Phenothiazine or haloperidol- extrapyridimal effects of these drugs may be potentiated due to  inhibitioin of catecholamine synthesis by metyrosine.

Pheochromocytoma


Agents for Pheochromocytoma includes-
Phenotolame, Phenoxybenzene HCL, Metryrosine ,
 

CNS- sedation is most common, moderate to severe at low and high dosages. Sedation begin within
 first 24 hours of therapy, are maximal after 2 to 3 days and tend to wane during the next few days
GI -diarrhea(10%) may be severe. May need antidiarrrheals., if drug is continued

GU- infrequent -impotence or failure to ejaculate. Crystalluria, transcient dysuria and hematuria

Body as a whole- infrequent- slight breast swelling, galactorrhea, nasal stuffiness. eosinophilla,
 anemia, thrombocytoma, thrombocytosis. Increased AST, periphreal edema, hypersensitivity  reactions as urticaria and pharyngeal edema (rare).

Hypersensitivity to metyrosine


Special precautions:
Maintain fliud volume during and after surgery- when metyrosine is used preoperatively, especially
 with alpha-adrenergic blocking drugs, maintain adequate intravascular volume intra-operatively
(especially after tumor removal ) and postoperatively to avoid hypotension. and decreased
 perfusion of vital organs resulting from vasodilation and expanded volume capacity.  

Intra-operative effects- while on preoperative use of metyrosine isthought to decrease intra-operative
 problems with blood pressure control. It does not eliminate the danger of hypertensive crises
 or arrhythmias during manipulation of the tumor. Phentolamine or an alpha-adrenergic blocking drug
 may be needed.

Renal/hepatic function impairment- use with caution

Pregnancy- Safety for use during pregnancy has not been established. Use only when clearly needed
 and when the potential hazards benefts outweigh potential hazards to the fetus

Lactaion- not known whether metyrosine is excreted in breast milk. safey for use in the nursing mother
 has not been established

Children- Safety and efficacy for use in children under 12 years of age have not been established

Precautions:
Long term use- human experience is limited and chronic animal studies have not been performed.
 Perform laboratory tests periodically in patients requiring prolonged metyrosine use and observe
 caution with patients with impaired hepatic or renal function.

Indication:
Pheochromocytoma

Dosage:
Initial dosage 250mg 4 times a day. This may be increased by 250 to 500mg every day top a maximum
 of 4g/day

Overdosage-

                           Symptoms                                                            

Signs of metyrosine overdosage include those central nervous system effects observed in some
 patients even at low dosages


Treatment
1. Reducing dose or discontinuing causes these symptoms to disappear at low doseages


Missed dose-

1. If you miss a dose of this medicine, take it as soon as possible.
2. However, if it is almost time for next dose, skip the missed dose and go back to your regular dosing
    schedule.
3. Do not double doses.  












 

METYROSINE- AGENTS FOR  PHEOCHROMOCYTOMA


1. Maintain a liberal fliud intake.

2. Avoid alcohol or other CNS depressants

3. Notify physician if any ofthe following occur, droolong, speech difficulty, trmors, disoreientation,
diarhea,   painful urination

4. Allergy-
    Tell your doctor if you are allergic to metyrosine or food substances, preservatives or
    dyestuffs

5. Pregnancy-
   No studied in pregnant women or animals.Make sure your doctor knows if you are pregnant
   or you become  pregnant  before taking phenoxybenzamine

6. Breast feeding-
   Not known  whether metyrosine   passes int breast milk. This medicine not reported to cause
   problems     in nursing  babies.

7. Children-
    No specific information about use of  this medicine  in children, Not expected to  cause
    side effects  or  problems than it does in adults.

8.Older adults-
   Not known  whethe it  works exactlyin the same way  as tey do in adults. No specific information
   comparing  use of metyrosine  in elderly with younger adults available.  

9. Other medicines-
    Tell  your doctor if you are taking other prescription medicines or OTC products.

10. Other medical problems-
    Presence of other medical problems especially the following may affect the use of this
    medicine-

    Kidney disease  or-
    Liver disease   -efffects of  metyrosine  may be icreased because of slower removal from
    the body.
    Mental depression  or
    Parkinsons  disease  - metyrosine  may make  these conditons worse.

11.  Dosing-
     Follow doctors instructions

12. Missed dose-
     If you miss a dose of this medicine take it as soon as possible. However if it is almost time
     for your next dose,  go back to your regular dosing schedule.
     Do not double doses.

13. Storage-
 
      Keep the medicines out of reach of children
      Store the medicines away heat and direct light
      Do not store tablets  or capsules in the bath room, in damp places near the kitchen sink
      Heat and dampness will cause the medicines to break down
      Keep  the medicine  from freezing
       


 

Agents for Pheochromocytoma includes-

Phenotolame, Phenoxybenzene HCL, Metryrosine ,

Pharmacology:
Mytyrosine inhibits tyrosine hydroxylase which catalyzes the first transformnation in catecholamine
biosynthesis ie the conversion of tyrosine to dihydrophenylamine (DOPA) . Because this is rate
 limiting step, hydroxlase blockade results in decreased endogenous levels ofcatecholamines,
 usually measured as decreased urinary excrtion of catecholamine and theie metabolites.

Pharmacokinetics:
Metyrosine is well absorbed from the GI tract. Approx 53% to 88% (mean 69% ) is recovered in the
 urine as unchanged drug following maintenance oral dosages of 600 to 4000 mg/24 hours.
 Less than 1% of the administerd drug is recovered as catechol metabolites. The plasma half life
 over 8 hours after single oral dose was 3.4 to 3.7 hrs in three patients.

Pregnancy- Safety for use during pregnancy has not been established. Use only when clearly needed
and when the potential hazards benefts outweigh potential hazards to the fetus

Lactaion- not known whether metyrosine is excreted in breast milk. safey for use in the nursing mother
has not been established

Children- Safety and efficacy for use in children under 12 years of age have not been established