Drugs Affecting the Kidneys and Micturition Flashcards
functions of the kidneys
Primary function of the kidneys is to regulate the volume (water) and chemical composition (electrolytes, acid-base) of the ECF
n glomerular filtration
n tubular secretion
n tubular reabsorption
<><>
Kidneys also play important role in regulation of arterial blood pressure
n sodium-water balance
n renin-angiotensin-aldosterone system
n vasoactive humoral factors (PGI2, endothelin)
<><>
Other functions
n removal of metabolic wastes, foreign chemicals and several hormones
n elaboration of Vitamin D
n production of erythropoietin
what is diuresis?
natriuresis
kaliuresis
chloruresis
n Diuresis…..”increase in urine volume”
n natriuresis: increased renal sodium excretion
n kaliuresis: increased renal potassium excretion
n chloruresis: increased renal chloride excretion
do all diuretics act on the same part of the nephron?
Generally each diuretic class acts on specific segments of the
nephron
n loop diuretics: loop of henle
n thiazide diuretics: distal tubule
n K+-sparing diuretics: collecting ducts/tubule
n osmotic diuretics: descending limb of loop of henle
Therapeutic use (indications) of diuretics
n maintenance of urine flow in oliguric acute renal failure
<><>
n mobilization of ECF stores; edema or ascites
> congestive heart failure and acute pulmonary or systemic edema
> partiurent edema of mammary gland
> nephrotic syndrome
> hepatic cirrhosis
> iatrogenic fluid overload
n correction of specific ion imbalances
n reduction in intraocular and intracranial pressures
<><>
ensure adequate hydration before using diuretics
what must we ensure before using diuretics?
ensure adequate hydration before using diuretics
> don’t want to collapse vascular space
classes of diuretics?
loop
Thiazide
K+-sparing
Osmotic
most commonly used diuretic; most potent drug class for systemic diuresis
Loop diuretics
loop diuretic drugs we use?
- Furosemide, Torsemide
- Furosemide (Salix®, Lasix®, generic), Torsemide (Demadex®, generic)
Loop diuretics
- how common? how effective?
- mechanism
- animals used for
- what they treat, how
- potency
- onset time
n most commonly used diuretic; most potent drug class for systemic diuresis
n works as a diuretic by inhibiting the Na+/K+/2Cl- co-transporter in the thick ascending limb of the loop of henle
n licensed for use in dogs, cats, horses, cattle as a diuretic
n most commonly used to treat CHF
> decrease pulmonary pressures and promote
venodilation by vascular PGI2 release
=> critical effect in acute congestive episodes
> most potent diuretic class based on site of action in the loop of henle that is responsible for reabsorbing ~25% of the filtered sodium load
n rapid onset of action after IV administration
loop diuretics plus NSAIDs interaction
Concurrent NSAID use can negate the venodilatory and diuretic effects of furosemide which involves NSAID blockade of PGI2 and PGE2 production
additional uses of Loop diuretics
n promotes calcium excretion–used for hypercalcemia
n parturient edema; promote urine flow in oliguric acute renal failure
n EIPH in horses ????
adverse effects of loop diuretics
n ototoxicity; potentiated by aminoglycosides
n hypokalemia and digoxin toxicities
n dehydration, hypotension and electrolyte disturbance
commonly used thiazide diuretics
- Hydrochlorothiazide
- Trichlormethiazide (Naquasone)
Hydrochlorothiazide - what kind of drug?
- mechanism? potency? effects?
- caution?
- use in vet med
- diabetes interaction
Thiazide Diuretics
n works as a diuretic by inhibiting the Na+/Cl- co-transporter in the distal tubule n moderately potent diuretics; less than loop diuretics
n also decrease renal excretion of calcium
> caution in hypercalcemic patients
<><>
n less use of hydrochlorothiazide in veterinary medicine
> may be added to loop diuretics for additive effects
> parturient edema (mammary gland and other structures)
<><>
n paradoxically decreases urine output in diabetes insipdus (nephrogenic DI)
Trichlormethiazide
- type of drug
- properties
- use
Thiazide Diuretics
- licensed for use in veterinary patients
n similar in properties to hydrochlorothiazide; also has dexamethasone
n inflammatory conditions in horses; parturient edema in cattle
K+-sparing Diuretics are primarily indicated in what cases?
