Red/Bolded Parts in PPTs that match Study Guide Flashcards
Study of what the drugs do to the body (i.e. target sites for drugs- receptors, ion channels, enzymes (MAOIs) and carrier proteins/reuptake pumps)
- Pharmacokinetics
- Pharmacodynamics
Pharmacodynamics
There are more than ___ NT in the brain.
- 10
- 30
- 50
- 70
50
___ Risk cannot be rule out
___ Controlled studies show no risk
___ No evidence of risk in humans
___ Absolutely contraindicated in pregnancy
___ Positive evidence of risk
A, B, C, D, X
Match letter to rating.
A: Controlled studies show no risk
B: No evidence of risk in humans
C: Risk cannot be rule out
D: Positive evidence of risk
X: Absolutely contraindicated in pregnancy
o Locus Cerelus: Key center of ___ production
Remember Fight/Flight - concentration, focus, energy, HR, BP, Glucose
- 5HT
- NE
NE
o Ralphe Nuclei: Key center for ___ production
NOTE: 90% of serotonin in found in the GI tract
- 5HT
- NE
5HT
Inhibitory at the postsynaptic neuron
- Acetylcholine (ACh)
- Glutamate = “on”
- Gamma-aminobutyric acid (GABA) = “off”
Gamma-aminobutyric acid (GABA) = “off”
Excitatory at the post-synaptic neuron
- Acetylcholine (ACh)
- Glutamate = “on”
- Gamma-aminobutyric acid (GABA) = “off”
Glutamate = “on”
Involved in learning and memory (brain’s cholinergic neurons play a critical role in dementias)
- Acetylcholine (ACh)
- Glutamate = “on”
- Gamma-aminobutyric acid (GABA) = “off”
Acetylcholine (ACh)
Antipsychotics must occupy more than ___% of D2 receptors to cause EPS
- 20%
- 40%
- 60%
- 80%
80%
- Blockade of DA in this pathway produces increased motor movements
e.g. EPS (Pseudo parkinsonism, Akathisia, dystonia & TD)
- Mesolimbic Pathway
- Mesocortical Pathway
- Tuberoinfundibular Pathway
- Nigrostriatal Pathway
Nigrostriatal Pathway
- Note: Dopamine inhibits prolactin.
- Therefore, blockade of dopamine= ↓DA= ↑ Prolactin
- Mesolimbic Pathway
- Mesocortical Pathway
- Tuberoinfundibular Pathway
- Nigrostriatal Pathway
Tuberoinfundibular Pathway
- Associated with the negative symptoms of Schizophrenia (i.e. cognition, affect, apathy, behavior etc.)
- Mesolimbic Pathway
- Mesocortical Pathway
- Tuberoinfundibular Pathway
- Nigrostriatal Pathway
Mesocortical Pathway
- Associated with positive symptoms of schizophrenia (i.e. hallucinations, delusions etc)
- Mesolimbic Pathway
- Mesocortical Pathway
- Tuberoinfundibular Pathway
- Nigrostriatal Pathway
Mesolimbic Pathway
______in the mesolimbic area
- ↑Dopamine
- ↓Dopamine
- ↓Serotonin
- ↑Dopamine
______ activity in the Mesocortical area
- ↑Dopamine
- ↓Dopamine
- ↓Serotonin
- ↓Dopamine
______ (down regulation) in the frontal cortex
- ↑Dopamine
- ↓Dopamine
- ↓Serotonin
- ↓Serotonin
Antipsychotic _____________ can increase the risk of or re-hospitalization, diabetes, EPS, sedation, seizures, metabolic effects, mortality, and sudden cardiac death.
- polypharmacy
- toxicity
- resistance
polypharmacy
Delusions
Conceptual disorganization
Excitement
Grandiosity
Hostility
Hallucinations
- Negative symptoms
- Positive symptoms
Positive symptoms
Affect (flat, constricted)
Alogia (absence of speech) (
Apathy/Avolition
Attention (poor, lacking)
Anhedonia
Asociality
- Negative symptoms
- Positive symptoms
Negative symptoms
_____ potency
Low EPS= High antiadrenergic, anticholinergic and antihistaminic s/e, more lethal in overdose d/t QTC prolongation
- Low
- High
Low
_____ potency
High EPS= Low antiadrenergic, anticholinergic and antihistaminic s/e
- Low
- High
High
These manage positive symptoms of schizophrenia
- Antidepressants
- Mood stabilizers
- FGAs
- SGAs
FGAs
IM administration in Acute agitation or psychosis
- Seroquel
- Haldol
- Abilify
- Clozapine
Haldol
FGA side effects:
QTC prolongation?
Obtain:
baseline EKG
FGA side effects:
Orthostasis
Blockde of?
blockade of α1 receptors
FGA Side Effects:
___________ liver enzymes
- Decreased
- Elevated
Elevated
FGA Side Effects:
EPS consists of these 3 things:
EPS (Akathisia, dystonia, Parkinsonism)
FGA Side Effects:
hyperprolactinemia
(decreased libido, galactorrhea, gynecomastia, impotence, amenorrhea)
FGA Side Effects:
hyperprolactinemia in men
- Men= Gynecomastia, erectile dysfunction, low libido, galactorrhea
- Women = galactorrhea and absence of menses, low libido
- Men= Gynecomastia, erectile dysfunction, low libido, galactorrhea
FGA Side Effects:
hyperprolactinemia in women
- Men= Gynecomastia, erectile dysfunction, low libido, galactorrhea
- Women = galactorrhea and absence of menses, low libido
- Women = galactorrhea and absence of menses, low libido
EPS – due to?
- alpha 1 blockade
- beta 1 blockade
- gamma 1 blockade
- delta 1 blockade
alpha 1 blockade
Tardive dyskinesia:
torticollis definition?
contraction of neck muscles
Tardive dyskinesia is mostly irreversible.
True or false?
