Block 2-Reymann (Diuretics)

Question 1

Acetazolamide & Dorzolamide (PK & PD)

Answer 1

• Carbonic anhydrase inhibitor (Proximal conv. tubule)
• Prevents conversion of Na bicarb into CO2 + H20 (blocking Na+/H+ antiporter)= increased H+ (metabolic acidosis)
• Dorzolamide: used topically for glaucoma
• _PK: _Effective w/in 30 min & works for 12 hours
• _PD: _Diuretic NOT used as one **(weak) **
• Blocking carbonic anhydrase = alkanisation of urine CAN lead to metabolic acidosis ALSO ammonia to brain
• More Na+ in lumen = K+ secretion (hypo)

Answer 2

• Use:
• decrease rate of aqeuous humour formation ^{<strong>(glaucoma)</strong>}
• Mountain sickness increased intracranial pressure relieved with decrease rate of CSF
• Offest resp alkalosis - eliminate Acidic drugs (aspirin)
• SE:
• Metabolic acidosis w/Hypokalemia (treats Resp. Alka)
• Renal stones due to decreased sol, of salts w/PH change ^{<u><strong>(staghorn)</strong></u>}
• Renal K+ loss ^{<u><strong>(hypokalemia)</strong></u>}
• CNS toxicity w/large doses(drowsiness)
• Contraindicated in hepatic cirrhosis=less ammonium trapped-alkalization of urine & ^{<u><strong>NH4 to brain</strong></u>}

Question 3

Mannitol

Answer 3

• Act everywhere non absorbable & non metabolizable sugar ^{<u><strong>(OSMOTIC)</strong></u>}
• Works @ the prox tubule (osmotic)
• PK:
• Must be given IV
• excreted w/in 30-60min
• PD:
• Helps in retaining water w/in tubule ^{<u><strong>(osmotic)</strong></u>}
• SE:
• Cause Extracellular volume expansion = increased CHF or pulmonary edema (FATAL)
• Headache, nausea, Dehydration & hypernatermia
• Use: Water diuresis maintain tubular flow^{<u><strong>(flush toxin)</strong></u>} & reduce intracranial/intraocular pressure

Question 4

Loop diuretics (Furosemide) PK&PD

Answer 4

• Fastest & strongest ^{<u><strong>(high ceiling) </strong></u>}others include: Bumetenide, torsemide, ethacrynic acid
• Inhibits transporter in T.A.L
• Area of action is collecting ducts
• PK:
• IV w/instant ONSET (see urine drip)
• Duration 2-3 hrs
• Glomular filtration & tubular secretion
• PD:
• Inhibits Na+/K+/2Cl- transporter T.A.L
• Impaired Ca+2 & Mg +2 absorption
• Strongest K+ wasting drug (hypokalemia)

Question 5

Loop Diuretics (furosemide) Uses

Answer 5

• Uses:
• Edematous (emergency) conditions (ex. Pulmonary edema, Acute CHF)
• Acute hyercalemia & hyperkalemia (need to get rid of it)
• Renal failure helps w/greater fluid flow allows failing kidneys to USE LESS energy
• Anion overdose combo w/Saline infusion (Bromide, fluoride, iodide)
• Forced diuresis (monitor electrolytes)
• Treat hypertension & CHF ONLY 2nd line or other drugs NOT working
• Vasodialate through prostaglandins (lower TPR)

Question 6

Loop Diuretics (furosemide) SE

Answer 6

• SE: HYPOkalemia = arrhythemias
• Metab alkalosis (excrete H+ w/K+)
• Ototoxicity w/complete deafness linked w/Gentimycin ^{<strong>(antibiotic)</strong>}
• SULFA drug = Allergic Rxns ^{<strong>(except etharcynic acid)</strong>}
• Hyperuricima induce gouty attack w/predisposed conditions due to WEAK organic acid transport =^{<u><strong> decreased uric acid removal</strong></u>}
• Hypomagnesaemia & Hypocalcemia
• Digitoxin competes w/K+ enhances effect = Possible pulm edema

