Nephro/uro: Drugs And The Kidneys

Front 1

How does kidney disease affect drug absorption?

Back 1

Fluid retention in kidney disease with oedema of the bowel wall can lead to reduced absorption of drugs given orally

↓ due to vomiting

Front 2

How does kidney disease affect drug distribution?

Back 2

Hypoalbunimaemia? → protein binding of drugs may be affected → ↑ drug plasma conc.

Uraemia? → retained substances compete for binding sites with drugs (ask dad) → ↑ drug plasma conc.

Fluid retention? → ↑ vol. of distribution

Front 3

How does kidney disease affect drug elimination and metabolism?

Back 3

Generally if metabolism/elimination is impaired → ↑ drug half-life and drug plasma conc. e.g. ↓ renal insulin metabolism → hypoglycaemia

> Uraemia alters hepatic drug metabolism

> Renal elimination is important for water-soluble drugs - minimally hepatic metabolism

Front 4

Which drugs should be avoided in kidney disease?

Back 4

Drugs containing nitrogen, sodium, potassium and magnesium:

Penicillin and blood transfusions - potassium

Many antacids contain sodium and magnesium

Soluble paracetamol - sodium

Front 5

Describe normal drug elimination in the kidneys.

Back 5

• Most drugs unless highly plasma protein bound freely filtered

• Most drugs esp. weak acids actively secreted into proximal tubule

• Lipid soluble drugs passively reabsorbed by diffusion across tubule - not much excreted in urine

• Weak acids more easily excreted in alkaline urine and vice versa

Front 6

Give examples of drugs where their elimination is significantly affected by loss of normal kidney function.

Back 6

Drugs like vancomycin and gentamicin are almost comletely excreted by the kidney

The kidneys are not involved in rifampicin excretion at all (all hepatic metabolism)

(anuria = 0 kidney function)

Front 7

How do you account for decreased elimination of a drug such as vancomycin?

Back 7

• Modify dose - simply ↓ the dose

• Loading dose - same loading dose but less frequently

• Monitoring - alter dose according to drug concentrations

Front 8

What factors alter kidney function.

Back 8

• Age - very young or old

• Renal disease e.g. diabetes

• Renal damage

Front 9

What formula is used to calculate GFR for prescribing?

Back 9

Cockcroft-Gault formula (based on CrCl)

Front 10

Describe dose adjustment for renal impairment.

Back 10

• ↓ dose → ↓ peak concentration

• ↓ dose interval → ↑ trough concentration

• Both → more uniform serum concentration

Front 11

Describe how drug protein binding is affected by renal impairment.

Back 11

Phenytoin - 90% bound to albumin

Only 10% is “free” and therapeutically active

Hypoalbuninaemia → plasma levels too high → toxicity

Front 12

Give examples of drugs which have an altered sensitivity due to renal impairment.

Back 12

• Increased sensitivity

> CNS depressants e.g. opioids → accumulation of metabolites + ↑ sensitivity → narcosis (reversed by naloxone)

> antihypertensives

• Reduced sensitivity

> diuretics

> urinary antibacterials

Front 13

Give examples of drugs that have reduced elimination in renal impairment.

Back 13

Aminoglycosides - gentamicin, vancomycin

Digoxin

Aciclovir

Front 14

When is dose adjustment needed for renal impairment?

Give examples of drugs that need dose adjustment in renal impairment.

Back 14

• Drug with at least 50% renal clearance

• Drug with low therapeutic index

e.g. digoxin, aminoglycosides, metformin, ACE inhibitors, MTX

Front 15

What factors need to be considered when considering dose adjustment for renal failure?

Back 15

• Extent of renal impairment

• Extent of renal elimination

• Concentration-dependent toxicity

• Therapeutic index

Front 16

Why is the kidney particularly vulnerable to the toxic effects of drugs?

Back 16

Large blood flow

Drugs become concentrated in the renal medulla

and further concentrated in tubular cells

Front 17

Which drugs tend to cause acute tubular necrosis?

Back 17

Aminoglycosides

Amphotericin B

Front 18

Which drugs tend to cause glomerulonephropathies?

Back 18

Gold salts

NSAIDs

Front 19

Which drugs tend to cause interstitial nephritis?

Back 19

Usually hypersensitivity reaction in acute interstitial nephritis

Antibiotics derived from penicillin

Allopurinol

Front 20

How do NSAIDs alter kidney physiology?

Back 20

Blood flow through kidney arterioles is maintained by vasodilator prostaglandins - NSAIDs inhibits COX → ↓ prostaglandins → ↓ renal blood flow and GFR

Front 21

What are adverse effects of NSAIDs on the kidney?

Back 21

Chronic use causes:

> AKI due to ischaemia - don't give to CKD patients

> Sodium retention (in body fluids - not hypernatraemia) - worsens oedema and HTN

Front 22

When can ACE inhibitors cause renal impairment and why does this happen?

Back 22

• Bilateral renal artery stenosis

• Co-administered with NSAIDs or large volume diuretics

• When dehydrated or septic

Because of their mechanism of action (constriction of the efferent arteriole → maintains intraglomerular pressure)

Front 23

Describe the mechanism of action of the major types of diuretics.

Back 23

Loop diuretics block NKCC in TAL

Thiazide diuretics block NCC in cortical diluting segment of DT

K⁺ sparing diuretics interfere with aldosterone action (dependent on type) in DT and CD

Front 24

Give examples of each of the major types of diuretic.

Back 24

Loop - Furosemide, Bumetanide

Thiazide - Bendrofluazide

K⁺ sparing - Spironolactone, Amiloride

Front 25

Describe the different pharmacologic properties of the major diuretic classes.

Back 25

Front 26

Describe the differing mechanisms of action of Spironolactone and Amiloride.

Back 26

• Spironolactone - mineralocorticoid receptor antagonist

• Amiloride – blocks ENaC in CD

Front 27

What are the general side effects of thiazide and loop diuretics?

Back 27

1) NON-SPECIFIC

> GI upset (nausea, vomiting)

> hypersensitivity reactions - skin rash, thrombocytopenia

2) METABOLIC EFFECTS

> hypokalaemia, hyponatraemia

> hypovolaemia → hypotension

> urate retention → gout (rare)

> exacerbate glucose intolerance

Front 28

What problems can you get as a result of hyperkalaemia and hypokalaemia?

Back 28

Both:

Cardiac arrythmias

Muscle weakness

Front 29

What are the specific adverse effects of loop diuretics?

Back 29

Ototoxicity (high doses) → deafness, NKCC found in ear

Metabolic alkalosis

Front 30

Describe the adverse effects of lithium (antipsychotic) on the kidney.

Back 30

Long-term therapy - reabsorbed by cells in CD and inhibits the action of ADH → can cause nephrogenic diabetes insipidus

Front 31

Describe how trimethoprim (antibiotic) affects kidney function.

Back 31

causes ↑ serum creatinine which is interpreted as ↓ in eGFR - not a true ↓ in GFR