Clinical Pharmacology and Renal Disease

Question 1

What is the therapeutic index?

Answer 1

Quantitative measure - relative safety of the drug
Ratio comparison of the does that produces desired effect and which causes toxicity

Question 2

What does it mean if the drug has a narrow therapeutic index?

Answer 2

Prescribe with care
Ratio is very close (largest non-toxic: minimum effective)

Question 3

What is the measurement of clearance?

Answer 3

PK measurement
Volume of plasma from which the drug would be totally removed per unit time

Question 4

What is low clearance equal to?

Answer 4

High systemic exposure

Question 5

What is renal clearance mainly a function of?

Answer 5

Glomerular filtration
Tubular secretion
Reabsorption

Question 6

What is filtration dependant on?

Answer 6

Drug must be free in plasma - Vd and protein binding
Kidney perfusion
Health of kidneys - specifically glomerulus

Question 7

What is total renal clearance?

Answer 7

No secretion/ reabsorption

Question 8

What is used to measure GFR?

Answer 8

Creatine and insulin

Question 9

Explain active renal secretion

Answer 9

Mainly occurs in proximal tubule
Can clear drugs too large to filter
Weak acid/base, nucleoside P-glycoprotein transporters
Saturable

Question 10

What drugs are actively secreted?

Answer 10

B-lactam antibiotics, frusemide, ranitidine, ribavirin and verapamil

Question 11

What is secretion equal to?

Answer 11

When renal clearance more than GFR

Question 12

Describe passive tubular reabsorption

Answer 12

Lipid solubility and conc. gradient
Depends on urine flow rate and pH

Question 13

What can be used to increase clearance of weak acids (aspirin)?

Answer 13

Urinary alkalisation
More alkaline the tubular fluid pH the more likely the drug is ionised so more likely reabsorbed

Question 14

Explain how volume of drug influences plasma conc.

Answer 14

Drugs with high Vd have longer elimination half life
Drug cleared from plasma redistributes from other tissues. Shift from compartments to plasma - plasma conc. maintained

Question 15

What is half life equal to?

Answer 15

0.693 x (Vd/clearance)

Question 16

Describe steady state

Answer 16

Attained approx. after 4-5 half lives
Peaks and throughs
Can take a while to get to steady state
Vd used to calculate loading does

Question 17

When is nephrotoxicity worse in patients?

Answer 17

Polypharmacy
Renally impaired
Age
Renal disease
Other illnesses - volume depleted, dehydrated and hypotensive

Question 18

What do we do about avoiding nephrotoxicity?

Answer 18

Measuring GFR
Recognise other risk factors and drugs with narrow TI
Know which drugs can be used safely with low GFR
Importance of reducing loading/ maintenance doses
Importance of TDM

Question 19

What needs to be considered when prescribing in renal impairment?

Answer 19

Risk/ benefit ratio
Severity of toxicity and possible adverse effects
Availability of TDM

Question 20

What should be done when prescribing in renal impairment?

Answer 20

Use drugs with wide therapeutic index
Consider changing to drug which isn’t renally excreted
Reduce dose and dose frequency

Question 21

Describe acute kidney injury

Answer 21

Clinical syndrome with multiple contributory factors - pre-renal (impacted perfusion), intra-renal or post-renal (structural obstruction)

Question 22

What are common causes of AKI?

Answer 22

Acute tubular necrosis - death of tubular epithelial cells
Glomerulonephritis - collection of conditions causing glomerular damage
Interstitial nephritis - inflammatory

Question 23

How do drugs exert nephrotoxic effects?

Answer 23

Immune drug effects
Combination of nephrotoxic drugs
Insoluble drug in urine
Increase in drug conc. within cells
Intracellular drug accumulation
Drug-uromodulin interaction
Direct drug nephrotoxicity

Question 24

What drugs can cause acute tubular necrosis - AKI?

Answer 24

Aminoglycoside antibiotics, amphotericin B, cisplatin, statins, Colistimethate, foscarnet and radiocontrast agents (rare)

Question 25

What drugs can cause acute interstitial nephritis (latency)?

Answer 25

Penicillin, cephalosporins, cocaine, omeprazole and herbal medicines

Question 26

What biotherapeutics can cause glomerulonephritis?

Answer 26

Thrombotic microangiopathy - cyclosporine, chemotherapeutic drugs and 19-oestrogen containing oral contraceptives

Question 27

What drugs can cause drug-associated obstruction of urine outflow?

Answer 27

Acyclovir, sulphonamides, triamterene, methotrexate and Vitamin C in large doses

Question 28

Describe nephrotic syndrome

Answer 28

Due to glomerular dysfunction and marked by heavy proteinuria
Hypoalbuminemia

Question 29

What are some drugs impacted by nephrotic syndrome?

Answer 29

DMARDs like gold and penicillinamine
NSAIDs, interferon and captopril

Question 30

What can NSAIDs cause?

Answer 30

AKI in 35% of drug induced AKI
Tow forms - haemodynamically mediated and immune mediated

Question 31

When should nephrotoxic drugs be avoided?

Answer 31

Volume depleted with renal disease
And if on other nephrotoxic drugs