diuretics

edema because of heart, kidney, liver

HTN

uses of diuretics in general

Carbonic anhydrase inhibitors

diuretics which act on PCT ?

The channel transport from lumen to epithelium is Na+/H+ antiportter system

PCT physiology link with CAIs ?

&

Where does the maximum amount of NA+ absorb in nephron?

CAIs cause maximum loss of HCo3 and cause metabolic acidosis

\
CAI s also cause H+ loss causing metabolic alkalosis but HCo3 loss predominant the H+ loss.

CAIs cause maximum loss of which ion and cause what ?

Na+ reabsorbed bt Na=/K+/2Cl- pump . and TAL is impermeable to water

TAL physiology link with CAIs ?

eNaC channel - sodium reabsorbtion

Proton ATPase- H+ loss in the lumen

ROMK Channel - loss K+ in the lumen.

\
By this mean loop diuretics and thaiazides cause metabolic alkalosis.

CAIS physiological link with collecting duct?

CAIS causes max hypokalemia at equal natriuretic doses.

\
\

maximum loss of potassium by which diuretics?

CAIs can lead to hyperammonemia by inhibiting CA enzyme

diuretics which cause hyper ammonemia ?

CAIs - MAX

Loop diuretics

thiazides

diuretics cause hypokalemia.

CAIs

\
Metabolic and respiratory alkalosis cause loss of HCO3-

OSA - make CSF PH acidic stimulating the medullary ventilatory center leading to hyperventilation. Hyperventilation causes compensatory respiratory alkalosis.

Diuretics used in Rx of metabolic respiratory alkalosis?

Rx for OSA - obstructive sleep apnea

nephrolithiasis - as urine became alkaline causes precipitation of calcium and form calcium stones.

S/E of CAIs in kidney?

Antiepileptics like zonisamide , topiramate

other drugs which cause nephrolithiasis like CAIs?

CAIs prevent cysteine stones in cystinuria.

Cystine is a AA which get more water soluble in alkaline urine.

CAIs used to prevent what stone formation?

CAIs

incre. CO2 in CNS neurons release of inhibitory neurotransmitters like glycine and GABA . which leads to somnolence.

diuretic choice for somnolence ?

CAIS can be used

Progesterone can be used.

but it can not be used for long-term therapy as it cause development of tolerance.

\

diuretics which can use for Rx for catamenial epilepsy?

liver cirrhosis - we use diuretics for edema cause by liver cirrhosis. but never used CAIs

\
REASON: CAIs leads to hyperammonemia. so giving CAIs may leads to hepatic encephalopathy.

CAIs C/I

Rx of hypokalemic periodic paralysis . MOA is unknown.

Postulated to be due to the direct action on the muscle.

paradoxical use of CAIs by hypokalemia?

HPP- CAIs acetazolamide may be used.

DOC: methanamide

CAIs diuretics used for hypokalemic preiodic paralysis.

CAIS used in glaucoma because it decrease the aqueous fluid production by blocking CA. by blocking CA H2O released from the breakdown of H2CO3 is required for synthesis of aqueous humor.

\
Acetazolamide - oral route - acute congestive glaucome.

diuretics used in glaucoma and ROA ?

Open angle glaucome.

Tropical brinzolamide & dorzolamide used for ?

acetazolamide.

DOC for acute mountain sickness?

CAIs are used. because it decrease the aqueous fluid & CSF production by blocking CA. by blocking CA H2O released from the breakdown of H2CO3 is required for synthesis of aqueous humor & CSF is blocked.

\
Used in

* idiopathic intracranial hypertension (pseudotumor cerebri)
* prevent CSF leak
* raised CSF pressure headache.

diuretic used for CSF leak?

CAIs are sulfonamide derivatives.

can be seen in the form of RASH & BONE MARROW SUPPRESSION.

Hypersensitivity for CAIs . Why? and how it is seen?

Na+/ K+/ 2Cl- pump in TAL of the nephrons absorb 25% of NA+ and this part is impermeable to H2O causing hyperosmolarity.

medullary hyperosmolarity acheived by which channel in the nephron?

Na+ / Cl- are extracellular ions. in TAL these 2 are reabsorbed by the Na+/K+/2Cl- pump. but the K+ which get reabsorbed due to high intracellular concentration push out immediately.

