Diuretics Flashcards
Functions of the Kidneys (5 main functions)
- Regulation of water and inorganic-ion balance
- Removal of metabolic waste products from the blood (urea, uric acid and creatinine)
- Removal of foreign chemical from the blood and their excretion in the urine
- Gluconeogenesis (during prolonged fasting)
- Secretion of hormone/circulating factors
a. EPO
b. Renin
c. 1,25-Dihydroxyvitamin D3
Macula densa senses what?
specialized cells sense Na+ load
JG cells are located? Secrete? (under what portion of the PNS?)
Afferent arteriole; Secrete Renin (modulated by sympathetic nervous system)
Reabsorption is accomplished through what two methods?
Diffusion and Mediated transport
Diuretics act predominantly on _____?
Reabsorption
Diuretics produce a _____ in volume of urine?
Increase in volume of urine;
Also can change composition of urine;
Predominant effect of diuretics: Na+ and H2O reabsorption
Glomerular process?
Formation of an ultrafiltrate of plasma (free of cells and protein)
Primary role of the Proximal Tubule?
Major site: _____ Na+ transport
Major site for solute secretion - EXCEPT for _______
Reabsorption of water and solutes;
ACTIVE Na+ transport;
Except for K+
__% of filtered Na+ load reabsorbed
~65%
H+ secretion/ exchanged for Na+;
helps in reabsorption of bicarbonate
Carbonic anhydrase
Loop of Henle:
creates hyp__osmotic interstitial fluid though the _______ multiplier system
Hyperosmotic;
Countercurrent
Descending thin limb:
highly permeable to ___? No ____ reabsorption
highly permeable to H2O; No Na+ reabsorption
Ascending thin limb is impermeable to?
Water; Na+ diffuses out
Thick ascending limb:
Active ___ transport
Na+; through Na+K+/2Cl- symport
LAte distal tubule and cortical collecting duct:
active Na+ _____ in exchange for ____?
reabsorption; K+
Aldosterone promotes ______ in Late distal tubule and cortical collecting duct?
Na+/K+ exchange
In collecting duct, luminal membrane has ___ channel? Unique to this part of renal tubule
K+
Aldosterone induces synthesis of _____ channels in luminal membrane of late distal tubule and cortical collecting duct?
Na+ and K+ channels;
Promotes Na reabsorption and K secretion
Na+/Cl- symport is _____ sensitive
thiazide;
this occurs proximal to site for aldosterone action
RAAS: JG apparatus
Macula densa senses _____ Na+ load => _____ cells secrete renin => increased renin => increased ____ => increased aldo => decreased na excretion
decreased Na load;
JG cells secrete renin;
increased AngII
Aldo also controlled by __
K+;
increased K in ECF of adrenal cortex => increased aldo secretion => increased K excretion by kidney
Medullary collecting duct is major site for ____ control of Na and water reabsorption
hormonal
_____ required for H2O reabsorption
ADH/vasopressin
Characteristics of Osmotic Diuretics?
Freely filtered; Limited reabsorption; pharmacologically inert; resistant to metabolism
Site/MOA of Osmotic diuretics
Proximal tubule and loop of Henle - osmotic effect, hold water in tubular lumen;
Reduced Na reabsorption
Effects of Osmotic diuretics
initial expansion of intravascular fluid volume, inreased renal blood flow;
Increased excretion of urinary electrolytes - isosmotic water loss;
Maintain diuretic effect during hypovolemia or shock - trauma
name 4 osmotic diuretics
Mannitol (preferred)
Glycerol
NaCl
Ammonium chloride
Mannitol-
Must be given ____
perenterally
Mannitol Indications
Cerebral edema, glaucoma, prophylaxis of acute renal failure (questionable value if given after renal damage), promote excretion of certain toxins
Mannitol contraindications
Congestive heart failure (esp with pulmonary edema);
Anuric renal failure that does not respond to a test dose
Mannitol- Large or small anmal
Both; no withdrawal time for food animals
Glycerol- can be given ____; metabolized and may cause ______
Orally;
Hyperglycemia
Glycerol Indication
Treatment of glaucoma - reduces ocular pressure, sometimes used in small animals, but mannitol is preferred osmotic agent
Glycerol Contraindications
Diabetes mellitus
NaCl - Increases ____ consumption
water
NaCl - added to ____
feed (sheep,calves)
NaCl- Increases ______ volume; in order to dilute ______
Increases urine volume; used for diluting stone forming substances - Ca2+, Mg2+
Ammonium chloride- given ____ - has ___ diuretic action
orally; transient
Main use of ammonium chloride
urinary acidifier; used to manage cystic calculi or chronic urinary tract infections
Ammonium Chloride Contraindications
Patients with systemic acidemia (can cause subclinical metabolic acidosis); use caution in patients with renal disease
Ammonium chloride
Large or small animals?
