SCRIPT: parenteral poisons

Question 1

Introduction.

a) Paracelsus quote (16th century physician)
b) Give some potentially dangerous but commonly prescribed IV drugs

Answer 1

a) “All things are poison, and nothing is without poison, only the dose permits something not to be poisonous”

b) - Potassium chloride
- Insulin
- Gentamicin (and other aminoglycosides)
- Vancomycin

Question 2

Hypokalaemia.

a) Severity grading
b) Presentation
c) Causes - drugs, other losses

Answer 2

a) - Mild: 3.0 - 3.5
- Moderate: 2.5 - 3.0
- Severe: < 2.5 (will require rapid correction)

b) - Asymptomatic
- muscle weakness and cramps, fatigue, constipation, and palpitations
- In more severe cases, heart arrhythmias

c) Drugs:
- Loop or thiazide diuretics
- Excessive use of laxatives
- Glucocorticoid therapy (e.g. prednisolone)
- Insulin
- Salbutamol
- Theophylline
- Some antibacterials (e.g. gentamicin, amphotericin)

Gastrointestinal losses:

• Diarrhoea
• Eating disorders (i.e bulimia)
• Malnutrition / malabsorption
• Vomiting

Other

• Mineralocorticoid excess (e.g. Cushing’s disease)
• Excessive alcohol consumption
• Renal Tubular acidosis
• Hypomagnesaemia*

*This should be corrected as it can make hypokalaemia resistant to treatment.

Question 3

Hypokalaemia: management

a) Monitoring
b) Treatment
c) Maximum potassium concentration via peripheral vein
d) Maximum flow rate

Answer 3

a) - ECG monitoring
- Bloods: U+Es, magnesium levels*

*Correct if low, as needed for potassium rise

b) Pre-made potassium-containing fluids*:
- 1 litre bag of 0.9% NaCl + 40 mmol KCl (over at least 4 hours)**
OR
- 2x 500 ml bags of 0.9% NaCl/0.3% KCl (20 mmol in each bag)

• Only use pre-packaged fluids. Mis-selection of a strong potassium solution is a never event!
  c) 40 mmol/L (any higher risks extravasation injury and tissue necrosis)

d) Rate should not generally exceed 10 mmol/hr
- In emergencies, may give up to 20 mmol/hr
(specialists may occasionally give higher rates, but there is an increased risk of cardiac arrest)

Question 4

Hyperkalaemia.

a) Severity grading
b) Presentation
c) Causes - drugs, other losses

Answer 4

a) - Mild: 5.5* - 6.0
- Moderate: 6.0 - 6.5
- Severe: > 6.5 (or ECG changes)

*Or 5.3

b) - Nausea
- Muscle weakness
- Palpitations, ECG changes, arrhythmias, arrest

c) Drugs:
- ACE inhibitors/ ARBs
- Potassium sparing diuretics (e.g. spironolactone)
- Potassium supplementation (oral/intravenous)
- Digoxin toxicity
- Heparin and low molecular weight heparins
- NSAIDs
- Penicillins
- Trimethoprim

Other:

• Renal failure
• Dietary excess/supplementation
• Adrenal insufficiency
• Metabolic acidosis
• Burns, trauma, rhabdomyolysis, tumour lysi

Question 5

ECG changes for:

a) Hypokalaemia - earliest sign, then…?
b) Hyperkalaemia - earliest sign, then…?

Answer 5

a) - First: flattening and inversion of T waves, followed by…
- Q-T interval prolongation
- visible U wave
- mild ST depression

b) - First: Tall tented T waves, followed by…
- Flattened / widened P waves
- Prolonged PR
- Prolonged QRS
- Sine wave

Question 6

Hyperkalaemia: management

• cardioprotection
• potassium lowering
• monitoring

Answer 6

Firstly:

• A-E assessment
• Involve senior
• Gain IV access
• Baseline bloods taken
• Baseline ECG

Cardioprotect:

• 10 ml of calcium gluconate 10% solution, by slow IV injection over 3-5 minutes*.
• Titrate and adjust to ECG improvement.
• If the patient is taking digoxin, rapid administration of calcium gluconate may precipitate myocardial digoxin toxicity. The 10 ml of calcium gluconate 10% solution should be mixed with 100ml of glucose 5% and administered slowly over 20 minutes.

Potassium lowering:

• Stop any potassium supplementation
• Stop any potassium-retaining drugs
• Insulin/dex: 5-10 units Actrapid with 50 ml glucose 50%, given over 5-15 minutes
• Nebulised salbutamol (stop beta-blockers or digoxin if patient is on these?)
• Calcium resonium + lactulose
• If these measures fail, consider RRT

Monitoring:

• U+E
• ECG

Question 7

Insulin.

a) Short-acting
b) Intermediate
c) Long-acting

Answer 7

a) - Used for bolus dosing, and in VRIII, and in SC insulin pumps.
- Examples: ActRapid, Humulin S, NovoRapid*

*Note: this is even quicker than short - it is rapid-acting

b) - Usually a twice-daily insulin
- Intermediate: Isophane, Humulin I, Insulatard
- Often mixed with a short-acting insulin (biphasic insulin)
- Mixed: NovoMix, Humulin M

c) - Usually OD or BD insulin
- Examples: insulin glargine, Lantus, Levemir

Question 8

Patient with dementia admitted from a care home with a fall. You notice he is on insulin, but can find no record of his dosing.

a) Who should you contact?

