Pharmacology

Question 1

Why does tubular reabsorption of drugs have an impact on half life of a drug?

Answer 1

Because if drugs are reabsorbed they stay longer in the

body(active or passive).

Question 2

What are diuretics?

Answer 2

Drugs that increase the rate of urine flow and excretion of Na and water from the filtrate.

Question 3

When is it appropriate to use diuretics?

Answer 3

. Oedema (of cardiac, hepatic or renal origin)
. Acute renal failure (shock) - iv
. Forced diuresis (stimulate the excretion of toxins,
intoxications)
. Correct specific ion imbalances

Question 4

What are the 2 groups of diuretics and how do they work?

Answer 4

1st group: act specifically on cells in the tubule; most common used. They interfere with transport mechanisms of Na in tubule.

2nd group: are osmotic diuretics. Drugs of high osmolality which are filtering into the urine and by passing through the tubule will attract water.

Question 5

What is carbonic anhydrase?

Answer 5

An enzyme catalyzing the reaction of carbon dioxide and water.

Question 6

What do carbonic anhydrase inhibitors do?

Answer 6

Carbonic anhydrase inhibitois block the reaction of carbon dioxide and water and so prevent Na/H exchange and bicarbonate reabsorption.
The increased bicarbonate levels in the filtrate oppose water reabsorption.
Proximal tubule sodium reabsorption is also reduced because it is partly dependent on bicarbonate reabsorption.

Question 7

What are carbonic anhydrase inhibitors used for?

Answer 7

Used for glaucoma, epilepsy (rarely), benign intracranial hypertension, and altitude sickness.

Question 8

What are loop diuretics?

Answer 8

Loop diuretics are strong diuretics and include furoseinide, bumetanide and ethactynic acid.
They are highly plasma bound, but are secreted into the proximal tubule by the organic anion transporter.

Question 9

How do loop diuretics work?

Answer 9

They bind the NKCC2 co-transporter in the thick
ascending limb of the loop of Henle. This binding inhibits sodium, potassium and chloride reabsorption causing diuresis with loss of these electrolytes.
The transcellular voltage difference falls, and paracellular calcium and magnesium reabsorption are also reduced.
Loop diuretics can reduce the ability of the kidney to concentrate urine.

Question 10

Thiazide diuretics do what to calcium?

Answer 10

Reduce urinary calcium excretion.

Question 11

Thiazides are generally weak diuretics and are secreted into the proximal tubule but where do they act?

Answer 11

They reversibly inhibit the NCC apical NaCl co-transporter in the early distal tubule by binding to
the chloride-binding site. More sodium is then delivered to the principal cells of the collecting duct.

Question 12

How can thiazades sometimes cause hypokalaemia?

Answer 12

Some of this excess sodium delivered to the collecting duct is exchanged for potassium causing hypokalemia.

Question 13

What are some adverse effects of thiazides?

Answer 13

Sodium, potassium. chloride, and
magnesium depletion.
Cholesterol and urate levels can rise.

Question 14

What does aldosterone do?

Answer 14

Aldosterone promotes sodium reabsorption and potassium secretion by increasing transcription of the ENaC channel and the NaK ATPase.

Question 15

What is the action of the aldosterone antagonists: SpronoIactone?

Answer 15

The cells are impermeable to Na+ in the absence of
aldosterone. Aldosterone acts on a nuclear receptor within the tubule cell and on membrane receptors.
Spironolactone competes with aldosterone at its
receptor site. Thereby reducing Na re absorption and K secretion.

Question 16

What are Amiloride and triamterene?

Answer 16

Potassium sparing collecting duct diuretics and act mainly to reduce potassium loss caused by loop diuretics.

Question 17

How do Amiloride and triamterene work?

Answer 17

Amiloride competes with sodium for a site in the ENaC channel and thus blocks sodium reabsorption and potassium secretion. Triamterene has a similar
action.
This promotes the loss of sodium and water from the body, but without depleting potassium.

Question 18

Name two osmotic diuretics?

Answer 18

Mannitol and glycerol.

Question 19

How do osmotic diuretics work?

Answer 19

Osmotic diuretics, such as mannitol or glycerol are filtered in the glomerulus and then not reabsorbed. As the filtrate passes along the nephron water is reabsorbed, and the concentration of the osmotic diuretic rises until its osmotic effect opposes
further reabsorption of water. Sodium is then reabsorbed without water. Eventually sodium reabsorption is also inhibited because the sodium gradient between filtrate and plasma
increases to the point at which sodium leaks back into the lumen.

Question 20

When would mannitol be used?

Answer 20

Mannitol, an osmotic diuretic, draws water from cells osmotically and is used to dehydrate brain cells in cerebral edema. It enhances renal blood flow by increasing extracellular and intravascular volume and reducing red cell volume and blood viscosity.

Question 21

How does glycerol work as an osmotic diuretic?

Answer 21

Glucose is filtered in the glomerulus. A high plasma glucose level causes a high filtrate glucose level which can exceed the tubular capacity for its reabsorption. Glucose then acts as an osmotic diuretic causing volume depletion during diabetichyperglycemia. High levels of urea from protein metabolism
can also promote an osmotic diuresis in a functioning kidney.