Special drugs

Question 1

how does Lithium work?

Answer 1

Mechanism of action is unknown

• Lithium ions may compete for sodium ions
• no discernible psychotropic effects in normal volunteers but considerable effect in patients suffering from affective disorders

Question 2

What are the special features of Lithium to be aware of

Answer 2

Narrow therapeutic index
Excreted primarily by the kidney
- causes CRF
Can cause nephrogenic diabetes insidious (40%)
Can be fatal in overdose
long-term lithium therapy can cause renal failure along with other metabolic adverse effects including hypothyroidism, weight gain, and hyperparathyroidism.

Question 3

Describe Lithium drug monitoring.

Answer 3

target 24 hour dose level of 0.5 - 0.8mmol/L (OD)

• levels should be monitored weekly initially and can be spaced out to a max of 3 monthly once stable
• monitor calcium level annually

Question 4

What are the recommendations for Lithium and pregnancy and breastfeeding?

Answer 4

No

• may be harmful to foetus
• crosses into breast milk

Question 5

What are the most common adverse effects of Lithium?

Answer 5

common: gastrointestinal discomfort with mild nausea and diarrhoea, vertigo, muscle weakness and a dazed feeling
- improve with stabilisation
fine tremor, fatigue, polyuria persist
hypercalcaemia
may precipitate goitre

Question 6

How does Lithium toxicity present?

Answer 6

Lithium levels > 1.5mmol/L (or sometimes lower e.g. elderly)

• Diarrhea, Dizziness, Nausea, Stomach pains, Vomiting
• Coma, tremor, ataxia, seizures, dysarthria, nystagmus , chorea, twitching, hyper-reflexia

chronic toxicity is less likely to give GI symptoms

Question 7

What drugs can increase Lithium levels?

Answer 7

SSRIs
Metronidazole
Tetracyclines
Topiramate
NSAIDs
ACE i and ARBs
Thiazides (may cause a paradoxical antidiuretic effect resulting in
possible water retention and lithium intoxication)
Spironolactone
Frusemide
Other drugs affecting electrolyte balance may alter lithium excretion, e.g. steroids

Triple whammy drugs will increase Lithium serum levels

Question 8

What drugs can lower Lithium serum levels?

Answer 8

• Xanthines (theophylline, caffeine)
• Sodium bicarbonate and Sodium Chloride containing products
• Psyllium or Ispaghula husk
• Urea
• Mannitol
• Acetazolamide

Question 9

What is the most common drug that increases lithium levels?

Answer 9

thiazides

Question 10

What is the treatment of diabetes insipidus when lithium needs to continue?

Answer 10

Amiloride - blocks ENac channels

Question 11

What is the metabolism of lithium?

Answer 11

No hepatic metabolism - all excreted unchanged by the kidneys

Question 12

What is SILENT syndrome?

Answer 12

Long term neurological side effects persist after acute lithium toxicity, due to demyelination of cerebellum

Question 13

Mechanism of action of digoxin?

Answer 13

inhibits Na/K ATPase on the cardiac myocyte
- keeps calcium inside cells via calcium/sodium antiporter (ionotropic)
decreased sympathetic activity and augments parasympathetic activity (rate controlling effect)

Question 14

What is the treatment for digoxin toxicity?

Answer 14

Digibind - binds to digoxin

Question 15

What are some pharmacokinetic properties involving digoxin?

Answer 15

Large volume of distribution

Anti-clockwise hysteresis loop - drug takes a long time to get to its target tissue and exert effect

Question 16

Symptoms of digoxin toxicity?

Answer 16

Bradycardia, bidirectional VT, heart blocks, junctional rhythm
Nausea, vomitting, dizziness, yellow vision