Answer 8

a) - Care home: they should have insulin administration charts, so will be an accurate source
- If this fails, speak to GP, or community pharmacist, or relative or carers, etc.

Question 9

Insulin: information to obtain in history

Answer 9

• The name of the insulin (as the brand name).
• Usual dose (or dose range) of insulin.
• The device used by the patient or their relative/carer to administer the insulin.
• The ‘usual’ time of administration.
• Whether they have an insulin passport or carbohydrate diary

Question 10

Glucose readings.

a) Usual range pre-meal
b) Usual post-prandial ideal glucose

Answer 10

• Before meals: 4 - 7 mmol/litre.

- After meals: < 9 mmol/litre

Question 11

Gentamicin.

a) Common indications
b) Contraindications
c) Routes of administration
d) Calculating dose
e) Monitoring levels
f) Toxicity - signs and treatment

Answer 11

a) - Neutropenic sepsis
- Gram negative sepsis
- Surgical prophylaxis
- Bacterial endocarditis

b) Myasthenia gravis

c) IV usually
- occasionally IM

d) - Actual body weight (ABW) usually
- Use IBW if the patient’s ABW is 20% heavier than ideal body weight (IBW) or has a BMI > 30
- Adult dose: 5-7 mg/kg/day as a single intravenous infusion over at least 1 hour
- Given as once-daily dose unless contraindicated or specialists advise mutliple-daily dosing

e) Nomograms*:
- Hartford nomogram, or Urban and Craig nomogram
- Generally measure level 6 - 14 hours after infusion started
- Nomogram will tell you how frequently dosing should be based on the serum level
- Repeat ~ every 3 days (more frequently in renal dysfunction or if dose needs changing)

*Generally used for once daily dosing

Pre- and post-dose**:

• 1 hour pre-dose (trough) and post-dose (peak)
• Trough target: usually < 1 mg/litre, or < 2 mg/litre (if trough level too high - increase dose interval)
• Peak target: usually 3 - 5 mg/litre, or 5 - 10 mg/litre (if peak level too high - reduce dose)

**Generally used for multiple daily dosing

f) Signs:
- Tinnitus/deafness/balance problems
- Nausea and vomiting
= Renal dysfunction
- Colitis
- Stomatitis
- Blood dyscrasias (e.g. neutropenia).

Treatment: haemodialysis

Question 12

Calculating ideal body weight (IBW).

a) Calculation - in men, in women
b) When is IBW used?

Answer 12

a) IBW (in kg):

Men: [(height in cm - 154) x 0.9] + 50

Women: [(height in cm - 154) x 0.9] + 45.5

b) - Extremes of body weight (BMI > 30 or < 18.5)
- With drugs that have a narrow therapeutic window

Question 13

Vancomycin.

a) Indications
b) Routes of administration
c) Dose calculation
d) Administration and risk mitigation
e) Monitoring
f) Possible adverse effects

Answer 13

a) - Gram-positive sepsis
- Neutropenic sepsis
- Prophylaxis/treatment of endocarditis
- ?MRSA
- C. diff (given orally - levels don’t need measuring)

b) - IV (not well-absorbed orally)
- Only given orally for c. diff

c) - Usually given twice-daily (as short half life of 5 - 7h)

d) - Give as SLOW infusion* to avoid red man syndrome, anaphylaxis or haemodynamic effects
- Ensure anaphylaxis medications are nearby in case of anaphylactic reaction
- If any adverse reaction, stop infusion immediately
- Antihistamine (eg. chlorphenamine) works well for red man syndrome

• dose should not exceed 10 mg/minute
• if 500 mg given, infuse over 50 minutes
• if 1 g given, infuse over 100 minutes

e) - Serum level taken 36 - 72 hours after starting treartment
- Pre-dose (trough) level needed
- Monitor renal function as vancomycin is nephrotoxic
- Note: do not need to take level if given orally, as systemic absorption from GI tract is negligible

f) - Blood dyscrasias
- Fever and chills
- Nausea and vomiting
- ‘Red man’ syndrome: this is more likely to occur if the infusion is administered too quickly
- Renal dysfunction
- Skin disorders (including TEN/SJS)

Question 14

Gentamicin: interpretation of serum levels

a) Peak and trough levels
b) Nomograms

Answer 14

Trough target:
- trough level too high - increase dose interval

Peak target:
- if peak level too high - reduce dose