AN UPDATE ON:

DRUGS ACTING ON GENITOURINARY

SYSTEM
Drugs acting on Uterus and cervix
Myometrial stimulants
Uterine relaxants
cervical dilators
Hormones
Drugs acting on Urinary system
Diuretics
Drugs for urinary retention and incontinence
Urinal acidifiers
Urinary alkalisers
Drugs fro urolithiasis
Myometrial Stimulants (ECBOLICS)
stimulate contraction of the oestrogen-sensitised uterine
myometrium and mammary myoepithelial cells.
Indications:
In dystocia due to secondary uterine inertia. However, should not
be used when dystocia is due to malpresentation or obstruction.
Control of postpartum hemorrhage to hasten uterine involution
immediately
after parturition in all species, to aid clearance of uterine discharge
they have no effect on separation of the placenta in ruminant
species
To reduce the size of a uterine prolapse after replacement in cattle.
agalactia due to failure of milk let down
Oxytocin
mediates contractility of the endometrium
which has been prestimulated with
estradiol.
facilitates some milk let-down without
having galactopoietic ability.
s mildly antidiuretic.
Inappropriate use- to uterine rupture,
anaphylactoid ,maternal death,fetal death.
Oxytocin
intravenous infusion (e.g., labor induction), intramuscular
injection (e.g., control of postpartum bleeding)
It is important to use calcium gluconate 10% solution (1
mL/5.5 kg SC q.46 h) minimum 15 min before oxytocin
even in eucalcemic bitches.
If one treatment of oxytocin for dystocia is unsuccessful,
repeated use must be questioned, given the likelihood of
inducing tetanic uterine contraction and fetal death
Contraindications and precautions
Obstructive dystocia
Any contraindication for vaginal delivery
(e.g.relative or absolute oversize)
Maternal toxemia.
Underlying causes of dystocia (e.g.
hypocalcemia) should be treated before
use of oxytocin.
Adverse effects
Use in obstructive dystocia can cause uterine
rupture
Overdose, either single large doses or multiple
doses, will cause spastic, hypertonic or tetanic
uterine muscle contraction with lack of
orchestration of contractions.
This may induce placental separation or
damage, fetal distress or death and uterine
rupture.
Incompatible with, noradrenaline
(norepinephrine) bitartrate, prochlorperazine
edisylate and warfarin sodium.
Prostaglandin F
2
alpha and derivatives
Alfaprostol, cloprostenol, dinoprost,
etiproston, luprostiol and tiaprost are
synthetic
As ecbolics: in obstetrics are dinoprostone
(PGE
2
), carboprost (15-methyl PGF
2
)
cloprostenol, and gemeprost or
misoprostol (PGE
1
analogues)
PGF2alpha
causes myometrial contraction
cervical relaxation
luteolysis.
regression of the corpus luteum
to treat open pyometra in bitches
to terminate pregnancy in bitches in combination with
cabergoline.
PGF2
to control cyclical ovarian activity in polyoestrous species
for termination of pregnancy, or for induction of
parturition.
a number of pathological conditions including
mummified fetus, pyometra, and luteal cysts in cattle
pseudopregnancy in goats
Abortion induction in the bitch and queen
Treatment of pyometra in the bitch and queen
Reduction of the duration of interestrus intervals.
Contraindications and precautions
during pregnancy or in animals
hepatic, renal or systemic disease
Not to be administered intravenously
Pregnant women or people with bronchial
disease,including asthma, should not handle or
administer these drugs.
side effects (emesis, salivation, defecation,
respiratory distress
PG
Accidental spillage on the skin should be
washed off immediately with soap and
water.
Cloprostenol has been proved to be an
efficient abortive agent: 2.5 g/kg 3
injections at 48-h intervals after d25 of
pregnancy.
Dinoprostone
synthetic PGE2
vaginally for oxytocic use.
stimulates the contraction of the uterus throughout
pregnancy.
directly affects the collagenase of the cervix, resulting in
softening.
