SCRIPT: monitoring drug therapy

Question 1

Reasons for monitoring.

Answer 1

• Encourage patient adherence
• Allow patients to achieve treatment targets
• Reduce adverse drug effects
• Increase patient confidence in your treatment and in the healthcare system

Question 2

Thyroxine.

a) How to titrate
b) When to check TFTs after dose adjustment
c) Frequency of monitoring when on maintenance dose

Answer 2

a) Start low and titrate up
b) Check TFTs 6-8 weeks after dose adjustment
c) Annual

Question 3

Give one thing that must be monitored with…

a) COCP
b) Amiodarone
c) Gentamicin
d) Methotrexate
e) Digoxin

Answer 3

a) Blood pressure
- every 6/12

b) TFTs (also a CXR)
- Pre-treatment and every 6/12

c) Plasma drug level

d) FBC
- every 2/52 for two months
- every 4/52 for four months
- then three monthly thereafter

e) Heart rate
(note: digoxin levels generally only taken if ?toxicity)

Question 4

Vitamin D deficiency.

a) Who is at risk?
b) What blood test is used to assess?
c) Thresholds for treatment
d) Monitoring when on treatment
e) Vitamin D toxicity - signs

Answer 4

a) - Age > 65
- Dark skin
- Poor sunlight exposure
- Malabsorption
- Primary hyperparathyroidism* may also cause ‘apparent’ vitamin D deficiency - as PTH converts all 25(OH)D into 1,25(OH)D which is not measured on blood test

• Note that vitamin D deficiency itself may cause low calcium and induce SECONDARY hyperparathyroidism
  b) 25-OH-Vitamin D

c) - Plasma 25(OH)D < 25 nmol/litre is deficient (need treatment)
- Plasma 25(OH)D of 25-50 nmol/litre is deficient for some of the population (require treatment only if at-risk of deficiency, concurrent osteoporosis or symptoms of vitamin D deficiency)
- Plasma 25(OH)D > 50 nmol/litre is sufficient for most of the population (no treatment)

d) Calcium level
- As vitamin D deficiency can mask undiagnosed primary hyperparathyroidism (with treatment, this will be unmasked and calcium levels will increase)

e) Hypercalaemia:
- confusion, depression
- dehydration, kidney stones
- muscle weakness, fatigue
- vomiting, abdominal pain, constipation, anorexia

Question 5

Adalimumab/infliximab.

a) Should undergo what test prior to treatment?

Answer 5

a) TB test - eg. Mantoux skin

at risk of more severe TB if on certain biologics

Question 6

Monitoring requirements.

• What?
• When?
• Why?
• How?

Answer 6

• When to monitor?
• What the evidence states to be a desirable range? - 5% will lie outside ‘normal’ reference range
• Why you are monitoring?
• How to monitor?
• How to interpret the results? - what will you do in the case of normal/abnormal results?
• How to apply the results to an ‘individual’ patient?

Question 7

Electrolyte derangement: K+

a) Drugs that can cause low K+ (hypokalaemia)
b) Drugs that can cause high K+ (hyperkalaemia)
c) Feedback loop imbalances causes hypo/hyperkalaemia

Answer 7

a) - Loop diuretics
- Thiazides/thiazide-like
- Beta-2 agonists (eg. salbutamol)
- Insulin
- Corticosteroids (mineralocorticoid/Conn’s-like effect)
- Laxatives

b) - ACE inhibitors / ARBs
- Potassium-sparing diuretics (eg. amiloride, spironolactone)
- Tacrolimus, ciclosporin
- Heparins

c) - Aldosterone excess: hypokalaemia
- Aldosterone deficiency: hyperkalaemia

Question 8

Electrolyte derangement: Na+

a) Drugs that can cause low Na+ (hyponatraemia)
b) Drugs that can cause high Na+ (hypernatraemia)
c) What feedback loop imbalances cause hypo/ hypernatraemia

Answer 8

a) - Loop diuretics*
- Thiazides
- Laxatives
- Antidepressants - eg. SSRI

*However, if patient is overloaded and has dilutional hyponatraemia, loop diuresis could actually offload the excess water and raise serum sodium

b) - Loop diuretics / laxative abuse (excess dehydration)
- Parenteral sodium - hypertonic saline / sodium bicarb
- Sodium excess in tablets

c) Dysregulation of ADH and plasma/urine osmolality:
- Dehydration - hypernatraemia, high plasma osmolality, high urine osmolality
- Overhydration - hyponatraemia, low plasma osmolality, low urine osmolality
- SIADH - hyponatraemia, low plasma osmolality, high urine osmolality
- Diabetes inspidus (DI) - hypernatraemia, high plasma osmolality, low urine osmolality (polyuria)

Question 9

Electrolyte derangement: Ca2+

a) Drugs that can cause low Ca2+ (hypocalcaemia)
b) Drugs that can cause high Ca2+ (hypercalcaemia)
c) Feedback loop imbalances causing hypo/hypercalcaemia

Answer 9

a) - Bisphosphonates
- Corticosteroids
- Loop diuretics

b) - Thiazides
- Vitamin D

c) - Excess PTH/ excess vit D: hypercalcaemia
- Deficient PTH/ deficient vit D: hypocalcaemia

Question 10

Why might LFTs be monitored before/during treatment?

Answer 10

1. The drug has hepatotoxic potential
2. The drug is metabolised by the liver (requires good hepatic function for utilisation/ clearance)
3. Concomitant treatment will increase the risk of liver damage

Question 11

Therapeutic drug monitoring (TDM).

a) Indications
b) Lithium - therapeutic range, and how to take?

Answer 11

a) Drug with a narrow therapeutic window:
- Warfarin - INR* (rather than drug level)
- Gentamicin
- IV vancomycin (not oral)
- Lithium
- Theophylline
- Digoxin (not unless toxicity suspected)

*Note: not required for LMWH or DOACs, just warfarin

Where toxicity is suspected:

• Paracetamol/ other OD
• Any known drug with narrow therapeutic window

b) Range: 0.4 - 1 mmol/litre
- perform weekly and after each dose change, then 3-monthly when stable
- take sample 12 hours after dose (trough)

Question 12

Parenteral iron infusions

Answer 12

• Risk of life-threatening hypersensitivity reactions (eg. anaphylaxis)
• Monitor patient for signs of adverse reaction DURING AND FOR 30 MINUTES AFTER EVERY DOSE of an iron infusion

(note: test doses are no longer recommended)