Final Exam Flashcards
SSRI stands for
selective serotonin reuptake inhibitor
Fluoxetine half life
1 week
Longest of SSRIs
What is discontinuation syndrome and what medications commonly cause it?
caused by stopping a short half life SSRI/SNRIs abruptly
Meds: Paroxetine, Fluvoxamine, Venlafaxine
What combination can cause serotonin syndrome
SSRI and MAOI used together
Most likely SSRI to cause weight gain
Paroxetine
What is the required washout period to switch from an MAOI to an SSRI?
2 weeks
What is the relationship between escitalopram and citalopram?
escitalopram is the S-enantiomer of citalopram
What is the common side effect to all SSRIs?
sexual side effects
SNRI stands for
serotonin norepinephrine reuptake inhibitor
What is the metabolite of venlafaxine?
desvenlafaxine
MOA of venlafaxine
blocks reuptake of serotonin at all doses, blocks dopamine at very high doses
Preferred use for duloxetine
Painful symptoms of depression, diabetic neuropathy pain, chronic pain (MSK, fibromyalgia, GAD, MDD)
What is “poop-out” syndrome?
decreased response to medication after initial response, seen with SSRI’s and SNRI’s
medical term: antidepressant treatment tachyphylaxis = progressive or acute tolerance development after chronic administration of SSRI/SNRI
Risk associated with SNRI use for bipolar patients
inducing mania
Venlafaxine effects
Helps with hot flashes/flushing in perimenopausal women Increases BP (dose dependent)
Major NDRI drug
Bupropion
MOA of Bupropion
Inhibits reuptake of norepinephrine and dopamine
Use of bupropion
Treats cravings from nicotine dependence
Antidepressant
May be useful for treating children with ADHD
Benefit of using bupropion as antidepressant
No sexual dysfunction effects, no effect on weight gain
Risks associated with bupropion
Lowers seizure threshold, significantly at high doses
Compare efficacy of bupropion to SSRI/SNRI for GAD treatment
Bupropion is less effective than SSRI/SNRIs for GAD treatment
Onset of action for bupropion
2-4 weeks
Mirtazepine MOA
pre-synaptic alpha 2 adrenergic antagonist increases release of NE and 5HT into the synaptic cleft, also blocks postsynaptic H1
Benefits of mirtazepine over SSRI/SNRI
decreased GI side effects due to specific 5HT3 antagonism
Side effects of mirtazepine
weight gain (F>M)
Combination of mirtazepine and MAOI can cause
Serotonin syndrome
Onset of action for insomnia and anxiety effects of mirtazepine
Immediate
Mirtazepine effect on CYP450
No effect
TCA mechanism
inhibits reuptake of 5HT and NE
TCA side effects
Anticholinergic effects: blurred vision, urinary hesitancy, dry mouth, constipation
Alpha1 adrenergic effects: dizziness, sedation, hypotension
Histamine effects: sedation, weight gain
Metabolite of amitriptyline
Nortriptyline (secondary amine) is metabolite of amitriptyline (tertiary amine)
Metabolite of imipramine
Desipramine (secondary amine) is the metabolite of imipramine (tertiary amine)
Gender differences in TCA antidepressant efficacy
TCAs may be more effective than SSRI’s for treating depression in men
TCA concentration is increased by
medications that inhibit CYP450 2D6 including fluoxetine, paroxetine, bupropion, duloxetine
Risk associated with TCA OD
Cardiac arrhythmia risk due to blockade of fast sodium channels
Lithium is approved for treatment of
acute manic episodes, maintenance therapy for bipolar disorder
Unique benefit of lithium
Decreases suicide risk
When should Li blood levels be drawn?
5d after starting/changing dose to confirm therapeutic levels
Should be trough levels (12 hours after previous dose)
Maintenance treatment levels for Li
0.6-0.8 mEq/L
How is Li toxicity > 4 mEq treated
dialysis
What conditions can increase risk for Li toxicity?
Renal impairment
Sodium depletion
Dehydration
Labs 1-2x/year for patients on Li
Li level, TSH, BUN/Cr
Labs before starting Li
TSH, BUN/Cr, Pregnancy
Li risk during pregnancy
Ebstein’s anomaly from exposure during first trimester
Li can cause tremor, which can be exacerbated or improved by what substances?
