Drugs and the kidneys

Question 1

What is the main organ responsible for eliminating drugs from the body?

Answer 1

The kidney

The kidney is the most important organ for drug excretion.

Question 2

What is the primary mechanism for renal excretion of drugs?

Answer 2

Tubular secretion

Tubular secretion occurs mainly in the proximal tubule (PT).

Question 3

What types of drugs are primarily excreted by the kidney?

Answer 3

Weak acids or bases

The degree of ionization depends on drug pKa and pH of the environment.

Question 4

What is the role of polar drugs or metabolites in renal excretion?

Answer 4

Excreted via specialized transporters

Mainly through the proximal tubule (PT).

Question 5

Fill in the blank: Diuretics increase urine output, also known as _______.

Answer 5

diuresis

Question 6

What are the clinical uses of diuretic drugs?

Answer 6

Acute pulmonary oedema, heart failure, hypertension

Diuretics reduce extracellular fluid (ECF) volume.

Question 7

List the classes of diuretic drugs.

Answer 7

• Carbonic anhydrase inhibitors
• Loop diuretics
• Thiazide diuretics
• K+ sparing diuretics
• Osmotic diuretics

Question 8

Where do carbonic anhydrase inhibitors act?

Answer 8

Proximal tubule

They inhibit carbonic anhydrase.

Question 9

What is the mechanism of action of loop diuretics?

Answer 9

Blocks NaK2Cl cotransporter

Most powerful class of diuretics.

Question 10

What side effect is commonly associated with loop diuretics?

Answer 10

Hypokalemia

Significant loss of potassium.

Question 11

Where do thiazide diuretics exert their effect?

Answer 11

Distal tubule

They block NaCl cotransporter.

Question 12

What is a key side effect of thiazide diuretics?

Answer 12

Hypokalemia and hypercalcemia

Increased calcium due to Na/Ca exchanger.

Question 13

What is the role of K+ sparing diuretics?

Answer 13

Counter hypokalemia from other diuretics

They retain potassium.

Question 14

What is an example of an osmotic diuretic?

Answer 14

Mannitol

Used to treat cerebral oedema.

Question 15

How do osmotic diuretics create an osmotic gradient?

Answer 15

Withdrawal of water from cerebrospinal fluid to plasma

They do not cross the blood-brain barrier.

Question 16

What effect do SGLT-2 inhibitors have on glucose reabsorption?

Answer 16

Impair glucose reabsorption

They lower plasma glucose concentration.

Question 17

True or False: Thiazide diuretics are no longer first-line treatment for hypertension in the NHS.

Answer 17

True

They may be used as second or third-line treatment.

Question 18

What is the mechanism of action of K+ sparing diuretics like Amiloride?

Answer 18

Blocks ENaC

They act at the end of the distal convoluted tubule (DCT) and collecting duct.

Question 19

What is the central role of the liver and kidney in drug excretion

Answer 19

The kidney is the most important organ for eliminating drugs from body
Most are metabolised by the liver to an inactive compound that can be
excreted by kidney

• Polar drugs or metabolites (water soluble, partially ionized) are
  excreted via specialized transporters (mainly PT)

Question 20

explain tubular secretion of drugs

Answer 20

-occurs mainly in PT
-most drugs are weakl acids or bases
penicillin is weak acid and morphine is a weak base

Question 21

explain diruetics

Answer 21

-increase urine output
-may increase electrolyte excretion
-very important drugs
-acute pulmonary oedma, heart failure
-hypertension

Question 22

explain osmotic diuretics

Answer 22

-freely filtered but not reabsorbed
-dilution of DT fluid impaired
-decreased gradient for water absorption
-commonly used to treat cerebral oedema
-does not cross blood-brain barrier
-creates osmotic gradient for withdrawal of water from cerebrospinal fluid

Question 23

explain carbonic anhydrase inhibitors

Answer 23

-Mild diuretics
-e.g. acetazolamide
-inhibit carbonic anhydrase activity
-net result is decreased NaHCO3 reabsoprtion

Question 24

explain loop diuretics

Answer 24

-e.g. frusemide
-powerful diuretics
-inhibit Na/K/2Cl cotransporter in thick ascending limb
-impedes concentration of interstitial fluid
-reduced osmotic drive

Question 25

explain thiazide diuretics

Answer 25

-moderately powerful -inhibit Na/Cl cotransporter in distal tubule -impedes dilution of tubular fluid -reduced osmotic drive for ADH-mediated water reabsorption

Question 26

explain K sparing diuretics

Answer 26

-weak diuretic action -important as they cause K retention--> countering the powerful electrolyte secretions of loop diuretics -act at the end of DCT and colecting duct -Amiloride -blocks ENaC -spironolactone -aldosterone antagonist -used to treat volume overload in heart failure

Question 27

explain diuretic uses

Answer 27

-thiazide -has been first line hypertension treatment for decads -no longer first line in NHS (2nd or 3rd) -low doses effective for hypertension -higher doses may be used for vol overload -severe volume overload

Question 28

explain recent drugs with mild diuretic action

Answer 28

1) Sodium glucose cotransporters: -secondary active transport -SGLT1: glucose absoprtion from the gut -SGLT1, SGLT2: glucose reabsoprtion from kidney (PCT) SGLT-2 inhibitors used to treat hyperglycaemia -impair glucose reabsorption -more remains in tubular fluid, lowers plasma concentration -mild osmotic diuresis