Lehne's Pharmacology CH 15M
Highly toxic Primarily used as insecticides Only clinical application is glaucoma All contain an atom of phosphorus Almost all are highly lipid soluble (readily absorbed) Readily absorbed from several routes Potential use in chemical warfare (nerve gases)
"Irreversible" Cholinesterase Inhibitors
Neostigmine
A nurse in the post-anesthesia recovery unit is caring for a client who received a nondepolarizing neuromuscular blocking agent and has muscle weakness. The nurse should anticipate a prescription for which of the following medications?
Ethosuximide Valproic acid Lamotrigine
A nurse is preparing to administer a medication to a client who has absence seizures. The nurse should anticipate administering which of the following medications to the client?
Hallucinations
A nurse is providing to a client who has early Parkinson's disease and a new prescription for pramipexole. The nurse should instruct the client to monitor for which of the following adverse effects of this medication?
"Use caution if given a prescription for a diuretic medication." "Consider using an alternate form of contraception if you are using oral contraceptives." "Avoid driving until you see how the medication affects you." "Notify your provider if you develop a skin rash."
A nurse is reviewing a new prescription for oxcarbazepine with a female client who has partial seizures. Which of the following instructions should the nurse include?
Take this medication with food
A nurse is teaching a client who has a new prescription for levodopa/carbidopa for Parkinson's disease. Which of the following instructions should the nurse include?
Stool incontinence
A patient goes to the emergency department after using organophosphate insecticides improperly. What assessment finding would the nurse expect?
Edrophonium [Tensilon]
A patient who has myasthenia gravis reports extreme muscle weakness. Which of the following medications should the nurse prepare to administer to distinguish myasthenic crisis from cholinergic crisis?
2.5 tablets
Ambenonium (Mytelase) 25 mg is ordered by mouth 3 times a day. The pharmacy stocks 10-mg tablets. How many tablets should the nurse administer for one dose?
Use a challenging dose of edrophonium History of medication use or signs of excessive muscarinic stimulation assist with differential diagnosis Identification by the patient
How can the nurse distinguish between cholinergic crisis and myasthenia crisis?
2.8 mL
Neostigmine (Prostigmin) is to be administered as a test for myasthenia gravis as a simple dose of 0.02 mg/kg. The patient weighs 154 lb. Neostigmine (Prostigmin) is available as an injectable solution of 0.5 mg/mL. How much neostigmine should be administered to this patient?
Obstruction of gastrointestinal or urinary tract Peptic ulcer disease Asthma Coronary insufficiency Hyperthyroidism
Precautions and contraindications of Neostigmine
Thymus gland involvement
Its cells form a part of the body's normal immune system. The gland is somewhat large in infants, grows gradually until puberty, and then gets smaller and is replaced by fat with age. In adults with myasthenia gravis, it remains large and is abnormal.
Bradycardia Bronchospasm Bronchorrhea
Killer B's of cholinergic crisis
Identical to those of the direct-acting muscarinic agonists Prevents breakdown of Ach Cholinesterase inhibitors can cause bradycardia, bronchial constriction, urinary urgency, increased glandular secretions, increased tone and motility of gastrointestinal smooth muscle, miosis, and focusing of the lens for near vision
Muscarinic Response of Neostigmine (Prostigmin)
Salivation Lacrimation Urination Diaphoresis/Diarrhea Gatrointestinal cramping Emesis
S L U D G E Mnemonic for cholinergic crisis
Reversal of competitive neuromuscular blockade Treatment of glaucoma, Parkinson's disease, Alzheimer's disease, and poisoning by muscarinic antagonists
Secondary uses for reversible cholinesterase inhibitors
Neostigmine
Short-acting reversible cholinesterase inhibitor that does not cross blood-brain barrier
physostigmine
This drug is the preferred cholinesterase inhibitor for treating poisoning by muscarinic antagonists because it crosses membranes easily
Blur vision Cause respiratory depression
Toxic levels of cholinesterase inhibitors can do what?
Edrophonium
Used to diagnose myasthenia gravis
Physostigmine
Used to treat drug-induced muscarinic blockade
It increases the force of skeletal muscle contraction.
What best describes the rationale for using neostigmine [Prostigmin] in the treatment of myasthenia gravis?
Intensify transmission at muscarinic, ganglionic, and neuromuscular junctions
What can cholinesterase inhibitors do?
Aspiration of secretions
What is a priority nursing concern when neostigmine is used to reverse neuromuscular blockade of postoperative patients?
Insufficient ACh at the NMJ
What is the pathophysiology for a myasthenic crisis?
Doses should be infused slowly. It cannot cross the blood-brain barrier. It is an antidote to organophosphate poisoning.
Which of the following statements about Pralidoxime are true?