Question 7

Thiazides PK&PD

Answer 7

• Not as STRONG as loops but are better tolerated LONG term.
• Prototype drug = Hydrochlorothiazide
• Other drugs = Indapamide, chlorothalidone, Metolazone
• Need sufficient GFR to be effective EXCEPT metolazone
• PK:
• Most often P.O. also excreted naturally by organic acid system
• PD:
• Inhibits Na+/Cl- symporter in D.C.T
• Enhance Ca+2 reabsorption
• PTH works on GS coupled receptor

Question 8

Thiazides Use&SE

Answer 8

• SE:
• Similar to loops but less pronounced K+wasting
• Less severe metab alkalosis
• Less severe hyperuricemia
• Less severe hypernatremia (elevated Na+)
• Hypercalcemia
• Couterindicated for Diabetics:
• Impaired Carb tolerance (Chronic)
• Hyperlipidemia & allergic rxn (Chronic)
• Use:
• Treat chronic hypertension
• No dose tritation needed (small doses have effect)
• Treat chronic CHF w/acute use Loops
• Treat Renal stones (nephrolithiasis) due to idopathic hypercalciurua (^{<u><strong>TOO MUCH IN URINE BUT NORMAL SERUM &amp; PTH lvls)</strong></u>}
• Treat nephrogenic diabetes insipidus ^{<u><strong>(extracellular volume contraction)</strong></u>} = reduced Urine ouput

Question 9

Thiazides (Metolazone)

Answer 9

• PK: Oral BA 65% lasts for 12-24 hrs
• PD:
• Similar to thiazides MOA (LDT)
• BUT can be used in LOW GFR (less than 30ml)
• Use:
• Hypertension, edema
• Used instead of prototype in combo treatment of furosomide ^{<u><strong>(LOOP)</strong></u>} resistance ^{<strong>(genetic component)</strong>}

Question 10

K+ Sparing Triamtrene & Amiloride

Answer 10

• PK:
• Triametrene-Hepatic metab w/renal excretion
• Amiloride-Renal excretion ONLY
• PD:
• Mild increase in NaCl excretion effects on LDT & collecting ducts
• Blocks Na+ channels = K+ is excreted into lumen^{<u><strong> (HYPERKALEMIA)</strong></u>}
• Use:
• Same as loop diuretics except no K+ wasting
• SE:
• Hyperkalemia-seen in combo w/ACE inhibit=Metab acidosis
• Triametrene cause acute renal failure

Question 11

K+ Sparing Spironolactone (aldosterone)

Answer 11

• Aldosterone:
• acts on LDCT & CD inserts MORE Na+ channels into apical membrane
• Increases transcription of Na+/K+ ATP pump to remove Na+ from cell
• PK:
• Prodrug = Canreonate (IV only)
• Spironolactone not good diuretic BUT treatment of cardiac remodeling ^{<u><strong>(AFTER MI)</strong></u>}
• PD:
• Aldosterone antagonist DELAYED onset due to transcription
• Mild increase Na/Cl excretion in LDT & CD
• SE:
• Hyperkalemia in combo w/ACE inhibit
• Spiro is steroid w/estrogen like effect = Gynaemastia in men

Question 12

Overall Uses of Diuretics

Answer 12

• Used in emergency states:
• Pulmonary edema
• CHF
• Kidney disease
• Hepatic cirrohosis
• NON emergency states:
• Chronic hypertension
• nephrolithiasis (stones) -^{<strong>Thiazides</strong>}
• Hypercalcemia ^{<u><strong>(LOOPS)</strong></u>}
• Diabetes insipudis _{<strong>(THIAZIDES)</strong>}
• Forced diuresis intoxication (^{<u><strong>LOOPS)</strong></u>}