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ANTIPSYCHOTIC DRUGS

Setyawati S Karyono

Antipsychotic (antipsychotics = neuroleptic)


Effect in Psychosis Patient
Excitation Agitation Hostile Irritable Anxious Suspicious More cooperative Begin to parcipitate in act Continued Therapy Hallucinations, delusions, paranoid (-) Disordered Thought Processes (-)

Relieve manic phase in bipolar

Antipsychotic -conventional / typical


Antagonist Dopamine receptor, 5-HT2 rec. Receptor Inhibition adrenergik-, muscarinic, ctz, histamine
Indication schizophrenia psychotic depression drug induced psychosis prevent psychosis rellaps

-atypical

Side effecct extrapyramidal symptoms

Atypical more effective & side effect <<

Antipsychotic conventional
1.Phenothiazine

(Phenothiazine, Haloperidol)

Pharmacological Effects

Behavioral quieting of agitated Px, hallucinations , sedation, spontaneous activity cataleptic state (in high doses)
Seizure threshold precipitate epilepsi Ekstrapyramidal effects

Antipsychotic effectblock rec.Dopamine (D2, D1


Parkinsonism, dystonia akut, tardive diskinesia (mayor problem), perioral tremor (rabbit syndrome)

Antiemetic effect Autonomic effects (-blocker, anticholinergic) Antihistaminic, antiserotonergic CVS qunidin-like effect Endocrine prolactin , gynecomastia, menstruation disturbances & ovulation

Side Effects
CNS drowsiness,parkinsonism etc Autonomics Endocrine Hypersensitivity allergy rash, photosensitivity, agranulocyitosis Toxic retinopathy BW gain Neuroleptic malignant syndrome (fever, musc. rigidity, stupor, respiratory & autonomic dysfungtion, leukocytosis) stop drug, supportive therapy, bromocriptine

Drug Interaction
Potentiation of CNS depressant & opioids Inhibition alcohol metab., phenitoin Effectiveness of levodopa in therapy parkinson
Additive anticholinergic & -blocker With antiarrythmia drug

2.Haloperidol
Mechanism and effect similar to the phenothiazines, but prefered in certain type of disorders Anticholinergic effect (-) Autonomic effect << hypotensive (+)

Atypical Antipsychotic
Receptor binding Antipsychotic D1 D2 5-HT2 -1 khol hist Clozapine ++ + +++ +++ +++ ++ Olanzepine ++ ++ +++ ++ +++ ++ Ouetiapine (+) + + ++ ++ Risperidone +++ +++ +++ Sertindole + +++ ++ Ziprasidone + +++ +++ ++

Relative Adverse Effect Profiles*


*1 is high, 4 is low
DRUG SEDATION EXTRAPYR ANTICHOLIN HYPOTENSION

Haloperidol
Fluphenazine

4
4

1
1

4
3

4
4

Thiothixene
Trifluoperazine Perphenazine Molindone Loxapine Chlorpromazine

3
3 3 4 3 1

2
2 2 3 3 3

3
3 3 4 3 2

4
4 4 4 3 1

Thioridazine Clozapine
Risperidone

1 1
4

4 4
4

1 1
4

1 1
3

ANTIDEPRESSANT

Depression Affective Disorders


- Major (Unipolar) Depression

- Dysthymia - Bipolar Affective Disorder

Major (Unipolar) Depression :


Two weeks or more of: -depressed mood -anhedonia -changes in appetite/ sleep -psychomotor agitation/ retardation -decreased concentration -thoughts of death/ suicide

Dysthymia
Persistent (2 + years) of: -depressed mood -poor appetite/ overeating -insomnia/hypersomnia -low energy, fatigue -poor self esteem -poor concentration -hopelessness

Mixed Disorder

Baseline of Dysthymia with intermittent bouts of major depression

Bipolar Disorder
Intermittent bouts of depression with mania or hypomania Depressive Phase: Varying degrees of depressed mood Mania Phase:

Inflated Self Esteem, decreased need for sleep, very talkative, flight of ideas, distractible, psychomotor agitation, excessive preoccupation with pleasurable activities

TREATMENT ANTIDEPRESSANT
Unipolar Depression/ Dysthymia
1.MAO Inhibitors monoamine (NE, dopamine) in synaps , improve mood response after several weeks
Side effects CVS, BW , intoxication brain, hepar Drug Interaction potentiation with sympatetic drug, tyramine, others antidepressant, inhibits drug metbolism Tranylcypromine- irreversible inhibitor of MAO-A,B uncommon use

2.Tricyclic Antidepressants:
(2nd Generation)

Inhibition uptake NE, 5-HT, DA Sedationantihistamine Anticholinergic effect CVS palpitation, tachycardi, arrythmia, hypotension down regulation 5-HT1A, D, & -2 receptors time delay in therapeutic action Metabolism : Imipramine Desipramine Amitriptylene Nortriptylene Parent Drug Active Metabolite

Tricyclic Antidepressants Side Effects


Sedation: H1-R blockade? Anticholinergic: Muscarinic Receptor blockade : dry mouth, blurred vision, urinary retention/ ileus/constipation, sexual dysfunction dellirium/confussion, precipitation of glaucoma Vascular: 1 blockade orthostatic hypotension Cardiac: quinidine-like effects concentration dependent T wave flattening or inversion myocardial depression arrhythmias (high conc.)

Tricyclic Antidepressants

Drug Interactions
Inhibition of P-450 Enzymes Reduction of Antihypertensive Actions Reduction of Seizure Threshold Additive Sedative Effects with Alcohol and other Depressants Enhancement of Anticholinergics

Tricyclic Antidepressants

Toxicity/Overdose
Narrow therapeutic window Restrict Rx amount Overdose may result in: Hypotension, shock, renal failure Grand mal seizures Hyperpyrexia Conduction disturbancesArrhythmias

Other indication Tricyclic Antideprssant


- Catalepsy (Narcolepsy) - Chronic Pain (Migraine) - Panic Disorder - Post-traumatic Stress Disorder - Enuresis - Eating Disorders

3rd Generation Antidepressants


Miscellaneous Drugs Heterocyclics Trazadone Buproprion Serotonin Selective Reuptake Inhibitors (SSRIs) Revolution in the treatment of depression: Safer! Less side effects: No Effects on Cholinergic, Histamine, or -adrenergic Receptors Fluoxetine- Most prescribed antidepressant

Misc. Antidepressants
HeterocyclicsAmoxipine- nonselective Maprotiline- NE selective Trazodone-5-HT selective atypical , sedating no antichol. actions Buproprion- DA selective smoking cessation, ADHD

Treatment Bipolar Disorder


Lithium : Acute Mania Prophylaxis (70% respond) Side Effects: Memory problems, weight gain, tremor, polyuria, drowsiness Hypothyroidism Cardiac Effects

Tx Bipolar Disorder
Valproate (anticonvulsant) Carbamazepine (anticonvulsant)
Haloperidol (antipyschotic)