Clinical Pharmacology in Renal Disease

Question 1

If renal function is impaired, there is a rapid build up of what?

Answer 1

Active drug

Toxins or active metabolites

Question 2

When is there not a problem of a drug or metabolites in renal impairment?

Answer 2

If the drug or metabolites have a high therapeutic index or low toxicity

Question 3

Example of a drug which has a high therapeutic index / low toxicity

Answer 3

Benzylpenicillin

Question 4

What toxicities can gentamicin cause?

Answer 4

Nephrotoxicity

Ototoxicity

Question 5

What can a build up of digoxin cause?

Answer 5

Arrythmia
Nausea
Death

Question 6

What can a build up of lithium cause?

Answer 6

Toxicity

Death

Question 7

What can a build up of tacrolimus cause?

Answer 7

Renal toxicity

CNS toxicity

Question 8

Mechanisms of renal excretion

Answer 8

Glomerular filtration
Passive tubular reabsorption
Active tubular secretion

Question 9

Where are all drugs and their metabolites filtered?

Answer 9

At the glomerulus

Question 10

What does a reduction in GFR lead to in respect to drugs?

Answer 10

Reduces clearance of drugs by the kidney resulting in accumulation
Protein binding also reduced

Question 11

What must be done in respect to drugs when there is a reduction in GFR?

Answer 11

Reduce doseage
Increase dose interval
TDM monitor blood levels for toxic drugs like gentamicin, lithium, digoxin and vancomycin

Question 12

What is the pharmacodynamic effect of renal disease on drugs?

Answer 12

Alters the actions of drugs on the tissues

Question 13

How does renal disease alter the action of drugs on the tissues?

Answer 13

The BBB becomes more permeable and the brain becomes more sensitive to tranquilisers, sedatives and opitates
Circulatory volume may be reduced making the patient more sensitive to antihypertensive agents, ACEIS or ARBs
Increased tendency to bleed to beware of warfarin or NSAIDs

Question 14

In renal disease, the direct nephrotoxic actions of drugs are synergistic. What does this mean?

Answer 14

For example gentamicin toxicity may be unmasked when used in conjunction with furosemide or lithium

Question 15

Ideally, if a patient suffers from renal impairment, we should use drugs that what?

Answer 15

Have a high therapeutic index

Are metabolised by the liver with the production of non toxic metabolites

Question 16

Are ACEIs potentially nephrotoxic?

Answer 16

Yes

Question 17

What can ACEIs produce in the kidneys?

Answer 17

Severe acute renal dysfunction

Question 18

What can direct vasodilators do to the kidneys?

Answer 18

Profound hypotenson

Salt and water retention

Question 19

What may thiazides and thiazide type diuretics precipitate?

Answer 19

Gout

Question 20

What are the common forms that renal involvement usually takes?

Answer 20

Salt and water abnormalities
- dehydration 
- oedema
Acute renal failure
- acute tubular necrosis
- acute intersitial nephritis 
Chronic renal failure

Question 21

Drug induced renal toxicity can cause what four major syndromes?

Answer 21

Acute renal failure
Nephrotic syndrome
Renal tubular dysfunction with potassium wasting
Chronic renal failure

Question 22

Definition of acute renal failure

Answer 22

A sudden deterioration in renal function which results in a rapid rise in creatinine

Question 23

Types of acute renal failure

Answer 23

Prerenal
Renal / intrinsic
Post renal / obstructive

Question 24

Who often gets acute renal failure?

Answer 24

Elderly patients who are sick, with a poor fluid intake, who are on multiple medications and who are not being monitored aggressively

Question 25

What drugs cause drug induced pre-renal disease and how?

Answer 25

``` Water and electrolyte abnormalities - diuretics - laxatives - lithium - NSAIDs Increased catabolism - steroids - tetracyclines Vascular occlusion - oestrogens / OCP ```

Question 26

What are the 3 types of intrinsic acute renal failure?

Answer 26

Acute tubular necrosis Acute interstitial nephritis Thrombotic microangiopathy

Question 27

Drug causes of acute tubular necrosis

Answer 27

Aminoglycosides Amphotericin B Cisplatin / radiocontrast agents Statins in combination with immunosuppresive agents e.g. cyclosporin

Question 28

Drug causes of acute interstitial nephritis

Answer 28

``` Penicillins Cephalosporins Cocaine Sulfonamides NSAIDs diuretics Lithium Ranitidine Omeprazole Captopril Phenytoin Valproic acid Amphotericin B Streptokinase 5-aminosalicylates Allopurinol Rifampicin Chinese herbs ```

Question 29

What can thrombotic microangiopathy cause?

Answer 29

Severe acute renal failure | - arteriolar and glomerular thrombosis

Question 30

Drug causes of thrombotic microangiopathy

Answer 30

``` Cyclosporin Tacrolimus Chemotherapeutic agents Clopidogrel Ticlopidine 19-oestrogen containing oral contraceptives quinine Cocaine ```

Question 31

Drugs implicated in crystal formation of obstructive renal failure

Answer 31

``` Acyclovir Sulfonamides Trimaterene Methotrexate Vit C in large doses Guaifenesin ```

Question 32

What is nephrotic syndrome marked by?

Answer 32

Heavy proteinuria

Question 33

Drugs causing nephrotic syndrome

Answer 33

``` Gold NSAIDs Penicillamine Interferon Captopril ```

Question 34

What can NSAIDs result in in kidneys?

Answer 34

``` Acute renal failure Nephrotic syndrome HTN Hyperkalaemia Papillary necrosis ```

Question 35

What % of hospital admissions are due to AKI that are drug related?

Answer 35

20%

Question 36

What % of patients prescribed ibruprofen does acute renal failure occur in?

Answer 36

18%

Question 37

What is the most common drug responsible for acquired renal insufficiency in the hospital?

Answer 37

Aminoglycosides

Question 38

Mechanism of NSAID induced pre renal acute renal failure

Answer 38

Decreased synthesis of renal vasodilator prostaglandins | Leads to reduced renal blood flow and reduced GF

Question 39

Mechanism of NSAID induced acute allergic interstitial nephritis

Answer 39

idiosyncratic reaction | Nephrotic syndrome in 90% cases

Question 40

Mechanism of aminoglycoside induced renal injury

Answer 40

Proximal tubular injury leading to cell necrosis

Question 41

How is the prevention of contrast induced nephropathy done?

Answer 41

IV 0.9% NaCl pre and post procedure