Diuretics

Question 1

Diuretics

Answer 1

group of drugs that increase the production of urine.
• Often associated with natriuresis {increase in sodium sodium excretion in
urine}
most severe side effects of using diuretics include volume
depletion
and excessive changes in electrolytes (mainly sodium and
potassium),
which increase the risk of cardiac arrhythmi

Question 2

Clinical Uses of Diuretics:

Answer 2

• Used to reduce edema in:
✓ Congestive heart failure.
✓ Some renal disease.
✓ Hepatic cirrhosis.
• Hypertension (mainly Thiazides)
• Glaucoma (Carbonic anhydrase inhibitors)

Question 3

1-Carbonic Anhydrase Inhibitors

Answer 3

At the PCT
catalyzes dehydration of carbonic
acid (H2CO3)
MOA:
Blockade of the carbonic anhydrase enzyme activity:
induces a NaHCO3 diuresis&raquo_space; reducing body
bicarbonate levels&raquo_space; Hypokalemic Metabolic acidosis
Tolerance devolved after 3days

Question 4

Clinical Application of CA inhibitors

Answer 4

• Rarely used for its diuretic action.
• Acute Glaucoma (Dorzolamide):block CA enzyme&raquo_space;decreases the rate of aqueous humour production» leads to a decline in intraocular pressure.
• In high altitude sickness
• Can be used in forced diuresis:for acid “aspirin “. Alkaline the urine
•Idiopathic intracranial hypertension
ACEzolamide =ACEdosis

Question 5

T oxicity of CA inhibitors

Answer 5

AHA DS

Question 6

2-Loop Diuretics

Answer 6

Furosemide (Prototype), Bumetanide, Torsemide
MOA:
inhibit the cotransport system of Na, k, and cl
(NKCC2)» loss in the urine.

Inhibition of the (NKCC2)&raquo_space; loss of the lumen-positive potential&raquo_space; reduces reabsorption of Ca+2 and Mg+2.

Increased PGE2 and I2 release&raquo_space; vasodilatation and ↓ BP.

↑ Na+ excretion&raquo_space; ↓ the sensitivity of vascular endothelial
cells to the circulating catecholamine

Question 7

Effect of Loop Diuretics

Answer 7

hypokalemic metabolic alkalosis : presentation of large amounts of Na 20-30% may cause K wasting + massive sodium chloride diuresis&raquo_space; Blood volume may be significantly reduced. “high- ceiling diuretics.”

short-acting, and rapid Onset
reduce pulmonary vascular pressures by ↑ PG
NSAID≠loop diuretics due to lowering of the PG

Question 8

Clinical application:

Answer 8

Edema (cardiac, renal, hepatic, and
acute pulmonary edema).

Sometimes, it is used in chronic hypertension when thaizied not enough but can’t really be used for the short action 4 h

treatment ofsevere hypercalcemia but less common

Question 9

Toxicity of loop diuretics

Answer 9

2G O PANDA
Metabolic Alkalosis

Question 10

Thiazide diuretics.

Answer 10

Hydrochlorothiazide

Act on the proximal segment of DCT»inhibit NaCl transport “NCC”

Increased PGE2 and I2 release&raquo_space; vasodilatation and ↓ BP (but
Less than loops). Also have direct VD effect.

Calcium is also reabsorbed in this segment under the control of (PTH)

Thiazides are active by the oral route and have a longer DOA
of 6–12 h,“ longer than the loop diuretics.”

Question 11

Effects of thiazide:

Answer 11

↓ the transport of Na to the tubular cell&raquo_space; Reduces intracellular Na&raquo_space; this willPromotes Na-Ca exchange pump
So
More reabsorbtion of ca “HypErcalcemia” and “HypOcalciurea”
(The opposite of the effect of loop diuretics)

Inhibition of PG (by NSAID) reduces efficacy of the thiazides.
Thiazide + loop diuretic, a synergistic effect

Moderate 7-10% but sustained action 6-10h

Hypokalemic metabolic alkalosis ↓ K ↓ H *

Question 12

Clinical Application of Thaizide :

Answer 12

Chronic therapy of edema
such as mild congestive heart failure and liver cirrhosis.

Hypertension.

Prevent the renal calcium stone and the Idopathic hypercalciurea لانه يوديه للدم because they ↓ urine Ca concentration.

Question 13

Toxicity of Thiazides

Answer 13

Hyper GLUC mia
Becareful with DM due to Hyperglaicemia
Allergic reactions
(metabolic alkalosis)
Not used with NSAIDs

Question 14

4-Potassium-Sparing Diuretics

Answer 14

At the D of DCT

primary site of acidification of the urine and the last site of potassium excretion

2-5% of Na reabsorbtion by Aldosterone via (ENaC, not a transporter) accompanied with ↓ K and H ions

Question 15

Potassium-Sparing Diuretics effect and MOA

Answer 15

MOA:
Spironolactone and Eplerenone: steroid like hormone
Inhibit the effects of aldosterone on (ENAC) receptor at the D of DCT

Triamterene and Amiloride:
Block Na+ channels

Effect:
Loss of Na and H2O
Hyperkalemia
Metabolic Acidosis

Question 16

Potassium-Sparing Diuretics uses:

Answer 16

1) Hypertension.
2) Chronic therapy of edema as in congestive heart failure (reduces mortality and morbidity) and liver disease (unable to metabolize aldosterone)
3) Conn’s Disease (Tumer excessive aldosterone production)
4) PCOS (hyperandrogenic status)تكيس المبايض
**to avoid the K impalance we combined THIAZIDE with K sparing&raquo_space; Aldactazide

Question 17

Potassium-Sparing Diuretics Toxicity

Answer 17

*hyperkalemia and acidosis.

NEVER be given with K supplements or other aldosterone antagonists (e.g., ACEI and ARB)

Spironolactone steroid like strucutre can cause
endocrine alterations, including gynecomastia صدر عند الرجال
and antiandrogenic effect (erectile dysfunction) in men

Question 18

5-Osmotic Diuretics

Answer 18

Mannitol
Given IV ,Urine volume increases in PCT and A loop

Clinical Use:
ICP
Acute glucoma
Forced diuretics سواء حمض او قاعده
Toxicity:

Dehydration
Pulmonary edema,
hyponatremia or hypernatremia