Primarily indicated to spare potassium wasting
K+-sparing Diuretics drugs commonly used
- Spironolactone (generic)
- Eplerenone (Inspra®)
Spironolactone, Eplerenone
- what type of drugs?
- mechanism
- efficacy
- cautions
K+-sparing Diuretics
<><>
n aldosterone receptor antagonists ie mineralocorticoid receptor antagonists
n block effects of aldosterone in the late distal tubules and collecting ducts
> aldosterone promotes sodium and water retention at the expense of excreting K+ and H+ ions
> aldosterone activates mineralocorticoid receptors in tubules; increases sodium channels and pumps; antagonists blocks mineralocorticoid receptors
> weak diuretics
> may be added to other diuretic classes
n aldosterone antagonists effective only in presence of aldosterone !!
<><>
n caution with hyperkalemia; hyponatremia also possible
Osmotic Diuretics properties, types used
low molecular weight substances freely filtered by the glomerulus, but poorly absorbed from the tubule fluid; generally pharmacologically inert
n mannitol; most commonly used osmotic diuretic; given IV
n glycerol; given by oral administration
Mannitol
- type of drug
- what it does, admin
- uses
- contraindications
n creates a hypertonic urine
n site of action is whole tubule, but primarily descending limb of loop of henle
n poorly absorbed orally hence given parenterally (IV)
n increases free water mobilization over sodium excretion
n uses include:
> oliguric acute renal failure
> increased intraocular and intracranial pressure
> promote excretion of toxins
n contraindicated in cranial bleeding and significant pulmonary edema
Hypokalemia and metabolic alkalosis relationship to diuretic therapy
Diuretics generally promote the increased delivery of NaCl to the distal tubules and collecting ducts
> distal exchange of Na+ for H+ and K+ yielding potential hypokalemia and metabolic alkalosis
> ensure adequate K+ intake in the diet
=> addition of a K+-sparing diuretic
Factors that can limit diuretic responses
nTolerance from long-term diuretic administration
n Reduced RBF and inadequate delivery of drug to site
n Proteinuria and increased fraction of bound drug
Drugs used to treat motor disorders of micturition target what broad issues
§ Urine storage; leakage
§ Urine voiding; retention, incomplete emptying
Physiology of Micturition
- important muscles and components for urination
- how the muscles work for contraction / relaxation ie. what neuro control
- Bladder
- Bladder wall with smooth muscle (detrusor)
- Involuntary muscle
§ sympathetic (relaxation)
§ parasympathetic (contraction) - Internal Sphincter
- Involuntary muscle
§ sympathetic (contraction)
§ parasympathetic (relaxation) - External Sphincter
- Voluntary muscle
§ sympathetic (contraction)
§ striated (contraction) - Urethra
Disorders of Micturition
- classification
Classification/mgmt. of disorders based on bladder and urethral function
- Hypocontractile Bladder
- Hypercontractile Bladder
- Hypertonic Urethra
- Hypotonic Urethra
Hypocontractile Bladder
- cause and signs
caused by:
n neurological lesions
n acute or chronic overdistension
<><>
signs: urinary retention and urine overflow is observed
drugs used for hypocontractile bladder?
mechanism?
contraindications?
reversal?
when most effective
Cholinomimetics used to promote bladder emptying
n Bethanechol (generic, Duvoid®); muscarinic (M3) receptor agonist
> contraindicated in urethral obstruction
> a-adrenergic antagonists & striated muscle relaxants can be given prior to promote urethral relaxation and maximal urine flow
> atropine is antidote to adverse effects
n most effective in atony secondary to overdistension
Hypercontractile Bladder cause, signs
caused by:
n neurological lesions
n chronic inflammation
n congenital disorder and tumors
<><>
signs:
n filling of the bladder decreased
n involuntary contractions of bladder at lower filling pressures and volumes; pollakiuria
Hypercontractile Bladder therapy is aimed at what? what drugs are used
- therapy is aimed ideally at underlying cause eg. Infection
- motor agents are used to reduce symptoms
<><> - Oxybutynin, Propantheline
- Imipramine
Oxybutynin use for disorder of micturition
- mechanism
- adverse effects
- similar drug
for hypercontractile bladder
n muscarinic antagonist; anti-spasmodic
n drowsiness, constipation and urine retention are adverse effects
n Others: Propantheline (Pro-Banthine®)
Imipramine use for disorder of micturition?
