Clinical pharmacology in renal disease

Question 1

What 2 things will there be a rapid build up of if renal function is impaired?

Answer 1

active drug

toxic or active metabolites

Question 2

When is a rapid build up of drug not a problem? give an example

Answer 2

high therapeutic index or low toxicity

benzylpenicillin

Question 3

What happens if there is a build up of a drug with low therapeutic index?

Answer 3

toxicity and death

Question 4

Toxicity associated problems with

a) gentamicin
b) digoxin
c) lithium
d) Tacrolimus

Answer 4

a - renal or ototoxicity
b - arrhythmia, nausea, death
c - renal toxicity and death
d - tacrolimus

Question 5

Pharmacokinetics

Answer 5

what they body does to the drug

Question 6

Pharmacodynamics

Answer 6

What the drug does to the body

Question 7

What factors increase likelihood to generate new renal failure or worsen pre-existing with some nephrotoxic medications?

Answer 7

old, volume deplete, multiple medications, hypotensive

Question 8

What will renal impairment do to the half-life of a drug?

Answer 8

prolong it

Question 9

Due to prolonging half life of drugs due to renal impairment what kind of therapeutic index drugs are we careful of?

Answer 9

low

Question 10

Pharmacokinetic effects of renal failure

Answer 10

reduce GFR –> accumulation

decreased protein binding

Question 11

3 things we need to do due to decreased protein binding in renal impairment

Answer 11

decrease dose
increase dose interval
TDM monitor blood levels for toxic drugs

Question 12

How can renal disease alter the actions of drugs on the tissues?

Answer 12

Blood brain barrier more permeable - more sensitive to opioids, tranquilisers and sedatives
circulatory volume decreased - sensitive to anti-hypertensives
Increased tendency to bleed - beware warfarin or NSAIDs

Question 13

Toxic effects of drugs are synergistic or antagonistic?

Answer 13

synergistic eg unmasked by each other - gentamicin +furosemide/lithium

Question 14

What do we need to know in terms of drugs and renal impairment?

Answer 14

what drugs are safe to use in reduced eGFR

narrow therapeutic index

Question 15

If a patient has renal failure suggest the 2 most important things when deciding on what drug to use

Answer 15

metabolised by liver –> non toxic metabolites

high therapeutic index

Question 16

Is hypertension common in renal disease?

Answer 16

yes - they both cause eachother

Question 17

Why are patients with renal disease more sensitive to hypertensive agents?

Answer 17

low GFR - uricaemia

volume deplete

Question 18

Advantage and Problem with ACEI used for hypertension in renal disease

Answer 18

metabolised by liver

nephrotoxic

Question 19

Problem with using vasodilators in hypertension in renal disease

Answer 19

profound hypotension - salt and water retention

Question 20

Problem with using thiazide’s in hypertension in renal disease

Answer 20

precipitate gout - high urea

Question 21

Problem with drugs metabolised solely by kidney in renal disease

Answer 21

concentrated as passed along tubule so exposing kidney to greater concentrations

Question 22

How does salt and water abnormalities in renal disease present?

Answer 22

oedema and dehydration

Question 23

List effects of drug induced renal disease

Answer 23

AKI, CKD, nephrotic syndrome, tubular dysfunction with potassium wasting

Question 24

Describe AKI

Answer 24

sudden deterioration in renal function
rapid increase in creatinine and decrease in urine
dehydrated

Question 25

3 prerenal causes of AKI and drugs which cause this

Answer 25

``` water and electrolyte abnormalities - diuretics, laxatives, lithium, NSAIDs increased catabolism - steroids vascular occlusion - OCP, oestrogen ```

Question 26

3 causes of renal AKI

Answer 26

acute tubular necrosis acute interstitial nephritis thrombotic microangiopathy

Question 27

Post renal causes of AKI

Answer 27

crystal formation in ureters or tubules | RPF

Question 28

Drugs causing crystal formation

Answer 28

acyclovir | vitamin c in high doses

Question 29

Drugs causing ATN

Answer 29

aminoglycoside antibiotics radiocontrast statin & immunosuppressant

Question 30

Drugs causing AIN and why?

Answer 30

NSAIDS, omeprazole, penicillins, cocaine, Chinese herbs | long or short latency period of drugs used on a daily basis

Question 31

3 things thrombotic microangiopathy can cause

Answer 31

severe AKI thrombi in microvasculature of many organs afferent arteriolar and glomerular thrombosis

Question 32

Drugs causing thrombotic microangiopathy

Answer 32

oestrogen OCP, cocaine, tacrolimus, cyclosporine, clopidogrel

Question 33

What is nephrotic syndrome due to?

Answer 33

glomerular dysfunction and heavy proteinuria

Question 34

Drugs implicated in nephrotic syndrome

Answer 34

NSAIDS and gold injections

Question 35

Renal syndromes caused by NSAIDs

Answer 35

``` AKI hyperkalaemia nephrotic syndrome hypertension papillary necrosis ```

Question 36

Explain the cause of NSAID induced prerenal AKI

Answer 36

decreased prostaglandin synthesis which vasodilate | reduced blood flow and GFR

Question 37

Why do aminoglycosides cause renal injury?

Answer 37

PCT injury and cell necrosis leading to AKI

Question 38

When is aminoglycosides used?

Answer 38

severe gram negative sepsis

Question 39

Main cause of acute allergic interstitial nephritis

Answer 39

propanionic derivatives eg ibuprofen