Antipsychotic drugs 1 Dopamine serotonin hypothesis of schizophrenia 2 Classification of antipsychotic drugs 3 Basic concepts about their receptors action 4 Basic concepts about their related effects side effects and how to manage them ID: 1047936
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1. Shaymaa F. AbbasMsc PharmacologyAntipsychotic drugs
2. 1. Dopamine- serotonin hypothesis of schizophrenia2. Classification of antipsychotic drugs3. Basic concepts about their receptors action4. Basic concepts about their related effects/ side effects and how to manage themLearning objectives
3. Dopamine Chemoreceptor trigger zoneDopamine= vomitingMesolimbic pathwayDopamine= PsychosisPituitary glandDopamine= ProlactinBasal ganglia Dopamine= Extrapyramidal symptoms (eg: parkinsonism)
4. The antipsychotic drugs Psychosis (from the Greek , psyche, "mind ", and -osis, "abnormal condition or derangement") refers to an abnormal condition of the mindThe antipsychotic drugs (also called neuroleptics or major tranquilizers) are used primarily to treat schizophrenia, but they are also effective in other psychotic and manic states.
5. Schizophrenia is a type of chronic psychosis characterized by: Positive symptoms: Thought disorders, Delusions, Hallucinations, Paranoia Negative symptoms: loss of motivation, Social withdrawal, Flat affect, Poverty of speechCognitive impairment "Dopamine hypothesis": Symptoms arise because of excessive dopaminergic activity in mesolimbic system. Serotonin is increasingly seen as a part of the etiology of schizophrenia. May be linked to negative symptoms
6. 1- Typical antipsychotics: 1st generationPhenothiazines: Chlorpromazine, Thioridazine, Promethazine Haloperidol: Most likely cause of neuroleptic malignant syndrome (NMS) and Tardive dyskinesia2- Atypical antipsychotics: 2nd generationClozapine: Agranulocytosis-requirement for frequent blood testOlanzapine, Risperidone Classification of antipsychotics
7. 1st generation antipsychotics are more likely to be associated with movement disorders known as extrapyramidal symptoms (EPS), particularly drugs that bind tightly to D2 receptors, such as haloperidolMovement disorders are less likely with medications that bind weakly, such as chlorpromazine.
8. Mechanism of action of antipsychoticsAll of the 1st generation and most of the 2nd generation antipsychotic drugs block D2 receptors in the brain & periphery.Atypical antipsychotics exert part of their action through blocking of serotonin receptors ((5-HT2A )) receptorsSome of atypical antipsychotics blocks D1,D4 receptors, with weak affinity to D2 receptorsAdditional mechanisms for both typical and atypicals: antagonism on α1, Muscarinic , H1
9. Clinical usesSchizophrenia and schizoaffective states Bipolar disorder Drug or radiation emesis Intractable hiccup—chlorpromazinePruritus —promethazineCo-analgesic in chronic pain and terminal illnessOthers
10. Side effects of antipsychoticsSide effects from dopamine blockade: 1- Dyskinesias (extrapyramidal symptoms [EPS]) mainly with typical(1st generation)Reversible EPS: Pseudoparkinsonism (drug-induced parkinsonism), dystonia, akathisia Chronic EPS: Tardive dyskinesia (TD)
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12. Side effects of antipsychoticsTardive dyskinesia—this important toxicity includes choreoathetoid movements of the muscles of the lips and buccal cavity and may be irreversible. It tends to develop after several years of antipsychotic drug therapy but may appear as early as 6 monthsAntimuscarinic drugs generally increase the severity of tardive dyskinesia symptoms.
13. 2- Endocrine dysfunctionHyper prolactinemia (galactorrhea, amenorrhea, gynecomastia), sexual dysfunctionMetabolic disorders: eating disorders (weight gain), glucose intolerance, dyslipidemia : mainly with atypical 3-Temperature regulation problems (Poikilothermia)Side effects –dopamine blockade –continue
14. 4. Neuroleptic malignant syndrome Rare but fatal adverse effect that can occur at any time during treatmentThe onset of symptoms is rapid with increased temperature, severe muscular rigidity, confusion, agitation, elevation in WBC count, elevated CPK concentrations, elevated liver enzymes, myoglobinuria, and acute renal failure. The antipsychotic should be immediately discontinuedAdequate hydration, cooling, and close monitoring of vital signs and serum electrolytes. Treated with dantrolene and bromocriptineThe risk of neuroleptic malignant syndrome is higher with first-generation antipsychotics, Second-generation antipsychotics also cause this adverse effect
15. Side effects from muscarinic blockade All cause dry mouth except clozapine causes hyper salivation Side effects from α-blockade (particularly hypotension)Side effects from H1 blockade: sedation Cardiotoxicity: prolongation of QT interval, myocarditis, sudden death Other side effectsSeizure: chlorpromazine, clozapineImmune mediated reactions: Photosensitivity, Cholestatic jaundice-especially with chlorpromazine, agranulocytosis (clozapine)
16. Parenteral forms of many agents (e.g. Fluphenazine decanoate, haloperidol decanoate and olanzapine pamoate) are long-acting injectable (LAI) formulations of antipsychotics. These formulations have a therapeutic duration of action of up to 2 to 4 weeks and, therefore, are often used to treat out- patients and individuals who are non-adherent with oral medications Long acting formulations
17. Typical Vs. Atypical Mainly DAMainly D2Treat mostly POSITIVE symptomsMore EPS adverse effectsLess useful in refractory diseaseDA and 5HTD1+D2+D4+5HTTreat POSITIVE and NEGATIVE symptomsLesser EPSUseful in refractory disease
18. A woman taking haloperidol developed a spectrum of adverse effects that included the amenorrhea-galactorrhea syndrome and extrapyramidal dysfunction. Another, newer, antipsychotic drug was prescribed which however caused weight gain and hyperglycemia due to a diabetogenic action. The drug prescribed was(A) Bupropion(B) Chlorpromazine(C) Fluoxetine(D) Lithium(E) Olanzapine
19. The reason why clozapine causes less extrapyramidal dysfunction than haloperidol when used in schizophrenia is that in the CNS, clozapine(A) Activates GABA receptors(B) Blocks dopamine release(C) Has greater antagonism at muscarinic receptors(D) Has a low affinity for dopamine D2 receptors(E) Is an α-receptor agonist
20. A young male patient recently diagnosed as schizophrenic develops severe muscle cramps with torticollis a short time after drug therapy is initiated with haloperidol. The best course of action would be to(A) Add risperidone to the drug regimen(B) Discontinue haloperidol and observe the patient(C) Give oral diphenhydramine(D) Inject benztropine(E) Switch the patient to fluphenazine
21. Thank you