For the induction of labor, dinoprostone is available
either as a gel (0.5 mg PGE2)
For softening of the cervix at term, the preparations used
are either a single vaginal insert containing 10 mg PGE2
or a vaginal gel containing 0.5 mg PGE2 administered
every 6 hours.
ERGOT ALKALOIDS
stimulate uterine smooth muscle directly,
thereby increasing muscular tone
enhancing the rate and force of rhythmical
contractions.
Ergometrine (ergonovine) maleate and
Methylergometrine (methyl ergonovine)
maleate
the routine expulsion of the placenta after
delivery
postpartum and postabortal atony and
hemorrhage.
Ergonovine also stimulates cervical
contractions.
These drugs are capable of inducing a sustained
tetanic contraction, which can shorten the final
stage of labor and aid in the reduction of
postpartum blood loss
Ergot alkaloids
excreted in milk
should not be administered longer than
necessary,since prolonged use can lead to
ergot poisoning (ergotism)
should not be used in cases of threatened
spontaneous abortion .
Dopamine agonists
Cabergoline, Bromocriptine
Antiserotoninergic compounds:.
Clinical applications
Galactostasis: prevent prolactin secretion and indirectly
impede milk production.
Overt pseudocyesis or pseudopregnancy:
Pregnancy termination: Oral may be combined with
cloprostenol (a synthetic prostaglandin analog) to reduce
the dose of both drugs in the bitch and queen.
MYOMETRIAL RELAXANTS( Tocolytics)
inhibit uterine contraction or result in relaxation of uterus
to aid obstetrical manoeuvres during dystocia
to facilitate handling of the uterus during caesarean
operation.
to facilitate the recovery of embryos from donors for embryo
transfer
to facilitate replacement of a prolapsed uterus.
to delay parturition so that it may occur when greater
observation and care are available
In addition, when used in heifers, calving can be delayed
sufficiently to allow better relaxation of the birth canal and
perineum.
incomplete cervical dilation (ringwomb) in sheep, although
their effect is questionable
Tocolytics
Precautions:
Extreme care, since pulmonary edema,
myocardial infarction, respiratory arrest,
cardiac arrest, and death can occur
Newborns of mothers given tocolytics
have had respiratory depression
Tocolytics
Contraindications:
acute fetal distress (except during
intrauterine resuscitation),
eclampsia or maternal hemodynamic
instability
Concurrent administration of atropine,
adrenoceptor stimulants, vasodilators, or
general anaesthetics, oxytocin,
prostaglandins

2
-adrenoceptor agonists
clenbuterol( Cattle: 300 micrograms as a single dose,
IM,IV) terbutaline, isoxsuprine, ritodrine or salbutamol
Magnesium sulfate
prevents convulsions in preeclampsia and directly
uncouples excitationcontraction in myometrial cells.
Mg toxicity can be life threatening.
Tocolyticscontd
Indomethacin
given orally or rectally for 24 or 48 hours
to delay premature labor.
. Long-term use of maternal indomethacin
is associated with primary pulmonary
hypertension, of intraventricular
hemorrhage in the newborn.
Tocolyticscontd
Nifedipine
calcium channel blocking agent
Hydroxyprogesterone
. A concern relating to teratogenic potential
has limited its use.
DIURETICS
increase urine flow by increasing renal plasma flow
or by altering nephron function
indicated to reduce oedema in cases of heart failure,
hepatic disease, cerebral oedema,
hypoproteinaemia, inflammation, and trauma.
Diuretics
Loop diuretics: furosemide, bumetanide,
ethacrynic acid- Most potent ones
Thiazide diuretics: hydrochlorothiazide,
chlorothiazide
Potassium-sparing diuretics:
spironolactone, triamterene,amiloride
Osmotic diuretics: Mannitol, urea,
glycerol
CAse inhibitors: Acetazolamide
Methyl xanthines: theophylline
Thiazides
reduce urinary calcium excretion
increase Na, Cl, K excretion
to treat cardiac/ hypoproteinaemic oedema
an adjunct to horm.therapy in pseudopregnancy.
