IC7 Flashcards

Question

BA, protein binding, vd for carbamazepine

Answer 1

F = 0.8 75-80% protein bound albumin alpha 1 acid glycoprotein vd = 1.4L/kg

Answer 2

3a4 > 99% metabolised into active metabolite = carbamazepine 10,11 epoxide

Answer 3

undergoes autoinduction, inducing its own metabolism = clearance increase and t1/2 shorten = concentration stabilises in accordance with new CL and t1/2 maximal autoinduction around 2-3 weeks after initiation. DOSING: do not start at maintenance dose but gradually increase over the first few weeks.

Answer 4

start low titrate slow avoid large dosage changes restrict therapy to one drug administration schedule = can take large dose at bedtime. OR divide daily dose into smaller doses. OR sustained release. OR reduce total daily dose

Answer 5

1) GI: N/V 2) Idiosyncratic reactions (SJS/TEN, hepatotoxicity, blood dyscrasias) 3) gingival hyperplasia (enlargement of gum tissue) AND hirsutism (including facial hirsutism) due to chronic therapy. 4) peripheral neuropathy due to chronic therapy (may improve with decreasing dose. response with folate supplementation) 5) Endocrine: osteomalacia (soft bone disease) from increased turnover of vit D = secondary hyperparathyroidism, increased bone turnover, reduced bone density. 6) megaloblastic anemia 7) neonatal congenital defects = major malformation risk (moderate), neonatal cognition

Answer 6

1) GI: N/V 2) Idiosyncratic reactions 3) peripheral neuropathy due to chronic therapy 4) Endocrine: osteomalacia (soft bone disease) from increased turnover of vit D = secondary hyperparathyroidism, increased bone turnover, reduced bone density. 5) megaloblastic anemia 6) neonatal congenital defects = major malformation risk (moderate)

Answer 7

Psych: behavioural disturbance (irritability, aggression)

Answer 8

1) cognition: speech fluency 2) weight loss (reversible on discont) 3) neonatal congenital defects = major malformation risk (high)

Answer 9

1) Idiosyncratic reactions 2) alopecia with chronic therapy 3) peripheral neuropathy due to chronic therapy 4) weight gain (most commonly w valproate). will reverse spontaneously with discontinuation of tx 5) neonatal congenital defects = major malformation risk (high) , neonatal cognition

Answer 10

almost all ASMs except some 2nd gen cause serious idiosyncratic reactions. all gen 1 causes hepatotoxicity others include: blood dyscrasia, pancreatitis, lupus like reaction, exfoliative dermatitis, TEN/SJS blood dyscrasia vv common though megaloblastic anemia is rare but occurs with gen 1 drugs (phenytoin, phenobarbital, carbamazepine) SJS/TEN very common (range from mild maculopapular rash to SJSTEN ALMOST all associated with suicidal ideation - close monitoring

Answer 11

– Risk management strategies: 1. Pharmacogenetic testing (carbamazepine) 2. Follow dosing guidance (lamotrigine) 3. Identify potential cross-sensitivity reaction (ASMs with aromatic rings)

Answer 12

hla-b*1502 carrier has increased risk of CBZ-induced SJS/TEN.

Answer 13

in patients taking valproate: week 1 and 2: 25mg every other day week 3 and 4: 25mg every day week onwards to maintenance: increase by 25-50mg/day every 1-2 week usual maintenance dose: 100-200mg/day with valproate alone; 100-400mg/day with valproate AND other drugs that induce glucuronidation (in 1-2divided doses). in patients not taking CBZ, PH, PHB, primidone, valproate week 1 and 2: 25mg every day week 3 and 4: 50mg every day week onwards to maintenance: increase by 50mg/day every 1-2 weeks usual maintenance: 225-375mg/day in 2 divided doses in patients taking CBZ, PH, PHB, primidone (BUT NOT VALPROATE) week 1 and 2: 50mg/day week 3 and 4: 100mg/day (divided 2) week onwards to maintenance: increase by 100mg/day every 1-2 weeks usual maintenance: 300-500mg/day (in 2 divided doses)

Answer 14

mechanism causing skin reactions unclear might be due to formation of arene-oxide intermediate = become immunogenic through interactions with proteins or cellular macromolecules

Answer 15

minimum 2 years unless increased risk of seizure recurrence OR patient who had a low freq of seizures less than once a year before remission. then wait longer than 2 years should be SDM with patient and caretaker for reasons to discontinue, plans for monitoring... etc

Answer 16

phenytoin 10-20mg/L valproate 50-100mg/L CBZ 4-12mg/L phenobarbitone 15-40mg/L

Answer 17

OC may lower lamotrigine concentrations, resulting in breakthrough seizures.

