Antipsychotics (Ch. 5)

Question 1

Re: nomenclature for meds, how should you refer to psych med names

Answer 1

use pharm. mechanism of action not their clinical indication

many drugs work on various disorders/syndromes/sx

Question 2

what receptors (generally) do “antipsychotics” work on

Answer 2

serotonin and dopamine but will affect other neurotransmitter systems secondarily

Question 3

D2 antagonists use, mechanism of action & examples

Answer 3

typical/conventional/first-generation antipsychotics

use if don’t respond to second generation or tx resistance or needed immediate/long acting injenctions

tx= bipolar mania, psychotic mania, psychotic depression, Tourette syndrome, gastroesophogeal reflux, gastroparesis, prevent n/v r/t chemo

mechanism of action= blocking D2 receptors in mesolimbic/mesostriatal pathways help positive sx of psychosis but this pathway is also for motivation & reward. “Pleasure center”. Can cause secondary negative sx

Question 4

“Other” pharmacological properties of D2 antagonists

Answer 4

muscarinic cholinergic antagonism
antihistaminic actions (H1 antagonism)
alpha 1 adrenergic antagonism

*linked to SE more than therapeutic

Question 5

muscarinic cholinergic antagonism SE

Answer 5

dry mouth, blurred vision, risk of paralytic ileus

Question 6

blockage of H1 histamine SE

Answer 6

weight gain, sedation

Question 7

blockage of alpha 1 adrenergic receptors SE

Answer 7

sedation, CV SE like orthostatic hypotension

Question 8

Ex D2 antagonist that also strongly binds to all three muscarinic, antihistamine (H1), alpha 1 adrenergic receptors and when indicated

Answer 8

chlorpromazine
when need sedation & antipsychotic

Question 9

what d2 antagonists are more likely to cause DIP

Answer 9

agents with weak anticholinergic (muscarinic) properties

Question 10

what d2 antagonists are less likely to cause DIP

Answer 10

agents with stronger anticholinergic properties

but higher incidents of constipation > life-threatening paralytic ileus

Question 11

Examples of D2 antagonists & potency

Answer 11

chlopromazine (Thorazine) - low potency
fluphenazine (Prolixin)- high potency
haloperidol (Haldol)- high potency
loxapine (Loxitane)
perphenazine (Trilafon)- high potency
pimozide (Orap)- high potency; QT issues
thioridazine (Mellaril)- high potency; QT issues
thiothixene (Navane)- high potency
trifluoperazine (Stelazine)- high potency

Question 12

How to treat negative secondary sx of D2 antagonists

Answer 12

lower dose or switch med; adjunct meds for depression can help (5HT2A antagonists or D3 partial agonists)

Question 13

Mesocortical dopamine D2 receptor antagonism effects

Answer 13

secondary neg sx, cognitive/affective sx since dopamine in this pathway is thought to already be low in schizophrenia leading to negative sx

Question 14

what SE if block D2 receptors in tuberoinfundibular pathway

Answer 14

increased prolactin

Question 15

what SE if block D2 receptors in nigrostriatal pathway

Answer 15

motor SE- DIP (bradykinesia/akinesia), akathisia, dystonia, tardive dyskinesia (chronic use)

Question 16

what is best to treat psychosis r/t dementia or Parkinson’s

Answer 16

a 2HT2A antagonist without a D2 antagonist

Question 17

antipsychotics with high metabolic risk

Answer 17

clozapine, olanzapine

Question 18

antipsychotics with moderate metabolic risk

Answer 18

risperidone, paliperidone, quetiapine, asenapine, iloperidone

Question 19

antipsychotics with low metabolic risk

Answer 19

lurasidone, cariprazine, limateperone, ziprasidone, pimavanserin, aripiprazole, brexpiprazole

Question 20

what to measure/monitor w/ antipsychotics for cardiometabolic SE risk

Answer 20

weight/BMI, fasting glucose, fasting triglycerides, BP

family hx DM

Question 21

what medication can be considered to mitigate weight gain/cardiometabolic risk with antipsychotics

Answer 21

metformin
less consistent results with topiramate

Question 22

*What causes elevated prolactin, med common with, sx, tx

Answer 22

• D2 blockade in the Tuberoinfundibular pathway= Hyper-prolactin
• Common with Risperdal
• Men= Gynecomastia, erectile dysfunction, low libido, galactorrhea
• Women = galactorrhea and absence of menses, low libido, galactorrhea

Management
1. Reduce or discontinue med
2. Switch to a different mediation
3. If the above techniques are not feasible, add Aripiprazole to the regimen

