Neuro+Psych Pharmacology Flashcards
sumatriptan
triptan used for acute migraine attack
MOA: 5HT1B/D agonist => block the release of vasoactive peptides from perivascular trigeminal neurons =? vasoconstriction
zolmitriptan
triptan used for acute migraine attack
MOA: 5HT1B/D agonist => block the release of vasoactive peptides from perivascular trigeminal neurons => vasoconstriction
triptan side effects
nausea, dizziness, parasthesias, somnolence, chest tightness
cerebral vasoconstriction and rebound headache with excessive dosing
triptan DDIs
MAOIs (serotonin syndrome), ergots (increased vasoconstriction)
lasmiditan
selective serotonin receptor agonist used for acute migraine attack
MOA: 5HT1F agonist => block release of vasoactive peptides from perivascular trigeminal neurons
lasmiditan side effects
nausea, dizziness, paresthesia, somnolence
ubrogepant
CGRP receptor antagonist to treat acute migraine attack
MOA: small molecule antagonist of CGRP receptors
CGRP receptor antagonists: ubrogepant, rimegepant
rimegepant
CGRP receptor antagonist to treat acute migraine attack
MOA: small molecule antagonist of CGRP receptors
CGRP receptor antagonists: ubrogepant, rimegepant
CGRP receptor antagonists
ubrogepant, rimegepant
CGRP receptor antagonist side effects
nausea, sedation
dihydroergotamine
ergot used to treat acute migraine attack
MOA: structurally similar to LSD; predominately 5HT1D agonist, but also 5HT-2A/B/C agonist, DA agonist, and a receptor agonist
dihydroergotamine DDIs
beta blockers (alpha vasoconstriction unopposed by B2 vasodilation => peripheral ischemia), protease inhibitors and macrolide antibiotics (excessive vasoconstriction and CYP450 interactions)
when dihydroergotamine is given parenterally, [drug] can help prevent vomiting
metoclopramide
dihydroergotamine is an ergot used in the treatment of acute migraine attack
galcanezumab
CGRP antibody used for migraine prophylaxis
MOA: prevents perivascular release of CGRP => prevents vasodilation
erenumab
CGRP receptor antibody used for migraine prophylaxis
beta blockers used for migraine prophylaxis
propranolol, timolol
MOA unknown in migraine
used in migraineurs with hypertension/angina, migraineurs with performance anxiety or aggressive behavior
beta blockers used for migraine prophylaxis - side effects
fatigue, exercise intolerance, cold extremities, diarrhea, constipation, dizziness, worsening depression
beta blockers used for migraine prophylaxis: propranolol, timolol
calcium channel blocker used for migraine prophylaxis
verapamil
MOA: blocks transmembrane influx of calcium across cells through their slow voltage-dependent channels => affects neurotransmission
used in migraineurs with hypertension, hemiplegic migraine
calcium channel blockers for migraine prophylaxis - side effects
constipation, hypotension, AV block, edema, nausea
CCB for migraine prophylaxis: verapamil
calcium channel blockers for migraine prophylaxis - contraindications
bradycardia, heart block, sick sinus syndrome
CCB for migraine prophylaxis: verapamil
tricyclic antidepressants used for migraine prophylaxis
amytriptyline, nortriptyline
MOA: central action via inhibition of 5HT and NE reuptake
used for headaches associated with premenstrual syndrome or premenstrual dysphoric disorder; migraineurs with depression, anxiety/panic disorders, or fibromyalgia
tricyclic antidepressants used for migraine prophylaxis - side effects
antimuscarinic effects (increased HR, blurred vision, difficulty urinating, dry mouth, constipation), weight loss/gain, orthostatic hypotension
tricyclic antidepressants used for migraine prophylaxis: amytriptyline, nortriptyline
TCA used for migraine prophylaxis - DDIs
MAOIs (serotonin syndrome)
tricyclic antidepressants used for migraine prophylaxis: amytriptyline, nortriptyline
tricyclic antidepressants used for migraine prophylaxis - contraindications
seizures, enlarged prostate, glaucoma
tricyclic antidepressants used for migraine prophylaxis: amytriptyline, nortriptyline
anti-epileptic medications used for migraine prophylaxis
topiramate, valproic acid
used in migraineurs that are overweight or have bipolar disorder
topiramate
anti-epileptic medication used for migraine prophylaxis in migraineurs that are overweight or have bipolar disorder
MOA: may antagonize AMPA receptors, inhibit sodium channels, or potentiate transmission at GABA-A receptors
valproic acid
anti-epileptic medication used for migraine prophylaxis in migraineurs that are overweight or have bipolar disorder
MOA: inhibits low threshold T-type calcium channels (use dependent block of sodium channels, increased GABA)
enfuviritide
fusion inhibitor to treat HIV patients that are resistant to other drugs
MOA: binds gp41 => interferes with entry into the cell
enfuviritide side effects
local injection site reactions (subcutaneous injection), increased rate of bacterial pneumonia, hypersensitivity reaction
maraviroc
CCR5 antagonist to treat HIV patients that are resistant to other drugs
MOA: blocks co-receptor => prevents entry
maraviroc side effects
cough, fever, rash, URT infection, musculoskeletal symptoms, abdominal pain, postural dizziness, hepatotoxicity, cardiovascular events
nucleoside reverse transcriptase inhibitors used to treat HIV
