Urinary Pharms

Question 1

Diuretics

Answer 1

• A substance which increases urine flow.

* Increases the quantity of urine and electrolytes secreted.

Question 2

Water

Answer 2

• Overhydration results in larger quantities of urine excreted
• Not a true diuretic
• No net loss of electrolytes

Question 3

Salt

Answer 3

• Oral administration causes increased water intake and increase in urine turn over
• Not a true diuretic
• No net loss of electrolytes
• Beware salt toxicity in dogs, adequate supply of water is essential

Question 4

Sugars and sugar-alcohols

Answer 4

• Mannitol, dextrose, sucrose, sorbitol, hypertonic saline
• Pharmacologically inert but osmotically active, filtered but not reabsorbed (except saline to a degree)
• Water drawn into and retained in the tubules.
• Dextrose is not as effective as mannitol as a diuretic; but it is safer than mannitol for anuric renal failure, since it can be metabolized if renal function is not re established.

Question 5

Mannitol

Answer 5

•Non metabolizable sugar alcohol, administered IV as 5 – 25% solution (usually diluted in fluids)
•Freely filtered by the glomerulus; poorly reabsorbed by the tubules
•Emergency drug for
o Intracranial edema, without haemorrhage
o Glaucoma
o Acute Renal Failure (ARF) to prevent renal shutdown (furosemide used more commonly)
o Acute lung edema, other than caused by CHF (furosemide used more commonly)
o Excretion of some drugs and toxins (aspirin, ethylene glycol)
- Decreases diffusion gradient from the central compartment to the cells and also results in retro-diffusion of the toxin
•Test with a bolus dose first for urine production
o Ensure no blockage of tubules otherwise mannitol remains in the central circulatory system
o Risk of pulmonary oedema
•Proceed with slow IV dose and monitor:
o Hydration status
o Urine output
o Electrolyte level

Question 5

Side effects Mannitol

Answer 5

• Fluid and electrolyte imbalances: Acidosis
• Circulatory volume overload: Pulmonary oedema
• GIT: nausea, vomiting

Question 6

Mannitol Contraindications

Answer 6

• Dehydration
• Severe pulmonary oedema/congestion
• Congestive heart failure
• Anuric renal failure
• Cerebral vasculature damage
• Intracranial haemorrhage

Question 7

Saluretics

Answer 7

• Cause a loss of sodium (and chloride) and thus water
• Carbonic anhydrase inhibitor (acetazolamide)
• Mainly used topically for the management of glaucoma
• Thiazides (chlorthiazide, hydrochlorthiazide)
• Loop diuretics (furosemide)
• All saluretics are also kaluretics.

Question 8

Loop diuretics

Answer 8

• Most effective diuretic drugs
• Inhibits the reabsorption of Na+ at Loop of Henle
• Inhibit the Na+/K+/2Cl- transporter
• Can still affect diuresis in the diseased kidney
• Highly effective.
• Increase sodium delivery to the distal segment of the distal tubule, thus increases potassium loss because the increase in distal tubular sodium concentration stimulates the sodium pump to increase sodium reabsorption, the major driving force behind secretion of potassium and hydrogen ions, which are lost to the urine.

Question 9

Furosemide (Salix) - absorption and administration

Answer 9

• Absorbed by all routes (IV and oral)
o IV: for life threatening situations (acute and severe pulmonary oedema, preventing renal shut down)
o Oral form: long term prevention of fluid accumulation and milder pulmonary oedema in congestive heart failure
• Extensively plasma bound; actively secreted in urine
• Effective for about 2-6 hours

Question 10

Furosemide (Salix) MOA

Answer 10

• Acts at the thick ascending loop of Henle (TAL)
• Inhibit the Na+/K+/2Cl0 transporter, thus inhibiting Na+, Cl-, K+ and water reabsorption
• Also Increases loss Ca2+ and Mg2+

Question 11

Furosemide (Salix) Clinical uses

Answer 11

• Oedema (acute treatment)
• CHF
o Long-term oral administration prophylactic use with ACE inhibitors
• Acute renal failure
o Prevent renal shutdown
• Exercise-induced pulmonary haemorrhage
– lowers pulmonary pressure (doping)
• Udder oedema
• Used as an emergency and long-term medication.
• Most commonly used diuretic.
• Removes fluid in general from the body, reduced accumulation in specific compartments.

