Psychiatry-Psycho-pharmacology

Typical Antipsychotics
• D2 receptors
• Phenothiazines
Aliphatic: Chlorpromazine; Triflupromazine
Piperidine: Thioridazine;
Piperazine: Trifluoperazine; Prochlorperazine.
• Thioxanthene: Thiothixene; Flupentixol
• Butyrophenone: Haloperidol
• Dibenzoxazepine: Loxapine
• Diphenylbutyl piperidine: Pimozide
• LA preparations
• Neurological: Akathisia
• Acute dystonia
• Drug-induced parkinsonism
• Neuroleptic malignant syndrome
• Tardive dyskinesia and dystonia; Perioral tremor; more with high
potency
• Sedation; Lowering of seizure threshold; Central and peripheral
anticholinergic side effects; Orthostatic Hypotension, cardiotoxicity,
allergic dermatitis, photosensitivity: more with low potency drugs.
• Thioridazine and mesoridazine, in particular, are associated with
substantial QT prolongation and risk of torsade de pointes.
• Cholestatic or obstructive jaundice can be caused by chlorpromazine.
 Atypical Antipsychotics : Serotonin-
Dopamine Antagonists (SDA)
• Risperidone :
– Undergoes extensive first pass hepatic metabolism to 9
hydroxyrisperidone, a metabolite with equivalent antipsychotic activity.
– Risperidone is the only SDA currently available in a depot formulation.
– Side effects: weight gain, hyperprolactinemia, anxiety and increased
pigmentation.
• Olanzapine:
– Available in injection form for acute care
– Side effects include: Weight gain: Somnolence, increased appetite,risk of
metabolic syndrome
• Quitiapine : Side effects: Somnolence, postural
hypotensions
• Ziprasidone : side effect : prolong the QT interval.
• Clozapine :Side effects:
• Arpiprazole
 Potent 5-HT2A antagonist but partial D2 agonist.
 Usually nonsedating and has not been found to pose an
increase risk of weight gain, diabetes and
hyperprolactinemia.
• Paliperidone : Active metabolite risperidone
• Asenapine: Only for sublingual use.
Medication-Induced Movement Disorder
Neuroleptic-Induced Parkinsonism:
Rabbit Syndrome: a tremor affecting the lips and
perioral muscles
Neuroleptic-Induced Acute Dystonia
Neuroleptic- Induced Acute Akathisia
Tardive dyskinesia
Neuroleptic Malignant Syndrome
• Medication-Induced Postural Tremor
Treatment: ß-adrenergic receptor antagonists can be given.
Lithium
Mechanism of action: Alterations of ion
transport and effects on neurotransmitters
and neuropeptides, signal transduction
pathways, and second messenger systems.
Relatively slow onset of action when used and
exerts its anti-manic effects over 1-3 weeks.
• Neurologic: Dysphoria, lack of spontaneity, slowed reaction time,
memory difficulties, postural tremor
• Toxic: Coarse tremor, dyarthria, ataxia, neuromuscular irritability,
seizures, coma, death
• Miscellaneous: Peripheral neuropathy; benign intracranial
hypertension, myasthenia gravis-like syndrome, altered creativity,
lowered seizure threshold
• Endocrine
• Thyroid: goiter, hypothyroidism, exophthalmos,
hyperthyroidism (rare)
• Parathyroid: hyperparathyroidism, adenoma
• Lithium-induced hypothyroidism is more common in
women (14 percent) than in men (4.5 percent). Women are
at highest risk during the first 2 years of treatment.
• Cardiovascular
• Benign T- wave changes (inverted T wave), sinus node
dysfunction
• Cardiac effects of lithium resemble those of
hypokalemia on the electrocardiogram
• Renal
• Concentrating defect, morphologic changes, polyuria
(nephrogenic diabetes insipidus), reduced GFR,
nephritic syndrome, renal tubular acidosis
• Most common adverse renal effect : polyuria with
secondary polydipsia
• Most serious: nonspecific interstitial fibrosis
• Dermatologic : Acne, hair loss, psoriasis, rash
• Gastrointestinal: Appetite loss, nausea, vomiting, diarrhea
• Miscellaneous : Altered carbohydrate metabolism, weight gain, fluid
retention

Lithium Toxicity
• Early signs and symptoms: coarse tremor, dysarthria, and ataxia; GI
symptoms; cardiovascular changes; and renal dysfunction
• Later signs and symptoms include impaired consciousness, muscular
fasciculation’s, myoclonus, seizure, and coma.
• Treatment
• Stop lithium, correct dehydration, ingestion of polystyrene sulfonate or
polyethylene glycol solution but not activated charcoal.
• Severe cases: haemodialysis
• Lithium in Pregnancy
– Should not be administered to pregnant women in the first trimester
because of the risk of birth defects
– Most common malformations involve the cardiovascular system, most
commonly Ebstein’s anomaly of the tricuspid valves.
