Prescribing in extremes of age and organ function Flashcards
Describe the impact of pregnancy on drug pharmacokinetics and pharmacodynamics
Pharmacokinetics:
Absorption:
- Gastric emptying is delayed for oral preparations - can have gastric upsets
Distribution:
- Total body water and fat are increased resulting in lower concentrations of water soluble and lipid soluble drugs - changing actual volume that the drug can dissolve in
- Protein binding is reduced increasing free drug (active drug) concentrations
Metabolism:
- Increased clearance of drugs which depend on liver enzyme activity- phenytoin, theophylline. - can be an up regulation of liver activity
Elimination:
- Increased renal plasma flow doubling the elimination of renally cleared drugs such as penicillins.
- can up to double elimination rate
Give examples of common drugs that must be used with caution or contra-indicated in pregnancy
Seven A’s + DMARDs:
- ACEi / ARBs
- Anticonvulsants (Phenytoin / carbamazepine / valproate)
- Antibiotics (tetracyclines / trimethoprim / metronidazole)
- Antipsychotics (Lithium)
- Antithyroid (Iodine / propylthiouracil)
- Anticoagulant (warfarin, DOACs)
- Abuse (drugs of) (alcohol / cigs / opiates / bzds) - baby have withdrawal effects
- DMARDS / cytotoxics (methotrexate / cyclophosphamide)
This in an aide memoire it is not a finite list - BNF
List safety precautions that should be taken when prescribing in pregnancy
- All drugs cross the placenta but the amount depends on their physico-chemical properties
- Drugs which are safe in adults can cause serious adverse effects in the fetus- thalidomide
- Few drugs are clearly teratogenic and most that cause problems increase the background risk
- Administration during the first trimester has the greatest risk
- There must always be sound reasons for prescribing a drug during pregnancy
- Avoid prescribing during the first trimester except during the most exceptional circumstances
- If possible choose a drug within a class which has a proven safety record e.g. labetalol rather than an ACE Inhibitor when treating hypertension
Discuss the drugs that are commonly prescribed for pregnancy induced symptoms (nausea etc)
Nausea and vomiting:
- If mild nothing – consider vitamin/electrolyte support
- 1st line: Promethazine, cyclizine (antihistamines), prochlorperazine. Reassess 24 hours
- 2nd line: metoclopamide or ondansetron* (<5 days)
- Methylprednisolone in severe cases**
Asthma:
- Maintain good control with inhalers
- Prednisolone ok if needed
Hypertension:
- Older drugs labetalol / methyldopa / nifedipine (NICE)
Prescribe an antibiotic to all women with a suspected urinary tract infection during pregnancy.Follow local prescribing guidelines that take into account local resistance patterns if these are available. Offer an immediate antibiotic prescriptiontaking account of previous urine culture and susceptibility results, previous antibiotic use (which may have led to resistant bacteria) and local resistance patterns – if unsure discuss with a specialist:
As first choice antibiotic consider prescribing:
- Nitrofurantoin (avoid at term) 100mg modified-release twice a day for 7 days if eGFR ≥45ml/minute.
As second-choice (no improvement in lower UTI symptoms on first-choice taken for at least 48 hours or when first-choice not suitable) consider prescribing:
- Amoxicillin (only if culture results available and susceptible) 500mg three times a day for 7 days.
- Cefalexin 500mg twice a day for 7 days.
- For alternative second-choices discuss with local microbiologist.
Anticoagulation:
- Heparin / LMWHeparins are relatively safe
- Warfarin should be avoided
- DOACs – manufacturers advise avoid
Anticonvulsants:
- Seizure more risk than drug
- Refer to specialist – changing guidance (joint Obstetric/neurology clinics)
what are the cautions when prescribing to a nursing mother
Most drugs are detectable in breast milk though concentration very low – consider timing
Caution with:
- Diazepam
- Alcohol
- Lithium
- Iodine / propylthiouracil
- Opiates
- Tetracyclines
- Corticosteroids
describe the difference in pharmacokinetics with neonates
Absorption:
- Skin- Surface Area/ Body weight is greater so the absorption of topical agents is increased e.g. Steroids.
- Intramuscular absorption is impaired due reduced muscle mass.
- Rectal absorption is relatively efficient e.g. diazepam, theophyllines
Distribution:
- Body water, as a %, is greater than older children so that the loading dose is greater for aminoglycosides, digoxin and aminophylline based on body weight
- Albumin binding is decreased increasing free concentrations of highly bound drugs and increasing the risk of drug/bilirubin interactions
Metabolism (~ 50% of an adult):
- Impaired oxidation increasing the concentration of drugs such as warfarin, diazepam and theophylline.
