Renal AE drugs

Question 1

What are 4 factors affecting renal excretion?

Answer 1

1) Renal perfusion
2) Urinary pH
3) Age
4) Disease

Question 2

How does impaired renal clearance affect T1/2 of drugs?

Answer 2

Increases half-life → drug toxicity

Question 3

How are drug doses adjusted when needed?

Answer 3

1) Same dose, prolong dosing intervals (eg. gentamicin)

2) ↓ dose, same dosing interval (eg. Digoxin)

Question 4

What is the biochemical criteria for dose adjustment for drugs that are primarily excreted renally?

Answer 4

Creatinine clearance < 60ml/min

30<CrCl<60 → Minor adjustment
15<CrCl → Major adjustment
All need to do therapeutic drug monitoring (narrow TI drugs)

Question 5

What are some examples of drugs that require dose adjustment?

Answer 5

ABs: eg. Aminoglycosides, Vanco, Ceftazidime, Cipro, Carbapenems, Sulfamethoxazole, Piperacillin

Anti-fungals: Fluconazole, Itraconazole

Anti-virals: A/Famci/Valacyclovir

Hypoglycemics: eg. Metformin, Insulin

Cardiac: Digoxin, ß-blockers

Psychotropics/Anti-convulsant: Li, SSRIs, Gabapentin, Levetiracetam, Topiramate, Vigabatrin

NSAIDs/Opioids: Aspirin, Paracetamol, Coxib, Morphine, Codeine, Pethidine

Drugs for Gout: Allopurinol, Colchicine

Anti-coagulants: LMW Heparin

Diuretics: K-sparing,Thiazide

Others: Immunosuppressants eg. cyclosporin, Anticancer eg. cisplatin

Question 6

True or False: Drugs that are excreted renally and biliary do not need dose reduction when prescribed to px with renal impairment.

Answer 6

True
eg. Ceftriaxone, Doxycycline

Question 7

What are 4 ways that Drug-Induced Kidney Disease can present?

Answer 7

1) AKI
2) Glomerular disorder
3) Tubular disorder
4) Nephrolithiasis/Crystalluria

Question 8

What are the components of the Bradford-Hill causal criteria?

Answer 8

1) Drug exposure >24hr

2) Causal drug must be plausible based on known mechanism, metabolism, immunogenicity, etc.

3) Complete data for drug exposure (to account for other risks/other nephrotoxic agents)

4) Strength of rs btwn drug and AE must be based on duration, severity, etc.

Question 9

KDIGOs (Kidney Disease Improving Global Outcomes) for DIKD?

Answer 9

1-7days: Acute
8-90days: Sub-acute
>90: Chronic

Question 10

What are 4 common mechanisms in DIKD/nephrotoxicity?

Answer 10

1) GFR alteration/hemodynamics @ glomerulus (eg. ACEI, ARB, Cyclosporin, NSAIDs, Tacrolimus)

2) Tubular cell toxicity
- via free radicals, mitochondrial dmg, transport system dmg
(eg. Aminoglycosides, Ampho B, Adefovir, Cisplatin, Foscarnet)

3) Interstitial nephritis
- Acute: inflammation by NSAIDS, Rifampicin
- Chronic by anticancer, Li, Calcineurin inhibitor, Analgesics

4) Crystal Nephropathy
(eg. Acyclovir, ABs)

Question 11

What are 6 example classes of nephrotoxic drugs?

Answer 11

1) Antimicrobials
2) Analgesics
3) Chemotherapeutic agents
4) Immunosuppressants
5) Diagnostic agents
6) Environmental intoxicants
7) Others (eg. ACEI, ARBs, SGLT-2, Methoxyflurance, Sucrose, Statins, etc.)

Question 12

What are 5 medication-specific risk factors for nephrolithiasis?

Answer 12

1) High dose/chronic drug use
2) High renal excretion of drugs/metabolites
3) Poor aqueous solubility of drugs/metabolites
4) Short T1/2 (w concomitant peaks of high urinary conc.)
5) Drug interactions modifying PK/metabolism
6) Size and shape of drug crystals

Question 13

What are the 2 subtypes of drug-induced calculi?

Answer 13

1) Drug-containing
2) Metabolically induced

Question 14

What is the different between drug-containing and metabolically-induced calculi?

Answer 14

Drug-induced: drugs are primary component
Metabolically-induced: drugs affect metabolism → facilitate stone formation (not directly part of stones)

Drug-induced: must discontinue
Metabolically-induced: can correct metabolic abnormally w/o discontinuation

Question 15

What are 3 types of renal calculi in order of descending frequency?

Answer 15

1) Calcium oxalate/phosphate
2) Struvite
3) Uric acid/cystine