True
Risk factors for tardive dyskinesia:
High doses, long duration, old age, women, hx of EPS, substance abuse (heavy smoking), diabetes
-
-Management of tardive dyskinesia:
benztropine (Cogentin); Dose reduction; D/C med; switch to an atypical antipsychotic; Clonazepam, Amantidine, Tetrabenazine.
-
First FDA approved treatment for TD:
- Inderal
- Valbenazine, Ingrezza
- Suboxone
- Tylenol
(Valbenazine, Ingrezza)
Regarding tardive dyskinesia:
-AIMS (Abnormal Involuntary Movement Scale) testing initially then Q3-6 months
-
-Patient Education for tardive dyskinesia:
TD symptoms may initially worsen transiently as medication dosages are lowered.
True or false?
True
Consider switching to clozapine (Clozaril) due to:
(Lowest risk of TD)
TX for akathisia:
- beta-blocker – propranolol
- benztropine (Cogentin)
beta-blocker – propranolol
TX for pseudo-parkinsonism:
- beta-blocker – propranolol
- benztropine (Cogentin)
- benztropine (Cogentin)
Life-threatening idiopathic reaction to antipsychotic medications (more common w/ FGAs)
Neuroleptic malignant syndrome (NMS)
Medical Emergency w/ 20% mortality rate if untreated
what is it?
Neuroleptic malignant syndrome
Per what syndrome?
Clinical features (FALTERED):
Fever
Autonomic instability (BP, HR)
Leukocytosis
Tremor
Elevated CK
Rigidity
Excessive sweating
Delirium
Neuroleptic malignant syndrome
Management of which syndrome?
- D/C medication
- Supportive care (hydration, IV benzos- for relaxation; cooling blankets)
- Administer sodium dantrolene, bromocriptine, amantadine
- ECT can be effective
Neuroleptic malignant syndrome
Do not co-prescribe drugs in efforts to prevent EPS. (Associated w/ high anticholinergic side effects)
True or false?
True
If necessary, anticholinergics should be prescribed at the lowest dose possible.
True or false
True
manage positive and negative symptoms of schizophrenia
Accounts for 80% of total antipsychotics prescribed.
- SGAs (-dones & -pines)
- FGAs
- SGAs (-dones & -pines)
SGAs MOA:
Blocks both dopamine and serotonin receptors
SGAs are used to treat:
acute mania, bipolar disorder and as adjunctive in unipolar depression
SE of SGAs:
obesity, elevated triglycerides, low HDL levels, BP greater than 135/85
Which syndrome is this?
Metabolic syndrome
Regarding SGAs and this SE syndrome:
Obtain baseline and monitor BMI, weight, fasting glucose, waist circumference, BP, HbA1c and fasting lipids
Metabolic syndrome
Regarding SGAs and this SE syndrome:
NOTE: For patients established on SGA medications, _________ labs should be considered.
- daily
- monthly
- quarterly
- yearly
yearly
SGAs SE:
Common with Clozapine, Olanzapine, Quetiapine
Weight gain
SGAs SE:
Least with Aripiprazole, haloperidol, ziprasidone and lurasidone
Weight gain
SGAs and weight gain:
Monitoring: Weight, BMI, waist circumference per guidelines
SGAs and weight gain:
- Management: Switch to weight neutral medication
- May add to regimen: Topiramate, Metformin, Orlistat, Aripiprazole.
H1 receptor antagonism is associated with sedation and weight gain
true or false?
true
SGA meds
Strongest H1 antagonism*
- quetiapine (Seroquel)
- olanzapine (Zyprexa)
- risperidone (Risperdal)
- ziprasidone (Geodon)
- aripiprazole (Abilify)
- lurasidone (Latuda)
- clozapine (Clozaril)
- Pimavanserin/Nuplazid
quetiapine (Seroquel)
SGA meds
- Causes significant weight gain, sedation and dyslipidemia (strong H1 antagonism)
- Acute agitation IM acts within 15 min
- Monitor for dose-related hyperprolactinemia
- PO/IM/LAI formulation
- Relprevv (Injection)= Monitor 3 hours post injection d/t risk of delirium & sedation syndrome (Post injection syndrome)
- quetiapine (Seroquel)
- olanzapine (Zyprexa)
- risperidone (Risperdal)
- ziprasidone (Geodon)
- aripiprazole (Abilify)
- lurasidone (Latuda)
- clozapine (Clozaril)
- Pimavanserin/Nuplazid
olanzapine (Zyprexa)
SGA meds
**Greatest prolactin elevation
- quetiapine (Seroquel)
- olanzapine (Zyprexa)
- risperidone (Risperdal)
- ziprasidone (Geodon)
- aripiprazole (Abilify)
- lurasidone (Latuda)
- clozapine (Clozaril)
- Pimavanserin/Nuplazid
risperidone (Risperdal)
SGA meds
**Weight neutral
- quetiapine (Seroquel)
- olanzapine (Zyprexa)
- risperidone (Risperdal)
- ziprasidone (Geodon)
- aripiprazole (Abilify)
- lurasidone (Latuda)
- clozapine (Clozaril)
- Pimavanserin/Nuplazid
ziprasidone (Geodon)
SGA meds
- Weight neutral
- Watch for orthostatic hypotension
- Adjunctive tx of depression, bipolar
- quetiapine (Seroquel)
- olanzapine (Zyprexa)
- risperidone (Risperdal)
- ziprasidone (Geodon)
- aripiprazole (Abilify)
- lurasidone (Latuda)
- clozapine (Clozaril)
- Pimavanserin/Nuplazid
aripiprazole (Abilify)
SGA meds
- Take w/ food
- Approved for bipolar depression
- Low risk for metabolic syndrome
- Use with caution in patients w/ hepatic impairment.
