Lecture 40: Drugs and the Kidney Flashcards
outline the pharmacokinetics of penicillins
- oral absorption variable
- widely distributed in body fluids
- mainly renal excretion (tubular secretion)
- short plasma half life
how might penicillin dose be adjusted for Px w/ renal impairment
- reduce dose delivery by extending period between each dose
- still give same amount w/ each dose
- (can also reduce dose amount but should check guidelines)
give an example of a drug that may be less effective in renal impairment and how this issue is resolved
- thiazide diuretics less effective
- can use an alternative e.g. loop diuretics (cautiously)
give examples of drugs that can have more adverse effects in renal impairment
^ effect of drug:
- opioids/ sedatives
^ toxicity:
- K+ sparing diuretics (hyperkalaemia)
- metformin (lactic acidosis)
- digoxin (arrhythmias/nausea)
- nitrofurantoin (neuropathy)
- tetracyclines (^ prot breakdown)
describe pre renal impairment in AKI and any pharmacological caution recommended in this case
pre renal impairment:
- dec. renal perfusion/ altered auto regulation, esp if sudden changes in volume state
caution:
- should discontinue potentially nephrotoxic drugs
- +/- support BP
give examples of drugs that can cause pre renal impairment
- diuretics
- antihypertensives
- NSAIDs
- ciclosporin (DMARD)
- radio contrast media
give examples of drugs that can have an intrinsic effect on renal impairment
- aminoglycosides (gentamicin)
- amphotericin B
- other antimicrobials (quinolone, macrolides)
- anti platelets (clopidogrel)
- anticonvulsants (carbamazepine, phenytoin)
- DMARDs (ciclosporin, gold, penicillamine)
- Lithium
- NSAIDs / COX 2 inhibitors
- radio contrast media
give examples of drugs that can cause post renal impairment
crystals/stones:
- aciclovir
- methotrexate
retroperitoneal fibrosis:
- ergot derivatives
- methyldopa/hydralazine/atenolol
what are the main drugs to look out for in Px w/ AKI
- NSAIDs
- ACEi/ARBs
- diuretics
- lithium
- digoxin
- gentamicin
- methotrexate
DAMN = diuretics, ACEi/ARBs, methotrexate, NSAIDs
describe how NSAIDs -vely affect kidney
- all cause nephrotoxicity
- can cause:
- -> acute tubular necrosis
- -> interstitial nephritis
- -> glomerulonephritis
- -> renal papillary necrosis
(must ask about over the counter use)
describe how ACEi/ARBs affect kidney
- complex relationship w/ renal impairment
- can be used to control BP and reduce intraglomerular pressure, reducing proteinuria
- may be assc. w/ deterioration of renal function and often need to be withheld when Px is acutely unwell
- contraindicated in renal artery stenosis
describe diuretic drug interactions that affect kidney function
- ^ electrolyte disturbances when combined w/ other diuretics
- (loop) ^ oto and nephrotoxicity when combined w/ amino glycoside antibiotics
- impaired renal diuresis when combined w/ NSAIDs
- hypotension when combined w/ ACEi and other vasodilators
- (thiazides) likely to cause lithium toxicity when co-prescribed
describe how lithium interacts w/ the kidney and any cautions
- excreted by kidney
- should be avoided in severe renal impairment
- dose often needs reduced in episodes of illness as renal excretion of lithium reduced
- can block effect of ADH on kidney –> diabetes insipidus
- long term use can cause tubule-interstitial damage
- risk of lithium toxicity ^ if co prescribed with diuretics/ACEi/ARBs
describe how digoxin interacts w/ kidney and any cautions
- primary excreted by kidney and has narrow therapeutic range
- half life and therefore time to steady state ^ as renal function dec.
- risk of dig toxicity ^ by hypokalaemia so caution w/ diuretics (common co prescription in HF)
describe how gentamicin interacts w/ kidney
- highly polar therefore IV admin
- variable penetration into body fluids
- eliminated by kidney T1/2 2-3hrs
- elimination mirrors eGFR
- nephrotoxic drug
- must reduce dose and freq. in renal impairment to prevent dose dependent side effects
what is important when adjusting dose of gentamicin in renal impairment
need to measure trough levels and U+E more often
what is important to remember when considering drug induced AKI
- injury usually reversible if detected early
- looking at serum creatinine and eGFR along w/ urinary sediment enables early detection
- stop potentially nephrotoxic drugs
- ensure appropriate supportive treatment e.g. IV fluids
describe the changes that should be made when prescribing a drug in renal impairment
- no change in loading dose of drug is required since volume of distribution is unaltered
- for drugs eliminated by kidney dose should be reduced in Px w/ significant renal impairment
- can be achieved by individual dose reduction or lengthening dose interval
- maintenance dose reduction is required for drugs which are primarily eliminated by kidney and have a narrow therapeutic index
- adjustment of dosage is usually achieved using eGFR (CrCl) or serum creatinine (less accurate)
what are the principles for prescribing drugs in renal failure
- for many drugs w/ only minor or no dose related side effects a simple scheme for dose reduction is sufficient
- reduce the dose of drugs eliminated by kidney as time taken to reach steady state will be increased
- avoid drugs which are nephrotoxic
- adjustment of maintenance dose should be made using GFR and where appropriate plasma drug levels
outline some treatment options in severe CKD
- phosphate binding agents –> calcium carbonate taken w/ meals
- in 2nd hyperPTH/ renal osteodystrophy –> 1,25-OH vit D (calcitrol) daily tablet
- if symptomatic anaemia –> specialist may use erythropoietins
- dialysis/ renal replacement therapy
describe the effect of dialysis on drug dosage and clearance
- solutes diffuse from blood into dialysis fluid
- drugs that are small molecules w/ low protein binding will be removed readily
- clearance of drugs may necessitate supplementary doses of drug e.g.
- -> theophylline
- -> metronidazole
- -> gentamicin/tobramicin
- -> antivirals
when else might dialysis be used other than severe CKD
certain acute poisoning (dictated by how readily drug molecule can diffuse across) e.g.
- aspirin
- lithium
- ethylene glycol
- methanol
- sodium valproate
