Adverse Effects

Question 1

Serotonin Syndrome

Answer 1

Most common culprits are SSRI and SNRI combination therapy.
Early symptoms: diarrhea, restlessness
Middle symptoms: extreme agitation
Late symptoms: autonomic instability, hyperthermia, rigidity, coma, and death

Question 2

Serotonin Syndrome Tx response

Answer 2

For early symptoms: stop medication and try different antidepressant after appropriate washout period OR decrease dose and have pt take lower dose for a length of time (Ex: pt on Zoloft 25mg per day → increased dose to 50mg → early symptoms → reduce dose back to 25mg for a few weeks before trying to increase again)
Middle and late symptoms = medical emergency, go to ER

Question 3

Syndrome of Inappropriate Antidiuretic Hormone (SIADH)

Answer 3

body makes too much antidiuretic hormone → kidneys retain water → diluted electrolytes and reduced sodium volumes (Hyponatremia)
-monitor sodium levels in first 2 weeks of meds
-can occur at any time on meds but most likely in first 2 weeks
-more common with Mirtazapine and Bupropion

Question 4

Withdrawal/Discontinuation Syndrome (SSRIs)

Answer 4

due to short half life of 5HT component; occurs in ⅓ of patients
Symptoms: dizziness, fatigue, headache, nausea, agitation, anxiety, insomnia, irritability, head zaps, and audio/visual hallucinations
Augmenting with long-acting SSRI can mitigate effects during discontinuation process

Question 5

Depakote (Valproic Acid) mechanism of action

Answer 5

MIGHT work by: 1) inhibiting VSSCs; 2) boosting actions of GABA; 3) regulating downstream transduction cascades

*Sedating and can cause fetal malformations

Question 6

Carbamazepine mechanism of action

Answer 6

Powerful inducer of CYP450 3A4 → prescribing carbamazepine with another 3A4 substrate will increase the metabolism of that substrate (need to prescribe higher doses of second med)

Question 7

Lamotrigine (Lamictal)

Answer 7

Tx: seizures and bipolar disorder (approved to treat recurrence of mania or depression in bipolar disorder (more for maintenance))
Mechanism of action: reducing release of glutamate
Adverse effects: Steven Johnson Syndrome Rash (toxic epidermal necrolysis); minimize risk by very slow up-titration
Educate pt to look for rash daily and stop taking immediately if rash develops
Co-administration with Depakote can double Lamotrigine levels

Question 8

Anticonvulsants with less efficacy in bipolar disorder

Answer 8

Oxcarbazepine, Topiramate, Gabapentin, Pregabalin

Question 9

Hyperammonemia

Answer 9

Symptoms: confusion, disorientation sleepiness, altered level of consciousness, mood swings, tremor, coma
Associated with Depakote (Valporic acid)

Question 10

Lithium Tx and monitoring

Answer 10

Tx: mania in bipolar disorder
Contraindicated in first trimester of pregnancy due to Epstein’s anomaly (defect of tricuspid valve in heart)
Labs before starting = renal function, pregnancy test, electrolytes, thyroid function, EKG
During titration check serum trough level 2x per week; after dose established, check serum trough level every 1-2 months

Question 11

Lithium Therapeutic and Toxic levels

Answer 11

Therapeutic level: Adults: 0.8 mEq/L; Elderly: 0.6 mEq/L; Toxicity above 1.2 mEq/L
Lithium toxicity mild/early symptoms: vomiting, diarrhea, abdominal pain, bloated stomach (1.5-2.5mEq/L)
Moderate symptoms: confusion, vision changes, uncontrolled shaking/hand tremors, muscle twitches hyperreflexia, slurred speech, nystagmus, seizures, coma (2.5-3.5 mEq/L)
Severe: fatal (>3.5 mEq/L) go to ER (could include: stomach pumping, whole bowel irrigation, activated charcoal, hemodialysis, IV fluids, ICU)

Question 12

Steven Johnsons Syndrome (SJS)

Answer 12

Starts with flu-like symptoms → painful rash spreads and blisters → top layer of skin dies, sheds, and heals after several days
Symptoms: skin pain, fever, body ache, red rash/blotches on the skin, cough, blisters/sores on skin or mucous membrane (mouth, throat, eyes, genitals, anus), peeling skin, drooling
MEDICAL EMERGENCY (especially if there is ocular involvement)

Question 13

Dosing Lamotrigine (Lamictal)

Answer 13

Typical = 25mg per day to start for 2 weeks → 50mg per day x 2 weeks as long as patient is tolerating it → 100mg per day 1 week → continue with this process to max daily dose of 400mg per day
Maintain at lowest effective dose that treats manic and depressive symptoms
If administering with Depakote = double half life → increased risk SJS
Smoking induces metabolism of lamotrigine and reduces half life by 50%

Question 14

Benzodiazepines

Answer 14

Tx: short-term anxiety, insomnia, seizures, sedation, alcohol withdrawal
AVOID in substance use disorder; high potential for dependence and abuse
Pts who exhibit tolerance or withdrawal between doses are not good candidates for long term use
Use with opioids → increased sedation (CYP450 3A4)

