Pharmacotherapy Test 3

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carbamazepine- brand name: tegretol
carbamazepine- seizure types: partial
tonic-clonic
carbamazepine- binding: high binding, low albumin can alter free concentration
carbamazepine- forms: tablet, SR, no IV due to low solubility
carbamazepine- metabolism: -liver converts cbz to cbz by 3A4 epoxide to cbz dihydrodiol
-cbz epoxide is active and toxic
-autoinduction of 3A4
carbamazepine- toxicity: -concentration related
-headache, anticholinergics, SIADH
-leukopenia, hepatitis, rash
carbamazepine- dosing/therapeutic range: -start low and titrate up due to autoinduction
-use tid and qid
-2-12 ug/ml
carbamazepine- drug interactions: -general inducer
Phenytoin- Brand name: Dilantin
Phenytoin- seizure types: partial
tonic-clonic
Phenytoin- binding: extensively bound
Phenytoin- metabolism: -t1/2= 24 hours
-saturable metabolism
-cyp 2c9, 2c19
-pregnants- increased metabolism and changes in binding
-old people- low vmax, low protein
-young people- high vmax
Phenytoin- doses: -tablets and suspensions are free acid
-capsules and inj are 92% phenytoin
-IM- painful, avoid, use fosphenytoin
IV- with NS
-Fosphenytoin is prodrug, give faster, less phlebitis
Phenytoin- toxicity: -CNS effects
-rash
-gingival hyperplasia
-hirsutism, coarse facial features
-osteoporosis due to Vit D metabolsim
Phenytoin- interactions: -cyp and ugt inducer
-ca antacids and sulcrafate
-enteral feedings decrease absoportion
phenytoin- therapuetic levels: 10-20 ug/ml total, 1-2 ug/ml free
valproic acid- brand name: dopakote, depakene, depacon
valproic acid- binding: saturable binding
valproic acid- metabolism: -mostly by liver, ugt, b-oxidation
-t1/2- 14 hours in adults, 11 hours in children
-toxic metabolite due to cyp oxidation
valproic acid- toxicity: -weight gain
-tremors
-hyperammonemia
-lowered clotting
-hair loss
valproic acid- dosing: -titrate slowly to avoid slowly
-ER- give once daily but bioavailability is 15% less
valproic acid- forms: -depakene capsules, syrup
-depakote capsules- divalproex sodium
-depacon- no IM
valproic acid- therapeutic range: 50-100 ug/ml
valproic acid- interactions: -inhibitor of cyp and udp
-metabolism can be induced
phenobarbital- binding: 50%
phenobarbital- metabolism: -about half by cyp, some renal excretion
-really long half life
phenobarbital- adverse effects: -sedation
-decreased cognitive function
-excites kids
-megaloblastic anemia (folate deficiency)
-osteomalacia
-rash
phenobarbital- forms: tablets
syrup
injection
phenobarbital- drug interactions: induces cyp and ugd
phenobarbital- therapeutic range: 15-40 ug/ml
gabapentin- brand name: neutontin
gabapentin- absorption: active absorption, saturable at 500 mg
gabapentin- binding: none
gabapentin- elimination: all renal
gabapentin- drug interactions: none
gabapentin- adverse effects: CNS effects
weight gain
edema
tolerate out
pregabalin- brand name: lyrica
pregabalin- absorption: not saturable
pregabalin- binding: none
pregabalin- elimination: renal
pregabalin- interactions: none
pregabalin- adverse effects: dizziness
blurry vision
somnolence
weight gain
euphoria
lamotrigine- brand name: lamictal
lamotrigine- binding: 55%
lamotrigine- elimination: mostly hepatic glucuronidation
t1/2- 15 hours with inducer, 60 hours with inhibitor, 24 hours alone
lamotrigine- drug interaction: -metabolism is induced by inducers (cbz, pht, pb, oxc) and bcp
-metabolism is inhibited by vpa
-does not cause interactions
lamotrigine- adverse effects: -modest sedation
-minimal cognitive impairment
-headache
-insomnia
-rash: due to rapid titration, concomitant VPA, kids, rash with other AEDs
lamotrigine- therapeutic monitoring: 4-20 ug/ml
Topiramate- brand name: topamax
Topiramate- mechanism: -blocks voltage-gated sodium and calcium channels
-enhance gaba activity
-blockade of excitatory glutamate
Topiramate- elimination: renal
Topiramate- binding: low
Topiramate- interactions: inhibits 2c19
induces 3a4
Topiramate- adverse effects: -with high doses
-CNS
-kidney stones
-weight loss
zonisamide- brand name: zonegran
zonisamide- binding: 40%
zonisamide- t1/2: long