lamivudine, emtricitabine, abacavir, zidovudine, tenofovir
tenofovir is only one that does not need to be phosphorylated
lamivudine
nucleoside reverse transcriptase inhibitor (NRTI) used to treat HIV
MOA: nucleoside analogue phosphorylated to triphosphates => cause chain termination of DNA as it is being transcribed from RNA
NRTIs used to treat HIV: lamivudine, emtricitabine, abacavir, zidovudine, tenofovir
emtricitabine
nucleoside reverse transcriptase inhibitor (NRTI) used to treat HIV
MOA: nucleoside analogue phosphorylated to triphosphates => cause chain termination of DNA as it is being transcribed from RNA
NRTIs used to treat HIV: lamivudine, emtricitabine, abacavir, zidovudine, tenofovir
abacavir
nucleoside reverse transcriptase inhibitor (NRTI) used to treat HIV
MOA: nucleoside analogue phosphorylated to triphosphates => cause chain termination of DNA as it is being transcribed from RNA
NRTIs used to treat HIV: lamivudine, emtricitabine, abacavir, zidovudine, tenofovir
zidovudine
nucleoside reverse transcriptase inhibitor (NRTI) used to treat HIV
MOA: nucleoside analogue phosphorylated to triphosphates => cause chain termination of DNA as it is being transcribed from RNA
NRTIs used to treat HIV: lamivudine, emtricitabine, abacavir, zidovudine, tenofovir
tenofovir
nucleoside reverse transcriptase inhibitor (NRTI) used to treat HIV
MOA: nucleoside analogue that does not need to be phosphorylated => cause chain termination of DNA as it is being transcribed from RNA
NRTIs used to treat HIV: lamivudine, emtricitabine, abacavir, zidovudine, tenofovir
nucleoside reverse transcriptase inhibitors to treat HIV - side effects
mitochondrial toxicity (lactic acidosis, pancreatitis, peripheral neuropathy, myopathy, cardiomyopathy, hepatic steatosis, lipid dystrophy)
zidovudine-induced anemia and neutropenia, abacavir hypersensitivity reaction
NRTIs used to treat HIV: lamivudine, emtricitabine, abacavir, zidovudine, tenofovir
abacavir hypersensitivity reaction is related to what genetic variant?
HLA-B*5701
nucleoside reverse transcriptase inhibitors to treat HIV - DDIs
cytochrome p450 inhibitors (cimetidine) increase levels; probenecid increases levels; cytochrome p450 inducers (rifampin) decrease levels
NRTIs used to treat HIV: lamivudine, emtricitabine, abacavir, zidovudine, tenofovir
tenofovir side effects
weakness, headache, diarrhea
nucleoside reverse transcriptase inhibitor (NRTI) used to treat HIV
efavirenz
non-nucleoside reverse transcriptase inhibitor (NNRTI) used to treat HIV
MOA: inhibits reverse transcriptase
efavirenz side effects
rash, Steven-Johnson syndrome, hepatitis, CNS effects
a non-nucleoside reverse transcriptase inhibitor used to treat HIV
integrase inhibitors used to treat HIV
bictegravir, dolutegravir, elvitegravir, raltegravir, cabotegravir/rilpivirine
bictegravir
integrase inhibitor used to treat HIV
MOA: targets viral integrase
integrase inhibitors: bictegravir, dolutegravir, elvitegravir, raltegravir, cabotegravir/rilpivirine
dolutegravir
integrase inhibitor used to treat HIV
MOA: targets viral integrase
integrase inhibitors: bictegravir, dolutegravir, elvitegravir, raltegravir, cabotegravir/rilpivirine
elvitegravir
integrase inhibitor used to treat HIV
MOA: targets viral integrase
integrase inhibitors: bictegravir, dolutegravir, elvitegravir, raltegravir, cabotegravir/rilpivirine
raltegravir
integrase inhibitor used to treat HIV
MOA: targets viral integrase
integrase inhibitors: bictegravir, dolutegravir, elvitegravir, raltegravir, cabotegravir/rilpivirine
cabotegravir/rilpivirine
integrase inhibitor used to treat HIV
MOA: targets viral integrase
integrase inhibitors: bictegravir, dolutegravir, elvitegravir, raltegravir, cabotegravir/rilpivirine
integrase inhibitors for HIV - side effects
hypersensitivity reactions or serious dermatological reactions, rhabdomyolysis, diarrhea, headache
integrase inhibitors: bictegravir, dolutegravir, elvitegravir, raltegravir, cabotegravir/rilpivirine
integrase inhibitors for HIV - DDIs
rifampin enhances elimination; antacid may bind raltegravir and inhibit its action
integrase inhibitors: bictegravir, dolutegravir, elvitegravir, raltegravir, cabotegravir/rilpivirine
protease inhibitors used to treat HIV
darunavir, ritonavir
darunavir
protease inhibitor used to treat HIV
MOA: targets a dipeptide region in HIV aspartate protease that is not seen in other mammalian proteins
ritonavir
protease inhibitor used to treat HIV
MOA: targets a dipeptide region in HIV aspartate protease that is not seen in other mammalian proteins
protease inhibitors for HIV - side effects
nausea, vomiting, diarrhea, hyperglycemia, lipodystrophy, hyperlipidemia, hepatotoxicity
protease inhibitors: ritonavir, darunavir
fostemsavir
HIV attachment inhibitor
MOA: binds gp120 to prevent virus from attaching to CD4 receptor on T cells => prevents viral attachment
ibalizumab
monoclonal Ab used to treat HIV
MOA: recombinant mAb against domain 2 of CD4 T cells => prevents viral entry
preferred drug combinations for the treatment of HIV
bictegravir + tenofovir/emtricitabine
dolutegravir + abacavir/lamivudine (test for HLA-B*5701 first)
dolutegravir + tenofovir + emtricitabine or lamivudine
