Pharmacology

Question 1

What are the functions of the kidney?

Answer 1

Excretion of metabolic waste products
Regulation of extracellular volume
Regulation of ionic concentration
Regulation of physiological pH
The metabolism of a small number of drugs such as insulin and vit D
Excretion of active drugs or their metabolites

Question 2

How does renal disease affect clinical pharmacology?

Answer 2

Rapid build up of

• Active Drug
• Toxic/Active Metabolites

Question 3

List some drugs that have a narrow therapeutic index, and may therefore have a greater impact in renal disease?

Answer 3

Gentamicin (Renal/Otoxicity)
Digoxin (arrhythmia, nausea, death)
Lithium (Renal Toxicity/Death)
Tacromilus (Renal/CNS Toxicity)

Question 4

What in-hospital factors may generate new renal disease/worsen existing disease?

Answer 4

• Patient Illness
• Volume Depleted
• Hypotensive
• Prescribed lots of potentially reno-toxic agents

Question 5

What are the mechanisms of renal filtration that if changed, will automatically change drug pharmacokinetics and pharmacodynamics?

Answer 5

• Glomerular filtration
• Passive tubular reabsorption
• Active tubular secretion

Question 6

How does renal impairment affect glomerular filtration?

Answer 6

-Renal impairment will prolong the half-life of all drugs or metabolites cleared by this route

(All drugs filtered at the glomerulus!)

Question 7

What should you do to drugs in response to decreasing GFR?

Answer 7

\/ GFR-\/ drug clearance
SO…

• REDUCE DOSAGE
• Increase dose interval
• TDM monitor blood levels for drugs like gentamicin, lithium, digoxin, vancomycin

Question 8

In renal disease, what can happen with the direct actions of multiple nephrotoxic drugs?

Answer 8

They can be synergistic

Gentamicin toxicity may be unmasked when used in conjunction with furosemide or lithium

Question 9

What can happen to drug protein binding with renal impairments?

Answer 9

Decreased protein binding - more free drug available.

Question 10

What alterations in pharmacodynamics may happen in renal impairment?

Answer 10

• Increased sensitivity to pharmacological action

- Increased sensitivity to toxicity and ADRs

Question 11

What else should be considered with prescribing in impaired renal function?

Answer 11

Consider -

• Risk/benefit ratio
• Severity of possible side effects
• Severity of toxicity
• The availability of TDM

Question 12

What kind of drugs should ideally be used if patient has renal impairment?

Answer 12

Drugs which

• have high therapeutic index
• are metabolised by the liver with the production of non-toxic metabolites

Question 13

-What is a common problem in renal disease?

Answer 13

Hypertension (causes renal disease, which in turn causes hypertension!)

Question 14

Why should antihypertensives (thiazide-type diuretics, CCBs, ACEIs) be considered more in renal disease?

Answer 14

• They have a lowered GFR, hyperuricaemia … reduced clearance
• More sensitive to the hypotensive actions of antihypertensive agents

Question 15

Why may some drugs induce renal disease?

Answer 15

If the drug is primarily cleared by the kidney, it will be increasingly concentrated as it is moves from the glomerulus and along the renal tubules

The concentrated drug exposes the kidney tissue to far greater drug concentration per surface area

Question 16

What conditions may arise as a result of drug-induced kidney damage?

Answer 16

• AKI (Acute Kidney Injury)
• Chronic Kidney Disease
• Nephrotic Syndrome
• Renal tubular dysfunction with potassium wasting

(-Acute Tubular Necrosis
-Inflammatory Disorders)

Question 17

What conditions are recognised to be adverse renal effects of non-selective NSAIDs?

Answer 17

AKI,
Nephrotic Syndrome,
Hypertension,
Hyperkalaemia,
Papillary necrosis

Question 18

What drugs are commonly responsible for Hospital Acquired Renal Insufficiency?

Answer 18

Aminoglycosides, NSAIDs, Piperacillin/tazobactam, amphotericin B etc

Question 19

How does the most common type of NSAID-induced AKI arise?

Answer 19

From decreased synthesis of renal vasodilator prostaglandins, which can lead to reduced renal blood flow and reduced glomerular filtration.

(Patients become susceptible to acute renal failure if their renal blood flow is already reduced.)

Question 20

What is a condition of allergy in the kidney in response to propionic acid conditions such as ibuprofen?

Answer 20

NSAID-induced acute allergic interstitial nephritis

Associated with nephrotic syndrome

Question 21

What is the mechanism of Aminoglycoside-induced renal injury?

Answer 21

Proximal tubular injury leading to cell necrosis. (Caused by Aminoglycoside antibiotics, used in severe gram-negative sepsis)