Tremor exacerbated by caffeine, improved by propranolol
Divalproex sodium (Valproic acid) is approved for treating
Antiepileptic approved for treatment of bipolar mania, migraine prophylaxis
Labs before starting valproic acid
LFT, platelets and pregnancy test
Risks associated with valproic acid treatment
Hepatotoxicity in children <2y
Spina bifida from exposure during first trimester
Aspirin + valproate increases risk of thrombocytopenia
Difference between depakene and depakote
Fewer GI side effects associated with depakote due to enteric coating
Interaction between valproate and lamotrigine
Valproate doubles lamotrigine concentration
When used in combination, dose of lamotrigine should be halved
Trough levels for valproate are drawn
19 hours after last dose
Carbamazepine is approved to treat
acute manic or mixed episodes of bipolar I disorder
Unique metabolism feature of carbamazepine
Autoinduction - half life decreases to less than 50% of initial because it is substrate and inducer of CYP3A4
Interaction between carbamazepine and oral contraceptives
CYP induction decreases concentration of oral contraceptives, increasing risk for pregnancy
Side effects of carbamazepine
Agranulocytosis, aplastic anemia
Hyponatremia
Hepatotoxicity
Regular labs for carbamazepine
Blood levels, platelets, CBC, LFT
Oxcarbazepine
similar to carbamazepine but not FDA approved for bipolar treatment
Lamotrigine is indicated for
maintenance of bipolar disorder, bipolar depression, but NOT acute mania
Medications approved for maintenance treatment of bipolar disorder
Lithium, lamotrigine, quetiapine, olanzapine, and aripiprazole
Medications approved for treating bipolar depression
Lamotrigine, quetiapine, lithium, olanzapine/fluoxetine and lurasidone
Medications indicated for treatment of acute mania
Lithium, divalproex, carbamazepine, quetiapine, ziprasidone and asenapine
Side effects of lamotrigine
Benign rash, severe rash, SJS
No risk for weight gain or sedation
DDI between lamotrigine and divalproex
divalproex doubles lamotrigine level, need to halve lamotrigine dose to keep at therapeutic level and prevent possible SJS
MOA of lamotrigine
Blocks sodium channels
What was the first antipsychotic medication?
Chlorpromazine
2 major categories of typical antipsychotics
high potency and low potency
Available haloperidol formulations
PO, IM, and IV
Use of haloperidol
Agitated psychotic patients
Can also treat Tourette’s syndrome
Typical antipsychotics available in IM forms given every 2-4 weeks
Haloperidol and fluphenazine
Medications to counter EPS effects of FGAs
trihexyphenidyl, benztropine, and diphenhydramine
Low potency antipsychotics act on what receptors
anticholinergic, antihistaminic and anti alpha1
Typical antipsychotic used more often as an anti-emetic
Prochlorperazine
Treatment for intractable hiccups
Chlorpromazine
Typical antipsychotic with highest risk of dose dependent QTc prolongation
Thioridazine
Most efficacious antipsychotic
Clozapine
Quetiapine use
Psychosis in lewy body dementia and Parkinson’s disease
Quetiapine has a low risk for this side effect
EPS
Atypical antipsychotics most likely to cause sedation and metabolic syndrome
Olanzapine and clozapine
Metabolically neutral SGAs
Lurasidone, asenapine, ziprasidone and aripiprazole
SGA with highest risk of QTc prolongation
Ziprasidone
Aripiprazole MOA and common side effect
Partial dopamine agonist, commonly causes akathisia
What is tardive dyskinesia?
repetitive, involuntary, purposeless movements, often of the face
Indication for abruptly stopping clozapine
WBC is <2,000 or ANC <1,000, indicating agranulocytosis
Paradoxical side effects of clozapine
dry mouth and excess salivation
Metabolic syndrome labs/tests
glucose, lipids, weight, waist circumference
What is dystonia
Muscle rigidity
What is an oculogyric crisis?