dolutegravir + lamivudine (in select individuals)
depolarizing neuromuscular blocker
succinylcholine
succinylcholine
depolarizing neuromuscular blocker
MOA: more stable agonist than ACh; initially causes persistent depolarization (=> fasciculations); with continuous exposure, desensitization of muscle nicotinic receptors => repolarization of the muscle but end plate is blocked (phase I); later, nicotinic receptors will inactivate (phase II)
used for brief procedures (mainly intubation)
succinylcholine side effects
apnea, hyperkalemia (precludes use in children), increased IOP, increased gastric pressure, malignant hyperthermia
genetic variability in [enzyme] affects duration of action of succinylcholine
plasma cholinesterase
homozygous individuals have greatly prolonged action; heterozygous individuals or those with severe liver disease have moderately prolonged action
non-depolarizing neuromuscular blockers
tubocurarine, pancuronium, cisatracurium, atracurium, vecuronium, rocuronium
tubocurarine
non-depolarizing neuromuscular blocker
long duration of action (kidney/liver metabolism); no longer available for use
MOA: basic competitive blocker of ACh at muscle nicotinic receptors; also blocks autonomic ganglia and causes histamine release
pancuronium
non-depolarizing neuromuscular blocker
long duration (kidney metabolism), moderate block of muscarinic receptors (cardiac)
MOA: basic competitive blocker of ACh at muscle nicotinic receptors
cistracurium, atracurium
non-depolarizing neuromuscular blocker
intermediate duration (spontaneous hydrolysis), widely used in surgery
MOA: basic competitive blocker of ACh at muscle nicotinic receptors
vercuronium
non-depolarizing neuromuscular blocker
intermediate duration (liver metabolism), widely used in surgery
MOA: basic competitive blocker of ACh at muscle nicotinic receptors
rocuronium
non-depolarizing neuromuscular blocker
rapid onset for brief procedures, shorter duration (lover metabolism)
MOA: basic competitive blocker of ACh at muscle nicotinic receptors
drugs used for reversal of non-depolarizing neuromuscular blockers
neostigmine (cholinesterase inhibitor)
atropine and glycopyrrolate (antimuscarinic given to prevent concomitant excess of ACh at muscarinic sites)
nitrous oxide
inhaled anesthetic
halogenated hydrocarbons
isoflurane, sevoflurane, desflurane, enflurane, halothane
inhaled anesthetics (* = used infrequently)
halogenated hydrocarbons side effects
renal toxicity (enflurane), hepatic toxicity (halothane), respiratory toxicity (sevoflurane)
intravenous anesthetics
thiopental, methohexital, etomidate, propofol, ketamine
inhaled anesthetics [increase/decrease] cerebral blood flow, while intravenous anesthetics [increase/decrease] cerebral blood flow
inhaled anesthetics increase cerebral blood flow, while intravenous anesthetics decrease cerebral blood flow
minimum alveolar concentration (MAC)
alveolar concentration at which 50% of healthy patients do not move (inhaled anesthetics)
the minimum alveolar concentration [increases/decreases] in elderly, pregnancy, and sickness
the MAC decreases in elderly, pregnancy, and sickness (need less inhaled anesthetics to achieve effect)
L-DOPA
dopamine precursor used to treat Parkinson’s
most effective at diminishing bradykinesia
MOA: taken up by neuron, converted to dopamine, stored in vesicle, and released
L-DOPA side effects
GI effects: anorexia, nausea, vomiting (decreased by giving drug with or after meals)
cardiovascular effects: orthostatic hypotension, tachycardia
dyskinesias (facial grimacing, restless feet syndrome, stereotyped behavior)
psychiatric and behavioral side effects: nightmares, anxiety, paranoia, hallucinations, mania
on-off phenomena
L-DOPA DDIs
MOAIs (hypertensive crisis)
L-DOPA contraindications
psychosis, closed angle glaucoma, melanoma
the presence of DOPA decarboxylase inhibitor [drug], much more L-DOPA enters the brain
carbidopa
sinemet
controlled release formulation of L-DOPA
bromocriptine
dopamine agonist used to treat Parkinson’s (also used at lower doses for hyperprolactinemia)
MOA: directly activate dopamine receptors (D2, D3); ergot alkaloid
bromocriptine side effects
cardiovascular effects: postural hypotension, erythromelalgia, digital vasospasm
GI effects: anorexia, nausea, vomiting, constipation, indigestion, peptic ulceration with bleeding, reflux esophagitis
dyskinesia (less than with L-DOPA)
mental disturbance (hallucinations, compulsive behaviors)
fibrosis
pramipexole
dopamine agonist used to treat Parkinson’s
MOA: D3>D2 agonist
ropinirole
dopamine agonist used to treat Parkinson’s
MOA: D2 and D3 agonist
pramipexole and ropinirole side effects
more likely to cause sudden sleep episodes; cardiovascular side effects are less common than bromocriptine; compulsive behavior; dyskinesia; hallucinations
dopamine agonists used to treat Parkinson’s
amantadine
dopamine releasing agent used in Parkinson’s to control for L-DOPA dyskinesias
MOA: antiviral drug that causes DA release in striatum; may also act at glutamate receptors
amantadine side effects
restlessness, agitation, hallucinations, livedo reticularis, peripheral edema
amantadine counterindications
seizures, CHF
selegiline
monoamine oxidase inhibitor used as an adjunctive therapy for Parkinson’s
