- antipsychotic effect (mesolimbic pathway) - worsens negative Sx (mesocortical pathway) - movement disorders and EPS (nigrostriatal pathway) - hyperprolactinemia (tuberoinfundibular pathway)

- Hyperactivity of DA -> hallucinations, delusions, thought disorders - Role in aggressive Sx - drugs that increase DA -> psychotic Sx - antipsychotics decreases Da (blocks receptors)

- Projects to different brain areas - DA deficit -> role in neg. and cogn. Sx

- excito-toxicity of glutamate system - 2ndary inhibition by excess serotonin - D2 block by antipsychotics

Psych Pharms Flashcards by Jene du Plessis

2 Major antipsychotic classes

Dopamine receptor antagonists (typical antipsychotics)

Serotonin-dopamine antagonists (atypical antipsychotics)

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Indications for antipsychotic use

psychotic disorders
dementia (esp. with behavioral Sx)
augmentation in MDD and OCD (major depressive disorder, obsessive compulsive disorder)
tic disorders

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Typical antipsychotic actions

D2 antagonists
Also antagonists of M1, H1 and alpha-1 receptors
-M1: muscarinic cholinergic block

DA receptor block is immediate, but antipsychotic effect takes weeks

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D2 block effects

antipsychotic effect (mesolimbic pathway)
worsens negative Sx (mesocortical pathway)
movement disorders and EPS (nigrostriatal pathway)
hyperprolactinemia (tuberoinfundibular pathway)

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Muscarinic cholinergic block effects

Ach and Da have reciprocal relationship in nigrostriatal pathway
cholinergic block mitigates effects of D2 block in nigrostriatal pathway
therefore less EPS

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4 Dopamine pathways

Mesolimbic
Mesocortical
Nigrostriatal
Tuberoinfundibular

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Mesolimbic pathway

Hyperactivity of DA -> hallucinations, delusions, thought disorders
Role in aggressive Sx
drugs that increase DA -> psychotic Sx
antipsychotics decreases Da (blocks receptors)

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Mesocortical Pathway

Projects to different brain areas

- DA deficit -> role in neg. and cogn. Sx

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Causes of low DA

excito-toxicity of glutamate system
2ndary inhibition by excess serotonin
D2 block by antipsychotics

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Nigrostriatal Pathway

part of extrapyramidal nervous system
controls motor movements
decreased DA -> movement disorders and EPS

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Tuberoinfundibular Pathway

-controls prolactin secretion

DA inhibits prolactin secretion

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Acute Management of Psychosis

Chemical restraints for aggression:
- Lorazepam 2-4mg IMI
                 \+
- Antipsychotic with acute onset IMI
     - Haloperidol
     - Olanzapine (not with BZ)
     - Ziprasidone
     - Zuclopenthixol acetate

-Decide if admission is necessary

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Haloperidol dose

5-10mg 2-4hrly (max 40mg/d)

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Olanzapine dosage

10mg 2-4hrly (max 30mg/d)

-don’t use with a benzodiazepine!! (Eg lorazepam)

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Ziprasidone dosage

10-20mg 4hrly (max 40mg/d)

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Zuclopenthixol acetate dosage

50-100mg per 72h (max 400mg over 2w)

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Typical Antipsychotics

Haloperidol
Chlorpromazine
Trifluoperazine
Fluphenazine
Pimozide
Sulpride
Flupenthixol
Zuclopenthixol

Peak [ ]

oral 1-4h
IV 30-60m

High potency ass. w.

increased EPS
decreased anticholinergic activity
decreased epileptogenic effect

Atypical Antipsychotics

Clozapine
Risperidone
Olanzapine
Quietapine
Aripiprazole
Ziprasidone
Paliperidone
Amisulpride
Sulpiride

5-HT2A and D2 antagonism
5-HT1A agonism - increases DA release in prefrontal cortex and decreased glutamate release (Clozapine, Quietapine, Ziprazidone)

Typical AP SE

Neuroleptic induced movement disorders

-EPSE & tardive dyskinesia

Atypical AP SE

Metabolic disturbances (dyslipidemia, hyperglycemia, obesity)
Cardiac conduction abnormalities