- type of drug? mechanism?
- when used
- other actions
- adverse effects
for Hypercontractile bladder
n classified as a tricyclic antidepressant
n inhibits amine (serotonin and norepinephrine) reuptake in prejunctional neurons…. results in increases in their levels and effects
n used in dogs and cats for urinary incontinence
n other actions include central and peripheral anticholinergic effects
n adverse effects include tremors, seizures, tachycardia
Hypertonic Urethra signs (and causes)
signs: urinary retention
n increased resistance to urine outflow and functional obstruction
<><>
caused by:
n neurological lesions
n inflammation
drugs used to solve Hypertonic Urethra
- a-adrenergic blockers
> Prazosin
> sildosin
<><> - Striated muscle relaxants
> diazepam
> dantrolene
use of a-adrenergic blockers for disorders of micturition?
- mechanism?
- adverse effects?
- which drugs are used? differences between them
for Hypertonic Urethra
n decrease internal sphincter resistance; more effective in dog, as cats have smooth
muscle limited to the proximal third of the urethra and more skeletal muscle n some may also decrease external sphincter resistance via central effects
n adverse effects include hypotension, reflex tachycardia, and GI disturbances
n Prazosin (generic, Minipress®); oral capsules
n Silodosin (Rapaflo®)
> oral capsules; highly selective a1a adrenergic antagonist; more selective for
urethral smooth muscle; less adverse effects on the CV system
> less experience with silodosin at this time
Striated muscle relaxants used for what disorder of micturition
used in cats and dogs with functional urethral obstruction
Diazepam use in disorders of micturition, mechanism
for hypertonic urethra
-centrally-acting relaxant
nDiazepam produces centrally mediated effects that are dose-dependent starting with anxiolytic effects, followed by relaxation, sedation and anticonvulsant effects at increasing doses
nWorks by enhancing GABAA receptor activity
nRare idiosyncratic hepatotoxicity in cats following oral administration
Dantrolene use in disorders of micturition, mechanism, adverse effects?
for hypertonic urethra
-peripheral-acting relaxant
nProduces skeletal muscle relaxation most likely by interfering with release of
intracellular calcium from skeletal muscle sarcoplasmic reticulum
nCan cause hepatotoxicity in humans but incidence in veterinary patients is unknown
hypotonic urethra signs, (Cause)
signs:
n poor outlet resistance leading to urinary leakage
<><>
caused by:
n neutered dogs and cats; hormone responsive
n neurological lesions or inflammation
types of drugs used for Hypotonic Urethra
Reproductive hormones
- Diethylstilbesterol
- Estradiol
- Testosterone
<><>
a-adrenergic agonists
- phenylpropanolamine
- ephedrine
- pseudoephedrine
Reproductive hormones used for treating hypotonic urethra, adverse effects?
n estrogen often effective in females
> Diethylstilbesterol (Stilbestrol®) licensed in spayed dog, cats
> Estradiol licensed for use in spayed dogs
> adverse effects include bone marrow suppression, alopecia and induction of estrus and tumors possible
n Testosterone can be used similarly in males
> aggressive behaviour, perianal and prostatic disease possible
a-adrenergic agonists for what disorder of micturition?
- mechanism
- which drugs?
- uses, adverse effects?
hypotonic urethra
- stimulate a-adrenergic receptors directly and promote release of norepinephrine; increase sphincter tone
n phenylpropanolamine (Proin®, Propalin®), ephedrine, pseudoephedrine
n phenylpropanolamine approved for use in dogs for urinary incontinence
n equally effective in males and females
n adverse effects; tachycardia, excitability & anorexia