Pharmacotherapy Test 3
Terms
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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