MOA: MOA-B inhibitor => retards breakdown of dopamine, prolongs the effects of DOPA
anticholinergics used in Parkinson’s
benzotropine, trihezyphenidyl
MOA: restores dopamine and cholinergic balance within the striatum => improves rigidity/tremor, minor effect on bradykinesia
selegiline side effects
insomnia (metabolized to L-methamphetamine and L-amphetamine)
benotropine, trihexyphenidyl side effects
restlessness, hallucinations, confusion, antimuscarinic effects
anticholinergics used for treatment of Parkinson’s
benzotropine, trihexyphenidyl contraindications
prostatic hypertrophy, obstructive GI disease, glaucoma
COMT inhibitors used in Parkinson’s
talcapone, entacapone
MOA: COMT converts DOPA to 3-O-methyldopa and DA to 3-methyoxytyramine => these agents enhance delivery of L-DOPA to the brain and stabilize DA
used to increase duration of effect of DOPA dose without increasing DOPA level (never used alone)
tolcapone, entacapone side effects
dyskinesias
tolcapone requires frequent blood tests to measure liver function
cholinesterase inhibitors used in Alzheimer’s
tacrine, donepezil, galantamine, rivastigmine
tacrine
first centrally-acting cholinesterase inhibitor used for Alzheimer’s
still on the market but generally not used because of significant hepatotoxicity
donepezil
cholinesterase inhibitor used in Alzheimer’s
MOA: reversible cholinesterase inhibitor that specifically and selectively inhibits cholinesterase in CNS and increases acetylcholine in the cortex*
*does also inhibit cholinesterase in periphery => side effects
galantamine
cholinesterase inhibitor used to treat Alzheimer’s disease with a cerebrovascular component
MOA: inhibit acetylcholinesterase + positive allosteric modulator of nicotinic receptors => enhance activation of nicotinic receptors
donepezil and galantamine side effects
nausea, diarrhea, headache, insomnia, anorexia, pain; urinary incontinence may also occur
cholinesterase inhibitors used to treat AD
donepezil and galantamine DDIs
may accentuate effect of succinylcholine; cytochrome p450 interactions with cimetidine, ketoconazole, ritonavir, etc.
donepezil and galantamine contraindications
cardiac conduction abnormalities, ulcers, seizures, asthma, COPD, older patients with low body weight
rivastigmine
cholinesterase inhibitor used to treat Alzheimer’s
MOA: inhibits acetylcholinesterase and butyrl cholinesterase in glia => makes more ACh available for cholinergic neurons
rivastigmine side effects
GI symptoms more severe than other drugs in this class (nausea, diarrhea, headache, insomnia, anorexia, pain; urinary incontinence may also occur)
cholinesterase inhibitor used to treat AD
memantine
NMDAR antagonist used to treat Alzheimer’s, Huntington disease, AIDS-related dementia, vascular dementia
MOA: NMDAR antagonist that blocks “open” NMDA channels with low to moderate affinity => blocks effects of glutamate “leak” at NMDA receptors caused by amyloid plaques without blocking all glutamate transmission
memantine side effects
dizziness, constipation, confusion, headache, hypertension
memantine contraindications
renal impairment, cardiovascular disease, history of seizures
raising urinary pH will [increase/decrease] elimination of memantine
decrease
memantine DDIs
other NMDAR antagonists (amantadine, ketamine, dextromorphan)
typical antipsychotics
high potency: haloperidol, fluphenazine
medium potency: periphenazine
low potency: chlorpromazine, thioridazine
MOA: D2 blockade
haloperidol
high potency typical antipsychotic (D2 blockade, low anticholinergic effect)
fluphenazine
high potency typical antipsychotic (D2 blockade, low anticholinergic effect)
periphenazine
medium potency typical antipsychotic (D2 blockade, medium anticholinergic effect)
chlorpromazine
low potency typical antipsychotic (D2 blockade, high anticholinergic effect)
thioridazine
low potency typical antipsychotic (high anticholinergic effect)
typical antipsychotics side effects
acute dystonia (treated with diphenhydramine), parkinsonism (treated with amantadine), akathisia (treated with propranolol), tardive dyskinesia (treated with valbenazine), orthostatic hypotension, male sexual dysfunction, constipation, dry mouth, urinary retention, visual problems, sedation, galactorrhea, amenorrhea, neuroleptic malignant syndrome (treated with dantrolene or bromocriptine)
acute dystonia (typical antipsychotic side effect) is treated with [drug]
diphenhydramine
parkinsonism (typical antipsychotic side effect) is treated with [drug]
amantadine
akathisia (typical antipsychotic side effect) is treated with [drug]
propranolol
tardive dyskinesia (typical antipsychotic side effect) is treated with [drug]
valbenazine
neuroleptic malignant syndrome (rare side effect of typical antipsychotics) is treated with [drug]
dantrolene or bromocriptine
atypical antipsychotics
clozapine, risperidone, olanzapine, quetiapine, ziprasidone, ariprazole
clozapine
atypical antipsychotic
MOA: serotonin 5HT2A receptor antagonist; D2 antagonists with rapid dissociation (decreases EPS)
atypical antipsychotics: clozapine, risperidone, olanzapine, quetiapine, ziprasidone, ariprazole
risperidone
atypical antipsychotic
MOA: serotonin 5HT2A receptor antagonist; D2 antagonists with rapid dissociation (decreases EPS)