- quetiapine (Seroquel)
- olanzapine (Zyprexa)
- risperidone (Risperdal)
- ziprasidone (Geodon)
- aripiprazole (Abilify)
- lurasidone (Latuda)
- clozapine (Clozaril)
- Pimavanserin/Nuplazid
lurasidone (Latuda)
SGA meds
- Used to treat refractory schizophrenia (i.e., treatment resistant)
- Only antipsychotic shown to decrease SI risk
- Less likely to cause TD
- Weight gain is most prominent
- More anticholinergic s/e- tachycardia, constipation etc.
- Hypersalivation (sialorrhea) occurs in 30-80%
- Chew sugarless gum
- Place towel over pillow especially if nocturnal sialorrhea is a problem
- Med: Glycopyrrolate (Robinul) -fewer Anticholinergic side effects)
- Benztropine, Artane etc.
- Agranulocytosis (highest first 3 months of treatment)= Monitor WBC and Absolute neutrophil count (ANC)
- **Perform WBC/ANC weekly for first 6 months of treatment and can decrease frequency there-after
- D/C med if ANC is <1.5 (1500)
- quetiapine (Seroquel)
- olanzapine (Zyprexa)
- risperidone (Risperdal)
- ziprasidone (Geodon)
- aripiprazole (Abilify)
- lurasidone (Latuda)
- clozapine (Clozaril)
- Pimavanserin/Nuplazid
clozapine (Clozaril)
SGA meds
Used in Parkinson’s related psychosis (newer med)
- quetiapine (Seroquel)
- olanzapine (Zyprexa)
- risperidone (Risperdal)
- ziprasidone (Geodon)
- aripiprazole (Abilify)
- lurasidone (Latuda)
- clozapine (Clozaril)
- Pimavanserin/Nuplazid
Pimavanserin/Nuplazid
_________ induces CYP1A2 enzymes and lowers the levels of certain antipsychotic medications.
- Drinking
- Smoking
- Exercising
Smoking
Haldol and Prolixin use _________ oil – watch for allergic reactions in patients sensitive to it
- olive
- chili
- grapeseed
- sesame
sesame oil
Increased risk of death when used in the elderly and those with dementia related psychosis.
What drug class?
Antipsychotics
Antipsychotics can be used for tx of agitation or psychosis in patients with dementia when symptoms are severe, dangerous and cause significant distress to the patient.
-
Antipsychotics are associated with an increased risk of falls and non-vertebral fractures in patients 65+.
True or false?
True
No antipsychotic medication is approved in patients with dementia.
True or false
True
Mood Disorders
Neurotransmitters/Monoamine hypothesis:
Depression = ↓Serotonin; ↓Dopamine; ↓NE
Monoamine Hypothesis:
Deficient brain 5HT and/or NE results in depression
-
Target symptoms for antidepressants:
Depressed mood, sleep/rest distress, anxiety, irritability, impaired concentration/memory, appetite disturbances, agitation, anhedonia, impaired energy/motivation.
Classes of antidepressants:
SSRI, SNRI, NDRI, SPARI, TCA, MAOI
Maintenance therapy for antidepressants:
- 2-4 months
- 6-13 months
- 8-14 months
- 3-7 months
6-13 months
Factors affecting drug choice of antidepressants
Cost, patient symptoms, previous treatment of patient or family member, side effect profile, comorbid conditions, risk of suicide.
Top distressing side effects of ADs
Sexual dysfunctions, sleep disturbance, weight gain
Meds to avoid in patients with SI
- SSRIs
- TCAs, benzos
- MAOIs
- SNRIs, benzos
TCAs, benzos etc
Adverse effects of ADs
- Sexual Dysfunction
o Highest with SSRI/SNRIs
o Impaired sexual motivation, desire, arousal, and orgasm affecting men and women
o Highest with Venlafaxine and SSRIs
o Lowest with Bupropion, trazodone, nefazodone, mirtazapine
o Management
First line- switch to bupropion (Wellbutrin)
Use of phosphodiesterase -5 inhibitors such as sildenafil (Viagra) or tadalafil (Cialis)
Sexual dysfunction and ADs are highest with:
- MAOIs
- SSRIs/SNRIs
- TCAs
- NDRIs
SSRIs/SNRIs
Sexual dysfunction and ADs are highest with:
- Venlafaxine and SSRIs
- Bupropion, trazodone, nefazodone, mirtazapine
Venlafaxine and SSRIs
Sexual dysfunction and ADs are lowest with:
- Venlafaxine and SSRIs
- Bupropion, trazodone, nefazodone, mirtazapine
- Bupropion, trazodone, nefazodone, mirtazapine
First line management of sexual dysfunction in ADs
- switch to acetaminophen (Tylenol)
- switch to bupropion (Wellbutrin)
- switch to alprazolam (Xanax)
- switch to bupropion (Wellbutrin)
Use of phosphodiesterase -5 inhibitors such as sildenafil (Viagra) or tadalafil (Cialis) can be used to treat sexual dysfunction in ADs
-
Serotonin Syndrome
o S=Shivering
o H=Hyperreflexia/Myoclonic jerks
o I = Increased Temp (Fever)
o V= Vitals Instability (↑↓BP; ↑RR; ↑HR)
o E= Encephalopathy (Confusion)
o R= Restlessness
o S= Sweating (Diaphoresis)
-
Progression of serotonin syndrome:
Rhabdomyolysis, renal failure, convulsions, coma= DEATH
-
Tx of serotonin syndrome:
- Stop medication
- Supportive care
- Cyproheptadine (5HT antagonist)
- ECT in emergencies
-
SSRIs MOA:
o Inhibit presynaptic serotonin reuptake pumps = ↑ availability of 5HT in synaptic clefts.
o Cause downstream effects increasing brain plasticity – explains the delay of antidepressant effect
-
SSRIs are 1st line treatment of depression.
True or false?
True
SSRIs may initially worsen anxiety or panic attacks.
