Antipsychotics

Question 1

Mention role of dopamine receptors in schizophrenia & effect if drugs

Answer 1

Positive symptoms result from inc dopamine activity on D2 receptor in mesolimbic pathway
Negative symptoms result from dec dopamine activity on D2 receptor in PFC or mesocortical pathway
All antipsychotics block D2 receptor
Atypical antipsychotics only block 5-HT2A, thus inc dopamine in PFC

Question 2

Mention advantages of typical antipsychotics

Answer 2

Cheaper
Fast actibg IM (Haloperidol) & inhalation of agitation
Long acting injectiable “depot” formulations for patients who can’t adhere to treatment

Question 3

Mention uses of typical antipsychotics

Answer 3

I. Antipsychotic
1. Violent patient
2. 1ry psychosis: dec hallucinations & delusions in few weeks
Schizophrenia, mania in bipolar depression, psychotic depression
3. 2ry psychosis: brain tumour, cocaine, dementia
II. Antiemetic

Question 4

Enumerate side effects of antipsychotics D2-action

Answer 4

1. Extrapyramidal side effects
2. Inc prolactin: gynecomastia, galactorrhea, amenorrhea, infertility
3. Inc body weight

Question 5

Enumerate effects of antipychotic autonomic blockade

Answer 5

H1: sedation, inc body weight
M: atropine side effects
A: postural hypotension

Question 6

Mention miscellaneous side effects of antipsychotics

Answer 6

Cardiotoxic (inc QT)
Convulsions
Corneal lens deposits
Cholestatic jaundice

Question 7

Enumerate extrapyramidal side effects of antipsychotics with mechanism

Answer 7

Akathisia, dystonia, both due to D2 blockade in basal ganglia
parkinsoism, due to D2 blockade in basal ganglia+ relative inc in cholinergic activity
Tardive dyskinesia: supersensitivity of DA receptors following choric blockade
Neuroleptic malignant syndrome due to excessive rapid blockade of DA receptors in patients sensitive to extrapyr effects of neuroleptics (idiosyncrasy)

Question 8

Describe managment of extrapyramidal side effects of antipsychotics

Answer 8

1. Propronolo for akathesia
2. Anticholinergics: benzotropine may be given routinely with antipsychotics as prophylaxis against extrapyramidal side effects but may exacerbate tardive dyskinesia

Question 9

Describe symptoms & management of neuroleptic malignant syndrome

Answer 9

Muscle rigidity, hyperpyrexia, stupor, altered mental status, myoglobinemia, unstable BP
Managed by dicontinuation of antipsychotic, muscle relaxant (dantrolene, diazepam), antiparkisonian durgs, DA agonist bromocriptine.

Question 10

Compare high & lowotency typical antipsychotics

Answer 10

Low: chlorpromazine & thioridazine, less autonomic side effects, more autonomic & miscellaneous side effects
High: haloperidol, fluphenazine, more central side effects, lessautonomic & miscellaneous thus preferred in elderly/cardiac patients

Question 11

Enumerate advantages of atypical antipsychotics

Answer 11

1. Less central side effects: less extrapyramidal s.e. & less prolactin induced side effects (ex respieridone)
2. More efficacy as they improve negative symptoms also.

Question 12

…….is effective & reserved for resistant cases
Justify.

Answer 12

Clozapine
Due to inc risk of agranulocytosis & seizures, inc autonomic side effects & inc body weight & insulib resistance (INC DM), but has least central side effects

Question 13

Disadvantages of resperidone

Answer 13

Inc prolactin & QT interval

Question 14

The antipsychotic causing most inc body wight is….., while…..is of choice in Parkison disease with psychosis, it is also used as……

Answer 14

Olanzapine
Quetiapine
Off-label hypnotic

Question 15

Mention advantages & disadvatages of aripiprazole

Answer 15

More extrapyramidal side effects esp akathesia
Favourable on cognitive function (preferred in children)
Lesser effect on body weight & lipids (preferred in obese & DM pateints)

Question 16

As regards antipsychotics, ….is used as tranquilizer, while……is used in severe emesis & intractable hiccups, …….are used in autism, ……are used in refractory depression, while…..are off-label hypnotics.

Answer 16

Haloperidol
Chlorpromazine
Resperidone & aripiprazole
Aripiprazole & quetiapine
Quetiapine, clozapine & chlorpromazine

Question 17

Enumerate uses of lithium carbonate

Answer 17

Mood stabilizer, anti-manic, recurrent endogenous depression, adjunct to antidepressants in refractory unipolar depression.

Question 18

First line treatment for bipolar depression is…….

Answer 18

Lithium or lamotrigine

Question 19

Mention adverse effect of Li

Answer 19

CNS, fine hand tremors and dec cognition
GIT upset
Renal: antagonizes ADH (polyuria and thirst) nephrogenic diabetes insipidus, renal tubular damage.
Thyroid benign enlargement with or without hypothyroidism
Toxic drug: narrow TI (Th 0.6-1.2 and TOX at more tgan 1.5 mEg/l), long t1/2, cumulative.

Question 20

Mention precautions of Li administration

Answer 20

1. Coarse tremors and inc GIT symptoms are early warning signs of toxicity
2. Monitor kidney and thyroid function
3. Monitor Li serim level
4. Adjust dose in reduced Li excretiom as in Na depletion by diuretics, renal dysfunction, old age (dec renal function)

Question 21

Manifestations of Li toxicity

Answer 21

Vomiting, diarrhea, coarse tremors (early signs)
Ataxia, drowsiness, slurred speech, arrhythmia, CV collapse
Confusion, convulsions, coma

Question 22

Describe managemney of Li toxicity

Answer 22

Stop Li, gastric lavage and A.charcoal if acute intake
Inc fluid intake (maintain electrolytes)
Diuresis, osmotic or forced (never thiazide or loop)
Dialysis: hemo- or peritoneal (hemo- more effective esp if severe toxicity or if fluid intake CI) repeated every 6-8 hrs