atypical antipsychotics: clozapine, risperidone, olanzapine, quetiapine, ziprasidone, ariprazole
olanzapine
atypical antipsychotic
MOA: serotonin 5HT2A receptor antagonist; D2 antagonists with rapid dissociation (decreases EPS)
atypical antipsychotics: clozapine, risperidone, olanzapine, quetiapine, ziprasidone, ariprazole
quetiapine
atypical antipsychotic
MOA: serotonin 5HT2A receptor antagonist; D2 antagonists with rapid dissociation (decreases EPS)
atypical antipsychotics: clozapine, risperidone, olanzapine, quetiapine, ziprasidone, ariprazole
ziprasidone
atypical antipsychotic
MOA: serotonin 5HT2A receptor antagonist; D2 antagonists with rapid dissociation (decreases EPS)
atypical antipsychotics: clozapine, risperidone, olanzapine, quetiapine, ziprasidone, ariprazole
ariprazole
atypical antipsychotic
MOA: serotonin 5HT2A receptor antagonist; D2 antagonists with rapid dissociation (decreases EPS); dopamine D2 partial agonist (unique to ariprazole)
atypical antipsychotics: clozapine, risperidone, olanzapine, quetiapine, ziprasidone, ariprazole
atypical antipsychotics side effects
increased appetite and weight gain (increased triglycerides, insulin resistance, diabetes, CV events); sedation, somnolence
+ agraunulocytosis, increased salivation, and seizures (clozapine)
+ cardiac arrhythmia (ziprasidone)
+ EPS at higher doses (risperidone)
atypical antipsychotics: clozapine, risperidone, olanzapine, quetiapine, ziprasidone, ariprazole
selective serotonin reuptake inhibitors (SSRIs)
fluoxetine, sertraline, citalopram, fluvoxamine, paroxetine
used in major depression, generalized anxiety disorder, PTSD, OCD, panic disorder, and premenstrual dysphoric disorder
fluoxetine
selective serotonin reuptake inhibitor
MOA: inhibit reuptake of serotonin
therapeutic effect occurs over 2-4 weeks; ultimately correlated with increased activation of postsynaptic 5HT1A receptors and decreased activation of 5HT2A receptors
SSRIs: fluoxetine, sertraline, citalopram, fluvoxamine, paroxetine
sertraline
selective serotonin reuptake inhibitor
MOA: inhibit reuptake of serotonin
therapeutic effect occurs over 2-4 weeks; ultimately correlated with increased activation of postsynaptic 5HT1A receptors and decreased activation of 5HT2A receptors
SSRIs: fluoxetine, sertraline, citalopram, fluvoxamine, paroxetine
citalopram
selective serotonin reuptake inhibitor
MOA: inhibit reuptake of serotonin
therapeutic effect occurs over 2-4 weeks; ultimately correlated with increased activation of postsynaptic 5HT1A receptors and decreased activation of 5HT2A receptors
SSRIs: fluoxetine, sertraline, citalopram, fluvoxamine, paroxetine
fluvoxamine
selective serotonin reuptake inhibitor
MOA: inhibit reuptake of serotonin
therapeutic effect occurs over 2-4 weeks; ultimately correlated with increased activation of postsynaptic 5HT1A receptors and decreased activation of 5HT2A receptors
SSRIs: fluoxetine, sertraline, citalopram, fluvoxamine, paroxetine
paroxetine
selective serotonin reuptake inhibitor
MOA: inhibit reuptake of serotonin
therapeutic effect occurs over 2-4 weeks; ultimately correlated with increased activation of postsynaptic 5HT1A receptors and decreased activation of 5HT2A receptors
SSRIs: fluoxetine, sertraline, citalopram, fluvoxamine, paroxetine
selective serotonin reuptake inhibitor side effects
nausea, diarrhea, sexual dysfunction, discontinuation syndrome serotonin syndrome, reduced platelet aggregation, sweating, suicide
[syndrome] is characterized by dizziness, tingling or numbness in skin
discontinuation syndrome
onset 1-2 days after stopping; continues for ~1 week
[syndrome] is characterized by hyperthermia, muscle rigidity, cardiovascular collapse, flushing, diarrhea
serotonin syndrome
[SSRI drug name] is relatively free of drug interactions, compared to other drugs in this class
citalopram
[SSRI drug name] has the longest half-life of drugs in this class
fluoxetine
needs to be discontinued 4 weeks before switching to MAO inhibitor to avoid serotonin syndrome
serotonin/ norepinephrine reuptake inhibitors
venlafaxine, duloxetine
used for major depression, atypical depression (venlafaxine), generalized anxiety, stress urinary incontinence, vasomotor symptoms of menopause, pain of diabetic neuropathy (duloxetine)
venlafaxine
serotonin/ norepinephrine reuptake inhibitor
MOA: inhibits serotonin transporter; inhibits NE transporter at higher doses
can be used for atypical depression
duloxetine
serotonin/ norepinephrine reuptake inhibitor
MOA: inhibits 5HT and NE transporter
can be used for diabetic neuropathy pain
venlafaxine and duloxetine side effects
nausea, discontinuation syndrome, serotonin syndrome, NE effects (increased HR and BP), CNS activation (insomnia, anxiety, agitation); high doses of venlafaxine are more likely to have adverse cardiac effects
tricyclic antidepressants
amitriptyline, nortriptyline, imipramine, desipramine, clomipramine
not commonly used; used in treatment resistant depression and for pain (at lower doses)
amitriptyline
tricyclic antidepressant
MOA: inhibit NE and 5HT reuptake to varying degrees (clomipramine inhibits primarily 5HT reuptake, desipramine is more selective for NE)
nortriptyline
