McKenna's Pharmacology for Nursing, 2e

492

P A R T 5  Drugs acting on the autonomic nervous system

■■ BOX 32.2  Nerve gas: An irreversible indirect- acting cholinergic agonist

■■ BOX 32.3  Pralidoxime: Antidote for irreversible indirect-acting cholinergic agonists

A gents for myasthenia gravis Myasthenia gravis is a chronic muscular disease caused by a defect in neuromuscular transmission. It is thought to be an autoimmune disease in which individuals make antibodies to their ACh receptors. These antibodies cause gradual destruction of the ACh receptors, resulting in fewer and fewer receptor sites available for stimu- lation. ACh is the neurotransmitter that is used at the nerve–muscle synapse. If the ACh receptors are blocked and cannot be stimulated, muscle activity is decreased. The disease is marked by progressive weakness and lack of muscle control, with periodic acute episodes. Some people have a very mild clinical presentation, such as drooping eyelids, and go into remission with no further signs and symptoms for several years. Other individuals have a more severe course of the disease, with progres- sive skeletal muscle weakness that may confine them to a wheelchair. The disease can further progress to paralysis of the diaphragm, which interferes with breathing and would prove fatal without intervention. Often, during the course of the disease, the person will experience a very intense phase of the disease, called a myasthenic crisis. Management of this crisis can be very challenging. Recent worldwide events and conflicts have made the potential use of nerve gas a major news story. Developed as a weapon, nerve gas is an irreversible acetylcholinesterase inhibitor. The drug is inhaled and quickly spreads throughout the body, where it permanently binds with acetylcholinesterase. This causes an accumulation of ACh at nerve endings and a massive cholinergic response. The heart rate slows and becomes ineffective, pupils and bronchi constrict, the gastrointestinal tract increases activity and secretions, and muscles contract and remain that way. The muscle contraction soon immobilises the diaphragm, causing breathing to stop. The bodies of people who are killed by nerve gas have a characteristic rigor of muscle contraction. If an attack using nerve gas is expected, individuals who may be exposed are given intramuscular injections of atropine (to temporarily block cholinergic activity and to activate ACh sites in the central nervous system) and pralidoxime (to free up the acetylcholinesterase to start breaking down ACh). An autoinjection is provided to military personnel who may be at risk. The injector is used to give atropine and then pralidoxime. The injections are repeated in 15 minutes. If symptoms of nerve gas exposure exist after an additional 15 minutes, the injections are repeated. If symptoms still persist after a third set of injections, medical help should be sought.

A gents for A lzheimer ’ s disease Alzheimer’s disease is a progressive disorder involving neural degeneration in the cortex that leads to a marked loss of memory and of the ability to carry on activities of daily living. Because of this, Alzheimer’s disease can have very negative effects on the individual and their family (Box 32.4). Dementia, of which Alzheimer’s disease is one of the common causes, is an area identi- fied by the Australian government as a National Health Priority Area (AIHW, 2013). The cause of the disease is not yet known, but it is known that there is a progressive loss of ACh-producing neurons and their target neurons in the cortex of the brain. These neurons seem to be related to memory and associations between memories that allow connec- tions between thoughts and stimuli (e.g. seeing a face and being able to know that it is a face and to name the person the face belongs to). There are four revers­ ible indirect-acting cholinergic agonists available to slow the progression of this disease. These include donepe- zil ( Aricept ), galantamine ( Galantyl , Reminyl ) and rivastigmine ( Exelon ) (see Table 32.2). In late 2003, an N- methyl-D-aspartate receptor antagonist, memantine ( Ebixa ), was also approved for use in the treatment of Pralidoxime, the antidote for irreversible acetylcholinesterase-inhibiting drugs, or nerve gas, is given intramuscularly or intravenously to reactivate the acetylcholinesterase that has been blocked by these drugs. Freeing up the acetylcholinesterase allows it to break down accumulated ACh that has overstimulated ACh receptor sites, causing paralysis. Pralidoxime does not readily cross the blood–brain barrier, and it is most useful for treating peripheral drug effects. It reacts within minutes after injection and should be available for any person receiving indirect- acting cholinergic agonists to treat myasthenia gravis. The person and a significant other should understand when to use the drug and how to administer it. Pralidoxime is also used with atropine (which does cross the blood–brain barrier and will block the effects of accumulated ACh at CNS sites) to treat organophosphate pesticide poisonings and nerve gas exposure (see Box 32.2), both of which cause inactivation of acetylcholinesterase. Adverse effects associated with the use of pralidoxime include dizziness, blurred vision, diplopia, headache, drowsiness, hyperventilation and nausea. These effects are also seen with exposure to nerve gas and organophosphate pesticides, so it can be difficult to differentiate drug effects from the effects of the poisoning.