Abstract

Atropine is commonly combined with alpha-2-adrenergic agonists to offset the bradycardia seen with these agents. Historically in small animal medicine, atropine and other anticholinergics have also been used to decrease salivary gland secretions, decrease gastric fluid acidity, and inhibit the effects of vagal stimulation. However, developments within veterinary anesthesia in the last decade have led to concerns when combining anticholinergics with alpha-2 adrenoceptors unless clinically indicated. This paper reviews the pharmacology of these two groups of agents, and the author provides his recommendations for prudent use of anticholinergics in wild mammal anesthesia.

Alpha-2 Adrenergic Agonists

The alpha-2-adrenergic agonists have been used for their often-reliable dose-dependent sedation, analgesia, and muscle relaxation. This family of drugs includes xylazine, medetomidine, detomidine, and romifidine. They are highly lipophilic and as such will pass rapidly across cellular membranes.

None of the alpha-2 adrenergic agonists are “pure” agonists; they show a higher selectivity for alpha-2 receptors compared to alpha-1 receptors; however, they still have effects at the alpha-1 receptors.¹ Alpha-2 adrenoceptors are found in the cardiovascular, respiratory, renal, endocrine, gastrointestinal, hematologic, reproductive, and central nervous systems.² The actual numbers of receptors, their sensitivity, and their distribution within the body may vary between species, and possibly with certain disease states.¹ Alpha-2 adrenoceptors are both presynaptic and postsynaptic.¹

Despite the large number of different body systems containing alpha-2 adrenoceptors, we will concentrate here on the cardiovascular system as this is the most important with regard to anticholinergic interactions. Full descriptions of adrenoceptor pharmaceutical interactions can be found elsewhere.² There is considerable variation between the different alpha-2 agonists, but the classic cardiovascular progression is as follows¹:

• Initial hypertension: this is due to peripheral postsynaptic alpha-2 receptor activation (and some alpha-1) resulting in peripheral vasoconstriction.
• Bradycardia: this is primarily a normal physiologic response to the hypertension, but also occurs due to central presynaptic alpha-2 receptor stimulation favoring parasympathomimesis combined with peripheral presynaptic alpha-2 activation, resulting in decreased noradrenalin release at peripheral sympathetic nerve terminals in the heart. This bradycardia can be in the region of half that seen pre-administration of alpha-2 adrenergic agonists. Cardiac output is calculated by heart rate multiplied by stroke volume, and therefore bradycardia will result in a reduced cardiac output. Therefore, it is recommended to give intravenous drugs administered later at a slower rate, or overdose may occur.
• Blood pressure returns to near normal: either normal or mild hypertension is seen, later developing to hypotension as baseline vascular tone decreases due to central effects and reduction in noradrenalin release peripherally.³

Anticholinergic Agents

Atropine has historically been used in small animal medicine to antagonize the bradycardia seen with the alpha-2 agonists, but they have also been used to decrease salivary gland secretions, decrease gastric fluid acidity, and inhibit the effects of vagal stimulation.⁴

Atropine is a parasympatholytic agent that inhibits the effects of acetylcholine on muscarinic receptors. The systemic effects are considerable, but the primary uses during anesthesia will only be discussed here.

Cardiovascularly, atropine has little effect on blood pressure but does dramatically increase heart rate. This effect is more pronounced in animals with higher vagal tone.⁵ Atropine decreases the watery component of saliva and respiratory secretions, but also decreases ciliary activity resulting in reduced clearance of more viscid mucus.¹ Atropine does increase relaxation of gastrointestinal smooth muscle, including esophageal sphincter pressure, and secretions of the gastrointestinal tract. However, gastric secretions are reduced only when using high doses that virtually block all other muscarinic sites.⁵ Atropine also has direct effects within the central nervous system, and at low doses can result in sedation, but in larger doses can cause delirium and excitement.⁵

Using Atropine with Alpha-2 Adrenergic Agonists

A large number of anesthetic regimes advocate the use of combining atropine with alpha-2 adrenergic agonists as part of an induction polypharmaceutical cocktail. Often the biggest concern is the bradycardia seen following induction. However, as this is a normal physiologic response to transient hypertension, this should not be “treated” unless the bradycardia is compromising hemodynamic function, resulting in hypotension.

The increased heart rate following atropine administration on a vasoconstricted vascular system can potentially result in massive hypertension, increased myocardial oxygen demand, decreased diastolic filling time, minimal increases in cardiac output due to massive afterload, and potential hypertension-induced damage in cerebral, retinal and renal vasculatures.¹

Tranquilli⁶ states, “The co-administration of an alpha-2 agonist and an anticholinergic should be restricted to patients with good cardiac function that are exercise tolerant and may be receiving additional agents that enhance vagal activity (such as the opioids).” However, in wild or zoo situations we are often unable to fully assess that a patient is healthy, and we incur a risk when utilizing these two pharmaceutical families together.

Use of atropine should be limited to cardiovascular resuscitation. If there are concerns regarding bradycardia following alpha-2 adrenoceptor administration, administration of a small dose of atipamezole has been advocated as a partial reversal to reduce cardiovascular effects.¹

In the United Kingdom, atropine and other anticholinergics are routinely used only in an emergency situation, and never as part of a standard induction protocol. In this author’s hands, at the time of writing, the use of alpha-2 adrenoceptor agonists without the use of atropine has never compromised a patient.

Literature Cited

1.  Dugdale A, Senior M. Handbook of Anaesthesia. Liverpool University Veterinary School, United Kingdom; 2002.

2.  Gross ME. Tranquilizers, alpha-adrenergic agonists and related agents. In: Adams HR, ed. Veterinary Pharmacology and Therapeutics. Ames, IA: Iowa State University Press; 2001:299–342.

3.  Ko JCH, Fox SM, Mandsager RE. Effects of preemptive atropine administration on incidence of medetomidine-induced bradycardia in dogs. J Am Vet Med Assoc. 2001;218:52–58.

4.  Martinez EA. Anesthetic agents. In: Boothe DM, ed. Small Animal Clinical Pharmacology and Therapeutics. Philadelphia, PA: W.B. Saunders Co.; 2001:425–430.

5.  Adams HR. Cholinergic pharmacology: autonomic drugs. In: Adams HR, ed. Veterinary Pharmacology and Therapeutics. Ames, IA: Iowa State University Press; 2001:117–136.