Urinary incontinence is defined as an involuntary leakage of urine and may have multiple causes (Edmunds, 2003).
In women, urinary incontinence arises from detrusor instability and stress incontinence. Forty-two per cent of women in the UK have urinary incontinence (Hunskaar et al, 2002). It often occurs due to tissue injury following childbirth, but may also occur as a result of degenerative changes due to hormonal deficiency and neurological defects of the pudendal nerve (Bardsley, 2004). In men urinary incontinence is often associated with benign prostatic hyperplasia with symptoms of frequency and urge incontinence, poor urinary stream and hesitance.
The Department of Health drew attention to continence care in a report published in 2000. The report aspires to integrated continence services with an emphasis on convenient treatment in primary care settings. Both drug and non-drug treatment options are used for treating incontinence. Drug treatment includes anticholinergic/antispasmodics, alpha-adrenergic agonists, estrogens, cholinergic agonists and alpha-adrenergic antagonists (Edmunds, 2003). Conservative methods include pelvic floor exercises and bladder training. In this paper anticholinergic drug treatment is considered and, specifically, antimuscarinic drugs.
Although antimuscarinic drugs are a type of anticholinergic agent their antagonist action is specific to the muscarinic receptors. Anticholinergic or cholinergic-blocking drugs also incorporate anticholinesterase drugs and drugs used to treat motion sickness, cardiac arrhythmias, parkinsonism, chronic asthma and pupil dilatation agents. They may also be used as antidotes to cholinergic agents (such as atropine for reversing the effects of nerve gas) (Spencer et al, 1993).
Anticholinergic drugs may be classified into three groups:
- Those used for smooth muscle relaxation, antispasmodics and antisecretory properties
- Those used for their effects on the central nervous system and treatment of parkinsonism
- Those used in ophthalmology.
The treatment of urinary incontinence concerns the first group. Antimuscarinic drugs reduce involuntary detrusor contractions and increase bladder capacity (BMA/RPSGB, 2004). They exert their antagonistic effect at postganglionic cholinergic nerve endings at muscarinic receptor sites in the parasympathetic nervous system (see Figure).
Atropine is the oldest anticholinergic alkaloid found originally in the belladonna plant and is the prototype of antimuscarinic drugs (Spencer et al, 1993). The newer synthetic drugs have greater specificity and reduced side-effects (Hopkins et al, 1999). Antimuscarinic drugs fall into three classes:
- Belladonna alkaloids (belladonna, homatropine hydrobromide, hyoscyamine and scopolamine hydrobromide)
- Quaternary ammonium agents (propentheline bromide)
- Tertiary amines (oxybutynin hydrochloride).
All of the antimuscarinic drugs used for urinary incontinence are given orally. Oxybutynin hydrochloride and tolterodine tartrate are also available as modified-release preparations.
The belladonna alkaloids are absorbed from the GI tract, the mucous membranes, the skin and the eyes and are widely distributed. Absorption of the synthetic derivatives is confined mainly to the GI tract. They are less lipid soluble and do not cross the blood-brain barrier. Some of the synthetic derivatives such as propantheline bromide undergo hydrolysis in the upper small intestine as well as metabolism in the liver and they are excreted in urine and faeces. The duration of action is up to six hours and the half-life is thought to be less than that of atropine (two to three hours) (Williams et al, 1998).
Antimuscarinic drugs interrupt parasympathetic nerve impulses by competing with the neurotransmitter acetylcholine at muscarinic receptor sites (Williams et al, 1998).
The parasympathetic nerves form one of two nerve channels within the autonomic nervous system that is responsible for transmission of impulses to the smooth muscle of the viscera, blood vessels, eyes and exocrine glands.
In the case of the sympathetic nervous system chemical transmission involves noradrenaline and in the parasympathetic system, acetylcholine. Acetylcholine is also released at the myoneural junction, where it binds to receptors on the innervated organ and initiates the necessary response.
Cautions and contraindications
The parasympathetic and sympathetic system counterbalance each other in order to maintain physiological equilibrium. As such the depression of one part of the system will produce an end result comparable with that of stimulating the opposite part (Hopkins et al, 1999). This dual opposing action (see Box below) warrants caution in many conditions:
- Prostatic hyperplasia - sphincter contraction may cause urinary retention.
- Glaucoma - the antimuscarinic drug effect of pupil dilatation may increase intraocular pressure
- Compromised cardiac function - tachycardia may result from inhibition of the parasympathetic stimulation
- GI tract obstruction - paralytic ileus, stenosing peptic ulcer and toxic megacolon may be intensified by slowing of GI activity.
Antimuscarinic drugs should be used with caution in elderly people and in those with autonomic neuropathy. Caution is also advised in hiatus hernia with reflux oesophagitis and in hepatic impairment and renal impairment (BMA/RPSGB, 2004).
Many of these drugs have been found in breast milk and either alternative infant feeding or incontinence treatment is advised.
The side-effects of antimuscarinic drugs are more pronounced in children and the elderly. Side-effects include: dry mouth; constipation; blurred vision; drowsiness; nausea; vomiting; abdominal discomfort (BMA/RPSGB, 2004); difficulty micturating; palpitations; skin reactions. Restlessness, disorientation and hallucinations may also occur as a result of central nervous system stimulation. A decreased ability to sweat can predispose to heat exhaustion.
Antimuscarinic drugs decrease gut motility and delay gastric emptying and therefore may increase the absorption of other medications.
The side-effects of antimuscarinic drugs may be exacerbated when given with antihistamines, anti-parkinsonism drugs, monamine oxidase inhibitors or tricyclic antidepressants
A comprehensive list of drug interactions is available in the BNF.
- Anticholinergic drugs are drugs that block the effects of acetylcholine at cholinergic receptor sites
- Antimuscarinic drugs block acetylcholine at muscarinic receptors sites
- Antimuscarinic drugs are indicated for urinary frequency, bladder instability, and nocturnal enuresis
- Antimuscarinic drugs act by reducing the contractile activity of the detrusor muscle
- Depression of the parasympathetic system may inadvertently cause stimulation of the sympathetic system
- Side-effects include dry mouth, blurred vision, constipation and tachycardia
- Drug interactions may occur with antihistamines, anti-parkinsonism drugs, monamine oxidase inhibitors and tricyclic antidepressants.
Bardsley, A. (2004) Key trends in the management and treatment of stress urinary incontinence. Professional Nurse 19: 10, 30-32.
BMA/RPSGB. (2004) British National Formulary 47. Available at: www.bnf.org.uk
Department of Health. (2000) Good Practice in Continence Services. London: The Stationery Office.
Edmunds, W.E. (2003) Introduction to Clinical Pharmacology (4th edn). Hong Kong: Mosby.
Hopkins, S.J., Kelly, J.C. (1999) Drugs and Pharmacology for Nurses (13th edn). London: Churchill Livingstone.
Hunskaar, S., Lose, G., Viktrup, L. et al. (2002) Prevalence of stress urinary incontinence in women in four European countries. Proceedings of the International Continence Society 32nd meeting, August, Heidleberg (Abstract) 257: 166.
Spencer, R.T., Wemett Nichols, L., Lipkin, G.B. et al. (1993) Clinical Pharmacology and Nursing Management (4th edn). Philadelphia, Pa: J.B. Lippincott.
Williams, B.R., Baer, L.C.Essentials of Clinical Pharmacology in Nursing. (2nd edn). Philadelphia, Pa: Springhouse.