Diuretics Flashcards by Lailak Al-Kahachi

What are diuretics?

A chemical agent that increases the rate of urine

or
any agent that will inhibit the tubular absorption of sodium

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What is the primary MOA of diuretics

Direct Inhibition of sodium transport at one or more of the four major anatomical sites of the nephron where sodium reabsorption occurs

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What are the major applications of diuretics agents

treatment of hypertension
mobilization of edematous fluid (HF, CKD, Hepatic diseases)

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How many nephrons does the kidney contain

1 million nephron

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What is each nephron made of

glomerulus and the renal tubule

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What is a glomerulus

a ball of capillary loops surrounded by bowmans capsule- blood flow in provides filtrates without molecules larger than 4nm in diameter

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T/F:
Diuretics that wonk on the earlier nephron have greatest effect since they are able to block more sodium and chloride reabsorption

True

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Where do the carbonic anhydrase inhibitors work

Proximal tubules

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Where do loop diuretics work

In the loop of henle

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Where do thiazides work

Between the thick ascending loop and the distal convuluted tubule

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Where do potassium sparring diuretics work

distal convuluted tubule

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Does the collecting tubule have good diuretic activity

No, least efficacious diuretic

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What is the primary indication of acetazolamide

glaucoma
mountain sickness (cns effects)

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does acetazolamide trigger metabolic acidosis or metabolic alkalosis

metabolic acidosis AND
respiratory alkalosis

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Is acetazolamide used as a diuretic nowadays

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What is the recent approval of acetazolamide

epilepsy

one of epilepsy triggers is the increase pressure in the cns due to increase fluid production
that is how acetazolamide is used in epilepsy

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What does acetazolamide prevent the production of what

aquous humor

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the body recycles what into carbonic acid

CO2 + H2O <-> H2CO3 (CARBONIC ACID)

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CO2 hydration occurs in …?

Kidney
co2 +h2o -> h2co3

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CO2 dehydration occurs in

Lungs
H2CO3 -> CO2 + H2O

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the function of carbon anhydrase can differ depending on

location of enzyme
PH

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What are the SE of acetazolamide

respiratory alkalosis
metabolic acidosis
renal stones

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We advice patients who take diuretics to drink more water, why?

some drugs are insoluble at urine pH -> precipitation -> stones
some basic drugs can increase pH of urine -> ppt.

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What are loop diuretics called

High ceiling diuretics

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Loop diuretics causes ____ loss? and decrase of what in the blood?

Na+ loss (diuretic effect) and decrease K+ in the blood -> hypokalemia

Do all diuretics cause hypokalemia

All except, potassium sparring diuretics

What is the MOA of loop diuretics

inhibits the na+/k+/2cl- carrier system primarily in the loop of henle

Mention 3 loop diuretics

1. Bumetanide 2. Furosemide 3. Etharcynic acid

Is bumetanide soluble in urine

YES completely excreted in urine

What are the uses of bumetanide?

1. edema 2. HF 3. hypercalcemia 4. hyperkalemia

What are the SE of bumetanide, furosemide

1. Ototoxicity REVERSIBLE 2. hyperuricimia 3. hypokalemia

does furosemide have a longer action duration than bumetaminide?

Yes due to the Cl- addition next to the sulfomyl group

Does the chemical structure of ethacrynic acid differ than other loop diuretics?

Yes but it acts on the same pump (that is why its classified in the loop diuretics section of diuretics)

Which is more dangerous, furosemide or ethacrynic acid?

Ethacrynic acid is more dangerous and casuses more ototoxicity and causes GI hemmorage

Does ethacrynic acid have a shorter or longer activity than other loop diuretics

longer , because it has 2 clorines

Is ethacrynic acid soluble in urine

yes

Does ethacrynic acid contain sulfur?

No, perfect for pts who need diuretics and have a sulfur allergy

What are thiazides called

low ceiling diuretics

Where do thiazide and thiazide look diuretics work

dital convoluted tubule on NA+/CL- pump

Is there a limited Na+ absorption in the distal convoluted tubule

Yes only 5-8% of the filtered load of sodium is reabsorbed

in thiazide/ thiazide like diuretics which placement of sulfomyl group is preequisite for diuretic activity

Sulfomyl at G7 is ESSENTIAL

in thiazide/ thiazide like diuretics , the sulfomyl at group 1 is essential

Yes, but if we replace it with any other isostere -> less activity

In thiazide like diuretics, can we substitute g 4,5,8?

NO they should remain free IF substituted -> diminished activity

In thiazide like diuretics, can we substitute g 6

Yes but only with Cl-, Br-, Cf3-, NO2-

In thiazide like diuretics, the double bond between G3-G4

It is better to remove the double bond for better diuretic activity removal of = -> inc in potency 3-10 times

In thiazide like diuretics, the NH2 in group 2, can i substitute it

only with small alkyl group CH3 (but the activity will be reduced)

In thiazide like diuretics, the C in G3 can i add R to it

Yes the more i add lipophilic group the duration increases

Are thiazide diuretics well absorbed

yes

When is the onset of action of thiazide diuretics

1-2 hours tmax 3-6 hr

Are thiazide diuretics protein bound

Yes

What are the SE of thiazide diuretics

1. hypersensitivity reaction (sulfomyl) 2. hypokalemia 3. hypercalcemia 4. hyperuricemia

Mention 3 thiazide diuretics

1. chlorothiazide 2. hydrochlorothiazide 3. Indapamide

What is the MOA of chlorthiazide

thiazide diuretic (low ceiling) Na+/C;- pump at distal tubule

Theraputic uses of chlorthiazide

HTN HF

Side effects of chlorthiazide

Hypokalcemia hyperuricemia hypercalcemia hypergylcemia hyperlipidemia

Is there a double bond in hydrochlorothiazide

Which is more potent chlorthiazide or hydrochlorothiazide

Hydrochlorothiazide

Is indapamide a thiazide diuretic

No, but since it works in the same place, it was classified under it

Does indapamide have a short or long duration of action

Longer than other thiazides

Potassium sparring diuretics work on ...?

Aldosterone

Mention potassium sparring diuretics

1. spiranolactone 2. eplerenone 3. Triamterene 4. amiloride

Spiranolactine are ...... antagonists

Aldosterone antagonist

What is spiranolactone a derivative of

Steroid derivative

What are the SE of spiranolactone

Gastric upset -> ulcers gynecomastia Irregular menstruation

What is contraindicated with spiranolactone and other potassium sparring diuretics

any drugs that could cause hyperkalemia like ACEi and ARBs

What is the mechanism of action of eplerenone

K-sparring diuretic aldosterone antagonist

Does eplerenone have endocrine activity

No, less endocrine activity

The epoxide in eplerenone is it stable or not

Stable

What is the MOA of amiloride

K-sparring diuretic Na+/K+ pump at COLLECTING TUBULE

What is the MOA of triamterene

K-sparring diuretic Na+/K+ pump at COLLECTING tubule

What are the side effects of triamterene

Leg cramps (electrolyte imbalances)