2. Preparatory Knowledge Task 1
• 4 sources to help with dosing drugs in BNF + advice about
Lithium
Source Advice
BNF Avoid if possible in the first trimester; dose requirements
increased during the second and third trimester; close
monitoring of serum-lithium concentration advised
EMC 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.
3. Preparatory Knowledge Task 1
Source Advice
UKTIS 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.
4. 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 concentrations
Suggested resource:
Dawes M & Chowienczyk PJ. Pharmacokinetic in Pregnancy. Best
Practice & Research Clinical Obstetrics and Gynaecology 2001; 15:819-
826
5. PKT 3
Drug Safe/U Why? All trimesters?
nsafe
Paracetamol Safe Not known to be harmful
Ibuprofen 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)
6. 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
7. 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)
8. 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
9. Lithium level subsequently
comes 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
10. Appropriate dose for Mrs
Adams
• 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.
11. 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?
12. Mrs Adams wants to breast
feed
• 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.
