Drugs and the kidneys Flashcards
What is the relation between half life of a drug and clearance rate?
- half life and clearance rate inversely proportional
- clearance rate lowered if renal impairment
What is the most common drug given in patients with sepsis?
Tazocin (piperacillin/tazobactam)
How does drug dosing change in patients with renal impairment?
Either:
- Give less frequently
- Or give lower dose
- Either way as half life of the drug will be extended due to impairment reduces overdosing
Which drugs are less effective in renal impairment due to effects on pharmacodynamics?
- Thiazide diuretics give loop instead
- Nitrofurantoin (antibiotic used for UTIs) give trimethoprim instead
Which drugs will produce more adverse effects in renal impairment?
- opioids/sedatives (will have an increased effect)
- Digoxin (arrhythmias/nausea)
- K+ sparing diuretics (Hyperkalemia)
- Nitrofurantoin (neuropathy)
- Tetracyclines (protein breakdown)
- Metformin (lactic acidosis)
What is the most common form of acute kidney injury?
- Pre-renal impairment
- change in BF going into the kidney
What are the types of AKI?
- decreased renal perfusion
- Altered auto regulation
What are the causes of acute kidney injury?
- vomiting/diarrhoea
- bleeding
- cardiac failure
- cirrhosis
What are the most important first steps in treating AKI?
- Discontinue nephrotoxic drugs
- Manage BP
- Supportive treatment usually IV fluids
Why does cirrhosis cause AKI?
- liver failure leads to low albumin
- can’t make proteins as so get fluid loss into abdominal cavity and peripheries (peripheral oedema)
- loss of volume from systemic system
What drugs can cause AKI by reducing BF?
- Diuretics (due to loss of fluid)
- antihypertensives e.g. ACE inhibitors, ARBs, (due to blocking of RAAS) CCBs and nitrates (exacerbate any problems of low BP)
- NSAIDs (cause peripheral oedema)
- Ciclosporin
- Radio contrast media (used in CAT/CT scan)
Why does fluid loss cause AKI?
Fluid loss means reduction in blood volume which means reduction in BP and so worse BF to kidney
Drugs which cause intrinisic renal impairment?
- Aminoglycosides
- Amphotericin B
- other Antimicrobials
- Anti-platelets
- Anti-convulsants
- DMARDs
- Lithium
- NSAIDs/COX-2 inhibitors
- Radio contrast media
Drugs causing post - renal impairment (not very important as usually caused by larger blockage)
- Aciclovir and methotrexate (Cause crystals/stones)
- Ergot derivaties and methyldopa/hydralazine/atenolol (Cause Retroperitoneal fibrosis)
What are the most important drugs to look out for in patients with AKI (stop use of these drug)
(DAMN drugs) Diuretics Digoxin ACE-I/ARBs Methotrexate NSAIDs Lithium Gentamicin
Why do NSAIDS need to be stopped in patients with AKI?
- Nephrotoxic
- mainly due to interstitial nephritis and can also cause necrosis of tubules and glomerular nephritis
When are ACE-I/ARBs useful in patients with kidney damage?
- Reduces hyperfiltration by controlling BP of afferent arteriole
- usually occurs in diabetes
- means reduction in proteinuria
When do ACE-I/ARBs cause further kidney damage to patients?
- patients with AKI
- BF already reduced so hypo filtration
- Drugs will worsen this as block RAAS
- RAAS is designed to increase BF/BP
- always contraindicated in Renal artery stenosis
- if on ACE/ARB and start feeling unwell stop drug and wait a few days
Why are diuretics contraindicated in patients with AKI?
Will further reduce blood volume and so blood flow to the kidney
What are the diuretic drug interactions?
- Diuretic + diuretic can increase electrolyte disturbances
- amino glycoside antibiotics further increase nephrotoxicity
- impaired diuresis with NSAIDs
- Cause hypotension when with ACE-I and the vasodilators
- with Lithium cause lithium toxicity when co-prescribed thiazides
Why is lithium avoided in patients with AKI?
- excreted by the kidneys
- dose needs reducing when ill as renal excretion of lithium reduced
- over time lithium will block effects of ADH (can diabetes insipidus where difficulty concentrating urine as excrete too much salt)
- get tubule-interstitial damage
Why is Digoxin contraindicate din patients with AKI?
- completely dependant on kidneys for clearance and very small therapeutic range
- so changes in kidney function will have massive effects
- risk of toxicity also increased by hypokalemia so caution with diuretics
Why is gentamicin contraindicated?
- elimination completely dependant on kidney
- nephrotoxic also so accumulation when not eliminated will cause further damage
- dose and frequency reduced in patients with renal impairment
- When dosing very important to keep checking trough levels and U+E
Is AKI reversible?
Yes if detected early
What tests should be done to assess AKI?
- Serum creatinine
- eGFR
- Urinary sediment
What are the stages of CKD?
1) >90
2) 80-89
3A) 45-59
3B) 30-44
4) 15-29
5) <15 Kidney failure
When would you qualify for kidney transplant or dialysis?
Stage 4
Stage 5 kidney no longer viable would need dialysis or transplant
How does renal impairment impact drug elimination?
- No affect on loading dose as doesn’t change volume of distribution
- Maintenance dose will need to be reduced by reducing individual dose or lengthening dose interval
- adjust dose based on eGFR levels and serum creatinine
What drugs will need to be given in patients with stage 5 CKD?
- phosphate binding agents (calcium carbonate with meals)
- Get secondary hyperPTH / renal osteodystrophy so need to take calcitriol daily
- symptomatic anaemia give erythropoetin
- Put on dialysis
What is dialysis?
- blood taken from systemic system out through artificial filtration system
- filtration system will remove small molecules with low protein binding more readily and clear drugs
- drug dose may therefore need to be increased
What drugs will need to have increased doses in patients on dialysis?
- Theophylline
- Metronidazole
- Gentamicin
- Anti-virals
For which drugs can dialysis be used to treat acute poisoning?
- Aspirin
- Lithium
- ethylene glycol
- Methanol
- Sodium valproate
What equation is used to calculate how quickly the drug will be eliminated?
5 x half life