-
Low incidence of side effects with SSRIs
o Transient (lasting 1-2 weeks especially GI)
-
BLACKBOX WARNING of SSRIs:
Increased suicidality in children, adolescents and young
-
SSRI Drugs: FFPECS
– Freaking Fabulous PECS
– fluoxetine, fluvoxamine, paroxetine, escitalopram, citalopram, sertraline
-
o Approved in use of Child/Adolescent
o Approved for Bulimia
o Can elevate levels of antipsychotics – watch for increased side effects
o Consider in patients w/ poor adherence d/t long half life
o Activating for patients wanting to avoid tiredness
- fluoxetine (Prozac)
- citalopram (Celexa)
- Sertraline (Zoloft)
fluoxetine (Prozac)
o Most Lethal in OD
- fluoxetine (Prozac)
- citalopram (Celexa)
- Sertraline (Zoloft)
citalopram (Celexa)
o This med is “activating” (causing agitation, anxiety)
- fluoxetine (Prozac)
- citalopram (Celexa)
- Sertraline (Zoloft)
Sertraline (Zoloft)
**Consider w/ patients who have significant fatigue or comorbid chronic pain
- SSRIs
- SNRIs
- TCAs
- MAOIs
SNRIs
SNRIs MOA:
↑ extracellular concentrations of NE and 5HT
-
SNRIS S/E:
sustained elevation in BP, nausea, diarrhea, dizziness, anticholinergic
-
SNRI drugs:
venlafaxine, duloxetine, levomilnacipran, milnacipran
-
o Useful in treating anxiety and panic attacks in depressed patients
o XR available
- venlafaxine (Effexor)
- gabapentin (Neurontin)
- duloxetine (Cymbalta)
venlafaxine (Effexor)
Norepinephrine dopamine reuptake inhibitor (NDRI):
MOA: Inhibits reuptake of NE and DA S/E: Headache, tremors, tachycardia, insomnia, anxiety, decreased appetite
NDRI drug: buproprion
-
o Contraindicated in patients with seizure and eating disorders = Lowers seizure threshold (at higher doses)
- venlafaxine (Effexor)
- citalopram (Celexa)
- aripiprazole (Abilify)
- buproprion (Wellbutrin)
buproprion (Wellbutrin)
o Used in ADHD and smoking cessation d/t effects on DA
o Weight neutral
o Contraindicated in patients with seizure and eating disorders = Lowers seizure threshold (at higher doses)
o Lacks sexual side effects – add to other antidepressants to tx sexual dysfunction
o Other available forms: XR= 24 hours; SR= 12 hours
o Less GI distress
- venlafaxine (Effexor)
- citalopram (Celexa)
- aripiprazole (Abilify)
- buproprion (Wellbutrin)
buproprion (Wellbutrin)
Serotonin Receptor Antagonist and Agonist:
o Acts on the Alph –adrenergic receptors
o Used for MDD, anxiety and insomnia
o Main SE: nausea, dizziness, orthostatic hypotension, sedation, Priapism
- trazodone (Desyrel)
- nefazodone (Serzone)
- mirtazepine (Remeron)
trazodone (Desyrel)
Serotonin Receptor Antagonist and Agonist:
o BLACKBOX warning for serious liver failure= rarely used
o Off the market
- trazodone (Desyrel)
- nefazodone (Serzone)
- mirtazepine (Remeron)
nefazodone (Serzone)
Serotonin Receptor Antagonist and Agonist:
o Alpha 2 adrenergic and 5HT2 antagonist =↑ 5HT and NE
o Sedating and promotes appetite (Used with patients who have weight loss and insomnia as primary symptoms of their depression) e.g., elderly
o SE: Sedation, weight gain, dizziness, tremor, dry mouth
o Inverse relationship between dose and sedation
- trazodone (Desyrel)
- nefazodone (Serzone)
- mirtazepine (Remeron)
mirtazepine (Remeron)
Used with patients who have weight loss and insomnia as primary symptoms of their depression
- trazodone (Desyrel)
- nefazodone (Serzone)
- mirtazapine (Remeron)
mirtazapine (Remeron)
o BLACKBOX warning for serious liver failure= rarely used
- trazodone (Desyrel)
- nefazodone (Serzone)
- mirtazapine (Remeron)
nefazodone (Serzone)
o Acts on the Alph –adrenergic receptors
o can treat insomnia
o SE: priapism
- trazodone (Desyrel)
- nefazodone (Serzone)
- mirtazapine (Remeron)
trazodone (Desyrel)
Tricyclic Antidepressants (TCAs): 2nd line treatment for depression
-
Tricyclic Antidepressants (TCAs) SEs:
Anticholinergic/Antimuscarinic: dry mouth, blurred vision, constipation, memory problems, urinary retention, narrow angle glaucoma
-
Tricyclic Antidepressants (TCAs) SEs:
Antiadrenergic: hypotension, orthostasis; dizziness, reflex tachycardia, arrhythmias, ECG changes – avoid in patients with pre-existing conduction abnormalities or recent MI
-
Tricyclic Antidepressants (TCAs) SEs:
Antihistaminic: sedation weight gain
EKG changes and Cardiac dysrhythmias
Seizure risk – related to the dose and serum level
-
TCAs are lethal in overdose (give 1-week prescription especially in high-risk patients).
NOTE: ____________ is the most lethal TCA
- carbamazapine
- despipramine
- aripiprazole
- venlafaxine
Desipramine
TCA overdose = gastric aspiration is helpful, cardiac monitoring is important
-
NOTE: 3Cs= Cardiotoxic (arrhythmia), Convulsions, Coma (caution w/ cardiac patients)
-
Tertiary Amines: amitriptyline, imipramine, clomipramine, doxepine
**These are highly anticholinergic/antihistaminergic, antiadrenergic and with greater lethality in overdose.
-
Used for enuresis
- clomipramine (Anafranil)
- imipramine (Tofranil)
imipramine (Tofranil)
o Used for OCD
- clomipramine (Anafranil)
- imipramine (Tofranil)
clomipramine (Anafranil)
Secondary Amines: nortriptyline, desipramine, amoxapine
Less anticholinergic/antihistaminic/antiadrenergic
-
o Useful in treating chronic pain
o Useful to obtain therapeutic level
o Can be safely used in geriatric population
- nortriptyline (Pamelor)
- amoxapine (Asendin)
nortriptyline (Pamelor)
o Metabolite of antipsychotic loxapine
o May cause EPS and has similar side effect profile to typical antipsychotics
- nortriptyline (Pamelor)
- amoxapine (Asendin)
amoxapine (Asendin)
MAOIs MOA: Deactivate MOA-A and MOA-B (enzymes needed to deactivate 5HT, DA, tyramine) = increases the number of neurotransmitters in the synapses. Prevents the inactivation of biogenic amines (NE, 5HT, DA and tyramine)
-
Selective and reversible MAO-A inhibitors are effective in treating major depression.