• Initial Medical Workup before starting lithium should include
– Serum creatinine concentration (or a 24 hour urine creatinine if the clinician
has any reason to be concerned about renal function)
– Electrolyes
– Thyroid function (TSH, T3, and T4)
– Complete blood count (CBC)
– ECG
– Pregnancy test
 Carbamezepine
Adverse effects
• Mild GI (nausea, vomiting, gastric distress, constipation, diarrhea,
and anorexia) and CNS (ataxia, drowsiness) are the most common
side effects.
• Most of the adverse effects are correlated with plasma
concentrations above 9 ug/mL.
• Dosage related Adverse effects
– Double or blurred vision
– Vertigo
– Gastro-intestinal disturbances
– Task performance impairment
– Hematologic effects
• Idiosyncratic Adverse Effects
– Agranulocytosis
– Stevens- Johnson syndrome
– Aplastic anemia
– Hepatic failure
– Rash Pancreatitis
• Blood dyscrasias:
• Hepatitis
• Dermatologic Effects
– About 10-15% develops a benign maculopapular rash within the first
3 weeks of treatment. Stopping the medication usually leads to
resolution of the rash.
– Exfoliative dermatitis, erythema multiforme, Stevens-Johnson
syndrome, and toxic epidermal necrolysis.
– Pretreatment with prednisone may suppress the rash.
• Renal Effects
– Occasionally used to treat diabetes insipidus not associated
with lithium use.
– Results from direct or indirect effects at the vasopressin
receptor
– Hyponatremia and water intoxication in some pts. Particularly
the elderly or when used in high doses.
• Minor cranial facial abnormalities, fingernail hypoplasia, and spina
bifida in infants may be associated with the maternal use during
pregnancy.
• The anticonvulsant blood concentration range for carbamazepine
is 4 to 12 ug/mL and this range should be reached before
determining that carbamazepine is not effective in the treatment
of a mood disorder
 Oxcarbazepine
• Structurally related to carbamazepine
• Most common side effects are sedation and nausea
• In contrast to carbamazepine, oxcarbazepine does not have
an increased risk of serious blood dyscrasias, so hematologic
monitoring is not necessary.
• The frequency of benign rash is lower than observed with
carbamazepine, and serious rashes are extremely rare.
• Oxcarbazepine is more likely to cause hyponatremia than
carbamazepine (3-5%)
Valproate
• Important side effects include weight gain,
sedation, teratogenicity (neural tube defects),
hair loss, tremors, thrombocytopenia
Tricyclics Antidepressants
• Adverse effects: Switch to mania, exacerbate
psychosis , Anticholinergic Effects , Cardiac
Effects , Orthostatic hypotension , Sedation
• Toxicity mngt: Sodium bicarbonate, magnesium
sulphate
• Selective serotonin reuptake inhibitors
• Fluoxetine, Sertraline, Paroxetine, Fluvoxamine, Citalopram Escitalopram
• Fluoxetine has the longest half-life 4 to 6 days; Other SSRI’s about 24
hour
• Adverse Reaction : Sexual Dysfunction, loose stool, diarrhea, anorexia,
• Serotonin syndrome : Concurrent administration of an SSRI with an
MAQI, L-tryptophan, or lithium can raise plasma serotonin
concentrations to toxic levels, producing a constellation of symptoms
• Diarrhea
• Restlessness
• Extreme agitation, hpyerreflexia, and autonomic instability
• Myoclonus, seizures, hyperthermia, uncontrollable shivering, and
rigidity
• Delirium, coma, status epilepticus, cardiovascular collapse, and death.
• Selective Serotonin – Norepinephrine Reuptake
Inhibitors
Venlaflaxine, Duloxetine, Milnacipran,
Desvenlaflaxine
• Venlafaxine can cause an increase in blood pressure
(BP) in some persons.
• Mirtazapine and Nefazodone : Does not cause the
sexual side effects and sleep disruption
• Bupropion
• Tianeptine : Increase (rather than inhibit) 5-HT
uptake.
Monoamine Oxidase Inhibitors
• Currently available MAOIs :Phenelzine, isocarboxazid,
tranylcypromine
• More effective than TCA’s in treatment of atypical
depression
• Tyramine-induced Hypertensive Crisis :MAOIs,
however, inactiviate GI metabolism of dietary
tyramine, thus allowing intact tyramine to enter the
circulation.
• Pts on MAOI’s should avoid tyramine reach foods :
Cheese, alcoholic beverages
Electroconvulsive Therapy
• Major Depressive Disorder
• Manic episodes
• Schizophrenia
• Catatonia
• Refusal to food (Life saving)
• Suicidal patient
• Methohexital
• Succinylcholine
• Bi-lateral
• Brief-pulse
• 25 seconds
• Contraindications :No absolute contraindicztions
• Relative contraindications
– Space-occupying central nervous system lesions.
– Increased intracerebral pressure
– Cerebrovascular disases and aneurysms
– Recent myocardial
– Hypertension
• Adverse effects
– Most common complication of un-modified ECT: Fracture spine
– Most common complication of modified ECT is amnesia.
• Most common is retrograde amnesia
• Recovery from amnesia occurs in 6-9 months