Pharmacology Flashcards
Aripiprazole
2nd gen antipsychotic
Indications: schizophrenia, mania, bipolar maintenance, depression adjunct, tourette’s
D2 partial agonist and partial 5Ht1a agonist
Potential 5HT2a antagonist - enhanced DA release at nigrostriatum, reducing motor SEs
SEs:
Akathisia, activation, dizziness, insomnia
Nausea and vomiting
Rare = impulse control disorder
Weight gain = unusual, seen more in children and those with lower BMIs
Sedation
Unusual, tends to be activating
Dose; max = 30mg. Minimum effective = 10 mg
Lamotrigine
- Voltage-gated sodium antagonist
- Inhibits glutamate and asparate
Indications
Bipolar depression (takes several weeks to improve bipolar depression)
- monotherapy or adjunct
- Focal seizures, primary and secondary tonic clinic, monotherapy of lennox-gastaut syndrome
Lamotrigine titration
25mg OD for 14 days 50 mg OD (can split dose) 14 days 100 mg (can split dose) 7 days 100 mg BD (or single 200mg dose) thereafter.
Need to re-start titration if miss more than 5 days.
Titration is slower with valproate as it inhibits lamotrigine and increase lamotrigine levels
To STOP - taper over 2 weeks
Lamotrigine: Interactions
Caution with other AED
Enzyme inducing -
carbamazepine, phenytoin, phenoarbital, primidone
Enzyme inhibiting - sodium valproate
Lamotrigine and side effects
Noteable:
- 10% benign rash
- Dose-dependent: blurred or double vision, nausea, dizziness, ataxia
- headache, tremor, cerebellar sx
Rare: sedation, insomnia, alopecia, seizure worse, irritability, suicidal ideation
Life-threatening
- Steven-Johnson Syndrome/TEN
- Blood dysplasia
- Aseptic meningitis
- Withdrawal seizures
- Rare activation of suicidal ideation and behaviour
Lamotrigine and rash
- Life-threatening rash has developed so discontinue at first sign of serious rash.
- Risk increased at higher dose, faster escalation, with valproate, <12
- Patient to report any sign of hypersensitivity.
- Rashes occurring in first 5 days or after 8-12 weeks are rarely drug related
- Risk of serious rash is <1%, very low (approaching zero in recent studies of BPAD).
- Benign rashes occur in 10% of patients and can resolve rapidly with drug discontinuation
- Benign rash can be slowly rechallenged
Steven Johnson Syndrome
Usually develops in 1st 7 days of antibiotics, but up to 2 months of anticonvulsant.
PRODROME
- Several days prodrome of a ‘flu-like illness’; fever >39, sore throat, rhinorrhea, cough, sore red eyes, conjunctivitis general aches and pains.
ABRUPT painful, tender rash
Starts on trunk and then rapidly to face/limbs over hours-days. Maximum extent over 4 days.
- macules (flat, red, diffuse), purpuric
- diffuse erythema, targetoid
- blisters
- prominent and severe mucosal involvement (at least 2 surfaces)
EYES - Red, sore, sticky, photosensitive
Lips/mouth - ulcers, crusty lips
Pharynx/oesophagus- difficulty swallowing
Gential/urinary - ulcers, retention
URT - cough, resp distress
GI - diarrhoea
Multi-organ involvement:
Bloods =
Anaemia, low wbc inc lymphocytes, neutropenia (poor prognostic marker), eosinophilia, mild raised LFT and mild proteinuria
Sodium Valproate
Depakote; semi sodium valproate
Indications;
- Acute Mania
- Hypomania
- Prophylaxis mania
- Biploar depression
- Aggression (data week)
Depakote
- Titration
- Withdrawal
1.Starting dose 750 mg (incl elderley)
in 2-3 divided doses
2. Increased to 1-2g
Withdraw:
Over at least 4 weeks
Depakote
Side effects
Very common; weight gain, increased appetite and fatigue
Common; abdo pain/ gastric irritation, hair loss and curly regrowth, anaemia, hyponatraemia, hepatic disorder, headache, tremor
Rare: pancreatitis, hyperammonia, fulimant hepatic failure, thrombocytopenia, parkinsonism, movement disorder
Unknown frequency;suicidal behaviour
Depakote
Interactions - CYP450 inhibitor
Highly protein-bound drugs, such as aspirin, displace valproate and pre-dispose to toxicity
Less strongly protein-bound (warfarin) can be displaced, increasing levels of other drug
Increase valproate; fluoxetine, erythromycin, cimetidine
Valproate can increase lamotrigine levels
Valproate and Quetiapine = Increase risk of leucopenia and neutropenia
Sodium valproate
Monitoring
Baseline FBC, LFT and BMI
6-monthly; LFT, PT, FBC, BMI and then annually
Counselling patients re severe SEs
Blood disorder;unexplained bleeding, bruising, sore throat, fever, recurrent infection
Pancreatitis; severe abdo pain, nausea, vomiting
Liver disorder; jaundice, anorexia, oedema, lethargy
Valproate in pregnancy
Contraindicated; if woman discovers she is pregnant it needs to be stopped.
10% major congenital malformation, in particular neural tube defect - spina bifida
Increased risk ASD, cleft palate, hypospadias, polydactyly, motor and neurodevelopmental delay. Lower IQ and increased ASD.
Pre-ecamplsia
Risperidone
