Stahl's psychopharm Flashcards
Acamprosate (Campral)
Glu-MM (glutamate multimodal)
FDA: maintenance of alcohol abstinence
-reduces excitatory glutamate NT and increases inhib. GABA NT (opposite effects of etoh w/d, so serves as “artificial alcohol”)
-binds to/blocks certain glutamate receptors
SEs: diarrhea, nausea, anxiety, depression, SI/suicidality
dose: 666 mg TID (666 mg BID if <60 kg)
half life: 20-33 hrs, excreted unchanged via kidneys
CI in severe renal impairment, in moderate 333 mg TID
no hepatic metabolism/interactions
not generally rec. in pregnancy
ADV: for use in chronic daily drinker
DISADV: if not abstinent time of initiation, binge drinkers
may be preferred if goal is complete abstinece by may not be preferred if goal is reduced-risk drinking
Alprazolam (Xanax)
GABA-PAM: GABA positive allosteric modulator
FDA: GAD (IR), panic d/o (IR, XR)
binds to bzo receptor at GABA-A ligand-gated Cl channel complex, enhances inhibitory effects of GABA, boosts Cl conductance through GABA-regulated channels, inhibits neuronal activity presumably in amygdala-centered fear circuits
SEs: sedation, depression, dizziness, ataxia, slurred spch, weakness, confusion, hyperexcitability, nervousness (paradoxical), rare hallucinations, mania, rare hypotension, hypersalivation, dry mouth
danger: resp. depression, exp. when taken with CNS depressants in OD, rare hepatic/renal dysfunction, blood dyscrasias
dose: anxiety: IR 1-4 mg/d, panic: IR 5-6 mg/d, XR: 3-6 mg/d (only needs to be taken qd or BID), start at 0.75-1.5 mg/d in 3 div. doses
about 1/2th equivalent of lorazepam, greater w/d risk above 4 mg, taper by 0.5 mg q3 ds
schedule IV (4)
metabolized by CYP450 3A4, has inactive metabolites, half-life (elim): 12-15 hrs
CI if angle-closure glaucoma, taking ketoconazole
Use with caution in renal impairment, begin with lower starting dose in hepatic impairment
generally not recommended in pregnancy, may cause neonatal flaccidity, recommend d/c breast feeding (difficulties, sedation, w/l)
ADV: rapid, less sedation than other bzo, XR form
DISADV: abuse potential
targets: panic, anxiety
XR may be less sedating than IR
amisulpride
atypical antipsychotic not FDA approved in the US (Europe)
amitriptyline (Elavil)
serotonin, NE multimodal (SN-MM), TCA, serotonin-NE/noradrenaline reuptake inhibitor
FDA: depression (non: neuro/chr pain, fibro, HA, anxiety, insomnia, TRD)
MOA: boosts serotonin/NE/NA, desensitizes both serotonin 1A and beta adrenergic receptors?, increase DA NT in frontal cortex
tests: baseline EKG, weight, fasting labs,
SE:
antichol: sedation, dry mouth, constipation, blurred vision
antihist: sedation, weight gain
alpha 1 block: dizziness, sedation, hypotension
ion channel block: cardiac arrhythmias, seizures
others: diarrhea, unusual taste, anxiety, nervousness, sexual dysfunction, sweating, rash, itching
dangerous SEs: paralytic ileus, hyperthermia (+antichol), cardiac, QTc prol, liver failure, EPS, incr. ocular pressure
dose: 50-150 mg/d, start with 25 mg QHS, increase by 25 mg every 3-7 days, max 300 mg /d
OD: CNS depression, convulsions, dysrhythmias, hypotension, EKG changes, coma
substrate for 2D6, 1A2
half life: 10-28 hours, metab to nortriptyline
tramadol incr. risk of seizures
use with antichol: hyperthermia, ileus
2D6/1A2 inhibitors increase levels
2 week washout period
Do not sue in cardiac impairment/recent MI
kids: up to 100 mg, may be used for enuresis or hyperactive/impulsive behaviors, not rec under age 12
ADV: severe/TRD, insomnia, chronic pain