-
Selective MAO-B inhibitors are used in the treatment of Parkinson’s Disease and Alzheimer’s Disease.
-
MAOIs: Used in refractory cases of depression
-
MAOIs:
Last resort secondary to dangerous food and drug interactions
Food restriction: Follow Tyramine free diet
-
MAOIs S/E:
Insomnia, weight gain, Anticholinergic, sexual SE, orthostatic hypotension, photophobia, drowsiness, sleep dysfunction
Liver toxicity, seizures and edema (rare)
-
This condition happens when an MAOI is taken with tyramine rich foods (inhibits catabolism of dietary amines). Tyramine exerts strong vasopressor effects stimulating the release of Epi and NE
Hypertensive Crisis (Life threatening)
Which life-threatening condition is this?
- S/S: Sudden explosive headaches, high BP, facial flushing, palpitation, diaphoresis, fever, n/v, photophobia, autonomic instability , chest pain, arrhythmia and death
Hypertensive Crisis (Life threatening)
- Treatment:
o D/C medication
o Supportive care
o Phentolamine administration (NE antagonist)
Hypertensive Crisis (Life threatening)
Tyramine rich foods:
red wine, aged cheese, chicken liver, fava beans, cured meats
-
Patients taking MAOIs should avoid the following:
TCA’s, Atypical antipsychotics, St. Johns Wort, Asthma meds, SSRI’s, decongestants, opiates (fentanyl, tramadol, meperidine)
-
Serotonin Syndrome “SHIVERS”: When SSRI’s are taken w/ MAOIs
Serotonin Syndrome
o S=Shivering
o H=Hyperreflexia/Myoclonic jerks
o I = Increased Temp (Fever)
o V= Vitals Instability (↑↓BP; ↑RR; ↑HR)
o E= Encephalopathy (Confusion)
o R= Restlessness
o S= Sweating (Diaphoresis)
-
NOTE: Wait at least 2 weeks before switching from SSRI to MAOI and at least 5-6 weeks with fluoxetine
-
MAOI drugs:
phenelzine, tranylcypromine, isocarboxazid, selegiline
-
more effective than placebo in the treatment of Animal Phobia
- phenelzine
- selegiline (Ensam)
phenelzine
o DOES NOT REQUIRE DIETARY RESTRICTION 6mg/24hr or lower
- phenelzine
- selegiline (Ensam)
selegiline (Ensam)
o Approved in 2013
o Activates glutamate (excitatory NT) in the frontal cortex
o Effective in patients with cognitive deficits associated w/ MDD
Which med?
- clomipramine (Anafranil)
- imipramine (Tofranil)
- vortioxetine (Trintellix or Brintellex)
- selegiline (Ensam)
vortioxetine (Trintellix or Brintellex)
Antidepressant Withdrawal:
F= Flu like symptoms (aches, pains, chills)
I= Insomnia
N= Nausea
I= Imbalance
S= Sensory disturbance (tremors, sensation of electrical shock)
H= Hyperarousal
- Gradual taper of medications
- Least likely with Fluoxetine and Vortioxetine (Trintellix/Brintellix)
- Symptoms usually begin within 5 days of treatment cessation
- Consider a 4-week taper (longer with Paxil and Effexor)
-
Treatment resistant depression:
Inadequate response to 2+ antidepressants
-
Treatment resistant depression:
NOTE: Each relapse increases symptom severity, decreases treatment response, and heightens risk of treatment resistance.
-
Treatment resistant depression:
Treatment options:
Neurostimulation therapies
o Repetitive transcranial magnetic stimulation (rTMS)
Electroconvulsive therapy
o Full ECT = at least 4-6 sessions over 2-3x/week
o S/E: Headaches; muscle soreness, nausea during ECT – transient ; loss of memory recall
o First line for severe melancholic
Ketamine and Esketamine
-
Bipolar Management
Acute mania: Lithium, valproic acid and Atypical antipsychotics
-
Bipolar Management
Acute mania w/ severe symptoms (agitation): atypical antipsychotic (e.g. Olanzapine, Ziprasidone, Haloperidol)
-
Bipolar Management
Bipolar Depression: Lithium, Seroquel, Latuda
-
Drugs for Bipolar Management:
lithium (Eskalith Lithobid)
carbamazepine (Tegretol)
valproic acid (Depakote and Depakene)
lamotrigine (Lamictal)
oxcarbazepine (Trileptal)
gabapentin (Neurontin)
pregabalin (Lyrica)
tiagabine (Gabitril)
topiramate (Topamax)
-
o Gold standard for the treatment of Bipolar (acute mania)
o Good prognostic indicator for Lithium - episode pattern of mania, depression, and euthymia
o Has antisuicidal properties (The only mood stabilizer shown to ↓ suicidality)
o Metabolized by the kidney = Special consideration in renal impaired patients
o Onset of Action= 5-7 days
o Has a narrow therapeutic index
o Check level 4-5 days after initiation and after every dose change
o Before starting: TSH, Creatinine, BUN, pregnancy testing, EKG (over age 50 or risk); CBC, Chemistries
o Regular Monitoring: Lithium levels, TSH, Kidney function.