both; no withdrawal time in food animals
Carbonic Anhydrase Inhibitors: Site/MOA
Primary proximal tubule - Decreased H+ secretion, Na+ and HCO3- reabsorption;
Minor effects at collecting duct
Carbonic Anhydrase Inhibitors: Effect
Increased excretion of HCO3, Na, K and water(transient);
Metabolic acidosis and decreased excretion of ammonia
Decreased production of aqueous humor
Name 3 Carbonic Anhydrase Inhibitors
Methazolamide
Acetazolamide
Dichlorphenamide
Carbonic Anhydrase Indications:
Major use: Glaucoma
(Methazolamide used more often; other regimens preferred for glaucoma)
Can be used to produce alkaline urine (transient)
Also been used for udder edema in cattle (extralabel)
Carbonic Anhydrase Contraindications
Allergy to sulfonamides
History of renal or urinary calculi that form in alkaline urine
Presence of Na or K depletion
Presence of metabolic or respiratory acidosis
Loop diuretics AKA
High Ceiling diuretics
Loop diuretics Site/MOA
Thick ascending limp of loop of henle;
inhibit Na/K/2Cl symport;
inhibit paracellular diffusion of Na, K, Mg, Ca;
Minor- some inhibition of Na and CL reabsorption in proximal and distal tubules
Loop diuretics characteristics
Most Common diuretic in VetMed
Highly protein bound in plasma, but actively secreted into proximal tubule
Profound diuresis - most effective for edematous conditions “high ceiling diuretics”
Loop diuretics Effects
1 Profound increase in Na excretion, also cl, h2o, k, h, ca, mg (most profound Na and Ca)
2 Mild systemic venodilator (acutely increase renal blood flow
3 Bronchodilator in humans horses and guinea pigs
4 Increased renin secretion (due to decreases plasma Na)
5 Metabolic alkalosis
Name 3 loop diuretics
Furosemide (preferred)
Bumetanide (25-50x more potent)
Torsemide (more potent and ~2x longer duration)
Furosemide PK:
Onset of action, peak effect, duration
Onset of action: IV-5 min, Oral-1hr
Peak effect: IV-30min, Oral- 1-2hrs
Duration: IV- 2-3hrs, Oral- 4-6hrs
Loop Diuretics Indications:
- Congestive heart failure (ascites, pleural effusion, pulmonary edema) ie noninflammatory edema
- Hypercalcemia
- prophylaxis for epistaxis (exercise induced pulmonary hemorrhage in the equine
- Udder edema (food animal withdrawal time = 48hrs)
- Cerebral edema (if havent had significant blood loss)
- Only diuretic with significant effect in patients with impaired renal function
Loop Diuretics: Contraindications/Cautions
- Anuria/progressive renal disease
- Hypokalemia
- Allergy to sulfonamides
- Possible ototoxicity with rapid IV administration (rare)
- Ca wasting cows may precipitate milk fever
- Beware of profound dehydration (esp if stops drinking)
- NSAIDs attenuate natriuretic effects of furosemide
Thiazide Diuretics AKA
Rescue Diuretics
Thiazide Site/MOA
Early distal tubule (before site for Na/K exchange)
Inhibit Na/Cl symport
Also minor inhibition carbonic anhydrase n proximal tubule
Thiazide Characteristics
- Secreted into proximal tubule
2. Decreased Na reabsorption and increased K secretion (increased Na load in tubular fluid, promotes Na/K exchange)
Thiazide Effects
- Moderate Diuresis - rarely used as a first choice diuretic
- increased excretion of Na, Cl, and K
- Decreased excretion of Ca
Name two Thiazide diuretics
Hydrochlorothiazide (preferred)
Chlorothiazide
Thiazide diuretics
PK
Onset of Action (oral): 2 hrs for hydrochlorothiazide, 1 hr for chlorothiazide
Peak effect at 4 hrs
Duration ~12 hours
Thiazide Indications
- Not first choice for monotherapy
- Refractory feart failure (resistant to furosemide) - a. Rescue with thiazide - canine (diuretic effect on own + restores diuresis to furosemide)
- Ascites due to liver disease
- Diabetes insipidus (paradoxically decreases urine flow)
- Udder edema (extralabel)
Thiazide Contraindications
1 Hypokalemia
2 Diabetes Mellitus
3 Use with caution in congestive heart failure
4 If using as “rescue” decrease dose of furosemide by 50%
K sparing agents Site/MOA
Site: late distal tubule and collecting duct
MOA: Atagonize Aldo (spironolactone) - blocks active Na/L exchange
OR
Block sodium channels (triamterine) in tubular cells of the late distal tubule and collecting duct
K Sparing Agents
Characteristics
Actively secreted by the renal tubules
K Sparing Agents
Effects
1 Increased excretion of NaCl
2 Decreases excretion of K, H, Ca, Mg
K Sparing Agents
PK: spironolactone
- protein bound, but actively secreted by renal tubules
2. gradual onset and offst of action - peak effect 2-3 days after therapy is started
K sparing agents
Indications: spironolactone
- Used in small animals - mainly dogs and cats
- Refractory heart failure
a. used mainly in combination with other diuretic agents (primarily furosemide-small additional diuretic effect and decreases K excretion)
b. spironolactone + ACE inhibitor: be aware of risk of hyperkalemia, unless furosemide is also given - Ascites caused by right heart failure, hepatic disease, or nephrotic syndrome
K sparing agents
Contraindications: spironolactone
- Hyperkalemia
- Use caution administering with other drugs that increase blood K such as ACE inhibitors or NSAIDS
- Not advisable to combine with ACE inhibitor unless also giving furosemide
- Induces hepatic microsomal enzymes (watch for drug interactions)
K Sparing Agents
PK: triamterene
Action begins within 2 hrs, peaks at 6-8hrs and lasts 12-16 hrs
Used infrequently in VetMed
Xanthines (mild diuretic effects)
Name two
Caffeine (toxicosis)
Theobromine (chocolate toxicitiy)
Xanthines Characteristics/effects
- not used as diuretics but have mild diuretic effect
- positive inotropic and chronotropic effects on the heart
- CV effects increase renal blood flow, glomerular filtration rate, and medullary blood flow
- Inhibit tubular NaCl reabsorption
- Major use = relax airway smooth muscle
- Can overstimulate the CNS
Xanthines: SIte of Action
We dont really know?
Compounds: Xanthines
Theophylline, aminophylline - drugs used to treat pulmonary hypertension, feline and equine asthma, canine chronic bronchitis (may have mild diuretic effect)