DISADV: young and old pts, weight gain, cardiac issues
increased levels in poor 2D6 metabolizers
Amoxapine (Asendin)
SN-RI, TCA, 5HT2A antagonist
FDA: neurotic or reactive depressive d/o, psychotic/endogenous depression, depression with anxiety/agitation (depressive phase of BPD, anxiety, insomnia, neuropathic pain/chronic pain, TRD)
MOA: boosts NE/NA, increase DA in PFC, boosts serotonin in high doses, can block D2 reducing
see amitriptyline for TCA lab tests, SEs, interactions ALSO can cause EPS, akathisia and theoretically TD
weight gain and sedation: common
dose: 200-300 mg/d, start with 25 mg BID/TID or single bedtime dose, max 400 mg/d
2D6 substrate, half life 8 hours
amoxapine is the metabolite of atypical loxapine
amoxapine metabolites are active for about 24 hrs and possess 5HT2A and D2 antagonistic properties
ADV: severe, TR or psychotic depression
DISADV: old/young, w/g, cardiac pts, PD or TD
may cause motor symptoms b/c of D2 action, similar to atypicals, faster onset than other ADs
amphetamine (D) (Dexedrine, Dexedrine Spansules, Zenzedi, ProCentra)
DN-RIRe: DA, NE reuptake inhibitor and releaser, stimulant
FDA: ADHD (older than 6 or 3 dep. on form), narcolepsy (6, 12 yo) (non FDA: TRD)
MOA: increases NE and DA by blocking reuptake and facilitating release, improve attn, concentration, executive function, wakefulness (DLPFC), enhancement of DA in basal ganglia may improve hyperactivity, DA enhanced. in medial PFC, hypothalamus may improve depression, fatigue, sleepiness
if ineffective, consider BPD
can combine IR with SR D-amphetamine, or combine with modafinil or atomoxetine
can combine with AD for TRD
monitoring: BP, cardiac hx, weight/height
SEs: Inc. in NE:
peripheral: ANS: tremor, tachycardia, TN, cardiac arrhythmias
central: insomnia, HA, agitation, psychosis, substance abuse
tic worsening, nervousness, irritability, anorexia, nausea, dry mouth, constipation, diarrhea, w/l, slow growth in kids?, sexual dysfunction long term (improves ST)
dangerous SEs: psychotic episodes, seizures, tachy, HTN, palpitations, activation of mania and SI, cardiac effects, sudden death
can use b-blockers for peripheral SEs
dosing: 5-40 mg/d ADHD up to 60 for narcolepsy IR, ER, IR oral solution
start with 5 mg/d, increase by 5 each week (2.5 mg if <6 yo)
IR: 3-6 hours of action
SR: (Spansule) up to 8 hr, swallow whole, may able only qd
taking with food may delay actions for 2-3 hrs
may only dose during weekdays and avoid summers
OD: hyperreflexia, rhabdo, confusion, tachypnea, confusion, hallucination, coma, BP changes, CV collapse
Schedule II
taper to avoid WD, may feel depressed
1/2 life: 10-12 hours
effects lowered by GI/urine acidifying agents (use after OD)
increased by alkalizing agents
haloperidol, chlorpromazine, lithium may inhibit stimulating effects
atypicals may inhibit effects and vis versa
recommend against use in pregnancy d/t risk of premature birth
DISADV: pts with current/past BPD, psychosis, anxiety
may be useful in post stroke depression, TRD
can reverse sexual dysfunction
amphetamine (D, L) (adderall, adderla XR, Evekeo, Adzenys, Dyanavel)
DN-RIRe
FDA: ADHD (3-12, 6-17), narcolepsy, exogenous obesity (evekeo), TRD
see amphetamine for rest
mixture of D and L amphetamine salts in 3:1 ratio
Aripiprazole (Abilify, Maintena, Aristada)
Dopamine, serotonin receptor partial agonist DS-RPA
FDA: Schizophrenia ages 13 and older, maintaining stability and schizophrenia, acute mania/mixed mania ages 10 and older, bipolar maintenance, depression (adjunct), autism related irritability in children ages 6-17, Tourette’s disorder in children ages 6-18, acute agitation associated with schizophrenia or bipolar disorder (IM)
