Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

CHAPTER 19 GASTROINTESTINAL DRUGS
circumstances, they should be used with caution. These
drugs have also been used frequently in the past as
antiemetics but usually inappropriately. They are usually
not effective unless vomiting is initiated by smooth
muscle spasm (an extremely uncommon occurrence).
They do not stop vomiting caused by stimulation of
peripheral receptors by other means such as inflammation.
Those anticholinergic drugs that can cross the
blood–brain barrier (e.g. hyoscine) are effective for
motion sickness through antagonism of M 1 -receptors in
the vestibular apparatus.
Anticholinergics have been used in the management
of pancreatitis on the basis that they may reduce pancreatic
secretion. However, no appreciable benefit has
been demonstrated experimentally or clinically from
this treatment. In fact, some clinicians consider that
their use is contraindicated in pancreatitis because they
cause thickening of pancreatic secretions.
Mechanism of action
Anticholinergics act as antagonists at central and peripheral
muscarinic receptors (M 1 and M 2 ). Quaternary
ammonium antimuscarinics, such as butylscopolamine
and propantheline, do not cross the blood–brain barrier,
so have a predominantly peripheral action, and CNS
side effects are minimal.
Formulations and dose rates
Atropine sulfate is available as an injectable preparation. No veterinary-approved
preparations of propantheline are available, but generic
human tablet formulations can be used (7.5 mg, 15 mg). In some
countries, butylscopalamine is available, as both injectable and oral
preparations (Buscopan®) and also in an injectable formulation in
combination with metamizole (dipyrone) (Buscopan Compositum®;
4 mg/mL butylscopalamine, 500 mg/mL metamizole); the latter is a
pyrazoline drug with anti-infl ammatory, analgesic and antipyretic
properties.
Atropine
• The standard dose rate is 0.02–0.04 mg/kg, IM or SC
Propantheline
• The dose for both dogs and cats is 0.25 mg/kg PO q.8 h
Butylscopalamine
• In dogs, the primary indication is as a long-acting antispasmodic
at a dose of 0.5 mg/kg IM or PO q.12 h (sole preparations)
or 0.1 mg/kg IV or IM (in combination with metamizole)
Adverse effects
● The major problem with anticholinergics is that they
also affect M 2 -receptors, potentially causing delayed
gastric emptying and ileus. This may potentiate vomiting
and exacerbate gastric hypomotility, which
occurs in many disorders causing vomiting. These
drugs should also be avoided in cases suspected to
have gastrointestinal obstruction.
● Overuse can result in gastric atony and intestinal
ileus, which may predispose to absorption of endotoxins
through damaged mucosa.
● Antimuscarinic agents should be used with caution
in cases with known or suspected enteric infections,
because the reduction in motility may prolong the
retention of the causative agent.
● Antimuscarinic agents should also be used with
caution in animals with hepatic or renal disease,
hyperthyroidism, congestive heart failure, hypertension,
concurrent myasthenia gravis, prostatic hypertrophy
and in geriatric or pediatric patients.
● Side effects are those expected for antimuscarinics,
e.g. xerostomia, dry eyes, hesitant urination, tachycardia
and constipation. CNS side effects include
stimulation, drowsiness, ataxia, seizures and respiratory
depression; however, these effects are unlikely
with the quaternary ammonium antimuscarinics.
Ocular side effects of this group include mydriasis,
cycloplegia and photophobia; again, these side
effects are less likely with quaternary ammonium
antimuscarinics.
Known drug interactions
● Antimuscarinics can enhance the actions of thiazide
diuretics and sympathomimetics and antagonize the
effects of metoclopramide.
● Antihistamines, procainamide, quinidine, meperidine,
benzodiazepines and phenothiazines can all
potentiate the effects of anticholinergics.
● Adverse effects can be exacerbated by corticosteroids,
primidone, nitrates and disopyramide.
Antihistamines
EXAMPLES
Diphenhydramine (Benadryl®), dimenhydrinate
(Dramamine®)
Clinical applications
Antihistamines are primarily indicated for treatment
and prevention of motion sickness in the dog.
Mechanism of action
Antihistamines block histamine receptors in the CTZ
and vestibular pathways. Histamine receptors in CTZ
are involved in motion sickness in the dog but not in
the cat.
In addition to its antihistaminergic effects, diphenhydramine
has substantial sedative, anticholinergic,
476