zonisamide- drug interactions: -does not inhibit or induce
zonisamide- metabolism: by cyp 3a4
zonisamide- adverse effects: -CNS
-depression
-kidney stones
-rash
-increse in serum creatinine
levatiracetem- brand name: keppra
levatiracetem- binding: low
levatiracetem- metabolism: mostly renal and metabolized outside of liver
levatiracetem- therapeutic monitoring: 10-50 ug/ml
levatiracetem- adverse effects: -sedation
-behavioral effects
-weight neutral
-titrate slowly
oxcarbazepine- brand name: trileptal
oxcarbazepine- interactions: -induces 3a4 and ugt
-inhibits 2c19
-increases pht levels
-pb, cbz, pht decreases levels
oxcarbazepine- adverse effects: -CNS effects
-abdominal pain
-tremors
-hyponatremia
mental status exam: joimat
judgement, orientation, intellectual function, memory/mood, apprearance/affect, thought
types of schizophrenia: -paranoid
-disorganized
-catatonic
-undifferentiated
-residual
-schizophreniform
-schizoaffective disorder
-psychotic disorder due to general medical condition or sunstance induced
criteria for schizophrenia: -2 or more of the following: dilusions, hallucinations, disorganized speech, disorganized or catonic behavior, negative symptoms
-social or occupational dysfunction
-continuous signs of the disorder for more than 6 months
-exclude mood disorders
-not due to medical disorder or substance
-PPD must have delusions or hallucinations for a month
epidemiology of schizophrenia- age: 15-25
epidemiology of schizophrenia- males to female: equal
clinical couse of schizophrenia- onset: abrupt or insidious, most have prodromal phase with negative symptoms
clinical couse of schizophrenia- intitial diagnosis: with positive symptoms
clinical couse of schizophrenia- disease course: fluctuates but ends up deteriorating
clinical couse of schizophrenia- remission: unlikely
schizophrenia- positive symptoms: hallucinations
delusions
disorganzed speech
bizarre behavior
psychomotor aggitation
schizophrenia- negative symptoms: alogia
flattened affect
avolition
anhedonia
poverty of speech
psychomotor retardation
schizophrenia- other symptoms: cognitive symptoms
mood symptoms
social and occupational symptoms
etiology of schizophrenia-: general 1%
sibling 10%
offspring 13%
dizygotic twin 10-15%
monozygotic twin 50%
pathophysiology of schizophrenia: -diseases or drugs that cause DA enhancement cause positive symptoms
--amphetamine and cocaine
-DA high in limbic
-DA low in prefrontal
-low glutamate
-NMDA receptor dysfunction
goals of schizophrenia: -acute stabalization: reduce threat, improve function, interventions
-stabalization: minimize relapse, compliance, optimize dose
-maintenance: improve QOL, maintain function, monitor for relapse, minimize ADR, maintain compliance and dose
conventional antipsychotics -mesolimbic -mesocortical -nigrotriatal -tuberoinfundibular: -stops positive symptoms
-increases negative symptoms
-causes EPS
-prolactin rises
high potency convential antipsychotics: haloperidol, fluphenazine
mid potency convential antipsychotics: loxapine, molindone, thiothixene, perphenazine
low potency convential antipsychotics: thioidazine, mesoridazine chloropromazine
EPS- acute dystonia: -acute muscle spasms
-within 5 days of initiation
-due to high potency, IM/IV, large dose
-treat with diphenhydramine, benztropine, anticholinergics, switch meds
EPS- pseudoparkinsonism: -20-40%
-starts within several months
-DA block cuases relative imbalance of DA and ACh
-decrease movement, muscle rigidity, resting hand tremor, drooling, mask-like face, shuffling gait
-treat by lowering dose, changing AP, give amantidine (antiparkinson agent)but will make worse
EPS- akathisia: -20% to all conventionals, 50% in high potency
-days to weeks, often months
-more presynaptic DA blockade vs postsynaptic DA blockade
-DA blockade in mesocortical tract increases locomotor activity
-can't distinguish from anxiety or psychosis
-inner restlessness, can't sit still
-treat- either up or lower dose, change AP or add b-blocker or add nezodiazepine
Tardive dyskinesia: -pathology: postsyn DA block leads to hypersensitivity
-Incidence: 20% on conventionals
-Risks: conventional AP, elderly, women
