Tricylic Compounds include-

Tertiary amines - Amitriptyline,Clomipramine,Doxepin,Imipramine,Trimipramine

Secondary amines - Amoxipine, Desipramine, Nortriptyline,Portriptyline

Refer Amitriptyliine

 Drug Interations -summary

 Clozapine + Anticholinergic drugs -

anticholinergic effects potentiated by clozapine

Clozapine + Antihypertensive drugs -

hypotensive effects potentiated by clozapine

Clozapine + agents that suppress bone marrow function -

do not use with agents that supress bone marrow function

Clozapine + protein binding -

admin. of clozapine to patient taking another highly protein bound drug (eg warfarin, digoxin,) may increase plasma conc. of these drugs and cause adverse reactions

 .

Tricylic Compounds include-

Tertiary amines - Amitriptyline,Clomipramine,Doxepin,Imipramine,Trimipramine

Secondary amines - Amoxipine, Desipramine, Nortriptyline,Portriptyline

Refer Amitriptyliine

CNS-

Drowsiness/sedation 39%,   dizziness /vertigo 19%,   headache 7%,   tremor 6%,    syncope 6%,      disturbed sleeping/nightmares 4%, restlessness 4%, 

hypokinesia.alkinesia 4%, , agitation 4%,   seizures.convulsion 3%,   rigidity 3%,        aksthisia 3%,    confusion 3%,    fatigue 2%,   insomnia 2%,       hyperkinesia 1%,

weakness 1%,    lethargy 1%,    ataxia 1%,    slurred speech 1%,       depression 1%, anxiety 1% 

Autonomic nervous system -

salivation 31%, sweating 6%, dry mouth 6%, visual disturbances 5%

Musculoskeletal - muscle weakness 1%, pain- back, neck,legs 1% , muscle spasm 1%, muscle pain ache 1%

Cardiovascular-

Tachycardia 25%,    hypotension 9%,               hypertension 4%,                 chest pain/angina 1%    ,ECG changes 1%

GI-

Constipation 14%,     nausea 5%     abdominal comfort /heartburn 4% ,         nausea/vomiting 3%      diarrhea 2% ,    liver test abnormality 1%, anorexia 1%

GU -

Urinary abnormalities 2%,      incontinence 1%,       abnormal ejaculation 1%,       urgency /frequency 1%    urinary retension 1%

Respiratory -

Throat discomfort 1%,    dyspnea, shortness of breath 1%,     nasal congestion 1%

Hemic/lymphatic -

Leukopenia/ decreased WBC /neutropenia 3% ,agranulocytosis 1%, eosinophilia 1%

Miscellaneous -

Fever 5%, weight gain 4%, rash 2%, tongue numbness/sore 1%

Myeloproliferative disorders,   history of clozapine-induced agranulocytosis or severe granulocytopenia,

simultaneous admin with other agents having well known potential to supress bone marrow function,

severe CNS depression or comatose states from any cause.

Special precautions:

Use caution when administering clozapine to patients with a history of seizures or other pre-disposing factors.

Advise patients not to engage in activity where sudden loss of consciousness could cause serious risk to themselves and to others.eg operating machinery, driving etc.

Cardiovascular disease- Carefully observe recommendation for gradual titration of dose.

Date of Approval      1995

Indications:

Scizophrenia

Dosage:

Initial -

Day 1 - 12.5mg once or twice daily

Day 2 - 25mg once or twice daily Increase by 25mg -50mg daily Over 2-3 weeks to 300mg daily in divided doses.

If necessary continue to increase by 50-100mg increments at 4-7 day intervals upto max dose of 900mg daily

Maint- 150-300mg daily in divided doses

If treatment break exceeds 2 days reititrate from initial dose of 12.5mg once or twice daily increasing gradually in increments of 25mg daily.

Refer Amitriptyline

 1.Warn patients about the significant risk of developing agranulocytosis. Inform them that weekly tests are required to monitor for the occurance of agranulocytosis.

2.Advise patients to report immediately appearance of lethargy,weakness,fever,sore throat,malaise,mucous membraine ulceration or other possible signs of infection.

3. Inform patients to avoid driving or doing other potentially hazardous jobs.

4. Advise patients of the risk of orthostatic hypotension,while during the period of treatment.

5. Patients should notify the physician if they are taking any prescription over -the -counter drugs or alcohol.

6. Patients should notify their physician,if they are pregnant or plan to become pregnant during therapy.

7.Patients should not breast feed an infant during therapy.

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

9. Pregnancy- has not been shown to cause birth defects or other problems in animal studies

10. Breast feeding- this medicine can pass into breast milk and cause sedation,decreased suckling, restlessness or irritatability, seizures or heart or blood vessel problems in nursing babies.

11.Children- no specific information available comparing use of clozapine in children with use in other age groups.

12.Elderly- clozapine is more likely to cause side effects in the elderly, including, dizziness, fainting, low blood presure and confusion or excitement.

13. Other medicines- tell your doctor if you are taking any other medicines- Alcohol or CNS depressants or Tricyclic antidepressants - clozapine may cause an increase in sedation or effects on the heart or increase the risk of seizures

14. Other medical problems- tell your doctor if you have any other medical problems- Blood diseases or Enlaged prostrate or difficult in urination or Gastrointestinal problems or Heart or blood vessel problems- clozapine may make the condition worse 

11. 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.

Pharmacology:

Clozapine is a tricyclic dibenzodiaziene derivative. and is classified as an atypical antipsychotic drug because its profile of binding to dopamine receptors.

Pharmacokinetics:

Clozapine is 95% bound to serum proteins. It is almost completely metabolised prior to excretion and only trace amount of unchanged drug are detected in the urine and feces.

Take with or without food

Pregnancy:

No adequate or well controlled studies on pregnant women. Use during pregnancy only if needed.

Lactation:

Women on clozapine therapy sholud not breast feed the infant.

Children:

Safety and efficacy in children below 16 years have not been established.