dystonic reaction resulting in involuntary upward deviation of the eyes
Side effect associated with alpha 1 adrenergic antagonism
Dose dependent orthostatic hypotension
Risk of using antipsychotics in early dementia patients
Sudden death
D2 blockade in the tuberoinfundibular tract can cause this side effect
Elevated PRL leading to gynecomastia
MOA of SGAs
D2 and 5HT2A antagonism
D2 occupancy required for antipsychotic effect
> 60% blockade
D2 occupancy causing side effects
> 80% blockade causes increased PRL and EPS
NMS is caused by
Excess D2 blockade
Tract associated with positive symptoms of schizophrenia
Mesolimbic pathway
Tract associated with negative symptoms of schizophrenia
Mesocortical pathway
Anti-emetics that can cause EPS or TD
Prochlorperazine, metoclopramide, droperidol, promethazine
Effect of smoking in schizophrenics
Cigarette smoke induces metabolism of antipsychotic medications, thus reducing levels
Also increases risk for CV disease
Lab that correlates with severity of NMS
Creatine kinase
Antipsychotics approved to treat bipolar depression
Olanzapine/Fluoxetine
Lurasidone
Quetiapine
Active metabolite of risperidone
Paliperidone
Demographic at greatest risk for dystonia from antipsychotics
Young males
First sign of NMS
mental status change (followed by rigidity, hyperthermia and autonomic instability)
Ratio of depression to mania in bipolar I patients
Depressed 2x more than manic
Gender differences for bipolar risk
Same in men and women
Ratio of depression to hypomania in bipolar II
Depressed 15x more than hypomanic
Which gender more likely to have first mood disturbance be manic
Men
Risk of future manic episode following a first episode mania
85%
Risk of bipolar disorder if identical twin has been diagnosed
70%
Difference in peak age onset of bipolar I and II
II onset mid 20s
I onset 18y
Which side of family history is more important for bipolar risk
Maternal side
After the first MDD mood disturbance, what is the risk of future episodes?
risk of future episodes is 50% (after 2 episodes, 70%; after 3 episodes, >90%)
With each episode of mania, what happens to episode duration and interepisode interval?
Duration increases and interval decreases
-spend more time in manic state
Average lifetime manic episodes without pharmacologic intervention
9-10 episodes
Percent of bipolar patients that end lives in suicide
16%
First sign of new manic episode
decreased need for sleep
Mania is first episode, followed by depression how often?
60% mania –> depression
40% depression–> mania
Avoid depakote treatment for these patients
Liver disease
Can you rapidly load depakote?
Yes, response seen within 3 days
Dose: multiply weight x 10
Response rate for lithium treatment in bipolar patients with euphoric mood, FHx of illness, and/or few lifetime episodes
70%
What is the rule of thirds?
With Li or depakote monotherapy, 1/3 respond well, 1/3 partially respond, and 1/3 respond poorly
Preferred treatment for severe acute mania
Li + antipsychotic
Depakote + antipsychotic
At what point is maintenance treatment always indicated
After 2 manic episodes
What decreases risk of conversion to mania when stopping Lithium?
Gradually discontinuing over months instead of abruptly stopping
Is Aripiprazole useful for bipolar depression?
No, but it is for MDD
Classes of medicine with increased switch rate and increase in number of rapid cycling cases
TCA’s and SNRI’s
Lowest risk antidepressant for causing switch to manic episode
Bupropion
What is anosognosia?
Lack of insight, patients do not recognize they are ill
Positive symptoms of schizophrenia
Delusions, hallucinations, disorganized thinking
Cognitive symptoms of schizophrenia
SMART - impaired speed, memory, attention, reading, and tact
What is catatonia?
Motor inhibition including stupor, waxy flexibility, mutism, negativism, stereotypy, and echolalia
Gender differences of schizophrenia symptoms
Males more likely to have negative symptoms, resulting in a more severe course. Men usually have earlier onset. Females have second peak of onset >40y
Negative symptoms of schizophrenia
alogia, affective flattening, avolition, anhedonia
Schizophreniform disorder
Schizophrenia A criteria met for a duration between 1 and 6 months
Diagnosis of schizophrenia requires these conditions to be ruled out
other psychotic disorders, developmental disorders, medical or neurological illness, substance abuse, medication induced, personality disorders, and mood disorders
Common symptom of schizophrenia and MDD
Anhedonia
What are hypnopompic hallucinations?
hallucinations only when waking up from sleeping
Course of negative symptoms during schizophrenia
present early in the illness, worsen during active periods and do not respond well to antipsychotic medications
Social effects of schizophrenia
Limited social contact, only 30-40% married, only 33% are able ot live independently
What percent of schizophrenics experience only a single active episode?
10%
What feature predates many schizophrenic psychotic episodes?
Prodrome seen 85% of the time, functional decline
Life expectancy of schizophrenics compared to normal
25 years less due to CV disease
How are relapses into active phase schizophrenia prevented?
Continuous antipsychotic treatment
Most common reason for hospitalization in schizophrenics
psychosis/active phase of illness
If antipsychotic not working at 2 weeks, then …
unlikely to work by 4 weeks
*Exception - clozapine
Dosage difference for first break of active psychosis
Lower dose due to greater sensitivity to medication side effects
Effect of using lowest effective dose
Increase risk of relapse
2 medications proven to decrease suicide risk
Lithium and clozapine
Indication for clozapine
persistence of positive symptoms, failure of > 2 antipsychotic trials, comorbid substance abuse and recurrent suicidality/violence
What is akathisia
Subjective sense of restlessness
Treatment of choice for akathisia
propranolol (can also use amantadine, lorazepam, clonidine, or mirtazapine)
Why are patients less likely to complain of EPS from low potency FGAs?