Non-FDA: Bipolar depression, other psychotic disorders, behavioral disturbances and dementia and in children/adolescents, disorders associated with problems with impulse control
Actions at D3 preceptors could theoretically contribute to efficacy, partial agonism at 5-HT1A, blockade of 5-HT2A, 2C, 7
(for atypicals) most schizophrenic patients have reduction of symptoms by third
5 to 15% of schizophrenic patients experience improvement greater than 50 to 60%, termed “super responders)
Many bipolar patients experience reduction of symptoms by half or more
Alpha-1 adrenergic blockade: Dizziness, sedation, hypotension
D2 partial agonism in striatum: akathisia, nausea/vomiting, activation
Others: Insomnia, constipation, headache, dystonia, sedation, TD?
Dangerous: Rare impulse control problems, NMS, seizures, increased risk of death in dementia related psychosis
Weight gain and sedation: Unusual
for akathisia: Anticholinergics, low-dose benzo, beta-blocker
Dose: 15 to 30 mg/day, 2 to 10 mg/day for augmentation
300 to 400mg/month for Maintena, 441,662,882 mg/6wks for Aristada
Metabolized by 2 D6, 3 A4, mean illumination half-life 75 hours and 94 hours for metabolite (long)
3A4 and 2D6 inhibitors may increase plasma levels, carbamazepine may decrease levels (3A4)
Lacks D1 antagonistic, anticholinergic, antihistamine properties which may explain the relative lack of sedation or cognitive side effects
-ED for D2 receptors means combining with other D2 antagonists could reverse their actions (may be useful to use if hyperprolactinemia on other antipsychs)
armodafinil (Nuvigil)
Dopamine reuptake inhibitor D-RI, wake promoting
FDA: Reducing excessive sleepiness in patients with narcolepsy, shiftwork sleep disorder, and OSA/hypopnea syndrome
Non-FDA: ADHD, fatigue and sleepiness and depression, fatigue in MS, bipolar depression
MOA: Different from stimulants, presumably enhances activity and hypothalamic wakefulness center (TMN, tuberomammilary nucleus) within the hypothalamic sleep-wake switch by an unknown mechanism, activated TMN neurons release histamine, activates other hypothalamic neurons that release orexin/hypocretin
Can work immediately to improve sleepiness and attention
Use as adjunct for OSAHS, combination with stimulants has not been well studied
Side effects: Headache, anxiety, dizziness, insomnia, dry mouth, diarrhea, nausea
Dangerous: Transient EKG ischemic changes in patients with MVP or LVH, rare activation of mania, anxiety, hallucinations, SI, rare skin reactions (SJS), angioedema, hypersensitivity reactions
Weight gain and sedation: Unusual
Dose: 150-250 mg/day, no titration necessary, given a.m. or prior to start of work shift
Lower doses may be better for concentration/fatigue, higher doses for sleepiness
Schedule IV
Half-life about 15 hours, inhibits 2C19, induces 3A4 (slightly 1A2)
May induce autometabolism at high doses via 3A4, may benefit from drug holiday
May decrease estradiol via 3A4 induction
Monitor INR/PTT when on warfarin
Generally discontinue in pregnancy due to risk of IUGR and spontaneous abortion
ADV: Selective for areas of brain involved in sleep/wake promotion, less activating and less abuse potential and stimulants
DISADV: May not work as well as stimulants
Targets: Sleepiness, concentration, physical/mental fatigue
Longer-lasting R enantiomer of racemic modafinil (qd dose)
Some control trials suggest efficacy in bipolar depression as an adjunct to atypicals