\
This cause the membrane negatively charge . cause the absorption of Ca+ & Mg2+ ion.

physiological link of loop diuretics

loop diuretics - high ceiling diuretics

Max loss of water and NA+/Cl- by which diuretics ?

Due to block of Na+/K+/2Cl- pump osmotic pressure is decreased in systemic circulation. result in decrease in plasma volume and blood pressure.

\
As a compensatory reabsorption of uric acid and water which leads to hyperuricemia. so loop diuretics can worse the gout.

why hyperurisemia is seen in loop diuretics & thiazides?

Stimulation of sympathetic nervous system which leads to release of catecholamines. It binds to the Beta3 receptors in adipocytes induce lipolysis - cause dyslipidemia

what happen to sympathetic nervous system regarding to loop diuretics?

* hyperurisemia - worsen gout
* Hyperglycemia- decrease insulin
* dyslipidemia
* hypocalcemia
* hypomagnesemia
* hyponatremia.
* metabolic alkalosis - H+ loss
* reversible ototoxicity

S/E of loop diuretics ?

Loop diuretics - effective in renal failure and insufficiency

Only drug effective when GFR < 40 ?

Mannitol

\

DOC for cerebral edema? (diuretics)

Loop diuretics

DOC for Rx of pulmonary edema?

Loop diuretics - indirect vasodilation - first effect -

First effect in diuretics in pulmonary edema?

NSAIDS - by blocking the prostaglandin. it decrease the effect of indirect vasodilatation of loop diuretics.

which drug can affect the effect of loop diuretics?

* DOC - for pulmonary edema
* all edema because of heart, kidney & liver
* Cerebral edema - DOC is mannitol
* nephrotic syndrome
* chronic kidney disease
* cirrhosis.
* hypertensive emergencies - preferred drug - furosemide
* Hypercalcemia of malignancy.

\

loop diuretics uses ?

Ethacrynic acid - most ototoxicity and currently not used.

Loop diuretics - C/I - with aminoglycosides / cisplatin

loop diuretics - C/I as ototoxicity and which drug is not used currently because of this property?

* furosemide (lasix)
* bumetanide - most potent ( low dose is required )
* torsemide - longest acting

loop diuretics examples.

Moderate diuretics .

moderate loss of solute and water.

here in DCT where the thiazides act only 10% of filtered sodium and water is reabsorbed. by blocking this not so significant effect. but better than CAI .not good as loop diuretics.

\

on the rank of poor, moderate & good diuretics. Thiazides are which diuretics/

* DCT.
* Act on Na+/Cl- co transporter and block it
* results in loss of sodium, chloride & water.

Thiazides act on which part of the nephron?

* thiazides - hypercalcemia
* loop diuretics - hypo calcemia. (loop looses calcium)

one difference between thiazides & loop diuretics which seperate them?

1. Loop diuretics ( only class of diuretics effective when GFR<40)
2. Combination of loop diuretics with thiazides - (only)Metolazone + loop diuretics

diuretics used if GFR < 40

* Metolazone - always combine with loop diuretics. used in edema than HTN (good diuretic) do used primarily in edema than HTN.
* chlorothiazide - short acting (least prefered)
* chlorthalidone- longest acting (24hr BP control) ( CHOICE IN HTN)
* indapamide- Rx HTN than edema as it is excreated by liver. (poor diuretic)
* polythiazide - 100% oral bioavailability
* Bendro-flume-thiazide - 100% oral bioavailabilty

Thiazide examples

* HTN
* because it cause DIRECT VASODILATATION by opening the K+ channel in the smooth muscles of blood vessels.



NOTE: indirect vasodilatation is cause by loop diuretics by release of PG2.

thiazide are first line of drugs for ? and why?

* DOC- HTN + osteoporosis ( as thiazides cause hypercalcemia)
* preferred - CKD + HTN
* other uses:

\- GFR < 40 - metolazone + loop diuretics

\-EDEMA - CKD edema , cirrhotic edema, nephrotic syndrome.

\

Thiazides are DOC for ? and on which pt thiazides are preferred ? other uses of thiazides?

* 1st - HTN
* 2nd - EDEMA ( liver & kidney)

In general thiazides are used in?