Side effects can mask the EPS symptoms
Most common outcome of TD
Symptoms remain static/unchanged
Treatment of choice for TD
Clozapine
50% show symptom reduction
What demographic is at highest risk for TD from FGAs?
The elderly (50% risk)
SGAs least likely to cause EPS
Clozapine and Quetiapine
Aripiprazole unique features
long half life and low risk of metabolic syndrome, high risk of akathisia, partial agonist
SGAs available in long acting injectable forms
Risperidone and paliperidone
Ziprasidone risks
Need to take with food
QTc prolongation risk
CATIE study found that Olanzapine
has the best compliance rates among SGAs
Mild side effects of clozapine
sialorrhea, weight gain, sedation, anticholinergic effects, myocarditis, and a lower seizure threshold
How long does a urine test stay positive after smoking marijuana?
4 days
Adverse effects of marijuana
Psychosis, anxiety/panic attacks, memory loss, amotivation, disorientation, unsteady coordination, altered perception, decreased consciousness
10% of users become dependent
What is dronabinol?
A synthetic cannabinoid agonist used to treat anorexia and weight loss in AIDS patients, nausea/vomiting in chemo patients
Clinical effects of marijuana
Anti-inflammatory, anti-convulsant, anti-emetic
What is the most common illicit drug used worldwide?
Marijuana
What are the common medications used for cessation of cigarette smoking?
Bupropion
Verenicline
Nortriptyline
Clonidine
Success rate for smoking cessation without ever relapsing
5%
It is unusual for individuals to start smoking after what age?
21 years old
Describe the course of nicotine withdrawal
Begins within 24h of cessation and peaks at day 2-3, lasts about 2-3 weeks
What chemical mediates rewarding effects associated with addiction?
Opioids mediate rewarding effects by enhancing midbrain release of dopamine
Disulfiram MOA
Inhibits breakdown leading to buildup of acetaldehyde and negative reinforcement of alcohol abuse
Naltrexone MOA and use for alcohol dependence
Mu receptor antagonist
Monthly depot injections
Most effective for treating cravings
Social/moderate drinkers have this many drinks per day
Men 2 or fewer
Women 1 or fewer
How does tolerance affect positive reinforcement
Tolerance leads to lack of positive reinforcement
How does negative reinforcement affect alcohol dependence
Individuals keep drinking to stave off negative effects of alcohol
Labs that indicate ongoing heavy drinking
GGT, CDT
*MCV not valuable due to long half life of RBCs
Comorbid disorders of alcohol use disorder
Bipolar disorder, schizophrenia, antisocial personality disorder
Risk for using inhalants
Sudden death due to cardiac arrhythmia
PCP
anesthetic agent produces feelings of separation from mind and body, detected in urine up to 8 days after use
Can cause nystagmus, decreased pain response, and violent behavior
How long can opioids be detected in UDS after using?
12-36h
Medical conditions IV opiate users are at risk for
hepatitis, TB, bacterial endocarditis
Opiate withdrawal symptoms
Dilated pupils, dysphoria, N/V, muscle aches, lacrimation/rhinorrhea, piloerection, fever and sweating
How is opioid intoxication diagnosed
Administration of naloxone stops symptoms
What is suboxone
Naloxone + buprenorphine
Drug most commonly involved in ER visits
Cocaine
Most rapid onset of action from cocaine is via this route
Smoking and injecting
What is a speedball?
Combination of cocaine and heroin
Neurotransmitters increased by cocaine
Glutamate and dopamine
How can PCP intoxication be distinguished from stimulant intoxication?
UDS
PCP may cause vertical nystagmus
Sign of stimulant withdrawal
Bradycardia
Disorders associated with caffeine use
Sleep disorder, anxiety
Disorders associated with marijuana use
Anxiety disorders, sleep disorders, psychotic disorders
Disorders associated with PCP use
Psychotic disorders, anxiety disorders, delirium and mood disorders
Disorders associated with opioid use
Sleep disorders, sexual dysfunction, delirium, and depressive disorders
Disorders associated with cocaine use
sexual dysfunction, delirium and psychotic disorders
Disorders associated with stimulant use
anxiety, OCD, sleep and mood disorders