Drugs and Therapeutics

Scenario 5 Mandy Adams

Mandy Adams
Mandy Adams is a 25 year old who has a history of bipolar affective disorder, she is 38 weeks pregnant. Prior to becoming pregnant she had been taking Lithium 300mg daily which she stopped before she became pregnant, as she didnt want to harm her baby. Her psychiatrist convinced her to recommence this in the 3rd trimester as she was beginning to develop features of hypomania, the Lithium improved these symptoms. She is now admitted acutely psychotic to the AMU. She is febrile although able to give a reasonable history, although her speech is rapid and copious. Her pulse rate 75bpm regular BP 145/95 mmHg. Her husband is with her and says that until 2 days before she was her normal self. She does not smoke, has not been drinking alcohol and does not take any recreational drugs and has NKDA

Medications
Lithium (Priadel) 300mg tablets 1 OD (at night), Ferrous Sulphate 200mg tablets TDS Folic acid 400 micrograms tablets OD.

Admission Investigations
HB 11.9 g/dl Normal MCV 94 fl Normal WCC 14.5 x109/L with a neutrophil leucocytosis Raised Platelets 367 x109/L Normal Ur 12.2 mmol/L Raised Sodium 130 mmol/L Low Cr 120 umol/L Normal Potassium 3.4 mmol/L Borderline/Low CRP 39 mg/L Raised (Mild inflammation)

1. Create a differential diagnosis for Ms Adams symptoms

1. Lithium overdose:
serum-lithium concentration above 2mmol/L. Toxic psychosis and renal failure, hypokalaemia. This patient may be dehydrated (increased urea) due to infection (leucocytosis, febrile and raised CRP). The most common infection during pregnancy is a UTI. Lithium toxicity is made worse by sodium depletion, due to the selective reabsorption of lithium at the proximal convoluted tubule which can increase lithium levels

1. Create a differential diagnosis for Ms Adams symptoms

2. Hypomania: due to reduced plasma concentration of
Lithium caused by the alteration drug pharmacokinetic during pregnancy:
Distribution: plasma volume and extracellular fluid increase by up to 50% thus reducing the plasma concentration of drugs Elimination: Glomerular filtration rate increases during pregnancy. The increase in GFR can increase renal

clearance of lithium

2. A lithium level subsequently comes back as low 0.3mmol/L (normal range 0.6 1.2 mmol/L). What are you going to do? The therapeutic range for lithium is between 0.6-1.2mM

1. Exclude infection Investigate and begin appropriate antimicrobials 2. Correct U&Es 3. Increase lithium dose The BNF recommends increasing the dose to 400mg during the second and third trimester

3. Write up Mrs Adams drug chart for this admission.

Lithium (Priadel) 300mg OD (at night)
Change dose of lithium to 400mg OD (Night)

Ferrous Sulphate 200mg TDS Folic acid 400 micrograms OD

4. Lithium follows 1st order pharmacokinetics, taking this into consideration what dose might be appropriate for this patient.
1st Order Pharmacokinetics: Elimination of the drug is directly proportional to its plasma concentration. Its dependent on its half life. First order implies no matter how much drug is given it will be eliminated by 50% by its first half life. It can therefore take several days before the plasma concentration of lithium remains stable within the therapeutic range. Serum concentration monitoring should be available. Should be between 0.4-1 mmol/L - check it 12 hours after a dose on days 4-7 of treatment, then every week until dosage remains constant for 4 weeks. Then check every 3 months.

Increase dose to 400mg

5. What significance does this BP measurement have in this patient? What further investigations need to be carried out now?

Normal blood pressure during pregnancy is 140/85 mm Hg. Ms Adams is 145/95 mm Hg and is mildly high There is a risk of pre-eclampsia or gestational diabetes, thus urinalysis is required to test for glucose, protein and ketones Ms Adams blood pressure and urine must be monitored frequently throughout the rest of her pregnancy

NICE Guidelines: Hypertension in pregnancy

Degree of hypertension Mild Hypertension (140/90 149/99mmHg)
NO

Moderate Hypertension (150/100159/109mmHg)

NO

Severe Hypertension (160/110mmHg or higher)

YES

Admit to hospital

Treat

NO

With oral Labetalol

With oral Labetalol

Measure blood pressure Test for proteinuria

Not more than once a week At each visit

At least twice a week

At least four times a day Daily

At each visit

Blood tests

Only routine antenatal

U&Es, FBC, bilirubin, transaminases

Monitor weekly: U&Es, FBC, bilirubin, transaminases

6. Mrs Adams wants to breast feed, what advice should you give to her regarding this?

Avoid breastfeeding whilst taking Lithium as it is present in the breast milk and their is a risk of toxicity in the infant.