THIAZIDE

Action USE SE
Diuresis SOA: luminal side in early DCT
MOA: ▼Na & Cl symport from lumen into early DCT Generalized or localized Oedema dehydration, hyponatremia,
 Na+ excretion (5-10%) along ĉ Cl- & H2O (eg. CHF, Nephrotic $) hypochloremic alkalosis, hypokalemia
(▼carbonic anhydrase:  H+ secretion,  HCO3- reabsorption, acidosis)
Reduction of BP Hypertension hypotension
VDn: (icNa+); sodium loss in urine (alone or ĉ others, sub-diuretic dose)
Antidiuresis in Diabetes insipidus
 GFR, compensatory Na+ & H2O reabsorption, Diabetes insipidus
 permeability of tubule to H2O, relief thirst & polyuria.
Effect on electrolytes
 Na+ & H2O excretion, diuresis hyponatremia, dehydration;  Li+ clearance
 Cl- excretion hypochloremic alkalosis
 Mg++, iodide & bromide excretion Mg++ loss (precipitate coma in hepatic encephalopathy)
 K+ excretion ( Na+-K+ exchange at the site distal to Thiazide action to conserve Na) hypokalemia
Glucose  open K+ channel,  insulin secretion,  blood glucose impair glucose tolerance ( effect of oral hypoglycemic agent)
Lipid   cholesterol,  TG,  LDL
Uric acid   urate excretion (compete ĉ uric acid at active tubular secretion) hyperuricemia, precipitate Gout
Calcium
Ca   Ca++ excretion Idiopathic hypercalciuria (to  stone formation)
Being a Sulphonamide (cross-allergy ĉ other sulphonamides) allergy, dermatitis, photosensitivity, cholestatic hepatitis
vasculitis, thrombocytopenia, purpura, pancreatitis
Others: potentiate Skeletal m/s relaxant: m/s cramp, fatigue
Impotency / Elevate renin

kinetic: incomplete absorption, variable PPB & DOA, excretion by glomerular filtration & active tubular secretion (▼ by Probenecid)

DI: Digoxin & Thiazide in HF: digoxin  FOC & thiazide  oedema. Digoxin actn: is potentiated by hypokalemic actn: of thiazide  danger of digoxin toxicity ĉ therapeutic dose
(dose adjustment / K+ supplement)
Thiazides & Antihypertensives in HT: thiazides prevent Na+ retention caused by RAA ▲ via sympathetic reflex d/t other antihypertensive agents; synergistic.
Thiazides & NSAIDs: sodium retention effect of NSAIDs blunt diuresis.

FRUSEMIDE

Action USE SE
Diuresis - powerful diuresis even ĉ low GFR; steep DR curve
 onset & DOA shorter than Thiazide;
MOA: ▼ Na-K-2 Cl symport SOA: TAL of LOH Oedema of cardiac, renal, hepatic origin dehydration, hyponatremia,
15-25% Na+ is lost in urine along ĉ large volume of water Forced diuresis to facilitate elimination of drug in overdose hypochloremic alkalosis, hypokalemia
 active reabsorption of Na+  less hypotonic tubular fluid & Refractory oedema (eg. chronic renal failure)
less hypertonic medullary interstitium   osmotic gradient  ĉ Thiazide or Spironolactone
 fluid reabsorption from collecting tubule  large volume of
OligUria in early renal failure (CI: anuria)
unconcentrated urine. (Both dilution & concentration of urine are impaired.)
(Frusemide & Bumethanide ▼ carbonic anhydrase) (Both are Sulphonamide)
Acute cerebral oedema Caution: danger of medullary herniation
(Not by Ethacrynic acid)
Reduction of BP
d/t VDn: when given IV, vascular effects appear before diuresis, RBF Hypertensive emergency (Not for routine use) hypotension
 LV filling pressure
d/t VDn:, mediated by PG. Beneficial even before diuresis. Acute pulmonary edema (IV) (emergency use)
Effect on electrolytes
 Na+, Cl- excretion hyponatremia, hypochloremic alkalosis
 Mg++ excretion Mg++ loss (precipitate coma in hepatic encephalopathy)
 K+, H+, ammonia excretion (d/t Na+- K+ & Na+- H+ exchange) Hyperkalemia hypokalemia
Glucose   insulin secretion,  blood glucose impair glucose tolerance ( effect of oral hypoglycemic agent)
Lipid   TG,  LDL,  HDL
Uric acid   urate excretion (compete ĉ uric acid at active tubular secretion) hyperuricemia, precipitate Gout
*Calcium
Ca   Ca++ excretion Hypercalcemia (+ isotonic saline to prevent volume depletion)
Effect on renal haemodynamics
 renal blood flow (MOA: unknown; m/b d/t ▼PG degradation) DI: NSAIDs can blunt natriuretic response
▲ renin release (d/t interfere ĉ NaCl transport & RX RAA ▲)
Sulphonamide diuretic (except Ethacrynic acid) allergy, skin rash, hepatitis, nephritis, bone marrow ▼
Others: muscle weakness; Myalgia (Bumetanide)
GI h’ge (Ethacrynic acid)
Alteration of electrolyte composition in endolymph in inner ear Deafness
Nephrotoxicity (esply when use ĉ Aminoglycoside, Cephalosporin)

kinetic: good absorption, F=60% , high PPB, excreted by tubular secretion (▼by Probenecid), v. rapid onset, shorter DOA (peak effect: 30 min after IV) (DOA: 3- 6 hr after p.o)
DI: Aminoglycosides, Cisplatin:  ototoxicity (furosemide- endolymph; gentamicin -8 th cranial nerve)
Hypokalaemia  potentiate digoxin toxicity,  arrhythmias Hyperglycemia  reduced effect of Sulphonylureas
NSAIDs, Probenecid: blunt diuretic response
 plasma level of Lithium (d/t sodium depletion)  anticoagulant effect of Warfarin (competes for albumin binding)

(DI: potentiate antihypertensives)

(DI: natriuretic effect is blunted by NSAID)
(DI: potentiate Digoxin toxicity)
(DI:  Warfarin effect by PPB displacement)