Antiadrenergic agents ( Peripherally acting )include- Reserpine, Guanithidine monosulphate, Guandrel sulfate, ( Alpha-1- blockers), Prazosin,Terazosin, Doxazosin, Tamsulosin, Silodosin, Alfuzosin Hcl Refer - Prazosin 

Interacting drugs 

with Guanethidine -

 Anorexiants-                                                                                                                        the hypotensive effects of guanethidine may be reversed

Haloperidol-                                                                                                                       haloperidol antagonizes the hypotensive efect of guanethidine

Methylphenidate-                                                                                                            hypotensive effects of guanethidine may be impaired. arrhythmias were reported in one case

Minoxidil-                                                                                                                          Admin of minodixil to patients on guanithedine can result in profound orthostatic effect. Discontinue guanethidine well before mixodil is begun, if possible. If not possible, hospitalize patient when starying minoxidil.

Mephantermine-                                                                                                      antihyperstensive effects of guanethidine or reserpine may be partially or totally reversed by the mixed acting sympathomimetics

MAO inhibitors-                                                                                                                   Discontinue atleast 1 week before starting guanethedine therapy. 

Phenothiazines-                                                                                                                      the hypotensive efect of guanethidine is inhibited

Sympathomimetics with - guanethidine                                                                                     the hypotensive effect of guanethidine may be reversed, also

Guanethidine with-Sympathomimetics-                                                                       guanethidine potentiates the effects of direct acting sympathomimetics 

Thioxanthenes-                                                                                                                    the hyptensive efect of guanethidine is antagonised.

Tricyclic antidepress-                                                                                                             the hypotensive action of guanethidine is inhibited

Digitalis-                                                                                                                            Digitalis and guanethedine both slow down heart rate. 

Antidiabetic agents-                                                                                                      Guanethedine posseses antidiabetic activity.Monitor patients on altered hypoglycaemic effects. 

Tricyclic antidepressants, phenothiazines,thioxanthenes, haloperidol and indirect-acting sympathomimetics and oral contraceptives-                                                               may reduce antihypertensive effect of guanethedine. 

Metraminol-                                                                                                                   antihypertensive effects of guanethidine may be partially or totally reversed by the mixed-acting sympathomimetics 

Guanethidine with Isoproterenol-                                                                        guanethidine may increase the pressor response of the direct-acting vasopressors, possibly resulting in severe hypertension

Dobutamine-                                                                                                                   guaniethidine may increase pressor response to direct acting vasopressors, resulting in severe hypertesion

Dopamine-                                                                                                                    antihypertensive rffects of guanethidine may be partially or totally reversed by mixed-acting sympathomimetics

Epinephrine-                                                                                                          guanithedine may increase the prssor response of the direct-acting vasopressors, possibly resulting in severe hypertension

Guanethidine Direct) incr guanethidine potentiates the effects of the direct acting agents with nasal

Mixed )-                                                                                                                      epinephrine) and inhibits the effects of the mixed acting agents nasal  deconges ) ephedrine ) Guanethidine hypotensive acton may also be reversed 

Moderate to severe hypertension, renal hypertension. 

CNS- Dizziness,weakness,lassitude and syncope resulting from postural or exertional hypotension, fatigue, muscle tremor, mental depression, chest paresthesis,ptosis of the lids, blurred vision.

Cardiovascular- Bradycardia, fluid retention, edema with occassional development of CHF, angina

GI- nausea, vomiting, dry mouth, parotoid tenderness, diarrhea ( may be severe and necessitate discontinuance of the medication, increase in bowel movements

GU- Inhibition of ejaculation, rise in BUN, nocturia, urinary incontinence, priapism, impotence (rare)

Hematologic- anemia, thrombocytopenia, leukopenia

Respiratory- Dyspnea,nasal congestion, asthma in susceptible individuals

Miscellaneous- myalgia, weight gain, dermatitis,scalp hair loss.

Known or suspected phechromocytoma, hypersensitivity to guanethidine,frank congestive heart failure(CHF) not due to hypertension, use of MAO inhibitors.

Special precautions:

Cumulative effects- the efects of guanithidine are cumulative,initial doses should be small and increased gradually in small increments.

Sodium retention- to minimize sodium retention and compulsorybfliud retention, gaunithidine is usually used with a thoiazide diuretic.

Cardiovascular disease- use very cautiously in hypertensive patients with coronarydisease with insufficiency or recent myocardial infarction, and in cerbral vascular disease especially with encephalopathy. Use with care in patients with severe cardiac failure.

Peptic ulcer- use cautiously in patients with a history of peptic ulcer or other disorders.

Warnings-

Potency- this is a potent drug, its use can lead to serious clinical problems.

Orthostatic hypotension- can occur frequently. Dizziness or weakness may be particularly bothersome during the initial dosage period and with postural changes.

Preoperative withdrawal- is recommended 2 weeks prior to surgery to reduce the possibility of vascular collapse and cardiac arrest during anesthesia.

