted patients alpa-1 blockers should
be used with caution, because of hypotension during intra-operative and
postoperative stage, managed with fluid and norepinephrine infusion.
Beta
blockers
Beta blockers should never be given alone in
patients of Pheochromocytoma. Beta blockers are to be given after adequately stabilizing
with alpha blockers (unchecked alpha stimulation can lead to severe
hypertension). Beta blockers are useful for controlling tachycardia.
Beta blockers are avoided in patients with LV
dysfunction in patients of Pheochromocytoma.
Combined
alpha and beta blockers
Labetalol a combined alpha and beta blocker is not a
primary drug for preoperative management of Pheochromocytoma.
Needed alpha and beta block is 4:1 but with
Labetalol it is 1:7, which may result in paradoxical episodes of hypertension
or even hypertensive crisis
Calcium
channel blockers.
These drugs are less effective than alpha blockers
but are still useful to control blood pressure and heart rate.
These drugs block Norepinephrine mediated calcium
influx into vascular smooth muscle, thereby controlling hypertension and
tachyarrhythmias.
Role of calcium channel blockers in pheochrocytoma
·
These drug are can be used to supplement
alpha blockers
·
Replace alpha blockers in patients with
severe side effects
·
To prevent catecholamine induced arrhythmia
·
To prevent adrenoceptor blocker-induced
sustained hypotension in patients with only intermittent hypertension
·
Useful when Pheochromocytoma is
associated with catecholamine-induced coronary vasospasm.
·
Primary drug in Pheochromocytoma
patients with normal blood pressure.
Catecholamine
Synthesis Inhibition
Alpha -Methyl-L-tyrosine or Metyrosine (Demser) is
an analog of tyrosine that competitively inhibits tyrosine hydroxylase, the
rate-limiting step in catecholamine biosynthesis
Metyrosine significantly depletes catecholamine
stores but not completely so it needs to be combined with catecholamine antagonists.
Metyrosine is useful in patients with extensive mets
and uncontrolled hypertension
Some centers use Metyrosine routinely see algorithm
Metyrosine controls blood pressure both pre and
intra operative stages, especially during surgical manipulation of tumor.
Side effects sedation, often sleepiness, depression,
anxiety, galactorrhea, and rarely causes extrapyramidal signs (e.g.
Parkinsonism in elderly patients)
 |
| Algorithm of Preoperative Management of Pheochromocytoma |
Drugs
and food to be avoided
Norepinephrine and Epinephrine release can be
provoked by glucagon, steroids,
histamine, angiotensin II, and vasopressin so avoided
Tyramine in cheese, bananas, wine, soy sauce,
avocados, and any fermented, smoked, or aged meat and fish are avoided.
Anti –obesity drugs, ephedrine,
pseudoephedrine, or phenylpropanolamine tricyclic and other antidepressants,
amitriptyline , nortriptyline , edronax , duloxetine , venlafaxine, cocaine are
also avoided.
