Prescribing in specific groups

Question 1

Prescribing in Hepatic Impairment

problems to consider

Answer 1

This is more information to aid their understanding – all just different versions of what is in the BNF

Impaired absorption -
Reduced bioavailability of lipid soluble drugs in cholestasis (flow of bile from your liver is reduced or blocked. Bile is fluid produced by your liver that aids in the digestion of food, especially fats. When bile flow is altered, it can lead to a build up of bilirubin
Impaired drug distribution

Hypoalbuminaemia - (hypoproteinaemia) in severe liver disease limits availability for drug binding, thus increasing unbound concentration
Toxicity may occur in highly protein bound drugs with a narrow therapeutic index eg phenytoin or prednisolone

Impaired metabolism-
Metabolism by the liver is the main route of elimination for many drugs, but hepatic reserve is large and liver disease has to be severe before important changes in drug metabolism occur. Routine liver-function tests are a poor guide to the capacity of the liver to metabolise drugs, and in the individual patient it is not possible to predict the extent to which the metabolism of a particular drug may be impaired.
Liver disease may reduce capacity to metabolise certain drugs causing toxicity
Due to reduced metabolic capacity and changes in liver blood flow
Particularly drugs with high first pass metabolism
Hepatic reserve is large & liver disease has to be severe before important changes occur
Routine LFTs are a poor guide to the capacity of the liver to metabolise drugs

Impaired excretion
Biliary obstruction may lead to drug toxicity for those drugs excreted by this route e.g. rifampicin and fusidic acid

Altered pharmacodynamics
Hepatic encephalopathy, ascites and deficiencies in clotting factors can increase sensitivity to some drugs
Drugs that cause sedation, constipation or hypokalaemia are contraindicated in severe liver disease as these can cause encephalopathy e.g. opiates & benzodiazepines
Ascites may be worsened by any drug that causes fluid retention e.g. NSAIDs
Anticoagulants will require careful monitoring if used at all & care with aspirin, NSAIDs

Hepatotoxicity
Many drugs can cause liver damage and theoretically should be avoided in patients with liver disease
In practice most can be used safely with dose adjustment e.g. paracetamol EXCEPT:
Methotrexate in alcoholic liver disease
Anti-TB and anti-HIV drugs in patients with hepatitis B or C

Question 2

Who are these specific groups of patients to be careful with when prescribing medication ?

Answer 2

Patients with hepatic or renal impairment

Elderly

Pregnant women

Breastfeeding women

Neonates, infants, young people, “children”

Terminally ill/end of life

Ethnic minorities or if English is not their first language
Incapacitated patients

Culturally diverse groups e.g. Travellers, immigrants, refugees

Patients unable to consent to treatment

A typical patient group in your own specialist area e.g. respiratory patients or patients with mental health problems

Those with co-morbidities

Question 3

Considerations when prescribing in renal impairment ?

Answer 3

Impaired distribution
Hypoalbuminaemia (proteinuria) & uraemia can reduce protein binding capacity. Can lead to toxicity in protein-bound drugs with a narrow therapeutic index

Impaired metabolism
Affects drugs metabolised in the kidney
Liver metabolism of drugs also tends to be slower in chronic renal disease

Impaired excretion
Glomerular filtration, active tubular secretion & resorption all reduced in renal disease
May require dose adjustment or avoidance for renally cleared drugs

Question 4

What are some nephrotoxins?

Answer 4

Antibiotics
Aminogylycosides highly nephrotoxic
Other ABs may need dose reduction

NSAIDs and COX-2 inhibitors (get a student to search naproxen and inform the class of its renal impairment info)

ACE inhibitors and ARBs
Can be beneficial in preserving renal function in diabetes and reducing renal damage in hypertension
Consider senior advice & regular monitoring

Diuretics
Thiazides ineffective if eGFR <30
Loop diuretics can induce hypovolaemia

Renally cleared drugs
May require dose reduction to limit toxicity e.g. insulins, digoxin, some opioids

Question 5

How to grade liver impairement?

Answer 5

Child-Pugh Score for Cirrhosis Mortality

Question 6

CLEARANCE

Answer 6

AMOUNT OF BLOOD THAT YOUR KIDNEYS CAN CLEAR WITHIN A MINUTE.

EG CREATINE CLEARANCE IS A STANDARD MARKER OF HOW WELL KIDNEYS ARE FUNCTIONED

Question 7

raMPIRIL AND KIDNEYS ?

Answer 7

DONT GET RAMIPRIL TO PEOPLE WITH DODGE KIDNEYS UNLESS THEY ARE DIABETIC AAND ARE FOR HTN.

Question 7

What is Cockcroft-Gault Formula

Answer 7

The Cockcroft and Gault formula (CG) was developed in 1973 using data from 249 men with creatinine clearance (CCr) from approximately 30 to 130 mL/m2. It is not adjusted for body surface area. CG is no longer recommended for use because it has not been expressed using standardized creatinine values.

Question 8

Normal creatine clearance?

Question 9

What is type A drug reaction

Answer 9

Type A Reactions Type A (augmented) reactions result from an exaggeration of a drug’s normal pharmacological actions when given at the usual therapeutic dose and are normally dose-dependent.

eg giving 10mg of ramipril to old women their BP will be in the boots.

Question 10

Manifestations of ageing

Answer 10

Signs of ageing can be mistaken for a disease.
eg muscle wasting.