asenapine (Saphris)
DSN-RAn dopamine, serotonin, norepinephrine receptor antagonist
FDA: Schizophrenia, acute mania/mixed mania (ages 10+), acute mania/mixed mania adjunct to lithium or valproate (adults)
Non-FDA: Other psychotic disorders, BP maintenance/depression, TRD, behavioral disturbances in dementia and in children/adolescents, disorders associated with problems with impulse control
MOA: blocks D2, 5HT2A, 2C, 7, alpha 2 (antidepressant actions)
See Abilify for side effects + theoretical prolactin elevation, oral hypoesthesia, application site reactions including ulcers, blisters, inflammation, EPS, may increase risk for diabetes and dyslipidemia weight gain: Not unusual, sedation: Common
Dose: 10 to 20 mg/day in 2 divided doses, sublingual tablets, do not eat or drink for 10 minutes following administration (2% vs 35% bioavailability)
May start with 10 mg (start with 20 mg and bipolar mania), do not give single dose more than 10 mg at a time
Rapid onset of action, may be used as PRN
Half-life 13 to 39 hours, inhibits 2D6, substrate for 1A2
can increase b-blockers, atomoxetine levels via 2D6 inhibition
ADV: rapid onset wtihout dose titration
DISADV: pts unlikely to be adherent
Structure related to mirtazapine
atomoxetine (Strattera)
N-RI, norepinephrine reuptake inhibitor
FDA: ADHD in adults and children over 6
Non-FDA: TRD
MOA: boosts NE/noradrenaline may increase dopamine in PFC, blocks NE reuptake pumps
Onset can be observed on first day of dosing, may continue to improve for 8 to 12 weeks
Side effects: Unwanted actions of an NE on ACh: Decreased appetite, increased HR, BP, dry mouth, urinary retention, constipation
Lack of enhancing DA activity in limbic areas may explain lack of abuse potential
Other side effects: Sedation, fatigue, rare priaprism, diarrhea, sweating, sexual dysfunction
Dangers: Increase HR, HTN, orthostatic hypotension, severe liver damage, hypomania and rare induction of mania, rare activation of SI
Weight gain: Unusual, sedation: Not unusual
Dose: 40-100 mg/d in adults, 0.5-1.2 mg/kg/day in kids up to 70 kg, give once a day in morning despite 5-hour half-life, however may increase GI side effects
metabolized by 2D6, poor metabolizers may be sensitive to side effects
Generally discontinue prior to pregnancy
ADV: No known abuse potential, not a scheduled substance
DISADV: May not act as rapidly as stimulants
Target symptoms: Concentration, attention span, motor hyperactivity, depressed mood
May not exacerbate tics or Tourette’s as with stimulants
benztropine (Cogentin)
Antiparkinson agent, anticholinergic
FDA: Extrapyramidal disorders, parkinsonism
Non-FDA: Acute dystonic reactions, idiopathic generalized dystonia, focal dystonia, dopa responsive dystonia
MOA: Diminishes excess ACh activity caused by removal of DA inhibition when DA receptors are blocked, may also inhibit reuptake/storage of DA at Central DA receptors, prolonging DA action
Onset can be minutes to hours
Side effects: Prevents action of ACh and muscarinic receptors: Dry mouth, blurred vision, diplopia, confusion, hallucinations, constipation, nausea/vomiting, dilation of:/Paralytic ileus, bowel obstruction, ED
Dangers: Acute angle-closure glaucoma, heatstroke, tachycardia, arrhythmias, hypotension, urinary retention, can exacerbate/unmask TD
Weight gain: Unusual, sedation: Common
Dose: EPS 2-8 (start 1-4) mg/day, parkinsonism 0.5-6 mg/day
Attempt withdrawal benztropine after 1 to 2 weeks and determine if still require, IM and IV dosing are equally effective and fast acting