Question 23

*Neuroleptic Malignant Syndrome (NMS)- what is it? Sx, risks, tx

Answer 23

• Life-threatening idiopathic reaction to antipsychotic medications (more common w/ FGAs)
• Medical Emergency w/ 20% mortality rate if untreated
• *Generally apparent 2 weeks of treatment initiation
  F= Fever
  A= Autonomic Instability (Tachycardia, HTN, Diaphoresis)
  L= Leukocytosis
  T= Tremor
  E= Elevated CPK
  R= Rigidity (lead pipe)
  E= Excessive sweating (diaphoresis)
  D= Delirium (mental status changes)

Risk factors: High doses, high potency, LAIs, Young males early in treatment with high potency antipsychotics

Management
1. D/C medication
2. Supportive care (hydration, IV benzos- for relaxation; cooling blankets)
3. Administer sodium dantrolene, bromocriptine, amantadine
4. ECT can be effective

Question 24

*tardive dyskinesia- what is it? Sx, risks, tx

Answer 24

Tardive= D2 Blockade in the Nigrostriatal Pathway =late occurring

• Involuntary Choreoathetoid movements of face, mouth, lips (lip smacking) tongue (fly catcher tongue)
  and other body parts (facial grimacing, eye blinking, trunk, limbs etc. )
• Occurs in patients who have used neuroleptics for months to years (Sooner in older adults)
• Risk factors: older age, women, patients with affective disorders, patients with substance abuse hx;
  FGA, duration of txt, higher dose, African American
• Affects about 20-30% of patients who on antipsychotics or months or years.
• Up to 50% of cases will remit (without further antipsychotic use)
• Mostly irreversible

Management: Dose reduction; D/C med; switch to an atypical antipsychotic; Clonazepam, Amantidine,
Tetrabenazine.
2017: First FDA approved treatment for TD (Valbenazine=Ingrezza); Deutetrabenazine (Austedo)

AIMS (Abnormal Involuntary Movement Scale) testing initially then Q3-6 months

Risk factors: High doses, long duration, old age, women, hx of EPS, substance abuse (heavy smoking),
diabetes

Patient Education: TD symptoms may initially worsen transiently as medication dosages are lowered.
Consider switching to Clozaril (Lowest risk of TD)

Question 25

*Lithium
type of med, therapeutic range, what’s toxic level & potentially lethal level? Sx

Answer 25

mood stabilizer
acutely stimulates the NMDA receptor, increasing glutamate availability in the postsynaptic neuron. After chronic administration, lithium induces NMDA downregulation, this way lithium modulates glutamate neurotransmission.`

Narrow therapeutic index(0.6-1.2 mEq/L)
Toxic >1.5
Potentially Lethal =>2.0

• Early: Nausea, vomiting, diarrhea, coarse tremors, ataxia
• Late: Seizures, Coma, death

Question 26

*Tegretol- therapeutic level, SEs, labs needed before and during

Answer 26

mood stabilizer
increases the inhibitory neurotransmitter GABA (gamma amino butyric acid) and decreases excitatory neurotransmitter glutamate

Therapeutic Level= 8-12 mcg/ml
Rare= Depakote induced thrombocytopenia
Elevation of liver enzymes causing hepatitis

Labs before initiating: Pregnancy test, CBC, LFTs
Regular Labs: CBC, LFTs

Question 27

*Depakote- therapeutic level/when to check, SE, labs

Answer 27

Therapeutic level = 80-120 ug/ml
Check level after 4-5 days

S/E: Nausea, diarrhea, Abdominal cramping,
sedation, tremor, hair loss
Rare= Depakote induced thrombocytopenia

Labs: CBC, LFTs
Watch for s/s of Hyperammonemia – confusion, lethargy, abnormal posture- ataxia, seizure,
agitation etc. – Check ammonia level first

Question 28

*what concern would there be if depakote & tegretol admin together

Answer 28

hepatotoxicity

Question 29

*Tegretol autoinduction

Answer 29

TEGRETOL AUTO-INDUCTION

• Tegretol level range=remember auto-induction of its own metabolism may start 3-5 days after initiation = therefore decreases plasma levels
• Can produce Ataxia even at therapeutic doses

Question 30

*Factors that can increase Lithium levels

Answer 30

• NSAIDS (e.g. ibuprofen)
• Aspirin
• Thiazide diuretics
• Dehydration (especially in the elderly)
• Salt deprivation
• Sweating (salt loss)
• Impaired renal functioning
• Ace Inhibitors
• Antihypertensives