Hydrochlorothiazide-Oedema; inhibition of
lactation in pseudopregnancy in the bitch
primarily used in canines that have developed
furosemide resistance.
Loop diuretics
most potent with a rapid onsetof effect but
a short duration of action.
These drugs block sodium reabsorption in
the loop of Henle
They increase magnesium excretion and,
as with thiazides, may cause severe
potassium loss.
May potentiate the ototoxic effects of
aminoglycoside antibiotics.
Frusemide
in conditions such as cardiovascular and
pulmonary oedema, hepatic and renal
dysfunction, hydrothorax, ascites, and
non-specific oedema.
results in enhanced excretion of sodium,
chloride, potassium, hydrogen,
calcium,magnesium and possibly
phosphate.
acts as a bronchodilator in humans,
horses and guinea-pigs
Furosemide
can potentiate the ototoxic and nephrotoxic effects of
other drugs-NSAIDs,aminoglycosides.
Injection- mixed with weakly alkaline and neutral
solutions having a pH of 710, such as 0.9% saline or
Ringers solution.
A precipitate may form if the injection is mixed with
strongly acidic solutions such as those containing
ascorbic acid, tetracycline, adrenaline (epinephrine) or
noradrenaline (norepinephrine).
Injection should also not be mixed with most salts of
organic bases, including lidocaine, alkaloids,
antihistamines and morphine.
Drug interactions
Acetazolamide
aminoglycoside
antidiabetic drugs
beta-blockers, captopril
cardiacglycosides
cephalothin and other cephalosporins
corticosteroids
lignocaine, quinidine
Osmotic Diuretics
Hypertonic solutions of mannitol, urea,
glycerol
mannitol causes water retention with in the
nephron,which dilutes urinary sodium and
opposes its reabsorption especially in the
proximal tubule and loop of Henle.
Mannitol
used to promote urine output, as in acute renal
failure, or to reduce cerebral oedema.
s not suitable for the mobilization of general or local
oedema because it may lead to cardiac overload.
Excessive administration- severe hypovolaemia and
maintenance of extarcellular fulid volume may
require administration of an electrolyte solution such
as compound of sodium lactate intravenous infusion.
Indications.:Cerebral oedema, forced osmotic dieresis.
Extravasation causes inflammation and
thrombophlebitis.
Potassium sparing diuretics
Act by inhibiting the action of aldosterone on distal tubular
cells or blocking sodium reabsorption in the latter regions of
the distal tubule and collecting tubules.
Weak diuretics when used alone as diuretics and thus should
never be used as sole agents
In a patient, refractory to other diuretics. administered with
other diuretics, potassium loss is decreased
Spironolactone: used in combination with other diuretics,
primarily furosemide, to produce additional diuresis/ to
decrease potassium excretion.
used in the management of fluid retention associated with
non cardiac disease-hepatic disease and nephrotic syndrome.
Diuretics Interactions
ACE inhibitors, potassium supplements increased risk
of hyperkalaemia with potassium sparing diuretics
Acetazolamide increased risk of hypokalaemia with
loop and thiazide diuretics
Aspirin antagonism of diuretic effect of
spironolactone
Beta-adrenoceptor blocking drugs increased risk of
ventricular arrhythmias in the presence of
hypokalaemia
Calcium salts increased risk of hypercalcaemia with thiazide
diuretics
Cardiac glycosides increased toxicity if hypokalaemia occurs;
enhanced effect of digoxin with furosemide or spironolactone
Cephalosporins increased risk of nephrotoxicity with loop diu.
