Interacting drugs- summary 

Diazoxide +  Phenytoin

 concomittant administratiion mat result in a loss of seizure control, possibly due to increased hepatic metabolism of phenytoin

Sulfonylureas

 addition of diazoxide to sulfonylurea therapy could destabilise the patient resulting in hyperglycemia

+ Diazoxide -

Thaiazide

 coadministration may potentiate the hyperuricemic and antihypertensive effects diuretics of diazoxide

Severe hypertension

Agents for Hypertensive Emergencies- Nitoprusside Sodium, Fenoldopam mesylate, Diazoxide Parentral

Interacting drugs- summary

Cardiovascular- Sodium and water retension after repeated injections, especially important patients with impaired cardiac reserve, hypotension to shock levels, myocardial ischemia, usually transcient and manifested by angina, atrial and ventricular arrhythmias and marked ECG changes

CNS- cerebral ischema, usally transcient but occasionally leading to infarction and manifested unconsciousness, convulsions, paralysis, confusion, or focal neurological defecit such as numbness of the hands, vasodilative phenomena (eg, orthostatic hypotension) sweating,flushing and generalized local sensation of warmth, transcient neurological findings secondary to alteration in regional blood flow to the brain, such as headaches (some times throbbing) dizziness, lightheadedness, sleepiness

GI -acute pancreatitis, nausea, vomiting, abdominal discomfort, anorexia, alteration in taste, parotoid swelling, salivation, dry mouth, ileus, constipation,diarrhea

Miscellaneous- hyperglycema in diabetic patients after repeated injections, hyperosmolar coma in an infant, transcient hyperglycemia in nondiabetic patients

Treatment of compensatory hypertension, such as associated with aortic coarctation or arteriovenous shunt, dissecting aortic aneurysm, hypersensitivity to diazoxide, thiazides, or to other sulfonamide derivatives.

Special precautions:

Monitoring- diazoxide requires close and frequent blood pressure monitoring, it may cause hypotension requiring treatment with sympathomimetic drugs.

Special risk patients- use with care in patients with impaired cerbral or cardiac circulation, in whom abrupt reductions in blood pressure might be detrimental or in whom mild tachycardia or decreased blood perfusion may be deleterious. Avoid prolonged hypotension so as not to aggravate pre-existing renal failure

Warnings-

Rapid decrease in blood pressure- observe caution while reducing severely elevated blood pressure

Fluid and electrolyte balance- diazoxide causes sodium retention, repeat injections may precipitate edema and CHF. This retention responds to diuretic agents if adequate renal function exists. Coadministered thiazides may potentiate diazoxides antihyperglycemic and hyperuricemic actions

Pheochromocytoma- diazoxide is ineffective against hypertension due to phenochromocytoma

Pregnancy:

Safety for use is not established. Not for use during pregnancy. IV administration during labor may stop uterine contractions.

Lactation:

Decide whether to discontinue nursing or discontinue the drug dependending of importance of the drug to the mother.

- Diazoxide requires close and frequent monitoring. It may cause hypertension requiring treatment

Special risk patients-

Use with care in patients with impaired cerebral or cardiac circulation in whom abrupt reductions in blood pressure might be detrimemental

Indications:

Severe hypertension Dosage: Adults- administer undiluted and rapidly by IV injections of 1 to 3mg/kg upto a maximum of 150mg in a single injection. Overdosage- Symptoms Treatment Overdose- Parentral Overdose may cause hypotension that can usally be controlled with Trendelenburg maneuver If necessary sympathomimetics agents such as dopamine or norepinephrine may be administered Failure of blood pressure to rise in response to such agents, suggest that the hypotension may not have been caused by diazoxide Excessive hypereglycemias will respond to conventional therapy of hyperglycemia Diazoxide may be removed from blood by hemodialysis

Missed dose

1. If you miss a dose of this medicine, take it as soon as possible.

2. However, if it is time for your next dose, skip the missed dose and go back to your regular dosing schedule.

3. Do not double doses.

DIAZOXIDE - AGENTA FOR HYPERTENSIVE EMERGENCIES

1. Monitor urine regularly for glucose and ketones,report abnormalities to physician.

2. During treatment, advise patients to consult physician regularly and to cooperate with periodic lab test monitoring

3. Take the drug on a regular schedule as prescribed.

4. Do not use the drug with other mediactions unless the physician has been consulted.

5. Do not allow any one else to take this medication.

6. Follow dietary instructions.

7. Report promptly any adverse effects such as increased urinary frequency , increased thirst or friuty breath odor.

8. Report pregnancy or discuss plans for pregnancy.

9. Allergies- Tell your doctor if you have ever had any unusual or allergic reactions to diazoxide or other related medicines. Also tell your doctor if youn are allergic to any other substances such as foods, preservatives or dyes.

10. Pregnancy- too much use of diazoxide during pregnancy may cause unwanted effects (high blood sugar, loss of hair, or increased hair growth,blood problems ) in the baby

3. Breast feeding- not reported to cause problems in nursing babies

4. Children- infants are more likely to retain body water because of diazoxide. In some infants this may cause heart problems. Few children who have received diazoxide for prolonged periods ( longer than 4 years) developed changes in their facial structures

5. Elderly- no specific information comparing use of diazoxide in the elderly in other age groups

6. Other medicines- tell your doctor if you are taking any of the following- Amantadine or Antidepessants or Antihypertensives or Antipsychotics or Bromocriptine or Cyclandelate or Deferoxamine or Diuretics or Hydralazine or Isoxsuprine or Levobunolol or Levodopa or Medicine for heart disease or Metripranol or Nabilone or Narcotic pain medicine or Nicotinyl alcohol or Nimodipine or Nylidrin or Papaverine or Pimozide or Promethazine or Timolol or Trimeprazine - use of any of these medicines with diazoxide may cause low blood pressure Etotoin or Mephenytoin or Phenytoin- use of any of these medicines and diazoxide may be less efective if taken at thesame time

7. Other medical problems- tell your doctor if you have any other medical problems- Angina or Gout or Heart attack or Heasrt or blood vessel disease Kidney disease - efects of diazoxide may last longer Liver disease or Recent stroke

8. 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. 9. 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

Pharmacology:

Diazoxide a non-diuretic antihypertensive is structurally related to the thiazides. It promptly reduces blood pressure by relaxing smooth muscle in the peripheral arterioles. Increase in heart rate and in cardiac output occur as blood pressure is reduced. Coronary blood flow is increased after initial decrease. Trancsient hyperglycomia occurs in the majority of patients treated

Pharmcokinetics:

Diazoxide is extensively bound to serum proteins (>90%) and may therefore displace other highly protein-bound agents. The plasma half life is 28* +/- 8.3 hours. The duration of antihypertensive effects varies but is generally < 12 hours.

Not reported

Pregnancy:

Safety for use is not established. Not for use during pregnancy. IV administration during labor may stop uterine contractions.

Lactation:

Decide whether to discontinue nursing or discontinue the drug dependending of importance of the drug to the mother.