* hyperuricemia (Na+/Cl-/ water loss lead to compensatory reabsorption of uric acid)
* dyslipidemia ( sympathetic overactivation leads to lipolysis)
* hypercalcemia ( when the thiazide block the Na+/ Cl- co transporter the intracellular NA+ drop. to compensate, Na+/Ca+ exchanger pumps Na+ from systemic circulation into the cell and pumps the Ca+ out of cell. Now the declining Ca+ level inside the cell draw Ca+ from the lumen into the cell.)
* Metabolic alkalosis (loss of H+)
* hypokalemia (loss of K+)
* Hypomagnesemia
* Hyperglycemia ( increase K+ loss leads to hypokalemia which decreases insulin release leading to this)

S/E of thiazides?

thiazides

which hypertensive drug precipitate the gout?

* loop diuretics
* thiazides

Both cause hyperurecemia.

\

which diuretics precipitate the gout?

Thiazides

dyslipidemia & hyperglycemia are seen both in loop and thiazides. In which it is prominant?

* Chlorthalidone
* it is longest acting (24hr BP control)

\

We know thiazides are 1st line of drug for HTN. Which thiazides is the most prefered and why?

* Indapamide - HTN ( because it is poor diuretics, It is excreted by liver. not so effective in edema Rx)
* Metolazone - EDEMA ( it is good diuretic, excreted by kidney)

you have indapamide & metolazone which one you use for EDEMA & which one you use for HTN?

* Aldosterone antagonist
* eNaC channel blockers

Diuretics which act on collecting duct?

* spironolactone
* eplerenone
* finrenone

Drugs examples of aldosterone antagonist?

* Amiloride
* triamterene

Drugs examples of eNaC channel blockers?

* these diuretics are poor diuretics.
* because only 2% of sodium and water are reabsorbed here in collecting duct.

diuretics act on collecting duct are they good diuretics?

* diuretics act on collecting duct are K+ sparing diuretics.
* it cause retension of K+ leads to hyperkalemia.
* so these diuretics are given along with other diuretics to prevent hypokalemia

K+ sparing diuretics ?

* metabolic acidosis ( retention of H+)
* hyperkalemia ( retention of K+)

\

S/E of diuretics act on collecting duct?

* spironolactone is a prodrug.
* Activated into CANRENONE block the receptor.

which part of spironolactone block the receptor?

* DOC - cirrhotic edema
* DOC - resistant hypertension
* DOC - drug resistant edema.
* can also used in patient with H/O of MI & chronic CHF. to reduce mortality.

spironolactone are DOC for?

similar to spironolactone ( so look for this drug in the option)

* DOC - cirrhotic edema
* DOC - resistant hypertension
* DOC - drug resistant edema.
* can also used in patient with H/O of MI & chronic CHF. to reduce mortality.

eplerenone uses?

* male - gynaecomastia (M/C) & impotence ( due to androgen receptor blockage)
* female- menstrual irregularities ( due to estrogen receptor blockage)

S/E of spironolactone?

* can be used in PCOS to Rx HIRSUTISM when OCP is not effective. due to androgen receptor blockage property.

spironolactone use in OBGN ?

* CKD + DM-2
* it help to prevent : progression to end stage renal disease(ESRD)
* MI
* CHF

uses of FINRENONE ?

* it is a eNaC channel blocker.
* DOC: liddle syndrome (over expression of eNaC)
* DOC: lithium induced DI ( Lithium has similar structure like sodium)
* DOC: inhalational amiloride for Rx of cystic fibrosis ( it cause the secretions become liquified)

\

uses of AMILORIDE ?

* DOC : amiloride
* thiazides can also be used to Rx the condition but not DOC. MOA: it induces solute and water loss which triggeres the proximal convoluted tubule to reabsorb more solute and water.

\

Rx for lithium induced diabetic incipidus?

* hyperkalemia - can cause arrhythemia , advice patient for potassium restricted diet.
* metabolic acidosis.

common S/E of pottasium sparing diuretics?

* EDEMA

uses of TRIAMTERENE?

* triamterene ( S/E is folic acid defeciency)
* CAIs ( cause hyperammonemia )

which diuretics are C/I in liver cirrhosis patient?