Wait 3-7 days after dose change for accuracy
Draw levels in the AM before giving first dose
o SE: Weight gain, cognitive slowing or dulling; Impaired thyroid function, GI disturbance, Sedation, fine tremor, ECG changes (T-wave inversion), Leukocytosis; hypothyroidism; Epstein anomaly – cardiac defect in babies
o Lithium Toxicity: Narrow therapeutic index (0.6-1.2 mEq/L); Toxic >1.5; Potentially Lethal =>2.0
Factors that impact lithium level
* NSAIDS (e.g., ibuprofen)
* Aspirin
* Thiazide diuretics
* Dehydration (especially in the elderly)
* Salt deprivation
* Sweating (salt loss)
* Impaired renal functioning
* Ace Inhibitors
* Antihypertensives
Early: Nausea, vomiting, diarrhea, coarse tremors, ataxia
Late: Seizures, Coma, death
o Patient Education: Drink @ least 6-8 glasses of water per day
o Emphasize the need for reliable birth control in women of childbearing age
- lithium (Eskalith Lithobid)
- carbamazepine (Tegretol)
- valproic acid (Depakote and Depakene)
- lamotrigine (Lamictal)
- oxcarbazepine (Trileptal)
- gabapentin (Neurontin)
- pregabalin (Lyrica)
- tiagabine
Gabitril) - topiramate (Topamax)
lithium (Eskalith Lithobid)
o Gold Standard for = Rapid- cycling mania
o Blackbox warning for Agranulocytosis & Aplastic Anemia
o Therapeutic Level= 8-12 mcg/ml
Check serum level initially then 3, 6 and 9 weeks.
Wait 3-7 days after dose change for accuracy
Draw levels in the AM before giving first dose
o Rare= Depakote induced thrombocytopenia
o Elevation of liver enzymes causing hepatitis
o Labs before initiating: Pregnancy test, CBC, LFTs
o Regular Labs: CBC, LFTs
o Associated w/ Neural tube defects
o Note: Auto-induction of its own metabolism;
Starts 3-5 days after initiating
Translates as decrease plasma levels
May need a dose increase in the first few weeks to months
o Toxicity: Confusion, stupor, motor restlessness, ataxia, tremor, nystagmus, twitching and vomiting
o ***Acute intoxication can produce Ataxia
- lithium (Eskalith Lithobid)
- carbamazepine (Tegretol)
- valproic acid (Depakote and Depakene)
- lamotrigine (Lamictal)
- oxcarbazepine (Trileptal)
- gabapentin (Neurontin)
- pregabalin (Lyrica)
- tiagabine
Gabitril) - topiramate (Topamax)
carbamazepine (Tegretol)
o MOA: Blocks sodium channels and increases GABA concentrations in the brain
o Blackbox warning for hepatotoxicity & pancreatitis
o Therapeutic level = 80-120 ug/ml
o Check level after 4-5 days
o Rare= Depakote induced thrombocytopenia
o Labs: CBC, LFTs
o Associated w/ Neural tube defects specifically spina bifida, atrial septal defects, cleft palate and possible long-term developmental deficits
o NOTE: Valproate will increase Lamictal levels
- -
- carbamazepine (Tegretol)
- valproic acid (Depakote and Depakene)
- lamotrigine (Lamictal)
- oxcarbazepine (Trileptal)
- gabapentin (Neurontin)
- pregabalin (Lyrica)
- tiagabine
Gabitril) - topiramate (Topamax)
valproic acid (Depakote and Depakene)
o RARE: Steven Johnson Syndrome (life threatening rash involving the skin and mucus membranes)
o ***Start low and go slow
o Lamictal dose must be halved when taken with Depakote
- lithium (Eskalith Lithobid)
- carbamazepine (Tegretol)
- valproic acid (Depakote and Depakene)
- lamotrigine (Lamictal)
- oxcarbazepine (Trileptal)
- gabapentin (Neurontin)
- pregabalin (Lyrica)
- tiagabine
Gabitril) - topiramate (Topamax)
lamotrigine (Lamictal)
Monitor Na+ levels = hyponatremia
- lithium (Eskalith Lithobid)
- carbamazepine (Tegretol)
- valproic acid (Depakote and Depakene)
- lamotrigine (Lamictal)
- oxcarbazepine (Trileptal)
- gabapentin (Neurontin)
- pregabalin (Lyrica)
- tiagabine
Gabitril) - topiramate (Topamax)
oxcarbazepine (Trileptal)
o Most limiting side effect= Cognitive slowing
- lithium (Eskalith Lithobid)
- carbamazepine (Tegretol)
- valproic acid (Depakote and Depakene)
- lamotrigine (Lamictal)
- oxcarbazepine (Trileptal)
- gabapentin (Neurontin)
- pregabalin (Lyrica)
- tiagabine
Gabitril) - topiramate (Topamax)
topiramate (Topamax)
**Note: All the mood stabilizers particularly the antiepileptics are associated with hepatic side effects (Gabapentin and Lyrica are the safest)
-
Teratogenic effects of various psychotropic medications:
- Benzodiazepines: Floppy baby syndrome, cleft palate
- Carbamazepine (Tegretol): Neural tube defects
- Lithium (Eskalith): Epstein anomaly
-
CYP-450 Induction/Inhibition:
- Induction increases metabolism and can reduce the effect of other medications
- Inhibition decreases metabolism and can cause drug levels to rise resulting in a harmful or adverse effect
- Inhibitors: buproprion, clomipramine, cimetidine, SSRIs, clarithromycin, fluoroquinolones, grapefruit/grapefruit juice, ketoconazole, nefazodone
- Inducers: carbamazepine, St. John’s Wort, phenytoin, phenobarbital, tobacco
-
lithium (Eskalith Lithobid)
Gold standard for the treatment of Bipolar (acute mania)
True or false?
True
lithium (Eskalith Lithobid)
Good prognostic indicator for Lithium - episode pattern of mania, depression, and euthymia
True or false?