-Presentation: involuntary movements, lip smacking, blinking, face, neck, trunk, extremities
-Treatment: none
-management: minimize exposure, minimize dose, Vit E, change to clozapine
neuroleptic mailignant syndrome: -inidence is .2%
-mortatlity is 5-20%
-mean age- 40
-higher risk: mood disorders, lithium, catatonia
- all classes of typical AP
-1/3 will represent if rechallenged
nms diagnosis criteria: -on AP for 7 days
-hyperthermia >38
-muscle rigidity
-5 of the following: change in mental status, tachycardia, labile bp, tachypnea or hypoxia, diaphoresis or sialorrhea, tremor, incontinence, CPK elevation or myoglobinuria, leukocytosis, metabolic acidosis
-no other drug or medical reason
NMS treatment: -reduce risk factors
-early recognition and dc of AP
-supportive care
--fluids
--temperature
--cardiac, respiratory, kidneys
-DA agonists- bromocriptine, amantadine
Depot Ap: -haloperidol- 10-15 times daily dose, once a month
-fluphenazine- 1.25 times daily amount, every 2 weeks
-z track method
-stabalize on oral first
olanzapine- brand name: zyprexa
olanzapine- EPS: none
olanzapine- TD: low
olanzapine- adverse effects: -sedation
-weight gain
-orthostatic hypotension
-anticholinergics
olanzapine- forms: -rapid dissolve- zyprexa zydis
-Im is short acting
olanzapine- dose: 5-20 mg/day
Riperidone- brand name: Risperdal
Riperidone- EPS: dose related > 6 mg
Riperidone- Td: low
Riperidone- adverse effects: -prolactin elevation
-othrostasis
-sexual dysfunction
Riperidone- forms: M tab
LA inj: risperdal consta (2 wk)
Riperidone- dose: 4-16 mg
quetiapine- brand name: seroquel
quetiapine- EPS: none
quetiapine- TD: low
quetiapine- adverse effects: sedation
hypotension
HA
weight gain
lenticular formation
quetiapine- dose: 250-750 mg
ziprasidone- brand name: geoedon
ziprasidone- eps: none
ziprasidone- td: low
ziprasidone- adverse effects: mild sedation
minimal weight gain
QTc prolongation
ziprasidone- forms: IM available
ziprasidone- dose: 40-160 mg/day
clozapine- brand name: clozaril
clozapine- eps: minimal
clozapine- td: low
clozapine- adverse effects: agranulocytosis
seizures
sedation
hypotension
salivatoin
weight gain
clozapine- who: refractory patients
clozapine-monitoring: -weekly 6 months, bi weekly 6-12 months, monthly post 12 months
-WBC and ANC
-don't do if WBC<3500 and ANC<2000
clozapine- dose: 200-900 mg
aripiprazole- brand name: abilify
aripiprazole- moa: partial agonist of D2 receports
antagonist of 5HT2A
partial agonist of 5HT1A
aripiprazole- EPS: none
aripiprazole- TD: none
aripiprazole- adverse effects: anxiety
HA
Nausea
constipatin
aripiprazole- dose: 5-30 mg/day
metabolic syndrome: -need 3 of the following: abdominal obesity, hypertension, impaired fasting glucose, decreased HDl, elevated triglycerides
-atypical AP have been associated with weight gain, diabetes, lipid abnormalaties
Good reponse to treatment: -have precipitating factors
-abrupt onset
-positive symptoms
-less frequent family history
-good premorbid adjustment
bad response to treatment: -no precipitating factors
-insidious onset
-negative symptoms
-frequent in family history
-poor premorbid adjustment
Criteria for depressions: ->5 of the following: DSIGECAPS
-social/occupational dysfunction
-not due to medical condition or drug use
-not due to bereavement
-not due to another mental health illness
types of depressions: -major (atypical, typical, psychotic)
-dysthimia
-organic caused
-substance induced
-medication induced
epidemiology of depression: -17%
-late 20s
-episode lasts 16 weeks
risks of depressions: family history
female
previous episode
chronic illness
substance abuse
pathophysiology of depression: -chemical imbalance
-decreased levels of neurotransmitter (5HT, DA, NE)
-dysregulation of receptors
Lab assessment for depression: -cbc for anemia
-thyroid- hypothyroid
-urine drug screen for substance abuse
amitriptyline-brand name: elavil
amitriptyline- antidepressant class: TCA
nortiptyline- brand name: pamelor
nortriptyline- antidepressant class: TCA
impiramine- brand name: tofranil
impiramine- antidepressant class: TCA
desipramine- brand name: norpramin
