eplipsy in clinical practice Flashcards

Question

what are the common sodium valporate side effects?

Answer 1

Alopecia (curly regrowth), tremor, weight gain, menstrual irregularities, GI disturbance, headaches, confusion

Answer 2

Hepatotoxicity –Pancreatitis –Blood disorders –Skin reactions e.g. SCARS, hypersensitivity

Answer 3

–Increases risk of toxicity with lamotrigine, phenytoin, phenobarbital, carbamazepine –Increased adverse effects with olanzapine

Answer 4

–Carbapenems e.g. ertapenem, meropenem reduce concentration of valproate –Enzyme inducing AEDs e.g. phenytoin, phenobarbital, carbamazepine

Answer 5

• TDM - Plasma-valproate concentrations are not a useful index of efficacy, therefore routine monitoring is unhelpful • LFTs – before treatment and during first 6 months • FBC (including platelets, PT) – before treatment and before any surgery

Answer 6

• Highly teratogenic –neurodevelopmental disorders (approx. 30–40% risk) –congenital malformations (approx. 10% risk) • Valproate must not be used in women and girls of childbearing potential unless: –The conditions of the Pregnancy Prevention Programme (PPP) are met and –only if other treatments are ineffective or not tolerated, as judged by an experienced specialist

Answer 7

– Original packs – must have warning label on box – Discuss risks in pregnancy with female patients each time valproate medicines are dispensed – Ensure they have the Patient Guide and – Have seen their GP or specialist to discuss their treatment and the need for contraception

Answer 8

– Highly effective contraception: a user independent form such as an intrauterine device or implant OR two complementary forms of contraception including a barrier method – Risk Acknowledgement Form: needs to be signed and up to date every time a prescription is issued (GP to check) – Annual review by specialist – Refer to the specialist urgently (within days) in case of unplanned pregnancy or where a patient wants to plan a pregnancy – Patient provided with patient guide

Answer 9

• Initiate at a low dose and build up slowly • Initially 100–200 g 1–2 times a day, increased in steps of 100–200 g every 2 eeks; usual dose 0.8–1.2 daily in divided doses

Answer 10

dizziness, drowsiness, GI disturbance, headache, ataxia • Hyponatraemia • Hepatotoxicity • Blood disorders – leucopenia, thrombocytopenia • Severe Cutaneous Adverse Reactions (SCARS) e.g. Stevens-Johnson syndrome, toxic epidermal necrolysis, Drug Hypersensitivity syndrome

Answer 11

recognise signs of blood, liver or skin disorders

Answer 12

Effects of carbamazepine on other drugs as an enzyme inducer (CYP3A4) – DOACS, warfarin, COC • Phenytoin • Carbamazepine can increase (via inhibition of CYP219) phenytoin levels • Phenytoin can reduce conc. of carbamazepine (enzyme inducer itself)

Answer 13

Increase conc. of carbamazepine – clarithromycin, fluconazole, diltiazem, grapefruit Juice – Decrease conc. of carbamazepine – phenytoin, rifampicin, theophylline, St. John’s Wort

Answer 14

Pre-treatment (MHRA guidance): –FBC, U&Es, LFTs –Test for HLA-B*1502 allele in patients of Han Chinese or Thai origin Test for HLA-A*3101 allele in patients of European descent or Japanese origin –Increased risk of potentially life-threatening skin-related adverse drug reactions, including Stevens-Johnson-syndrome

Answer 15

–Plasma concentration for optimum response 4–12 mg/litre - measure after 1–2 weeks –Not routinely monitored – only if toxicity or non- compliance suspected –Trough level

Answer 16

Increase dose gradually – narrow therapeutic range, increase in increments of 25-50mg • Initially 150–300 g once daily, alternatively 150–300 g daily in 2 divided doses; usual maintenance 200–500 g daily

Answer 17

``` Route: (note sodium and base are NOT bioequivalent) –Tablets/capsules (phenytoin sodium) –Chewable tablets (phenytoin base) –Suspension (phenytoin base) –IV (phenytoin sodium) ```

Answer 18

