Diuretics Flashcards
Diuretics
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
Clinical Uses of Diuretics:
• Used to reduce edema in:
✓ Congestive heart failure.
✓ Some renal disease.
✓ Hepatic cirrhosis.
• Hypertension (mainly Thiazides)
• Glaucoma (Carbonic anhydrase inhibitors)
1-Carbonic Anhydrase Inhibitors
At the PCT
catalyzes dehydration of carbonic
acid (H2CO3)
MOA:
Blockade of the carbonic anhydrase enzyme activity:
induces a NaHCO3 diuresis»_space; reducing body
bicarbonate levels»_space; Hypokalemic Metabolic acidosis
Tolerance devolved after 3days
Clinical Application of CA inhibitors
• Rarely used for its diuretic action.
• Acute Glaucoma (Dorzolamide):block CA enzyme»_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
T oxicity of CA inhibitors
AHA DS
2-Loop Diuretics
Furosemide (Prototype), Bumetanide, Torsemide
MOA:
inhibit the cotransport system of Na, k, and cl
(NKCC2)» loss in the urine.
Inhibition of the (NKCC2)»_space; loss of the lumen-positive potential»_space; reduces reabsorption of Ca+2 and Mg+2.
Increased PGE2 and I2 release»_space; vasodilatation and ↓ BP.
↑ Na+ excretion»_space; ↓ the sensitivity of vascular endothelial
cells to the circulating catecholamine
Effect of Loop Diuretics
hypokalemic metabolic alkalosis : presentation of large amounts of Na 20-30% may cause K wasting + massive sodium chloride diuresis»_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
Clinical application:
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
Toxicity of loop diuretics
2G O PANDA
Metabolic Alkalosis
Thiazide diuretics.
Hydrochlorothiazide
Act on the proximal segment of DCT»inhibit NaCl transport “NCC”
Increased PGE2 and I2 release»_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.”
Effects of thiazide:
↓ the transport of Na to the tubular cell»_space; Reduces intracellular Na»_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 *
Clinical Application of Thaizide :
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.
Toxicity of Thiazides
Hyper GLUC mia
Becareful with DM due to Hyperglaicemia
Allergic reactions
(metabolic alkalosis)
Not used with NSAIDs
4-Potassium-Sparing Diuretics
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
Potassium-Sparing Diuretics effect and MOA
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
Potassium-Sparing Diuretics uses:
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»_space; Aldactazide
Potassium-Sparing Diuretics Toxicity
*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
5-Osmotic Diuretics
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