tricyclic antidepressant
MOA: inhibit NE and 5HT reuptake to varying degrees (clomipramine inhibits primarily 5HT reuptake, desipramine is more selective for NE)
imipramine
tricyclic antidepressant
MOA: inhibit NE and 5HT reuptake to varying degrees (clomipramine inhibits primarily 5HT reuptake, desipramine is more selective for NE)
desipramine
tricyclic antidepressant
MOA: inhibit NE and 5HT reuptake to varying degrees (clomipramine inhibits primarily 5HT reuptake, desipramine is more selective for NE)
clomipramine
tricyclic antidepressant
MOA: inhibit NE and 5HT reuptake to varying degrees (clomipramine inhibits primarily 5HT reuptake, desipramine is more selective for NE)
tricyclic antidepressants side effects
anticholinergic (dry mouth, tachycardia, urinary retention, etc.), postural hypotension, weight gain, sedation, sexual side effects, discontinuation syndrome, serotonin syndrome
TCAs: amitriptyline, nortriptyline, imipramine, desipramine, clomipramine
TCA toxicity is treated with [drug]
sodium bicarbonate
TCA toxicity: coma, convulsions, cardiotoxicity; caused by conduction delays
5HT2A receptor antagonists
trazadone, mirtazapine
trazadone
5HT2A receptor antagonist used to treat insomnia
MOA: 5HT2A antagonist => enhances 5HT transmission at postsynaptic 5HT1A receptors and other 5HT2 receptors
trazadone side effects
sedation, GI upset, hypotension and priapism (rare); sexual side effects NOT common
trazadone = 5HT2A receptor antagonist used for insomnia
mirtazapine
5HT2A receptor antagonist used to treat melancholic depression or depression with insomnia
blocks 5HT2A/2C and 5HT3 receptors and presynaptic a2 receptors => enhance release of 5HT and HE, enhance transmission at other 5HT receptors, especially 5HT1A
mirtazapine side effects
increased appetite and weight gain, sedation; does NOT cause sexual side effects
mirtazapine = 5HT2A receptor antagonist used to treat melancholic depression or depression with insomnia
bupropion
unicycle antidepressant used to treat atypical depression or for smoking cessation
MOA: resembles amphetamine => CNS activation properties; causes NE release and DA release to a lesser degree; moderate inhibitor of NE and DA reuptake
bupropion side effects
agitation, insomnia, anorexia; NOT associated with sexual side effects
bupropion = unicycle antidepressant used to treat atypical depression or for smoking cessation
monoamine oxidase inhibitors
phenelzine, tranylcypromine, isocarboxazid, selegiline
rarely used because of toxicity and potential for food interactions; used for treatment resistant depression or for Parkinson’s
phenelzine
MOAI used to for treatment resistant depression or Parkinson’s
MOA: irreversibly inhibit both MOA isozymes => increase monoamine transmission
tranylcypromine
MOAI used to for treatment resistant depression or Parkinson’s
MOA: irreversibly inhibit both MOA isozymes => increase monoamine transmission
isocarboxazid
MOAI used to for treatment resistant depression or Parkinson’s
MOA: irreversibly inhibit both MOA isozymes => increase monoamine transmission
selegiline
MOAI used to for treatment resistant depression or Parkinson’s
MOA: primarily inhibits MOA-B => protects DA from catabolism*
*at high doses to treat depression, probably loses isozyme selectivity
monoamine oxidase inhibitor side effects
dramatic hypertension (because tyramine escapes normal enzymatic destruction and causes NE release from sympathetic neurons), serotonin syndrome, CNS stimulation in overdose, postural hypotension, weight gain
MAOIs cause serotonin syndrome when combined with what drugs?
SSRIs, SNRIs, TCAs, and meperidine
lithium
mood stabilizer used for acute mania, bipolar long-term treatment, severe recurrent depression with cyclic pattern, and psychosis
MOA: unknown
lithium MOA is unknown; theories include:
(1) inhibition of inositol monophosphatase => depletion of brain inositol => inhibits receptor-activated phosphoinositide hydrolysis and formation of second messengers (IP3 and DAG)
(2) inhibits NE-stimulated adenylyl cyclase and some G-protein coupled receptors
(3) inhibition of growth factor pathways => neuroprotective effects and long-term plasticity
lithium side effects
tremor (frequent), sedation, decreased cognition, incoordination
decreased thyroid function, polydipsia and polyuria (occasionally diabetes insipidus), tubulointerstital nephropathy
nausea, vomiting, diarrhea, weight gain
dermatitis, exacerbation of psoriasis, hair loss, acne
reversible increase in PMNs
though considered safe in pregnancy, lithium use during the first trimester can cause [?]
cardiac malformations
[drugs] reduce lithium clearance
diuretics, NSAIDs, and ACE inhibitors
lithium overdose is characterized by [symptoms]
convulsions, coma, confusion, coarse hand tremor, muscle rigidity, fasciculations, ataxia
treated with fluids (mild) or hemodialysis (severe)
lithium overdose is caused by Li accumulation due to decreased serum [?]
sodium
benzodiazepines
diazepam, chlordiazepam, flurazepam, clonazepam, alprazolam, temazepam, triazolam, lorazepam, oxazepam
used for anxiety, insomnia, and alcohol detox
MOA: allosterically increase GABA-A receptor channel open frequency
benzodiazepine receptors: BZ1 mediates [?] and BZ2 mediates [?]