``` Coarsening of facial features • Gingival hyperplasia • Bone marrow suppression • Vitamin D deficiency, bone fractures • Folate deficiency • Hepatotoxicity • Rash, SCARS • Signs of toxicity - nystagmus, diplopia, slurred speech, ataxia, confusion, and hyperglycaemia ```

Answer 19

Phenytoin is susceptible to inhibitory drug interactions – Saturable metabolism - significant increase in circulating phenytoin concentrations (toxicity) e.g. clarithromycin, valproate, fluconazole • Phenytoin levels can be reduced by enzyme inducers e.g. St. John’s Wort, rifampicin • Some drugs can increase OR decrease levels of phenytoin e.g. carbamazepine, ciprofloxacin • Phenytoin is a potent inducer and can decrease levels of some drugs e.g. carbamazepine, digoxin, warfarin

Answer 20

``` • Pre-treatment - HLAB* 1502 allele in individuals of Han Chinese or Thai origin • Baseline: –LFTs –FBC –U&Es ```

Answer 21

Plasma-phenytoin concentration: 10–20 g/litre

Answer 22

Highly protein bound – if low albumin (<32g/L), free phenytoin conc. is increased –Need to correct for albumin before can interpret level –Corrected phenytoin = measured phenytoin level ( (adjustment* x albumin, g/L) + 0.1) (*Adjustment = 0.0275; in patients with creatinine clearance <20 mL/min, adjustment = 0.02)

Answer 23

Intravenous infusion - Loading dose 20 g/kg (max. per dose 2 ) – Note: If patient is already on phenytoin then only need a ‘top up’ dose: Top-up dose (mg) = [20 – (phenytoin level (mg/L)] x 0.7 x weight(kg) • Maximum rate of administration is 50mg/min (25mg/min in elderly patients or pre-existing cardiac disease) • Monitoring - Continuous BP, RR and ECG • Administered using with 0.2 micron filter into large vein • Maintenance dose (by IV) - 100 g TDS adjusted according to plasma-concentration monitoring

Answer 24

wrong weight estimated or patient not weighed – failure to take account of existing phenytoin levels for loading dose – misreading 100mg as 1,000mg and vice versa – wrong diluent used – failure to use an in-line filter – wrong infusion rate – loading dose continued for maintenance without dose change – monitoring equipment not available – failure to monitor the effectiveness of phenytoin and any toxic effects

Answer 25

Slow dose titration – Initially 25 g once daily for 14 days, then increased to 50 g once daily for further 14 days, then increased in steps of up to 100 g every 7–14 ays; maintenance 100–200 g daily in 1–2 divided doses • Lower dose if given with valproate: initially 25mg on alternate days for 14days.... • Higher dose if given with enzyme inducers: initially 50mg once daily for 14days

Answer 26

• Common - agitation, arthralgia, diarrhoea, dizziness, drowsiness, dry mouth, fatigue, headache, nausea, sleep disorders, tremor • Serious skin reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis – increased risk - concomitant use of valproate, initial lamotrigine dosing higher than recommended, and more rapid dose escalation than recommended • Hepatic disorders • Blood disorders • Rare: disseminated intravascular coagulation

Answer 27

``` • Valproate • Enzyme inducers e.g. carbamazepine, rifampicin • COC – increases clearance of lamotrigine by 2- fold –Lack of efficacy of lamotrigine –Ideally use alternative contraception –If use COC - double lamotrigine dose and stop pill free interval ```

Answer 28

–Initially 250 g once daily for 1–2 weeks, then increased to 250 g twice daily, then increased in steps of 250 g twice daily every 2 weeks (max. per dose 1.5 twice daily)

Answer 29

Headache, asthenia, irritability, ataxia, drowsiness

Answer 30

–Reduced clearance of methotrexate | –Drugs the cause CNS depressant effect

Answer 31

in renal impairment

eplipsy in clinical practice Flashcards

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