True
lithium (Eskalith Lithobid)
Has antisuicidal properties (The only mood stabilizer shown to ↓ suicidality)
-
lithium (Eskalith Lithobid)
Metabolized by the kidney = Special consideration in renal impaired patients
-
lithium (Eskalith Lithobid)
Onset of Action = 5-7 days
-
lithium (Eskalith Lithobid)
Has a narrow therapeutic index
-
lithium (Eskalith Lithobid)
Check level 4-5 days after initiation and after every dose change
-
lithium (Eskalith Lithobid)
Before starting: TSH, Creatinine, BUN, pregnancy testing, EKG (over age 50 or risk); CBC, Chemistries
-
lithium (Eskalith Lithobid)
Regular Monitoring:
Lithium levels, TSH, Kidney function.
Wait 3-7 days after dose change for accuracy
Draw levels in the AM before giving first dose
-
lithium (Eskalith Lithobid)
o SE: Weight gain, cognitive slowing or dulling; Impaired thyroid function, GI disturbance, Sedation, fine tremor, ECG changes (T-wave inversion), Leukocytosis; hypothyroidism; Epstein anomaly – cardiac defect in babies
-
lithium (Eskalith Lithobid)
(0.6-1.2 mEq/L)
-
Epstein anomaly – cardiac defect in babies
- Lithium (Eskalith)
- Carbamazepine (Tegretol)
- Benzodiazepines
Lithium (Eskalith)
Neural tube defects
- Lithium (Eskalith)
- Carbamazepine (Tegretol)
- Benzodiazepines
Carbamazepine (Tegretol)
Floppy baby syndrome, cleft palate
- Lithium (Eskalith)
- Carbamazepine (Tegretol)
- Benzodiazepines
Benzodiazepines
Lithium toxicity:
- > 0.5
- > 0.7
- > 1.0
- > 1.5
> 1.5
Lithium Toxicity (potentially lethal):
- =>1.0
- =>1.7
- =>2.0
- =>1.5
=>2.0
lithium (Eskalith Lithobid)
Patient Education: Drink @ least 6-8 glasses of water per day
-
lithium (Eskalith Lithobid)
Emphasize the need for reliable birth control in women of childbearing age
-
Note: Lamictal will decrease valproate levels
-
Emphasize the need for reliable birth control in women of childbearing age
- lithium (Eskalith Lithobid)
- carbamazepine (Tegretol)
- valproic acid (Depakote and Depakene)
- lamotrigine (Lamictal)
- oxcarbazepine (Trileptal)
- topiramate (Topamax)
lithium (Eskalith Lithobid)
Therapeutic Level= 8-12 mcg/ml
- lithium (Eskalith Lithobid)
- carbamazepine (Tegretol)
- valproic acid (Depakote and Depakene)
- lamotrigine (Lamictal)
- oxcarbazepine (Trileptal)
- topiramate (Topamax)
carbamazepine (Tegretol)
Check serum level initially then 3, 6 and 9 weeks.
- lithium (Eskalith Lithobid)
- carbamazepine (Tegretol)
- valproic acid (Depakote and Depakene)
- lamotrigine (Lamictal)
- oxcarbazepine (Trileptal)
- topiramate (Topamax)
carbamazepine (Tegretol)
Draw levels in the AM before giving first dose (besides lithium).
- lithium (Eskalith Lithobid)
- carbamazepine (Tegretol)
- valproic acid (Depakote and Depakene)
- lamotrigine (Lamictal)
- oxcarbazepine (Trileptal)
- topiramate (Topamax)
carbamazepine (Tegretol)
Rare = Depakote induced thrombocytopenia
- lithium (Eskalith Lithobid)
- carbamazepine (Tegretol)
- valproic acid (Depakote and Depakene)
- lamotrigine (Lamictal)
- oxcarbazepine (Trileptal)
- topiramate (Topamax)
carbamazepine (Tegretol)
Elevation of liver enzymes causing hepatitis
- lithium (Eskalith Lithobid)
- carbamazepine (Tegretol)
- valproic acid (Depakote and Depakene)
- lamotrigine (Lamictal)
- oxcarbazepine (Trileptal)
- topiramate (Topamax)
carbamazepine (Tegretol)
Associated w/ Neural tube defects
- lithium (Eskalith Lithobid)
- carbamazepine (Tegretol)
- valproic acid (Depakote and Depakene)
- lamotrigine (Lamictal)
- oxcarbazepine (Trileptal)
- topiramate (Topamax)
carbamazepine (Tegretol)
Note: Auto-induction of its own metabolism;
- lithium (Eskalith Lithobid)
- carbamazepine (Tegretol)
- valproic acid (Depakote and Depakene)
- lamotrigine (Lamictal)
- oxcarbazepine (Trileptal)
- topiramate (Topamax)
carbamazepine (Tegretol)
Acute intoxication can produce Ataxia
- lithium (Eskalith Lithobid)
- carbamazepine (Tegretol)
- valproic acid (Depakote and Depakene)
- lamotrigine (Lamictal)
- oxcarbazepine (Trileptal)
- topiramate (Topamax)
carbamazepine (Tegretol)
Therapeutic level = 80-120 ug/ml
- lithium (Eskalith Lithobid)
- carbamazepine (Tegretol)
- valproic acid (Depakote and Depakene)
- lamotrigine (Lamictal)
- oxcarbazepine (Trileptal)
- topiramate (Topamax)
valproic acid (Depakote and Depakene)
Check level after 4-5 days (besides lithium)
- -
- carbamazepine (Tegretol)
- valproic acid (Depakote and Depakene)
- lamotrigine (Lamictal)
- oxcarbazepine (Trileptal)
- topiramate (Topamax)
valproic acid (Depakote and Depakene)
Rare= Depakote induced thrombocytopenia
- lithium (Eskalith Lithobid)
- carbamazepine (Tegretol)
- valproic acid (Depakote and Depakene)
- lamotrigine (Lamictal)
- oxcarbazepine (Trileptal)
- topiramate (Topamax)
valproic acid (Depakote and Depakene)
Associated w/ Neural tube defects specifically spina bifida, atrial septal defects, cleft palate and possible long-term developmental deficits. Besides carbamazepine.
