McKenna's Pharmacology for Nursing, 2e

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C H A P T E R 3 2 Cholinergic agonists

Neostigmine is a synthetic drug that has a strong influence at the neuromuscular junction. Neostigmine has a duration of action of 2 to 4 hours and therefore must be given every few hours, based on individual response, to maintain a therapeutic level. Pyridostigmine has a longer duration of action than neostigmine (3 to 6 hours) and is preferred in some cases for the management of myasthenia gravis because it does not need to be taken as frequently. Edrophonium is administered intravenously and has a very short duration of action (10 to 20 minutes). It is an orphan drug currently not approved by TGA and remains an unapproved medicine in New Zealand. The drugs used to treat Alzheimer’s disease are well absorbed and distributed through the body. They are metabolised in the liver by the cytochrome P450 system, so caution must be used for individuals with hepatic impairment and for cases in which many interacting drugs are used. The drugs used to treat Alzheimer’s disease are excreted in the urine. Galantamine is available in tablet and oral solution form. It has a half-life of 7 hours and is taken twice a day. An extended release form, recently available, can be taken just once a day. Rivastigmine is available in capsule and solution forms to help with people who have swallowing difficulties, as well as a transdermal patch that is applied once a day. The duration of effects for rivastigmine is 12 hours. Donepezil, with a 70-hour half-life, is available in oral form, as tablets, as an oral solution and as a rapidly dissolving tablet. It can be given in once-a-day dosing, which is advantageous with a disease that affects memory and the person’s ability to remember to take pills throughout the day. Contraindications and cautions Anticholinesterase inhibitors are contraindicated in the presence of allergy to any of these drugs to avoid hyper- sensitivity reactions ; with bradycardia or intestinal or urinary tract obstruction, which could be exacerbated by the stimulation of cholinergic receptors ; in pregnancy because the uterus could be stimulated and labour induced ; and during breastfeeding because of the poten- tial effects on the baby. Caution should be used with any condition that could be exacerbated by cholinergic stimulation. Although the effects of these drugs are generally more localised to the cortex and the neuromuscular junction, the possibility of parasympathetic effects must be con- sidered carefully in individuals with asthma, coronary disease, peptic ulcer, arrhythmias, epilepsy or par- kinsonism, which could be exacerbated by the effects of parasympathetic stimulation. Drugs used to treat Alzheimer’s disease are metabolised in the liver and excreted in the urine, so caution should be used in the presence of hepatic or renal dysfunction, which could

interfere with the metabolism and excretion of the drugs. Adverse effects The adverse effects associated with agents for treating myasthenia gravis or Alzheimer’s disease are related to the stimulation of the parasympathetic nervous system. GI effects can include nausea, vomiting, cramps, diarrhoea, increased salivation and involuntary defecation related to the increase in GI secretions and activity due to para- sympathetic nervous system stimulation. Cardiovascular effects can include bradycardia, heart block, hypotension and even cardiac arrest, related to the cardiac-suppressing effects of the parasympathetic nervous system. Urinary tract effects can include a sense of urgency related to stimulation of the bladder muscles and sphincter relaxa- tion. Miosis and blurred vision, headaches, dizziness and drowsiness can occur related to CNS cholinergic effects. Other effects may include flushing and increased sweating secondary to stimulation of the cholinergic receptors in the sympathetic nervous system. Clinically important drug–drug interactions There may be an increased risk of GI bleeding if these drugs are used with non-steroidal anti-inflammatory drugs (NSAIDs) because of the combination of increased GI secretions and the GI mucosal erosion associated with the use of NSAIDs. If this combination is used, the person should be monitored closely for any sign of GI bleeding. The effect of anticholinesterase drugs is decreased if they are taken in combination with any cholinergic drugs because these work in opposition to each other. for non-depolarising neuromuscular junction blockers, increased survival after exposure to nerve gas. Actions: Reversible cholinesterase inhibitor that increases the levels of ACh, facilitating transmission at the neuromuscular junction. Pharmacokinetics: Route Onset Duration Oral 35–45 mins 3–6 hours IM 15 mins 3–6 hours T 1/2 : 1.9 to 3.7 hours; metabolism is in the liver and tissue, and excretion is in the urine. Adverse effects: Bradycardia, cardiac arrest, tearing, miosis, salivation, dysphagia, nausea, vomiting, increased bronchial secretions, urinary frequency, and incontinence. Prototype summary: Pyridostigmine Indications: Treatment of myasthenia gravis, antidote