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Thursday, 1 August 2013

Pharmacology Of Pheocromocytoma

Ø Pheochromocytoma:    
                A pheocromocytoma is a rare, usually benign tumor that develops most commonly in the core of an adrenal gland. Tumors that occur outside of the adrenl gland are referred as paragangliomas.
                Generally 80% of pheochromocytomas are located in the adrenal medulla. Extraadrenal sympathetic paragangliomas commonaly located in the abdomen. Extra- adrenal parasympathetic paragangliomas are most commonly found in the neck and head.
                 A pheochromocytomas cause adrenal glands to produce too much of  hormones, raising blood pressure and heart rate. it may be life-threatening if unrecognized or untreated.
                A pheochromocytoma can develop at any age, but most commonly occurs in middle age. Usually, treatment for pheochromocytoma can return blood pressure to normal.
                Sometimes pheochromocytoma is part of another condition called multiple endocrine neoplasia syndrome (MEN).
Ø Signs and Symptoms:
  • High blood pressure
  • Rapid heart rate
  • Forceful heartbeat
  • Excessive sweating
  • Abdominal pain
  • Sudden-onset headaches — usually severe — of varying duration
  • Anxiety
  • Feeling of extreme fright
  • Pale skin
  • Weight loss
  • Amyloid deposits found microscopically
  • Elevated blood glucose level

o   These signs and symptoms develop because this type of tumor produces an excess of chemical compounds called catecholamines.

o   Excessive secretion of catecholamines — the hormones adrenaline and noradrenaline lead to high blood pressure.  High blood pressure is a common sign of a pheochromocytoma.

o   Elevated blood glucose level arise due to cateholamines which stimute lipolysis which leads to high levels of free fatty acids that cause inhibition of glucose uptake by muscle cells. Further, stimulation of beta-adrenergic receptors leads to glycogenolysis and gluconeogenesis and thus elevation of blood glucose levels.

o   Not all patients experience all of the signs and symptoms listed. The most common symptoms are headache, excessive sweating, and increased heart rate, with the attack subsiding in less than one hour.

Ø Causes:
·          Up to 25% of pheochromocytomas may be familial. Hereditary conditions associated with pheochromocytomas include
 Multiple endocrine neoplasia 2A and 2B(MEN IIA,MEN IIB),
 Von Hippel–Lindau disease(VHL),
 Neurofibromatosis I(NF-1),
 RET Oncogene,
 SDHB,
 SDHC and
 SDHD

Ø Diagnosis:
·         The diagnosis can be done by measuring catecholamines and metanephrines in blood or through a 24-hour urine collection. Imaging by computed tomography or a T2 weighted MRI of the head, neck, and chest, and abdomen can help localize the tumor.

·         Blood and urine tests:- These tests can measure elevated levels of the hormones adrenaline and noradrenaline and their breakdown products (metanephrines). It need to collect urine samples over a 24-hour period for testing. The increased level of this metabolites in blood or inceased excretion of these metabolites is indicative of the disease, but does not completely rule out other diseases which may cause the same excretion values.

·         Imaging scans. A CT scan of your abdomen can detect the tumor in most cases. However, it may be necessary to scan other areas of body, such as neck, chest and pelvis. Scanning with other diagnostic imaging techniques, such as magnetic resonance imaging (MRI), a metaiodobenzylguanidine (MIBG) scan or a positron emission tomography (PET) scan, may be done to detect the tumor.



Ø Treatment:-
                Surgery is the treatment of first choice.  It is important to stabilize blood pressure and pulse with medication before surgery.  When the tumor cannot be surgically removed, medication is needed to manage it. This usually requires a combination of medications to control the effects of the excessive hormones.
v  Medications used to treat high blood pressure associated with pheochromocytomas include:
§  Alpha blockers. Alpha blockers  is used to block noradrenaline activity. They work by keeping the hormone noradrenaline from stimulating the muscles in the walls of smaller arteries and veins. This stimulation makes the vessel walls constrict. Blocking that effect causes the vessels to remain open and relaxed. This improves blood flow and lowers blood pressure.
o   Drugs: phenoxybenzamine, doxazosin, prazosin and terazosin.
o    Side effects: headache, pounding heartbeat, nausea and weight gain.
§  Beta blockers. Beta blockers make heart beat more slowly and with less force. They work by blocking the effects of the hormone norepinephrine. This action slows down the nerve impulses that travel through heart. That means heart doesn't pump as hard because it needs less oxygen and blood. Beta blockers also slow down the release of the enzyme renin from kidneys, helping keep blood vessels dilated.
o   Drugs: atenolol, metoprolol and propranolol .
o    Side effects: fatigue, headache, upset stomach and dizziness.
§  Calcium channel blockers. Calcium channel blockers  relax and widen blood vessels in arteries. They lower blood pressure by preventing calcium from entering the cells of heart and blood vessel walls.
o   Drugs: amlodipine, diltiazem and nicardipine.
o    Side effects: constipation, headache, tachycardia and drowsiness.
§  Metyrosine. This drug lowers blood pressure by inhibiting the production of catecholamines. It may be used when other drugs haven't worked or with other drugs.
o    Side effects: drowsiness, depression, anxiety and diarrhea.
v Surgery:
90% of patients are cured by surgery. Surgery for tumors is usually done by laparoscopy. Once the tumor is removed, blood pressure usually falls to normal or low normal. Patients who have blood pressure that stays too low, or who have poor circulation in the arms and feet, may need transfusions of blood, plasma, or other fluids. After surgery, some patients have a fall in blood pressure followed by a rise in blood pressure. Sometimes surgery is not an option because of the type of tumor growth or because the tumor spreads (metastasizes) to other parts of the patient's body.

v  Malignant tumors:
Current treatments for malignant tumors include chemotherapy, or radioactive MIBG. For patients in whom surgery is not successful, or for those who cannot undergo surgery, symptoms are controlled with medications.

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