Egleton: Antipsychotics

Question 1

Nigrostriatal tract

Answer 1

Extrapyramidal side effects

Question 2

Mesolimbic tract

Answer 2

Positive symptoms
Increased DA
Treat with Typical antipsychotics

Question 3

Mesocortical tract

Answer 3

Negative symptoms
Decreased DA
Treat with Atypical antipsychotics

Question 4

Tuberoinfundibular tract

Answer 4

Inhibit DA

Prolactin related side effects

Question 5

Causes of acute psychosis: meds

Answer 5

Phencyclidine/ Hallucinogengs
Amphetamins, Cocaine
Alcohol withdrawal
Sedative-hypnotic withdrawal

Almost all lead to Visual hallucination

Question 6

Causes of acute psychosis: toxic agents

Answer 6

Heavy metals (Hg)
Digitalis toxicity
L-Dopa

Question 7

Causes of acute psychosis: metabolic causes

Answer 7

Hypoglycemia
Acute intermittent porphyria
Cushing's syndrome
Hypo/hypercalcemia
Hypo/hyperthyroidism

Question 8

Causes of acute psychosis: nutritional

Answer 8

Thiamine, Niacin Vit B12 deficiencies

Question 9

Causes of acute psychosis: neurological

Answer 9

Stroke
Brain tumor
Early Alzheimer’s/ Pick’s
Hypoxic encephalopathy

Question 10

Positive symptoms of Psychosis

Answer 10

Agitation
Delusions
Disorganized speech and thinking
Hallucinations
Insomnia

Question 11

Negative symptoms of Psychosis

Answer 11

Apathy
Affective flattening
Lack of motivation and pleasure
Poverty of speech
Social isolation

Question 12

Antipsychotics: MoA

Answer 12

Competitive blockade of DA and 5-HT
Typical: affinity = D2 > 5HT2
Atypical: affinity= 5HT2 > D2
{Selectivity for Mesolimbic over Nigrostriatal}

Question 13

Antisychotics: ADR causes

Answer 13

Blockade of alpha1 adrenergic/ Histamine H1/ Muscarinic

Question 14

Receptor binding profiles for Typical and Atypical

Answer 14

Typical: mostly D2
Atypical: better 5-HT2 but all over otherwise

Question 15

D2 receptors action

Answer 15

Coupled to Gi and Go

Blockade= increase DA synthesis, and release, increase cAMP, decrease K current

Question 16

Dopaminergic presynaptic effects

Answer 16

Short term treatment: Activated neurons

Long term treatment: Inactivated neurons

Question 17

Doperminergic postsynaptic effects

Answer 17

Short term treatment: Receptor blockade

Long term treatment: Receptor supersensitivity

Question 18

All antispychotics can be used as anti-emetics except

Answer 18

Aripiprazole, Thioridazine

{By blocking D2 receptors in CTZ}

Question 19

Haloperidol

Answer 19

Treat Gilles de la Tourette’s syndrome/ Huntington’s disease

Question 20

Chlorpromazine

Answer 20

For intractable hiccough,
Deposits in lens and cornea
Contra: Seizures {lower threshold}

Question 21

Thioridazine

Answer 21

Deposits in retina at higher doses

Question 22

Prochlorperazine

Answer 22

Treat drug induced nausea for chemo

Question 23

Scopolamine

Answer 23

For Motion sickness

Question 24

Droperidol

Answer 24

Component of neuroleptanesthesia

Question 25

Dopamine: Extrapyramidal side effects

Answer 25

Akinesia (feeling of restlessness)
Pseudoparkinsonism (Rigidity, pill-rolling etc)
Dystonias (Facial grimacing, Torticollis)

More common in typicals (D2 specific)

Question 26

Dopamine: Tardive dyskinesia

Answer 26

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)

Question 27

Dopamine: Neuroleptic malignant syndrome

Answer 27

{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

Question 28

Dopamine: prolactin

Answer 28

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}

Question 29

Cholinergic (M1): side effects

Answer 29

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

Question 30

Adrenergic (alpha1A, 2A): side effects

Answer 30

Orthostatic hypotensin
Syncope
Inhibit ejaculation without affecting erection

Switch to drug with lower alpha activity

By Chlorpromazine and Mesoridazine

Question 31

Histamine (H1): side effects

Answer 31

Sedation

Switch drug

By Chlorpromazine, Olanzapine, Quetiapine, Clozapine

Question 32

Antipsychotics: metabolic side effects

Answer 32

Sedation, Lack of movement
Endocrinological changes
Cause Type II diabetes, Hypertension, Hyperlipidemia

More common with Atypicals
Substantial but reversibe

Question 33

Antipsychotics: other ADR

Answer 33

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)

Question 34

Antipsychotics: Contra

Answer 34

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)