BZ1 mediates sedation and anticonvulsant effects
BZ2 mediates anxiolytic effects and impairment of cognitive function
diazepam, chlordiazepam, and flurazepam are metabolized by [?]
phase I and phase II metabolism in the liver => long-acting metabolites with a longer duration of action
clonazepam, triazolam, lorazepam, and oxazepam are metabolized by [?]
phase II only (liver) => no active metabolites, shorter duration of action
benzodiazepine side effects
sedation (may potentiate sedating effects of alcohol or barbiturates => cardiac and respiratory depression), physical dependence, psychological dependence, toxicity
benzodiazepine toxicity is treated with [drug]
flumenazil
benzodiazepine toxicity is characterized by impaired judgement, slurred speech, incoordination, stupor, respiratory depression, and death
buspirone
a non-benzodiazepine anxiolytic used for its relatively non-sedating properties
MOA: partial agonist at both presynaptic and postsynaptic 5HT1A receptors => inhibit normal inhibitory feedback of serotonin => increased 5HT release; also blocks DA D2 receptors
does NOT have problematic interactions with alcohol
non-benzodiazepines used for insomnia
zolpidem, zaleplon, eszopiclone, suvorexant (orexin antagonist), rameltean (melatonin 1 and 2 receptor agonist)
zolpidem, zaleplon, eszopiclone side effects
ataxia, nightmares, headache, confusion
methylphenidate/ dexmethylphenidate
stimulants used for treatment of ADHD in children aged 6 and above
MOA: blocks reuptake of DA and NE
*dexmethylphenidate is a more active enantiomer of methylphenidate
methylphenidate/ dexmethylphenidate side effects
anorexia, nervousness, growth suppression, GI distress, irritability/ increased crying, tachycardia, increased BP, tics
dextroamphetamine, lisdextamfetamine, mixed amphetamine salts
amphetamines used for the treatment of ADHD in children aged 3 and above
MOA: enhances release and blocks reuptake of DA and NE
dextroamphetamine, lisdextamfetamine, mixed amphetamine salts side effects
sudden death in children with cardiac abnormalities
+ same as methylphenidate (anorexia, nervousness, growth suppression, GI distress, irritability/ increased crying, tachycardia, increased BP, tics)
atomoxetine
non-stimulant for treatment of ADHD (2nd line therapy)
MOA: NE reuptake inhibitor
atomoxetine side effects
nausea, anorexia, increased HR and BP, constipation, hepatotoxicity
clonidine, guanfacine
nonstimulants for treatment of ADHD (most effective for impulsivity and hyperactivity rather than inattentiveness)
MOA: central a2 agonist
clonidine, guanfacine side effects
sedation, orthostatic hypotension, dry mouth
what medication is used off-label for ADHD treatment?
bupropion
MOA: DA and NE reuptake inhibitor
dissolution/absorption of drugs may be [?] in the elderly
slowed
due to decreased saliva production, decreased gastric fluid, decreased acidity, weaker peristalsis, decreased jejunal surface area
generally does NOT affect total amount of drug absorbed
while the dissolution/ absorption of drugs may be slowed in the elderly, the total amount absorbed generally remains the same; a common exception to this is [?]
L-DOPA
more L-DOPA is absorbed with age because there is less DOPA decarboxylase to catabolize it
also, drugs that require active transport are less absorbed in old age
the concentration of water soluble drugs [increases/decreases] with age
increases
decreased lean body mass means there is less volume of distribution and increased drug concentration
example: digoxin levels increase with age
the duration of action of fat-soluble drugs [increases/decreases] with age
increases
more adipose tissue => increased volume of distribution and increased duration of action
example: diazepam duration of action increases with age
phase [I/II] metabolism in the liver decreases with age
phase I metabolism decreases with age, while phase II metabolism does not decrease with age
metabolism of drugs metabolized by both phases (diazepam) decreases with age, while drugs metabolized by only phase II (lorazepam) are not as affected
serum creatinine [increases/decreases] with age
trick question!!!
serum creatinine levels stay the same with age, despite decreasing GFR, due to simultaneous decreased creatinine production
opioids use disorder is treated with [drugs]
clonidine, methadone, buprenorphine, naltrexone, and SSRIs
nicotine MOA
activates nicotinic receptors in CNS, periphery, and NMJ; activation of receptors in the ventral tegmental area => DA release in nucleus accumbens
nicotine effects
anxiolytic affects, increased arousal, decreased appetite
nicotine withdrawal is characterized by [?]