Cause of Myasthenia Gravis
a defect in the transmission of nerve impulses to muscles. It occurs when normal communication between the nerve and muscle is interrupted at the neuromuscular junction—the place where nerve cells connect with the muscles they control. Normally when impulses travel down the nerve, the nerve endings release a neurotransmitter substance called acetylcholine. Acetylcholine travels from the neuromuscular junction and binds to acetylcholine receptors which are activated and generate a muscle contraction.
Cholinergic Crisis
Characterized by extreme muscle weakness or frank paralysis and signs of excessive muscarinic stimulation Treatment with respiratory support and atropine
Muscarinic antagonists Nondepolarizing neuromuscular blockers Depolarizing neuromuscular blockers
Drug interactions of Neostigmine
Cholinesterase Inhibitors
Drugs that prevent the degradation of acetylcholine (ACh) by acetylcholinesterase indirect-acting cholinergic agonists Lack selectivity (muscarinic, ganglionic, and neuromuscular) Limited therapeutic applications
"Reversible" Cholinesterase Inhibitor: Neostigmine [Prostigmin]
-Quaternary ammonium: Cannot readily cross membranes -Absorbed poorly with oral administration -Minimal effects on brain and fetus Poor substrate for cholinesterase (ChE)
Myasthenia Gravis -pathophysiology & symptoms
-autoimmune disease where antibodies attack nicotinicM receptors on skeletal muscle -characterized by fluctuating muscle weakness and predisposition to rapid fatigue -Symptoms: ptosis, dysphasia, and weakness of skeletal muscles
-Excessive muscarinic stimulation Neuromuscular blockade -Treatment with antagonist [Atropine] - Admin: IV (also IM, SubQ)
Adverse effects/acute toxicity of Neostigmine administration
Atropine
Antidote for cholinergic crisis
Pralidoxime
Antidote for poisoning by organophosphate insecticides
Myasthenia crisis
Inadequate medication Extreme muscle weakness Caused by insufficient ACh at the neuromuscular junction Left untreated, myasthenic crisis can result in death as a result of paralysis of the muscles of respiration A cholinesterase inhibitor (such as neostigmine) is used to relieve the crisis
Tabun
Irreversible cholinesterase inhibitor nerve gas that can be used in bioterrorism
Echothiophate
Irreversible cholinesterase inhibitor used to treat glaucoma
Malathion
Organophosphate insecticide
-Physostigmine: Nonionic, can cross BBB. Preferred for anticholinergenic OD bc it can reverse CNS effects. Can induce seizures, arrhythmias Ambenonium, edrophonium, and -pyridostigmine (mestinon): primary agent for MyGrav Echothiophate Drugs for Alzheimer's disease: donepezil, rivastigminem galantamine
Other "Reversible" Cholinesterase Inhibitors
Cholinergic crisis Respiratory depression Excessive muscarinic stimulation
Overdose of cholinesterase inhibitors causes which of the following?
Assess the patient's ability to swallow a sip of water.
The nurse cares for a patient with myasthenia gravis. Before administering pyridostigmine [Mestinon], it is most important for the nurse to take which action?
"A medical alert bracelet should be worn at all times."
The nurse instructs a patient with myasthenia gravis who is taking neostigmine (Prostigmin). Which statement, if made by the patient to the nurse, indicates an understanding of the instructions?
Immediately assess the patient for other symptoms including excessive muscarinic stimulation, and contact the prescriber with patient's request and assessment findings
The nurse is caring for a male patient who is prescribed pyridostigmine (Mestinon) 240 mg, three times daily for myasthenia gravis. The patient states that he is experiencing an extreme increase in muscle weakness and that he needs the nurse to administer 300-mg doses. What should the nurse do?
Neostigmine [Prostigmin]
The nurse is caring for a patient with a suspected overdose of pancuronium, which was used during surgery. Which drug does the nurse anticipate will be used as a reversal agent?
Assess the patient's ability to swallow.
The nurse is caring for a patient with myasthenia gravis who is beginning a new prescription of neostigmine [Prostigmin], 75 mg PO twice daily. What is the most important initial nursing action?
It prevents inactivation of acetylcholine.
The nurse is preparing to give neostigmine [Prostigmin]. What best describes the action of this drug?
Atropine
The nurse prepares to administer the antidote to a patient in cholinergic crisis. What medication does the nurse anticipate the healthcare provider to order?
Edrophonium
The provider elects to administer a medication to distinguish myasthenic crisis from cholinergic crisis. What medication would the nurse anticipate giving?
Neuromuscular Effects of Neostigmine (Prostigmin)
Therapeutic dose: Increases force of contraction in skeletal muscle Toxic levels: Decrease force of contraction
Constrict pupils Strengthen skeletal muscle contraction
Therapeutic doses of cholinesterase inhibitors have which effects?
Central Nervous System Effects of Neostigmine (Prostigmin)
Therapeutic levels: Mild stimulation Toxic levels: Depression of the central nervous system
organophosphates
These cholinesterase inhibitors are highly lipid soluble -they can be absorbed directly though the skin and distributed easily to all tissues and organs