Anti-Depressant

Mohd Fikry bin Mohamad Tahir

(Student)
Classifications
Class
Tricyclic anti-depressant (TCA)
Monoamine oxidase inhibitors (MAOIs)
Selective 5-HT reuptake inhibitors (SSRIs)
Atypical anti-depressant (2nd generation)
Examples
Imipramine, Desipramine, Amitriptyline
Tranylcypromine, Phenelzine, Isocarboxazide
Fluoxetine,Fluvoxamine, Paroxetine, Setraline
Maprotiline, Mianserine
Tricyclic anti-depressant (TCA)
• Kinetics
• well absorbed from GIT
• widely distributed all over the body (lipopilic)
• highly bound to plasma protein > longer half life
• metabolized by the Liver (Hepatic Microsomal Enzymes)
• Excretion by Kidney
Mechanism of action
• Decrease level and activity of NA and 5-HT in CNS in depression.

• TCA reduce active reuptake of NA and 5-HT by nerve terminal > rise in
the level of these amines at the receptor side.

• Blockage occur immediately but the effects requires several weeks.

Actions
• CNS
• elevate mood, elevate mental alertness, increase physical activity, increase
appetite, increase sexual drive, reduce preoccupation with morbid thoughts.
• patient with depression, onset is delayed for 2-3 weeks.
• ANS
• anticholinergic effects (atropine like action)
• block alpha adrenergic receptor, serotonon & histamine
• CVS
• orthostatic hypotension
• tachycardia arrhythmia
• myocardial depression
Uses
• Unipolar depression
• Bipolar depression with lithium
• Paranoid schezohrena with antipsychotic agents
• Bulimia nervosa
Adverse effects
• delayed onset of action
• CNS: delirium, confusion, manic
• ANS
• atropine like action
• alpha blocking effect
• CVS : depression of myocardium
• Acute intoxicity
• Seizures
• Treatment
• gastric lavage, bicarbonate, benzodiazepines, physostigmine, phenytoin.
Drug interaction
• phenytoin, aspirin, phenothiazine compete with TCA for plasma
binding site.
• antipsychotic inhibit hepatic TCA metabolism.
• TCA can prevent action of antihypertensive agents
• potentiate CNS depressant, anticholinergic drugs
• serious ineraction exists between TCA and MAOI result in severe CNS
toxicity.
• advisable to stop TCA first (2-3weeks) before start of MAOI
Contraindication
• Glaucoma
• Benign Prostate Hypertrophy.
Monoamine Oxidase Inhibitors (MAOIs)
• Kinetics
• well absorbed orally
• distibuted all over the body
• metabolized by acetylation leading to inactive compound
• excreted in urine
Uses
• depression
• narcolepsy
• phobias
• Parkinson's disease: selegilline
Adverse effets
• delayed onset
• CNS : excitation, hallucination, hyperthermia, seizures
• anticholinergic synptoms
• orthostatic hypotension
• weight gain
• hepatotoxic
Drug Interaction
• cheese reaction: tyramine ingestion
• interaction with TCA may cause hyperthermia, hypertension,
convulsion and death
• serotonin syndrome: with SSRI
Selective serotonin reuptake inhbitors (SSRI)
• Drugs inhibit 5-HT specifically.
• Advantages:
• lack of anticholinergic and CVS side effect
• low acute toxicity
• no food reaction
Uses
• depression
• panic disorder
• obsessive compulsory disorder
• bulimia nervosa
• anorexia nervosa
Adverse effects
• anxiety, restlessness, insomia
• nausea, vomiting, diarrhea
• loss of libido, delayed ejaculation
Atypical anti-depressant
• Advantages
• fewer side effect
• lower acute toxicity
• less delayed in action
• efficacy in patients non responsive to TCA and MAOI.
adverse affects
• hypertension
• seizures
thank you