- lithium (Eskalith Lithobid)
- -
- valproic acid (Depakote and Depakene)
- lamotrigine (Lamictal)
- oxcarbazepine (Trileptal)
- topiramate (Topamax)
valproic acid (Depakote and Depakene)
NOTE: This will increase Lamictal levels
- lithium (Eskalith Lithobid)
- carbamazepine (Tegretol)
- valproic acid (Depakote and Depakene)
- lamotrigine (Lamictal)
- oxcarbazepine (Trileptal)
- topiramate (Topamax)
valproic acid (Depakote and Depakene)
RARE: Steven Johnson Syndrome (life threatening rash involving the skin and mucus membranes)
- lithium (Eskalith Lithobid)
- carbamazepine (Tegretol)
- valproic acid (Depakote and Depakene)
- lamotrigine (Lamictal)
- oxcarbazepine (Trileptal)
- topiramate (Topamax)
lamotrigine (Lamictal)
Start low and go slow
- lithium (Eskalith Lithobid)
- carbamazepine (Tegretol)
- valproic acid (Depakote and Depakene)
- lamotrigine (Lamictal)
- oxcarbazepine (Trileptal)
- topiramate (Topamax)
lamotrigine (Lamictal)
Dose must be halved when taken with Depakote
- lithium (Eskalith Lithobid)
- carbamazepine (Tegretol)
- valproic acid (Depakote and Depakene)
- lamotrigine (Lamictal)
- oxcarbazepine (Trileptal)
- topiramate (Topamax)
lamotrigine (Lamictal)
Monitor Na+ levels = hyponatremia
- lithium (Eskalith Lithobid)
- carbamazepine (Tegretol)
- valproic acid (Depakote and Depakene)
- lamotrigine (Lamictal)
- oxcarbazepine (Trileptal)
- topiramate (Topamax)
oxcarbazepine (Trileptal)
Most limiting side effect = Cognitive slowing
- lithium (Eskalith Lithobid)
- carbamazepine (Tegretol)
- valproic acid (Depakote and Depakene)
- lamotrigine (Lamictal)
- oxcarbazepine (Trileptal)
- topiramate (Topamax)
topiramate (Topamax)
buproprion, clomipramine, cimetidine, SSRIs, clarithromycin, fluoroquinolones, grapefruit/grapefruit juice, ketoconazole, nefazodone
CYP-450 inhibitors or inducers?
Inhibitors
carbamazepine, St. John’s Wort, phenytoin, phenobarbital, tobacco
CYP-450 inhibitors or inducers?
inducers
Only SSRI not indicated for depression, but for OCD and social anxiety disorder (SAD)
- Sertraline
- Citalopram
- Fluvoxamine
- Escitalopram
Fluvoxamine
Indicated for social anxiety disorder as well as MDD, OCD, panic D/O, PTSD, PMDD. Most lethal of SSRI in OD.
- Sertraline
- Citalopram
- Fluvoxamine
- Escitalopram
Sertraline
short half-life = discontinuation syndrome also indicated for PTSD, SAD, MDD, OCD, GAD
- Sertraline
- Paroxetine
- Fluvoxamine
- Escitalopram
Paroxetine
Steven-Johnson syndrome - titrate slowly
Concomitant use with divalproex must titrate more slowly and halve the dose
Weight neutral
- Lamotrigine
- Gabapentin
- Carbamazepine
- Fluvoxamune
Lamotrigine
Considered the gold standard of treatment for bipolar-anti-suicidal properties
- Carbamazepine
- Lithium
- Divalproex
- Lamotrigine
Lithium
This short half-life SNRI often produces discontinuation syndrome (electric zaps).
- Duloxetine
- Milnacipran
- Venlafaxine
Venlafaxine
SARI more useful for sleep than depression. Educate about risks of priapism for males. Orthostatic hypotension due to α-blockade.
- Trazodone
- Nefazodone
- Vortioxetine
Trazodone
SPARI that must be taken with food.
(SPARI-Serotonin-Norepinephrine Reuptake Inhibitors)
- trazodone
- nefazodone
- vortioxetine
- vilazodone
vilazodone
An NDRI (Norepinephrine-Dopamine Reuptake Inhibitors)
Do not use with Hx of seizures or eating disorders
Can aid in smoking cessation
Lowest risk for sexual SE
Used as augmenting agent to SSRI
Lowest risk for “switch” to mania in bipolar
- bupropion
- citalopram
- trazodone
- venlafaxine
bupropion
Class Profile-Highly anticholinergic-dry mouth, constipation, blurred vision
- FGAs
- ADs
- TCAs
- SSRIs
TCAs
TCAs are lethal in overdose - _____________ especially.
- clomipramine
- nortriptyline
- amitriptyline
- desipramine
Desipramine
Must adhere to dietary restrictions, extreme caution with medications, must have 4-5 week wash out period of meds before initiating.
- TCAs
- SNRIs
- SGAs
- MAOIs
MAOIs
This MAOI is for depression with atypical features.
- phenelzine
- isocarboxazid
- selegeline
- trancyclopromine
phenelzine
This med stimulates appetite, sedation greater at lower doses, and can be useful in the elderly population.
- mirtazapine
- carbamazepine
- venlafaxine
- phenelzine
Mirtazapine-
Therapeutic Level = 8-12 mcg/ml
- divalproex
- lamotrigine
- topiramate
- oxcarbazepine
- carbamazepine
- lithium
carbamazepine
BLACKBOX WARNING: Increased suicidality in children, adolescents, and young adults.
- SNRIs
- TCAs
- SSRIs
- MAOIs
SSRIs
This medication, a TCA, is used to help alleviate chronic pain and migraines.
- amoxapine
- desipramine
- amitriptyline
- imipramine
amitriptyline