* mannitol (i/v for diuretic effect)

\

drug example for osmotic diuretic?

* laxative effect to create osmotic diuretic.

oral route of osmostic diuretic used in ?

* pulmonary edema
* renal failure ( but used in impending renal failure in shock/ trauma)
* hemorrhagic stroke ( cause cerebral edema but used in Rx of cerebral edema)

C/I of mannitol?

DUE TO CELLULAR MECHANISM:

* Relative hyponatremia
* hypokalemia(relative)

\
DUE TO RENAL MECHANISM:
* hypernatremia
* hyperkalemia

OTHER S/E
* pulmonary edema ( paradoxical )

S/E of mannitol?

* pulmonary edema - mannitol can move out of pulmonary capillaries ( unlike cerebral capillaries) dragging water along with it.

paradoxical S/E of mannitol?

* DOC: cerebral edema
* can also use loop diuretics.
* DOC: acute congestive glaucoma (CAIs - acetazolamide oral can also be used)

Mannitol is a drug of choice for?

cellular & renal .

\
CELLULAR:

* extract water from the cells.

RENAL
* it induces solute free water loss.

two mechanisms of action of mannitol:

CELLULAR: extract water from the cells. it is hence the

DOC: cerebral edema and acute congestive glaucoma to decrease the IOP . then swifted to PILOCARPINE.

cellular use of mannitol:

RENAL: it induces solute free water loss and is hence used in;

* diuretic breaking ( diuretic resistance)
* inpending renal failure in shock/ trauma
* dialysis disequilibrium

renal use of mannitol?

DOC: mannitol (Given i/v route to decrease IOP then Rx swifted to pilocarpine )

\
Acetozolamide - oral can be used. it is CAI

Rx of acute congestive glaucoma?

1. VASOPRESSIN ANALOGUES
* Synthetic vasopressin
* terlipressin
* desmopressin
2. VASOPRESSIN ANTAGONISTS
* parenteral - conivaptan
* oral- mozavaptan

- tolvaptan

drugs of anti- diuretics ?

* DOC: vasopressin analogues ( anti-diuretics)
* DESMOPRESSIN : given S/C for central DI (not for nephrogenic DI)

DOC for central diabetic insipidus?

act by stimulating vasopressin 1 & 2 receptor

* V1R - blood vessels & GIT ( it is a GQ subtype cause release of Ca2+ ) cause vasocontriction & contraction of GIT
* V2R - kidney - ( it is a Gs subtype) act as a vasopressin analogue used in central DI

\

MOA of synthetic vasopressin ?

* acute variceal bleeding
* norepinephrine resistant shock
* abdominal distension
* paralytic ileus

uses of synthetic vasopressin?

* vasocontriction causes facial pallor.
* GI side effects include nausea and vomiting due to increased contraction.

\

S/E of synthetic vasopressin?

DOC: terlipressin

prophylaxis: propranolol

TOC: endoscopic band ligation

Acute variceal bleeding - DOC, PROPHYLAXIS , TOC?

DOC: terlipressin , better than octreotide.

* it maintains a more stable portal pressure compared to octreotide.

for acute variceal bleeding terlipressin or octreotide which is better and why?

* DOC : nocturnal enuresis
* DOC; von willebrand’s disease(VWD)
* DOC: hemophillia A

It increases release of VW factor and factor VIII by acting on the endothelium.

DESMOPRESSIN is the DOC for ?

* headache ( water intoxication)

DEMOPRESSIN S/E ?

* SIADH ( syndrome of inappropriate antidiuretic hormone secretion

use of vasopressin antagonists?

Rx : vasopressin antagonist

CONVIVAPTAN - for emergency treatment

long term treatment ; free water restriction

V2 R receptor blockers are used in resistricted cases: oral mozavaptan 7 tolvaptan

\
it can only use for a month not more than that. because of it hepatotoxic property(tolvaptan)

Rx for SIADH?

* hyperglycemia
* hypokalemia
* hepatotoxicity- tolvaptan

S/E of vasopressin antagonists

* CAIs - increase +ve free water clearance
* loop diuretics - decrease both +ve & -ve free water clearance
* thiazides - decrease +ve free water clearance.

free water clearance