Indications for Atypicals

Severe EPS
Tardive dyskinesia
Young person with 1st episode
Better for neg. Sx
Rx resistant: clozapine
Rechallenge after NMS
Unacceptable prolactin levels
Mood Sx and suicide risk
Elderly with behavioural Sx

Acute Dystonia

Risk of acute dystonia increased:

high potency meds
young males

Def: painful, prolonged contraction of muscles resulting in abnormal movements/posture

torticollis of neck
trismus of jaw
protrusion of tongue
dysphagia
laryngo-pharyngeal spasm
oculogyric crisis (eyes turn upwards)

Acute Dystonia Rx

Biperidine 5mg IVI/IMI

Parkinsonism Rx

Tremors, rigidity, bradykinesia

Anticholinergics
-orphenadrine 50mg PO 1-3x/d
OR
-biperidine 2mg 1-3x/d
Lower the dose of AP meds
If severe, replace with atypical

Akathisia Sx

- restless & agitated | - unable to sit still

Akathisia Rx

1. B-blocker: propranolol 10-30mg tds 2. Benzodiazepine: eg lorazepam 3. Lower the AP dose (if possible) or change to atypical

Tardive Dyskinesia

Abnormal involuntary movements - oral movements, tongue protrusion, grimaces - choreoathetosis (involuntary twitching or writhing) of extremities and abnormal postures Appears very late (>4y); irreversible Risk fx: female, elderly, high dose

Tardive dyskinesia Rx

-irreversible Reduce dose Stop anticholinergics Try atypical esp. clozapine

Neuroleptic Malignant Syndrome Sx

- emergency - potentially lethal - occurs in 1st week of Rx Muscle rigidity and fever with: - diaphoresis - autonomic instability (labile BP/tachycardia) - tremor - dysphagia - mutism - incontinence - leukocytosis - change in lvl of consciousness (delirium) - lab evidence of injured muscle (increased CK)

Neuroleptic Malignant Syndrome Management

1. Stop antipsychotics 2. Admit to high care 3. Exclude other serious conditions 4. Supportive measures: - cool off pt - hydrate - monitor vitals - nasogastric tube 5. Diazepam/Lorazepam for muscle rigidity 6. DVT prophylaxis / avoid anticholinergics 7. Beware renal failure (increased CK/myoglobin) 8. If all else fails: dantrolene/bromocriptine 9. If no response: ECT 10: rechallenge - with low dose, atypical, or ECT

Clozapine indications

Rx resistant schizophrenia Intolerable EPS Tardive dyskinesia Commonly causes sedation and hypersalivation

Clozapine risks

``` Granulocytosis (monitor WBC) Myocarditis Toxic megacolon Seizures at high doses Metabolic syndrome ```

Depot AP preparations

Use in those who are non-compliant to treatment regimen | Use after oral medication efficacy has been demonstrated

MDD Rx

Psychoeducation Meds CBT, ECT, DBS SSRI - selective serotonin reuptake inhibitors SNRI - serotonin and norepinephrine reuptake inhibitors TCA - tricyclic antidepressants MAOI - Monoamine oxidase inhibitors NDRI - Norepinephrine dopamine reuptake inhibitors SARI - Serotonin antagonist and reuptake inhibitors NASSA - Noradrenergic and specific serotonin antidepressants NRI - Norepinephrine reuptake inhibitors

SSRI - selective serotonin reuptake inhibitors

Fluoxetine Citalopram Paroxetine Sertraline

SNRI - serotonin and norepinephrine reuptake inhibitors

Venlafaxine | Duloxetine

TCA - tricyclic antidepressants

Amitryptiline Imipramine Desipramine

MAOI - Monoamine oxidase inhibitors

Tranylcypromine | Moclobemide

NDRI - Norepinephrine dopamine reuptake inhibitors

Buproprion

SARI - Serotonin antagonist and reuptake inhibitors

Trazodone

NASSA - Noradrenergic and specific serotonin antidepressants

Mirtazapine

NRI - Norepinephrine reuptake inhibitors

Reboxetine | Atomoxetine