Preparatory Knowledge Task 1• 4 sources to help with dosing drugs in BNF + advice about LithiumSource AdviceBNF Avoid if possible in the first trimester; dose requirements increased during the second and third trimester; close monitoring of serum-lithium concentration advisedEMC Should not be used during pregnancy, especially during the first trimester, unless considered essential. If used, serum lithium levels should be closely monitored and measured. Dosage adjustments are required. Recommended that lithium be discontinued shortly before delivery and reinitiated a few days post-partum.
Preparatory Knowledge Task 1Source AdviceUKTIS In some women with antenatal and postnatal mental health, it is possible to discontinue lithium during the first trimester if the woman is well and not at high risk of relapse. If the woman is not well or is at high risk of relapse, continuation of lithium therapy in the pregnant patient will require close monitoring of the maternal serum levels of lithium and if necessary the dose should be adjusted.NICE the dose should be adjusted to keep serum levels towards the lower end of the therapeutic range, and the woman should maintain adequate fluid intake.
PKT 2• Pharmacokinetic changes in pregnancy Changes to PK How it affects drug therapy IM and inhalation absorption Faster drug effect enhanced Reduced plasma albumin Increased drug effect (for concentration albumin-bound drug) Higher rate of metabolism slightly lower steady-state drug concentrations enhanced elimination slightly lower steady-state drug concentrationsSuggested resource:Dawes M & Chowienczyk PJ. Pharmacokinetic in Pregnancy. BestPractice & Research Clinical Obstetrics and Gynaecology 2001; 15:819-826
PKT 3Drug Safe/U Why? All trimesters? nsafeParacetamol Safe Not known to be harmfulIbuprofen Unsafe 3rd trimester (closure of fetal ductus arteriosus in utero and possibly persistent pulmonary hypertension of the newborn)Ramipril Unsafe All (adversely affect fetal and neonatal blood pressure control and renal function)Sodium Valproate Unsafe 1st and 2nd trimester (Liver toxicity)Trimethroprim Unsafe 1st trimester terotogenic risk (folate antagonist)
Summary (Meet Ms Adams)• 25 years old female• History of bipolar affective disorder• 38 weeks pregnant (around 6 months)• Been taking Lithium 300mg daily but stopped before pregnancy• Recommence it in the 3rd trimester as she was beginning to develop features of hypomania – symptoms improved• Admitted “acutely psychotic” to AMU• Febrile although able to give reasonable history, athough her speech was rapid and copious• Pulse rate 75bpm. Regular BP 145/95 mmHg• Husband says she was normal until 2 days before
Summary• Does not smoke, has not been drinking alcohol and does not take any recreational drugs and has NKDA• Medications • Lithium (Priadel) 300mg tablets OD (at night) • Ferrous Sulphate 200mg tablets TDS • Folic acid 400 micrograms tablets OD• Admission investigations: • HB 11.9g/dl (low) • MCV 94 fl • WCC 14.5x109/l with neutrophil leucocytosis (high) • Platelets 367x109/l • Sodium 130 mmol/l (low) • Urea 12.2 mmol/l (high) • Potassium 3.4 mmol/l • Creatinine 120 µmol/l (slightly low) • CRP 39 mg/l (high)
Differential diagnosis• Points to consider: • “acute psychosis” or delirium or mania? • High BP • Low HBC, High WBC • High Urea, high CRP • Low sodium levels• DD • UTI • Chest Infection • Pre-eclampsia • Bipolar affective disorder with any of the above
Lithium level subsequentlycomes back as low 0.3mmol/l• Target plasma concentration (0.6 – 1.2 mmol/l)• Drug interaction in pregnancy • Any drug - enhanced renal clearance (slightly lower steady state plasma concentration) • Lithium - Teratogenicity only in first trimester• Current dose = Lithium (Priadel) 300mg OD• BNF 62 advised: • initially 0.4–1.2 g daily as a single dose or in 2 divided doses (prophylaxis and therapeutic) • Dose requirement increased during 2nd and 3rd trimester• What would you do? • Increase the dose for lithium
Appropriate dose for MrsAdams• Lithium follows 1st order pharmacokinetics• Mrs Adams is in her 2nd trimester• Therapeutic range for Lithium (Priadel): initially 0.4–1.2 g daily as a single dose or in 2 divided doses• Current lithium level: 0.3 mmol/L (Therapeutic aim is 0.6-1.2 mmol/L)• Appropriate dose? • Start with 400mg and titrate until reach therapeutic aim and symptom improvement.
Mrs Adams’ BP• BP: 145/95 mmHg• What is her normal BP?• Caution: Pre-eclampsia• Investigation: • BP & Urinalysis (check for hypertension and proteinuria) – BP and urinalysis should be part of routine antenatal check• Complete blood cell (CBC) count• Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels• Serum creatinine• Uric acid• Other tests – CT scan? MRI? Ultrasonography?
Mrs Adams wants to breastfeed• BNF: Lithium should be avoided in breast feeding (high levels in breast milk may is toxic to infant)• NICE: Women with bipolar disorder who are taking psychotropic medication and wish to breastfeed should be offered a prophylactic agent that can be used when breastfeeding. The first choice should be an antipsychotic.• Advice: She’ll be given a new medication (most conventional antipsychotic are safe - chlorpromazine, trifluoperazine or perphenazine) and she should stop taking lithium.