Prescribing in Special Circumstances Flashcards
How is drug handling affected in elderly patients?
Drug distribution changes are important in the elderly.
1) Half-life of FAT soluble drugs is increased (because of increased fat providing greater volumes of distribution)
2) Concentration of WATER SOLUBLE drugs is increased (because free water is decreased, providing smaller volumes of distribution)
3) Level of active protein-bound drugs is increased (because albumin is decreased)
Drug metabolism and drug excretion decrease with ageing which can reduce clearance leading to drug accumulation.
Changes in drug absorption are probably not clinically important.
What drugs are contraindicated in breastfeeding?
Infants under 1 month of age are at the greatest risk from drugs in breast milk due to immature metabolism and excretion.
Drugs that are excreted in breast milk and are contraindicated during breastfeeding include:
- amiodarone: thryoid anomalies
- cytotoxics and chloramphenicol: blood dyscrasia
Other drugs that should not be taken by breastfeeding mothers include:
- psychiatric drugs: lithium, barbiturates
- antibiotics: ciprofloxacin, sulphonamides, tetracyclines and chloramphenicol
- gold: haematological reactions and renal impairment
- oestrogens: feminisation of male infants
- carbimazole
- methotrexate
Most AEDs are actually quite safe in breast feeding
Which drugs are contraindicated early in pregnancy?
During the first 16 weeks of pregnancy, drugs may exert teratogenic effects on the fetus, leading to malformations.
Important drugs to know about are:
- ACEi and ARBS = oligohydramnios
- Lithium = cardiac abnormalities
- Phenytoin = facial fusion abnormalities such as cleft lip and palate
- valproate and retinoids = neural tube defects
- warfarin = long bone and cartilage abnormalities
Which drugs should be avoided later in pregnancy?
Some drugs may cross the placenta and harm the fetus. This includes:
- carbimazole = neonatal goitre (which may even be large enough to obstruct labour)
- Gentamicin = cranial nerve VIII deafness in the newborn
(NB - carbimazole is usually actually given during the second trimester for treatment of maternal Graves disease during pregnancy)
What drugs are particularly important to avoid in liver failure?
Patients with liver impairment are more prone to sedative effects of drugs, and certain drugs may induce hepatic encephalopathy.
This includes opioids and benzodiazepines. Thiazides and loop diuretics may worsen hypokalemia and provoke encephalopathy.
Other aspects to bear in mind:
- drugs excreted in bile can accumulate in obstructive jaundice, e.g. rifampicin
- hypoalbuminaemia may reduce available protein binding, and increase the proportion of drug that is unbound (“free”) which increases the risk of adverse side effects
- reduced clotting factor synthesis may enhance the risk of bleeding associated with warfarin
- salt and water retention and ascites may be made worse by NSAIDs and steroids
- drugs with significant first pass metabolism will accumulate if there is decreased hepatic blood flow (e.g. right sided heart failure)
How does renal failure affect prescribing of some drugs?
In patients with established renal impairment, nephrotoxic agents may exacerbate renal damage (especially in AKI).
Patients with low GFR will be prone to accumulation of drugs normally eliminated by the kidney, e.g. water soluble drugs.
What drugs should be avoided in patients with pre-existing low GFRs?
Atenolol - bradycardia and heart block
Digoxin - cardiac arrhythmias, heart block
Enoxaparin - bleeding risk
Erythromycin - encephalopathy
Lithium - cardiac arrhythmias and seizures
Penicillins (high dose) - lead to encephalopathy
Cephalosporins (high dose) - encephalopathy
Which parts of the glomerulus do NSAIDs and ACEi/ARBs affect?
NSAIDs reduce prostaglandin synthesis which is important for afferent arteriolar vasodilatation.
ACEi/ARB adversely affect angiotensin II mediated vasoconstriction of the efferent arteriole and lead to reduced glomerular filtration pressures in the face of overall reduced renal perfusion pressure.