irritability, anxiety, autonomic arousal, intense cravings
nicotine use disorder is treated with [drugs]
varenicline, bupropion
cocaine MOA
blocks reuptake of monoamines in presynaptic terminal; predominately DA but can also block NE and 5HT transporters at high concentrations
amphetamine MOA
substrate for NE transporter; enters synaptic terminal and displaces NE => release of NE
name the intoxication syndrome:
increased arousal and vigilance; profound sense of wellbeing, energy, and optimism that can progress to psychomotor agitation, paranoia, and psychosis; altered tactile sensation
cocaine/amphetamine
amphetamine effects last longer
name the withdrawal syndrome:
listlessness, drowsiness, depressed mood, dysphoria, anhedonia
cocaine/amphetamine
cocaine/amphetamine withdrawal is not typical of withdrawal syndromes because [?]
re-administration of the drug does not alleviate symptoms
withdrawal symptoms may occur in the presence of the drug (tachyphylaxis) when target becomes less responsive to the drug
methamphetamine MOA
decreased DA reuptake and increased DA release via DA transporter
caffeine MOA
blocks presynaptic adenosine receptors that normally inhibit the release of DA and NE => increased DA and NE release
cannabis MOA
active metabolite (delta-9-THC) is a partial agonist at the cannabinoid receptor (CB1); stimulation of receptor leads to release of DA in the nucleus accumbens
name the intoxication syndrome:
euphoria, laughter, giddiness, feeling of detachment, cognitive function deficits, trouble concentrating; high doses cause panic reactions, perceptual distortions, and changes in perception of reality
cannabis
name the withdrawal syndrome:
insomnia, loss of appetite, irritability, anxiety
cannabis
synthetic cannabinoids “spice” MOA
full agonist at CB1 receptor (more potent than cannabis)
phencyclidine (PCP) MOA
NMDAR antagonist => disinhibition of pyramidal neurons
name the intoxication syndrome:
euphoria, hallucinations, psychotic behavior, hostility, violent behavior; nystagmus, ataxia, seizures, coma; hypertension, tachycardia; reduced sensation to pain
PCP
lysergic acid (LSD) MOA
synthetic ergot derivative; activation of 5-HT2 receptors in cortical layers => increased glutamate release (mesolimbic DA system is not targeted)
name the intoxication syndrome:
perceptual changes, illusions, depersonalization, derealization, hallucinations, synesthesia, pupillary dilation, tachycardia, sweating, incoordination
hallucinogens
ethosuximide (MOA, indication, AE)
MOA: T-type calcium channels (involved in absence seizures)
indication: absence seizures
AE: nausea, Steven-Johnson syndrome and aplastic anemia (rare)
gabapentin (MOA, indication, AE)
MOA: binds to voltage-gated calcium channels => halts influx of calcium at presynaptic terminal, reducing the release of neurotransmitter into synapse during excitation
indication: focal seizures
AE: weight gain
carbamazepine (MOA, indication, AE)
MOA: target sodium channels to inhibit depolarization selectively during period of hyperexcitability, but permit depolarization during normal neuronal transmission
indication: focal seizures
AE: hyponatremia, leukopenia (rare aplastic anemia), Steven-Johnson syndrome, hepatotoxicity, osteopenia
oxcarbazine (MOA, indication, AE)
MOA: target sodium channels to inhibit depolarization selectively during period of hyperexcitability, but permit depolarization during normal neuronal transmission
indication: focal seizures
AE: hyponatremia
lacosamide (MOA, indication, AE)
MOA: target sodium channels to inhibit depolarization selectively during period of hyperexcitability, but permit depolarization during normal neuronal transmission
indication: focal seizures
AE: dizziness/syncope, prolonged PR interval on EKG
levetiracetam (MOA, indication, AE)
MOA: inhibit the release of excitatory neurotransmitters from the synapse by binding to synaptic vesicle 2A protein
indication: focal and generalized seizures
AE: mood changes including psychosis
lamotrigone (MOA, indication, AE)
MOA: target sodium channels to inhibit depolarization selectively during period of hyperexcitability but permit depolarization during normal neuronal transmission
indication: focal and generalized seizures
AE: Steven-Johnson syndrome, commonly rase; levels increased by valproate
phenytoin (MOA, indication, AE)
MOA: target sodium channels to inhibit depolarization selectively during period of hyperexcitability but permit depolarization during normal neuronal transmission
indication: focal and generalized seizures but NOT for absence or myoclonic seizures
AE: gingival hyperplasia, cerebellar atrophy, neuropathy, Steven-Johnson syndrome, osteopenia; phlebitis and rarely hand necrosis (purple glove syndrome) if given IV; several drug interactions (warfarin, valproic acid, some antibiotics)
valproic acid (MOA, indication, AE)
MOA: enhance GABA transmission; inhibit T-type calcium channels; target sodium channels
indication: focal and generalized seizures
AE: liver toxicity, hyperammonemia, pancreatitis, tremor, thrombocytopenia, weight gain, PCOS, insulin resistance, hyperandrogenism; very teratogenic
topiramate (MOA, indication, AE)
MOA: enhance GABA transmission; inhibit AMPA receptors; target sodium channels
indication: focal and generalized seizures
AE: weight loss, renal stones, acute angle-closure glaucoma, cognitive side effects, paresthesia
zonisamide (MOA, indication, AE)
MOA: inhibit T-type calcium channels and sodium channels
indication: focal and generalized seizures
AE: weight loss, renal stones, cognitive side effects, oligohydrosis, sulfa allergy cross-reactivity, acute angle-closure glaucoma
phenobarbital (MOA, indication, AE)
MOA: enhance GABA-A transmission
indication: focal and generalized seizures but NOT for absence seizures
AE: liver toxicity, sedation, cytopenias, osteopenia, contractures