desipramine- antidepressant calss: TCA
clomipramine- brand name: anafranil
clmipramine- antidepressant class: TCA
TCA mechanism of action: -5HT and NE reuptake inhibitor
-amount of 5HT and HE effects depends on structure:
--three amines: 5HT
--two amines: NE
TCA side effects: -cardiovascular
-anticholinergic
-sedation
-weight gain
-sexual dysfunction
Phenelizine- brand name: nardil
phenelizine- antidepressant class: MAOI
tranylcypromine- brand name: parnate
tranylcypromine- antidepressant class: MAOI
MAOI mechanism of action: irreversible inhibition of MAOA and MAOB which increases 5HT, DA, NE
MAOI side effects: -hypotension
-dizziness
-weight gain
-insomnia
-cardiac effect
-constipation
-sexual dysfunction
MAOI risks: -hypertensive crisis
-food-drug interaction with tyramine
MAOI drug interactions: -stimulants
-CNS antihypertensives
-antidepressents
-start SSRI after 14 days
-5 half-life wash out of previous antidepressant
Tyramine contraindications: -absolute: aged cheese, aged and cured meats, banana peel, sauerkraut, soy sauce, tap beer, marmite
-moderate: red/white wine, bottled/canned beer
MAOI and merperidine/demerol: agitation, seizures, coma
MAOI and SSRI: hypertensive crisis
MAOI and TCA: hypertensive crisis
MAOI and stimulants: hypertensive crisis
MAOI and levadopa: hypertensive crisis
selegiline patch- brand name: emsam
selegiline patch- indication: major depression
selegiline patch- Mechanism of action: -MAOA inhibitor, MAO B at dose dependent
-food restrictions at 9 mg
-start low
citalopram- brand name, andtidepressant class: celexa
SSRI
escitalopram- brand name, antidepressant class: lexapro
SSRI
Fluoxetine- brand name, antidepressant class: prozac, prozac weekly, sarafem
SSRI
Fluvoxamine- brand name, antidepressant class: luvox
SSRI
Paroxetine- brand name, antidepressant class: paxil, paxil CR
SSRI
sertraline- brand name, antidepressant class: zoloft
SSRI
fluoxetine- half life: long (72 hours)
fluoxetine- metabolism: 2d6, 3a4, 2c inhibition
sertraline- metabolite: active
fluoxetine- metabolite: active
fluvoxamine- metabolism: 1a2, 3a4, 2c inhibition
paroxetine- side effects: anticholinergic
paroxetine- half life: shortest
paroxetine- metabolite: not active
paroxetine- inhibition: 2d6
citalopram- activity: only 5HT activity
escitalopram- what is it: s-enantiomer of citalopram
SSRI side effects: -2 weeks: nausea, diarrhea, sedation, insomnia, anxiety
-chronic: headache, sexual dysfunction, night sweats, nightmares
SSRI toxicity: serotonin syndrome: hyperthermia, excitement, rigidity, hypotensinon, diaphoresis, tachycardia
Venlafaxine- brand name: effexor, effexor ER
Venlafaxine- MOA: SNRI but only at higher doses
Venlafaxine- metabolite: active
Venlafaxine- side effects: -N/D
-headache
-hypertension
-sexual dysfunction
-nervousness
-anxiety
-XR reduces side effects
Duloxetine- brand name: cymbalta
Duloxetine- MOA: SNRI
Duloxetine- side effects: nausea
insomnia
headache
Duloxetine- substrate fo: 2d6, 1a2
Buproprion- brand name: wellbutrin, wellbutrin SR, wellbutin XL
Buproprion- MOA: NDRI
Buproprion- contraindications: seizure disorder
eating disorder
zyban
Buproprion- side effects: GI upset
headache
restlessness
seizures
insomnia
no sexual dysfuntion
Nefazodone- brand name: serzone
Nefazodone- MOA: SRI and S2 antagonist
Nefazodone- drug interactions: 3a4 inhibitor
Nefazodone- forms available: only generic due to liver damage
Nefazodone- side effects: dry mouth
nausea
dizziness
constipation
sedation
liver failure: monitor LFT
no sexual dysfunction
Mirtazapine- brand name: remeron, remeron sol tabs
Mirtazapine- MOA: -alpha 2 antagonist, 5HT3, 2A, 2C antagonist
-increased NE, 5HT
Mirtazapine- side effects: Sedation
weight gain
dry mouth
constipation
no sexual dysfunction
Trazodone- class: heterocyclic antidepressant
Trazadone- MOA: increase 5HT, block H1
Trazadone- uses: insomnia now, not depressino
SJW-interaction: bcp
refractory depression: -adequate trial of initial agent
-assess for unrecognized drug and medical causes
-combo antidepressants
-augmentation: lithium, antipsychotics, stimulants, thyroid
-ECT

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