Question 12

Furosemide (Salix®)** Side effects

Answer 12

• Hypokalaemia (prolonged use) - arrhythmias
• Hypotension,
• Dehydration
• Pre-renal azotemia
• Ototoxic at high doses

Question 13

Furosemide (Salix) Drug interactions

Answer 13

• Corticosteroids and NSAIDs decrease efficacy

Question 14

Furosemide (Salix) Precautions

Answer 14

• Liver disease – hepatic coma if levels of urea increase
• Digitalis therapy
o Supplement K+if needed

Question 15

Furosemide (Salix) Contra-indications

Answer 15

• Dehydration
• Unsuccessful treatment of uraemic patients
• Repeated doses in anuric patients
o No role for furosemide in these patients
o May precipitate ototoxicity

Question 16

Potassium-sparing diuretics

Answer 16

• Site of action; DCT and collecting ducts
• Inhibit the exchange of sodium and the secretion of potassium
• Override the renal effects of aldosterone
• “Anti-kaliuretic, potassium sparing or potassium retaining”
• Aldosterone acts to conserve Na+ and is important for preservation of blood pressure.

Question 17

Triamterene and amiloride

Answer 17

• Direct acting on Na+ channels to prevent reabsorption of Na+(K+spared)
• Used sometimes, usually in combination with loop diuretics/thiazides for K+ sparing effect
• Not very effective as they are weak diuretics
• When the Na+ channel is inhibited, there is reduction in activity of the Na+/K+ ATPase pump and inhibition of K+secretion.
• Moduretic contains amiloride and hydrochlorthiazide.

Question 18

• Methenamine

Answer 18

• At pH < 6.5, converted to formaldehyde (non specific antibacterial action G+ & G- and antifungal action)
• Efficacy not proven in dogs and cats

Question 19

• Ca2+ mandelate

Answer 19

• Used for weeks to months to treat chronic urinary tract infections, following antibiotics

Question 20

Acidifiers

Answer 20

• Lower urine pH
• Used in cats to dissolve or prevent struvite crystals
• Ammonium chloride
• Given as granules in food; unpalatable
• Metabolized in liver to urea, H+, Cl-
• H+ acidifies the urine which promotes struvite dissolution
 Hills s/d®, c/d® are now more commonly used
• Promotes urinary activity of some antibiotics
• Promotes excretion of some basic drugs (amphetmaines, quinidine) and toxins (strychnine)
• Careful treatment of metabolic alkalosis (i/v; be careful of inducing acidosis)

Question 21

Alkalinizers

Answer 21

• Increase urinary pH
• Enhance secretion of acidic drugs (E.g., barbiturates, aspirin)
• Enhance antibiotic effects (E.g., aminoglycosides)
• Sodium bicarbonate, organic acids such as sodium citrate
• Very seldom used in veterinary medicine
• Sodium citrate is metabolized to bicarbonate ions in the liver.

Question 22

Allopurinol

Answer 22

• Decreases the production of uric acid
• Used to treat:
• Biurate urolithiasis in Dalmatians
• Renal failure/gout in birds and reptiles
• Gouts in humans

Question 23

COX 2 selective NSAIDS (and COX 1!)

Answer 23

• Inhibit prostaglandins (including constitutive prostacyclin or PGI2) involved in renal haemodynamic homeostasis and preservation of GFR
• These PGs act on afferent and efferent vessels
• Risk of NSAID-induced nephropathy occurs in hypovolaemic nephron-compromised (e.g. dehydration), elderly and animals, when prostaglandin action becomes vital for perfusion of the kidney

Question 24

Aminoglycosides

Answer 24

• Cause tubular dysfunction and necrosis
• Filtered by glomerulus and accumulate in proximal tubular epithelial cells
• Interferes with phospholipid metabolism and may also cause vasoconstriction
• Dose and duration of treatment very important in toxicity