Antipsychotics (Ch. 5) Flashcards
Re: nomenclature for meds, how should you refer to psych med names
use pharm. mechanism of action not their clinical indication
many drugs work on various disorders/syndromes/sx
what receptors (generally) do “antipsychotics” work on
serotonin and dopamine but will affect other neurotransmitter systems secondarily
D2 antagonists use, mechanism of action & examples
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
“Other” pharmacological properties of D2 antagonists
muscarinic cholinergic antagonism
antihistaminic actions (H1 antagonism)
alpha 1 adrenergic antagonism
*linked to SE more than therapeutic
muscarinic cholinergic antagonism SE
dry mouth, blurred vision, risk of paralytic ileus
blockage of H1 histamine SE
weight gain, sedation
blockage of alpha 1 adrenergic receptors SE
sedation, CV SE like orthostatic hypotension
Ex D2 antagonist that also strongly binds to all three muscarinic, antihistamine (H1), alpha 1 adrenergic receptors and when indicated
chlorpromazine
when need sedation & antipsychotic
what d2 antagonists are more likely to cause DIP
agents with weak anticholinergic (muscarinic) properties
what d2 antagonists are less likely to cause DIP
agents with stronger anticholinergic properties
but higher incidents of constipation > life-threatening paralytic ileus
Examples of D2 antagonists & potency
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
How to treat negative secondary sx of D2 antagonists
lower dose or switch med; adjunct meds for depression can help (5HT2A antagonists or D3 partial agonists)
Mesocortical dopamine D2 receptor antagonism effects
secondary neg sx, cognitive/affective sx since dopamine in this pathway is thought to already be low in schizophrenia leading to negative sx
what SE if block D2 receptors in tuberoinfundibular pathway
increased prolactin
what SE if block D2 receptors in nigrostriatal pathway
motor SE- DIP (bradykinesia/akinesia), akathisia, dystonia, tardive dyskinesia (chronic use)
what is best to treat psychosis r/t dementia or Parkinson’s
a 2HT2A antagonist without a D2 antagonist
antipsychotics with high metabolic risk
clozapine, olanzapine
antipsychotics with moderate metabolic risk
risperidone, paliperidone, quetiapine, asenapine, iloperidone
antipsychotics with low metabolic risk
lurasidone, cariprazine, limateperone, ziprasidone, pimavanserin, aripiprazole, brexpiprazole
what to measure/monitor w/ antipsychotics for cardiometabolic SE risk
weight/BMI, fasting glucose, fasting triglycerides, BP
family hx DM
what medication can be considered to mitigate weight gain/cardiometabolic risk with antipsychotics
metformin
less consistent results with topiramate
*What causes elevated prolactin, med common with, sx, tx
- 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
*Neuroleptic Malignant Syndrome (NMS)- what is it? Sx, risks, tx
- 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
*tardive dyskinesia- what is it? Sx, risks, tx
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)
*Lithium
type of med, therapeutic range, what’s toxic level & potentially lethal level? Sx
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
*Tegretol- therapeutic level, SEs, labs needed before and during
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
*Depakote- therapeutic level/when to check, SE, labs
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
*what concern would there be if depakote & tegretol admin together
hepatotoxicity
*Tegretol autoinduction
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
*Factors that can increase Lithium levels
- NSAIDS (e.g. ibuprofen)
- Aspirin
- Thiazide diuretics
- Dehydration (especially in the elderly)
- Salt deprivation
- Sweating (salt loss)
- Impaired renal functioning
- Ace Inhibitors
- Antihypertensives
