-
Phenothiazines
- chlorpromazine
- fluphenazine
- thioridazine
-
Thiozanthenes
Thiothixene
-
Butyrophenones
Haloperidol
-
atypicals
- clozapine
- olanzapine
- riperidone
-
antiemetics
- promethazine
- prochlorperazine
-
Positive symptoms of schizophrenia:
- hallucinations
- false ideas/beliefs (delusions)
- paranoid delusions
- mood disturbances
- confusion and suicidal thoughts
-
Negative symptoms of schizophrenia
- loss of normal function
- social withdrawal
- reduced speech and thought
- Loss of energy and inability to exp mental or physical pleasure
-
Etiology of schizophrenia:
- Biochemical abnormality: inc. # of DA rec
- Structural abnormalities: enlarged ventricles, atrophy of cortical layers, reduced volume of the basal ganglia
- Functional abnormalities: reduced cerebral blood flow, reduced glucose utilization in prefrontal cortex
- Genetic abnormalities: genetic predisposition, involvement of multiple genes
-
Therapeutic goals of antipsychotic drugs
prevention of self-inflicted harm or harm to others, provide the pt's basic needs, improve quality of life
-
Drugs to tx schizophrenia
- primarily block the response to inc/abnormal NT levels
- does not cure and/or eliminate disorder but dec the intesity of hallucinations and delusions
- control + symptoms; no direct control of - symptoms
- Non-compliance major reason for therapeutic failure
-
Dopamine hypothesis for schizophrenia
Drugs that are efficacious in tx of schizophrenia block DA recand drug efficacy correlates best to D2 rec binding
-
Antipsychotics: Efficacy and Metabolism
- provide symptomatic relief in 70% of pt
- sig dely of 4-8 weeks in onset of action
- met by liver
- Fluphenazine, haloperidol, resperidone: slow release formula - give IM for noncompliant pt
- Some tolerance, little dependence
-
Antipsychotics: side effects
- Cholinergic Muscarinic Rec Block (chlorpromazine, thioridazine) = dry mouth, urinary retention, memory impairment, blurred vision, constipation and confusion
- Alpha-Adrenorec Block (chlorpromazine) - orthostatic hypotension & light headedness, reflex tachycardia, sexual dysfunction
- Pituitary D2 Rec Block (All, mostly haloperidol) = inc in prolactin release --infertility and impotence
- H1-his Rec Block (chlorpromazine and clozapine) = sedation and weight gain
- Neuroleptic Malignant syndrom = collapse of ANS, fever, diaphoresis, CV instability -*immediate tx:bromocriptine (DA ag)
- Emetic Effects: nausea and vomiting
-
Antipsychotics: Central side effects
- Striatal DA rec block: Parkinsonian effects (bradykinesia, tremor, m. rigidity), dystonias (neck and facial spasms)
- DA rec upreg/supersensitivity: occurs after sev mo to yrs, tardive dyskinesias (invol oral-facial movements) which are irrev or slowly rev
-
Antipsychotics: interactions and adverse effects
- Induction of sev hepatic drug met enzymes: inc drug met
- Potentiation of CNS dep effects: analgesics, gen anesthetics and CNS dep
- Blockage of the therapeutic efficacy of L-DOPA: used to tx parkinson's disease
- Acute adverse effects only see @ very high doses: hypotension, hyper/hypo-thermia, seizures, coma, ventricular tachycardia
-
Typical vs. Atypical
- Typical (older): Fluphenazine, thioridazine, haloperidol = rel more selective for D2 rec + high potential for extrapyramidal effects (parkinsonism)
- Atypical (newer): Clozapine, olanzapine, risperidone = as/more selective for 5HT than D2 rec, some are effective @ low doses, low incidence of extrapyramidal effects, no inc prolactin, high risk agranulocytosis, inc weight gain
-
Implications to Dentistry
- Can add to CNS dep effects of antianxiety/sedative/hypnotic drugs, anesthetics, opiod analgesics
- secondary inf: oral candidiasis, agranulocytosis->susceptibility to infection
- Antipsychotics: dec salivary flow, inc caries
|
|