Half-life 36 hours, greatest effect is 68 hours
May increase serum levels of digoxin, can lower concentrations of haloperidol and other phenothiazines, can decrease gastric motility, have additive effects when used with DOAs: THC, etOH, barbs, opioids
ADV: EPS related to antipsychotic use, especially in acute setting
DISADV: Long-standing EPS, generalized dystonias (use trihexyphenidyl)
Target: Tremor, akinesia, rigidity, drooling
Useful in treatment of post encephalitic Parkinson’s disease
Sedation limits use especially in older patients and those with cognitive impairment
Blonanserin (Lonasen)
atypical antipsychotic not FDA in the US
Brexpiprazole (Rexulti)
Dopamine partial agonist (Levin: SDAM serotonin dopamine activity modulator)
FDA: schizophrenia, TRD (adjunct)
non FDA: acute/mixed mania, other psychosis, BP maintenance/depression, behavioral disturbance in dementia and kids, d/o with impulse control
MOA: partial agonism at D2, partial agonist at 5HT1A, blocks 5HT2A (DA rel. in certain brain region), alpha 2C block, D3 actions, 5HT7 block
SEs: adrenergic, motor, D2 and 5HT1A partial agonism: N/V, activating
weight gain and sedation: not unusual
dose: 2-4 mg/d (schizo), 2 mg/d (depression) start with 0.5-1 mg/d
1/2 life: 91 hrs (may not require taper)
metabolized by 2D6, 3A4 (admin double or half or 1/4)
ADV: pts who don’t tolerate abilify
DISADV: $$$
*approved as adjunct for MDD, may improve cognition in schizo, being studied for PTSD, ADHD, agitation in AD, theoretically less akathisia than abilify and more potent binding of 5HT1A, 5HT2A, alpha 1 relative to D2 binding (compared to abilify)
buprenorphine
(suboxone (with naloxone))
(probuphine (implant))
mu opioid receptor partial agonist
FDA: maintenance tx of opioid dependence, and in pts who have achieved/sustained prolonged clinical stability on low-moderate doses (<8mg) of a trans mucosal buprenorphine-containing product (implant)
MOA: binds with STRONG affinity to mu R, preventing opioid from binding, can cause immediate w/d or alleviate w/d, blocks kappa opioid receptor, naloxone has poor sublingual and good parental availability
works to: reduce cravings, decrease opioid consumption, diminishes rewarding effects and WD effects
tests: LFTs before and during
SEs: HA, constipation, N, oral hypoesthésie, glossodynia, ortho. hypotension, implant SEs
dangerous: respiratory depression, hepatotoxicity
weight gain: unusual, sedation: common
dose: (sublingual) 8-32 mg/d (2 and 8 mg tablets)
(implant) 4 implants in place/6 months
film and tablet with naloxone: naloxone is 1/4th dose bup: 2/0.5, 4/1, 8/2, can be dosed less than 1/x (I.e. double dose for every 2 days) film has greater bioavail. than tablet
must be in a WD state prior to initiation, observe 2 hours after initiation, stabilization dose typ. 8-24 mg, see 1/wk then 1-2/month
need a DEA DATA 2000 waiver, for implant need to be on transmucosal dose of 8mg/d or less for 3+ months
OD: resp. depression, sedation, constricted pupils, bradycardia, hypotension, coma (can be fatal but less common than w/ methadone)
Schedule III, can cause physical dependence, may exp. mild w/d syndrome, taper to avoid
metabolized by 3A4, 1/2 life of sublingual is 24-42 hrs, naloxone 2-12 hours, implant Tmax: 12 hours, time to steady state is 4 wks
see handbook for medical cautions
do not use as analgesics, if severe hepatic impairment (with naloxone)
may be preferable to methadone in pregnant women
ADV: mild-mod physical dependence
DISADV: pts unable to tolerate mild WD symptoms