Answer 18

1) establish individual's therapeutic range - once stable, document. can help with any subsequent dosing changes. 2) assess lack of efficacy - fast metaboliser? adherence issues? 3) assess potential toxicity - changing physiology? slow metabolisers? change in disease or drugs? 4) assess loss of efficacy DUE to breakthrough seizure - change in physiology/pathology/formulation/DDI?

Answer 19

counselling on the importance of early discussion on family planning potential risk of fetus - uncontrolled seizure and teratogenic potential use of oral contraceptives - some OCs may be rendered ineffective, will require alternative methods (eg add on barrier methods)

Answer 20

levetiracetam and lamotrigine

Answer 21

valproate CONTRA valproate in female children, PREGNACY or women of childbearing potential. - for women of childbearing potential, conditions of the pregnancy prevention programme must be fulfilled. = counsel and contraception - risk of serious developmental disorders and congenital malformation NOTE phenobarbital pregnancy risk

Answer 22

incr risk of neurodevelopmental disorders (NDDs) in children born to men treated with valproate in the 3 months prior to conception Patient education: o potential risk + need for effective contraception, including for the female partner, while using valproate and for 3 months after stopping the treatment Patient to be advised: o not to donate sperm during treatment and for 3 months after stopping the treatment o the need to consult his doctor to discuss alternative treatment options, as soon as he is planning to father a child, and before discontinuing contraception o he and his female partner should contact their doctor for counselling in case of pregnancy if he used valproate within 3 months prior to conception.

Answer 23

ALL BREASTFEEDING women encouraged to breastfeed. refer to specialist

Answer 24

TIME seizure is likely to be prolonged leading to continuous seizure activity - 5min TIME when a seizure may cause long term consequences = 30min

Answer 25

failure of the mechanisms responsible for seizure termination or from the initiation of mechanisms which lead to ABNORMALLY PROLONGED SEIZURES will have long term consequences: neuronal death, injury, alteration of neuronal networks.

Answer 26

0-5MIN STABILISATION PHASE: - stabilise ABC - time seizure, monitor vitals. - ECG, O2, BGM (if BG<60mg//dL, then adult 100mg thiamine IV then 50ml D50W IV OR child ≥2yo 2ml/kg D25W IV) normal BG around 70-100. - IV - collect electrolytes, hematology, toxicology screen, anticonvulsant drug levels 5-20MIN INITIAL THERAPY - if seizure continues then initiate benzodiazepines 1) IM midazolam single dose; 10mg for >40kg, 5mg for 13-40kg 2) IV lorezapam (may repeat dose once). 0.1mg/kg/dose, max 4mg/dose. 3) IV diazepam (may repeat dose). 0.15-0.2mg/kg/dose, max 10mg/dose 20-40MIN SECOND THERAPY - no evidence for preferred second line choose 1) IV fosphenytoin 20mg PE/kg max 1500mg PE/dose single dose 2) IV valproic acid 40mg/kg max 3000mg/dose single dose 3) IV levetiracetam 60mg/kg max 4500mg/dose single dose 40-60min THIRD THERAPY - repeat second line agents

Answer 27

STRONG RECOMMENDATION for HLA-B*15:02 (high prevalence in Asian ancestry) AND HLA-A*31:01 carriers to avoid carbamazepine - choose alternative UNLESS patient has been taking carbamazepine for >3 months = continue therapy (usually onset of induced hypersx is within the first month) - there is a chance of cross reactivity with HLA-B*15:-02 carriers using aromatic anticonvulsants (phenytoin, phenobarbital, lamotrigine)

Answer 28

neuropathic pain: gabapentin mood stabiliser: lithium, valproate, quetiapine, aripiprazole, olanzapine epilepsy: levetiracetam, valproate, topiramate, perampanel

Answer 29

glaucoma hyperammonemia metabolic acidosis hyperthermia (decreased sweat production) paraesthesia renal stones

IC7 Flashcards

(53 cards)