Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

CHAPTER 4 THE PHARMACOLOGY OF THE AUTONOMIC NERVOUS SYSTEM
(phenoxybenzamine) and the management of hypertension
associated with Ixodes holocylus toxicity
(phenoxybenzamine).
Prazosin has clinical applications in the management
of heart failure in dogs as it results in a significant reduction
of cardiac afterload. This is discussed in more detail
in Chapter 17.
The selective α 2 -receptor antagonist atipamezole is
commonly used as an antidote for the central sedative
and analgesic effects of medetomidine and xylazine.
Ergot alkaloids such as ergotamine, bromocriptine
and cabergoline, which are partial agonists at α-adrenoceptors,
can have effects on vascular tone depending on
the level of basal sympathetic stimulation. In veterinary
medicine they are mainly used for their effects in the
reproductive tract which are mediated via the activation
of α-adrenoceptors and dopamine receptors.
b-Adrenoceptor antagonists
β-Adrenoceptor blockers are used extensively in human
therapeutics in the management of hypertension due to
their potential to induce slow-onset reduction of blood
pressure by reducing cardiac output, reducing the release
of renin from the juxtaglomerular cells of the kidney
and inhibiting central sympathetic activity. The main
veterinary application of β-blockers is their use as antidysrhythmic
drugs for the treatment of supraventricular
tachyarrhythmia in cats and dogs. Furthermore, the use
of β-blockers can be indicated in treating hypertension
associated with renal failure and hyperthyroidism.
Despite their negative inotropic effects, β-blockers have
been shown to improve survival in human patients with
heart failure and recently have been suggested as treatment
for heart failure in cats and dogs. More detail on
the use of β-blockers in the treatment of cardiovascular
disease can be found in Chapter 17.
The prototype of these agents is propranolol, a nonspecific
β-blocker affecting both β 1 and β 2 receptors
which, alongside the desired effects on heart and vasculature,
can therefore induce bronchoconstriction.
This is a potential problem in patients with asthma.
Alternatively, the use of selective β 1 -adrenoceptor antagonists
such as atenolol can prevent these unwanted side
effects. Nonselective blockers of β 1 or β 2 receptors with
partial agonist properties (oxprenolol, alprenolol) in
future may provide the clinical advantage that they
support cardiac function at rest but block the detrimental
effects of excessive sympathetic activation in heart
failure.
The topical administration of β-blockers to the eye is
commonly used to treat glaucoma. Their application
results in the inhibition of β 2 -mediated relaxation of
the ciliary muscle, thus facilitating drainage of aqueous
humor via the canal of Schlemm and reducing intraocular
pressure (see Chapter 25).
DRUGS ACTING ON THE AUTONOMIC
NERVOUS SYSTEM AND THEIR CLINICAL
APPLICATION
Cholinergic agonists
(parasympathomimetics)
Bethanechol
Clinical applications
Bethanechol can be used in cases of paralytic ileus following
surgery and for the treatment of nonobstructive
urinary retention. Approved veterinary drugs are not
available in the USA and UK, but approved human
preparations can be used for extra-label use and under
the requirements of the UK/European prescription
cascade.
Mechanism of action
Bethanechol directly stimulates muscarinic acetylcholine
receptors. It has negligible nicotinic activity when used
at therapeutic doses. It has a longer duration of activity
than ACh as it is more resistant to cholinesterasemediated
hydrolysis.
Formulations and dose rates
Bethanechol chloride is supplied as tablets for oral use and in solution
for parenteral use.
DOGS
• 5–25 mg PO q.8 h
CATS
• 2.5–7.5 mg q.8 h
Pharmacokinetics
There is no information on the pharmacokinetics of
bethanechol in dogs and cats. In humans it is poorly
absorbed from the gastrointestinal tract. After oral
dosing, onset of action is 30–90 min; after subcutaneous
dosing onset of action is 5–15 min. The duration of
action can persist for up to 6 hours after oral dosing
and 2 hours after subcutaneous dosing. Subcutaneous
administration results in a greater stimulatory effect on
the urinary tract than oral dosing. Bethanechol does not
cross the blood–brain barrier. The metabolic and elimination
fate of bethanechol is unknown.
Adverse effects
● Adverse effects are usually mild and may include
vomiting, diarrhea, salivation and anorexia.
● Overdosage may result in cardiovascular signs
(bradycardia, arrhythmia, hypotension) and
bronchoconstriction.
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