- Impaired glucuronidation increasing the risk of toxicity to drugs which are metabolised by this mechanism e.g. Chloramphenicol ( grey baby syndrome)
Elimination:
- Glomerular Filtration/tubular secretion and reabsorption are all impaired, requiring dose reduction for renally cleared drugs based on body weight- aminoglycosides, digoxin and penicillins.
- By 6 months renal function is usually normal and standard doses based on body weight can be used.
Rules for Prescribing to neonates
- When possible base doses on estimated body surface area.
- Use a paediatric formulary
- Special adjustments are necessary in neonates especially those who are premature
- Avoid new drugs if possible and remember that most drugs are not licensed for use in children and that information is often poor
- Adverse effects are often different from adults
describe the changes in pharmacokinetics and pharmacodynamics in the elderly
Pharmacokinetics:
Absorption:
- Absorption of orally administered drugs is delayed due to reduced motility and blood flow. This is of little importance.
Distribution:
- Lean body mass/ total body water and albumin binding tend to decrease, increasing the plasma concentrations of tissue bound drugs, water soluble drugs and drugs with high albumin binding
Metabolism is generally slower due to reduced liver mass and blood flow. Therefore-
- Drugs undergoing metabolism act longer
- Enzyme induction is impaired
Elimination by the kidney is reduced so that the risk of drug toxicity is increased for drugs that have a narrow therapeutic index and are mainly eliminated by the kidney
Pharmacodynamics:
- Elderly patients are more sensitive to the effects of centrally acting drugs and may predispose to falls, confusion ,hypothermia and respiratory depression
- Responses to beta blockers are impaired in the elderly and are not as effective as other antihypertensive drugs
- Baroreceptor function is impaired increasing the risk of postural hypotension for drugs which reduce blood pressure
Rules for prescribing in the elderly
- Carefully weigh up benefits and risks before prescribing. Is drug therapy the best option?
- In most cases, start low and go slow in terms of dose, especially if the drug has a narrow therapeutic index.
- Choose the most appropriate formulation.
- Check for possible interactions including
‘’over the counter’’ and herbal medications - Rationalise existing therapy and discontinue those treatments which are not essential. (STOPP criteria)
Describe the impact of renal and liver disease on drug pharmacokinetics and pharmacodynamics
List safety precautions that should be taken when prescribing in renal and liver disease
Give examples of common drugs that must be used with caution or contra-indicated in renal and liver disease
Discuss the drugs that are used to treat liver failure
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Give examples of common drugs that must be used with caution or contra-indicated in renal disease
Diuretics
Antihypertensives – especially:
- ACE inhibitors / ARBs
- Other vasodilators (CCBs, nitrates etc)
NSAIDs
Ciclosporin (DMARD)
Radio contrast media
NSAIDs ACE- I / ARBS Diuretics Lithium Digoxin Gentamicin Methotrexate
describe diuretic drug interactions in relation to renal impairment
Increased electrolyte disturbances when combined with other diuretics
Increased oto and nephrotoxicity when combined with aminoglycoside antibiotics (loop)
Impaired diuresis when combined with NSAIDs
Hypotension when combined with ACE inhibitors and other vasodilator drugs
Likely to cause lithium toxicity when co- prescribed (thiazides)
describe the issue with using lithium in renal impairment
Lithium is excreted by the kidney
It should be avoided in severe renal impairment
Dose often needs reduced during episodes of illness as Lithium renal excretion is reduced
Can block the effect of ADH on the kidney – diabetes insipidus – Why is this a problem?
Long-term use can cause tubulo-interstitial damage
Risk of Lithium toxicity increased if co-prescribed with diuretics / ACE-i / ARBs
describe the issue with using digoxin in renal impairment
Primarily excreted by the kidney and has a narrow therapeutic range
Half-life and therefore time to steady state increases as renal function decreases
Risk of Dig toxicity increased by hypokalaemia so caution with diuretics (common co-prescription in heart failure)
Impact of renal impairment on drug elimination
No change in the loading dose of a drug is required since the volume of distribution is unaltered.
For drugs eliminated by the kidney the dose should be reduced in patients with significant renal impairment.
This can be achieved by individual dose reduction or lengthening the dosage interval.