Corticosteroids, corticotropin antagonism of diuretic effect;
increased risk of hypokalaemia with loop and thiazides
Insulins possible increase in insulin requirement with thiazide
lidocaine effect antagonised by hypokalaemia with loop and
thiazide diuretics
Mannitol decreased effect of loop diuretics
NSAIDs antagonism of diuretic effect; increased risk of
hyperkalaemia with potassium-sparing diuretics
Oestrogens antagonism of diuretic effect
Sulphonamides increased risk of sulphonamide allergy with
loop diuretics
Adverse effects
electrolyte disturbances
dehydration and prerenal and renal azotemia. T
azotemia -when they are used concurrently with ACE
inhibitors and/or NSAIDs and other potential renal
toxins.
Cats more susceptible than dogs to becoming
electrolyte depleted and dehydrated with diuretic
therapy.
Hypokalemia , hypomagnesema, Hyponatremia may
occur in patients on high dose diuretic therapy.
URINARY ACIDIFIERS
Ascorbic acid (Horses: 2 g/kg daily,PO; Dogs: 100500 mg 3
times daily,PO; Cats: 100 mg 3 times daily)
Ammonium chloride (Dogs: 100 mg/kg 12 times daily,PO;
Cats: 400 mg/4.5 kg body-weight twice daily with food. Adjust
dose until desired urinary pH change achieved) ;
Ammonium sulfate (Horses: 175 mg/kg daily,PO);
ethylenediamine, arginine HC1,
Calcium chloride , methionine and sodium acid phosphate
may be used to acidify the urine.
useful in the management of urinary tract infection to
enhance antimicrobial activity
URINARY ALKALINISERS
in preventing certain drugs, such as some
sulfonamides, from crystallising out in the urine
decreases the formation of uric acid and cystine
stones
to manage some forms of urolithiasis
to increase the excretion of drugs that are weak
acids (e.g. salicylates and some barbiturates) by
alkalinising the urine
reduces irritation of an inflamed urinary tract,
discourages the growth of certain organisms,
e.g.Escherichia coli
Sodium bicarbonate, sodium citrate, and potassium
citrate
some antibacterial effects, as well as decreasing
irritation or inflammation in the urinary tract.
Potassium citrate: Dose: . Dogs, cats: 75 mg/kg , PO,
twice daily or 2mmol/kg twice daily
Sodium bicarbonate: Dose. Dogs, cats: 1050 mg/kg
23 times daily,PO
DRUGS FOR URINARY RETENTION AND
INCONTINENCE
Urinary incontinence
hypercontractility or decreased
accommodation of the urinary bladder,
flaccidity of the urethral sphincter, or
urethral incompetence.
Bladder wall irritability leading to frequent
micturition, which may be confused with
incontinence, may be caused by cystitis .
Propantheline
antimuscarinic drug, which reduces urinary urgency and
frequency by diminishing unstable muscle contractions
oral estriol (Dogs: initial dose, 1 mg daily. If response,
reduce to 0.5 mgdaily
oral diethylstilbestrol at doses of up to 1.0 mg daily for
3 to 5 days, followed by weekly treatment.
Phenylpropanolamine
alpha adrenergic compound used to treat urinary
incontinence in spayed bitches
dose should be reduced if used concurrently with
oestrogen therapy.
Parasympathomimetics-bethanechol
DRUGS FOR UROLITHIASIS
Urate uroliths are more soluble in alkaline urine.
Dietary control to reduce protein intake and urine alkalinisers
Allopurinol (Dogs: urate calculi, 10 mg/kg,PO, 3 times daily
for 4 weeks then 10 mg/kg once daily) reduces the formation
of uric acid from purines by inhibiting xanthine oxidase.
Penicillamine (Dose. Dogs: cystine calculi, 15 mg/kg,PO,
twice daily preferably on an empty stomach.
Thiazide diuretics may be used to reduce the recurrence of
calcium-containing uroliths (for example, calcium oxalate
calculi) in dogs.
Dietary management and potassium citrate have also been
used in the control of calcium oxalate urolithiasis.