Egleton: Antipsychotics Flashcards
Nigrostriatal tract
Extrapyramidal side effects
Mesolimbic tract
Positive symptoms
Increased DA
Treat with Typical antipsychotics
Mesocortical tract
Negative symptoms
Decreased DA
Treat with Atypical antipsychotics
Tuberoinfundibular tract
Inhibit DA
Prolactin related side effects
Causes of acute psychosis: meds
Phencyclidine/ Hallucinogengs
Amphetamins, Cocaine
Alcohol withdrawal
Sedative-hypnotic withdrawal
Almost all lead to Visual hallucination
Causes of acute psychosis: toxic agents
Heavy metals (Hg)
Digitalis toxicity
L-Dopa
Causes of acute psychosis: metabolic causes
Hypoglycemia Acute intermittent porphyria Cushing's syndrome Hypo/hypercalcemia Hypo/hyperthyroidism
Causes of acute psychosis: nutritional
Thiamine, Niacin Vit B12 deficiencies
Causes of acute psychosis: neurological
Stroke
Brain tumor
Early Alzheimer’s/ Pick’s
Hypoxic encephalopathy
Positive symptoms of Psychosis
Agitation Delusions Disorganized speech and thinking Hallucinations Insomnia
Negative symptoms of Psychosis
Apathy Affective flattening Lack of motivation and pleasure Poverty of speech Social isolation
Antipsychotics: MoA
Competitive blockade of DA and 5-HT
Typical: affinity = D2 > 5HT2
Atypical: affinity= 5HT2 > D2
{Selectivity for Mesolimbic over Nigrostriatal}
Antisychotics: ADR causes
Blockade of alpha1 adrenergic/ Histamine H1/ Muscarinic
Receptor binding profiles for Typical and Atypical
Typical: mostly D2
Atypical: better 5-HT2 but all over otherwise
D2 receptors action
Coupled to Gi and Go
Blockade= increase DA synthesis, and release, increase cAMP, decrease K current
Dopaminergic presynaptic effects
Short term treatment: Activated neurons
Long term treatment: Inactivated neurons
Doperminergic postsynaptic effects
Short term treatment: Receptor blockade
Long term treatment: Receptor supersensitivity
All antispychotics can be used as anti-emetics except
Aripiprazole, Thioridazine
{By blocking D2 receptors in CTZ}
Haloperidol
Treat Gilles de la Tourette’s syndrome/ Huntington’s disease
Chlorpromazine
For intractable hiccough,
Deposits in lens and cornea
Contra: Seizures {lower threshold}
Thioridazine
Deposits in retina at higher doses
Prochlorperazine
Treat drug induced nausea for chemo
Scopolamine
For Motion sickness
Droperidol
Component of neuroleptanesthesia
Dopamine: Extrapyramidal side effects
Akinesia (feeling of restlessness)
Pseudoparkinsonism (Rigidity, pill-rolling etc)
Dystonias (Facial grimacing, Torticollis)
More common in typicals (D2 specific)
Dopamine: Tardive dyskinesia
Develops after months/ years of treatment
Abnormal oral/ facial movements
{Due to supersensitivity to DA after long term DA receptor blockade}
Worse with withdrawal
No adequate therapy for advanced case
More common in typicals
Low incidence with Clozapine (Atypical)
Dopamine: Neuroleptic malignant syndrome
{Medical emergency}
Muscle rigidity
Elevated temperature
Altered consciousness
Autonomic dysfunction (Tachycardia, Diaphoresis, Tachypnea, Urinary/ Fecal incontinence)
Stop antipsychotics
Treat with Bromocriptin (D2 agonist) and Dantrolene
More common in Typicals
Dopamine: prolactin
Increased serum Prolactin by blockade of DA receptors in Tuberoinfundibular pathway
Issues with compliances (loss of libido, menstrual irregularities, osteoporosis etc)
Switch treatment
Common with Phenothiazines (Chlorpromazine, Fluphenazine, Thioridazine, Trifluperazine, Mesoridazine, Perphenazine)
{-zine’s}
Cholinergic (M1): side effects
Dry mouth Blurred vision Urinary retention Constipation Confusion
Switch to drug with lower M1 activity
By Thioridazine, Chlorpromazine, Olanzapine
Clozapine too, but it increases salivation
Adrenergic (alpha1A, 2A): side effects
Orthostatic hypotensin
Syncope
Inhibit ejaculation without affecting erection
Switch to drug with lower alpha activity
By Chlorpromazine and Mesoridazine
Histamine (H1): side effects
Sedation
Switch drug
By Chlorpromazine, Olanzapine, Quetiapine, Clozapine
Antipsychotics: metabolic side effects
Sedation, Lack of movement
Endocrinological changes
Cause Type II diabetes, Hypertension, Hyperlipidemia
More common with Atypicals
Substantial but reversibe
Antipsychotics: other ADR
Leukopenia, Agranulocytosis (by Clozapine)
Occur in 6-18 weeks of treatment
Monitor blood cell count
Perioral tremor= Rabbit syndrome
Rare, with prolonged antipsychotic use (years)
Can be treated with anticholinergic antiparkinson drugs
Minor T wave abnormality (by Thioridazine)
QT prolongation (by Ziprasidone)
Antipsychotics: Contra
Pregnant, Nursing mothers
Opioid analgesics and Central depressants.
Anogetanubes (antagonize antipsychotic effects)
Centrally acting anticholinergics (worsen Tardive dyskinesia)
SSRI (worsen extrapyramidal symptoms)
Antihypertensives (more hypotensive effects)