Fever- reduces dosage requirements

Bronchial asthma- patients require specialconsideations as they are more apt to be hypersentive to catecholamine depletion and their condition may be aggravated.

Renal function impairment- use very cautiously in hypertensive patients with renal disease and nitrogen retension or rising BUN levels since decreased blod pressure may firther compromise renal function.

Pregnancy- safety for use duringpregnancy has not been established

Lactation- becuase ofte serious adverse reactions innursing infants, decided whether to discontinue nursing or disacontinue the drug depending upon the importance of the drug to the mother.

Children- safety and efficacy for use in children has not been established.

Indications:

Moderate to severe hypertension, renal hypertension.

Dosage:

Begin with 10mg daily. Average dose is 25 to 50mg once daily.

Overdosage Symptoms Postural hypotension and brdaycardia are most likely to occur, diarrhea, possibly severe,may also occur. Unconsciousness is likely if adequate blood pressure and cerbral perfusion can be maintained

Treatment

1. There is no specific antidote

2. Consider gastric lavage,activated charcoal and laxatives, if conditions permit.

3. In previously normotensive patients,treatment has consisted ssentially of keeping the patients supine

4. Homeostatic control usually returns over 72 hours

5. In prevoiusly hypertensive patients paticularly those with impaired cardiac reserve or other cardiovascular-renal disease intensive treatment may be required if vasopressors are required.

6.Guanethidine may increase responsiveness to blood pressure rise and occurance of cardiac arrhythmias.

7. Administer atropine for sinus bradycardia

8. Treat severe or persistent diarrhea symtomatically.

9. Monitor cardiovascular and renal functin for a few days.

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.

Swelling of salivary glands-

Drugs causing Adverse Reactions- ( 385 )

1. Phenylbutazone

2. Guanethidine

3. Bethanidine

4. Bretyium

5. Clonodine

6. Iodides

GUANETHIDINE HCL- ANTIADRENERGIC AGENT

1. Notify physician of severe diarrhoea,frequent dizziness or fainting.

2. Allergies- tell your doctor if you have ever had any unusual or allergic reaction to guanethidine. Also tell your doctor if youare allergic to any other substances, such as foods, presrvatives or dyes.

3.Pregnancy - studies on effects in pregnancy have not been done in either humans or animals.

4.Breast feeding- this medicine has not been reported to cause problems in nursing babies

5 Children - this medicine has not been been shown to cause different side effects or problems than it does in adults.

6. Elderly- diziness, lightheadedness or fainting may be more likely to occur in the elderly, who are sensitive to gaunathidine

7. Other medicines - Antidiabetics - effects any be increased by guanethidine Loxapine or Thioxanthenes or Tricyclic antidepressants or Trimeprazine - may decrese the effects of guanethidine on blood pressure Minoxidil - effects on blood pressure may be greatly increased MAOI- taking guanethidine while you are taking or within 1 week of taking MAOI may cause a severe increase in blood pressure

8. Other medical problems - Tell your doctor if you have any other medical problems especially - Asthma or Diarrhea or Pheochromocytoma or Stomach ulcer -guanethidine may worsen these conditions Diabetes mellitus - effects of these medicines used to treat these conditions may be increased by gaunethidine Fever - effects of guanethidine may be increased Heart attack or stroke or Heart or blood vessel disease - lowering of blood pressure may make the conditions worse Kidney disease - guanethidine may worsen this condition. Also effects of guanethidine may be increased because of slower removal of this medicine from the body

9.Liver disease- effects of guanethidine may be increased because of slower removal from the body

10. Dosage- Follow doctors instructions

11. Missed dose - If you miss a dose of this medicine, take it as soon as possible. however, if it is almost time for the next dose, skip the missed dose. Do not double doses.

12. Storage - Keep out of reach of children. Store away from heat or direct sunlight. Do not store the capsule in bathroom, near the kitchen sink, or in other damp places.

13. Outdated medicines - Do not keep outdated medicine or medicine no longer needed. Be sure that any discarded medicine is out of reach of children.

 Antiadrenergic agents ( Peripherally acting )include- Reserpine, Guanithidine monosulphate, Guandrel sulfate, ( Alpha-1- blockers), Prazosin,Terazosin, Doxazosin, Tamsulosin, Silodosin, Alfuzosin Hcl Refer - Prazosin 

Pharmacology:

Guanethidine inhibits or interferes with release or distribution of the chemical mediator (presumbaly norepinephrine) at the sympathetic neuroeffector junction.

Pharmacokinetics:

Guanethidine is incompletely absorbed about 3% to 50% upon oral administration. It is actively transported into adrenergic neurons. Guanethidine is partially metabolised by the liver to three metabolites. The parent drug and the metabolites are excreted primarily in the urine.

Not available

Pregnancy:

Safety for use during pregnancy has not been established. Use only when clearly needed.

Lactation:

Excercise caution and decide whether to discontinue nursing or discontinue the drug.

Children:

Safety and efficacy for use in children has not been established.