Question 15

Quetiapine (Seroquel) dosing

Answer 15

Bipolar depression: 300mg 1x daily
Bipolar mania/schizophrenia: 400-800mg per day
Higher dose required for psychosis than depression

Question 16

Quetiapine (Seroquel) before initiating tx

Answer 16

BEFORE initiating:
-EKG to ensure patient doesn’t already have prolonged QT interval (could be lethal)
-Not required but smart to do: Baseline weight, BMI, BP, waist circumference, fasting plasma glucose, fasting lipid profile,
-Baseline personal and family history of: diabetes, obesity, dyslipidemia, hypertension, and cardiovascular disease
Avoid combining multiple meds that could prolong QT interval (e.g., citalopram)

Question 17

Quetiapine (Seroquel) monitor during tx

Answer 17

-Fasting triglycerides and BMI monthly for 3 months and then quarterly after that
-BP, fasting plasma glucose, and fasting lipids within 3 months of starting the med and annually after that

Question 18

Clozapine Tx and adverse effects

Answer 18

Tx: antipsychotic for schizophrenia or schizoaffective disorder
Adverse effects: agranulocytosis (monitor absolute neutrophil counts); severe neutropenia (ANC < 500/ml)
-adverse events occur within the first 6 months of treatment

Question 19

Clozapine dosing

Answer 19

Starting dose = 12.5mg 1-2x daily → increased AT MOST 25-50mg per day to target dose of 300-450mg per day –> If need more doses, should be 100 mg or less 1-2x weekly
Titrate slow to avoid: seizure, orthostatic hypotension, and excessive sedation
Large increase in dose can lead to cardiovascular collapse/death especially in patients on benzodiazepines
Titrate at a slower rate if there was an initial episode of schizophrenia, elderly, severely debilitated, or sensitive to side effects,preexisting nervous system condition
Use of divided doses can be helpful during titration, but usually pt given single dose at bedtime to minimize daytime sedation
Max dose = 900mg

Question 20

Drug-Induced Parkinsonism (DIP)

Answer 20

Antipsychotic Adverse Effects
From drugs that target D2 receptors
treatment : drugs that block muscarinic-cholinergic receptors, especially post-synaptic M1 receptor

Question 21

Drug-Induced Acute Dystonia

Answer 21

Antipsychotic Adverse Effects
Exposure to D2 blockers without 5HT or anticholinergic properties; usually on first exposure to D2 blockers; chronic exposure to D2 blockers –> late onset tardive dyskinesia
Treatment: anticholinergic injection effective within 20 min

Question 22

Akathisia

Answer 22

Antipsychotic Adverse Effects
Commonly seen after treatment with D2 blockers
Symptoms: Mental unease, dysphoria, restless movements = lower limb movements (rocking from foot to foot, marching in place when standing, pacing)
Regalin and metaclopimide can also cause akathisia

Question 23

Neuroleptic Malignant Syndrome (NMS)

Answer 23

Antipsychotic Adverse Effects
Caused by D2 receptor blockade
Symptoms: extreme muscle rigidity, high fevers, coma, and possible death
Most extreme form of DIP
MEDICAL EMERGENCY (Dantrolene & DA agonists, ICU)

Question 24

Tardive dyskinesia (Tardive syndromes)

Answer 24

Chronic blockade of D2 receptors in the nigrostriatal dopamine pathway. Acute dystonia, akathisia, or medication-induced Parkinsonism
Assess with: Abnormal Involuntary Movement Scale (AIMS) at baseline & every 6-12 months OR with onset/exacerbation of abnormal movements
Treatment: vesicular monoamine transporter 2 (VMAT2):: Deutetrabenazine, valbenazine, tetrabenazine [Deutetrabenazine and Valbenazine preferred over Tetrabenazine (shorter half life and greater rates of depression); Valbenazine use if severe renal impairment]

Question 25

Depakote (valproic acid) treats _________

Answer 25

Tx: anticonvulsant, antiepileptic, bipolar disorder, migraines

*Sedating and can cause fetal malformations

Question 26

Depakote (valproic acid) adverse effects

Answer 26

pancytopenia, liver toxicity, hyperammonemia, thrombocytopenia, weight gain

Question 27

Depakote (valproic acid) monitoring and dosage

Answer 27

Monitor for: mental status changes, CBC for thrombocytopenia, liver function tests (LFTs), check serum trough level 2x week during titration
Treat with lowest dose possible (don’t exceed 60mg per kg per day)

Question 28

Carbamazepine treats _______

Answer 28

Tx: seizures, neuropathic pain, bipolar disorder

Question 29

Carbamazepine adverse effects

Answer 29

suppressant effects on bone marrow, agranulocytosis (deplete all blood cells)

Question 30

Carbamazepine monitoring

Answer 30

Monitor CBC:
Initial = every 2-4 weeks for 2 months
Every 3-6 months throughout treatment