Cholinomimetics: Indirect agonists (anticholinesterases)

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Cholinomimetics: Indirect agonists (anticholinesterases)

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A 43-year-old woman comes to the emergency department because of weakness. The patient recalls being so fatigued and weak at the end of the day that she is often unable to perform chores around the house. She has also developed difficulty chewing and swallowing foods. Past medical history is significant for major depressive disorder, hypertension, and seasonal allergies. Temperature is 36.7°C (98.0°F), pulse is 82/min, respirations are 12/min, and blood pressure is 124/84 mmHg. Physical examination is notable for 2/5 strength in the upper extremities and 4/5 strength in the lower extremities. Visual examination is notable for mild diplopia. The patient is started on the appropriate treatment and undergoes significant improvement. However, she is now experiencing frequent nausea, diarrhea, abdominal cramps, and excessive sweating. Which of the following is the most likely cause of this patient’s current symptoms?  

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Acetylcholine (ACh)

anticholinesterase effect on p. 239

Acetylcholinesterase (AChE)

cholinesterase inhibitor poisoning p. 239

Anticholinesterase drugs p. 239

Atropine p. 240

cholinesterase inhibitor poisoning p. 239

Bradycardia

cholinesterase inhibitor poisoning p. 239

Cholinesterase inhibitors

diarrhea with p. 248

poisoning from p. 239

Diarrhea

cholinesterase inhibitor poisoning p. 239

Miosis

cholinesterase inhibitor poisoning p. 239

Physostigmine

anticholinesterase p. 239

Transcript

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The nervous system is divided into the central nervous system, that is the brain and spinal cord, and the peripheral nervous system, which includes all the nerves that connect the central nervous system to the muscles and organs.

The peripheral nervous system can be divided into the somatic nervous system, which controls voluntary movement of our skeletal muscles; and the autonomic nervous system, which controls the involuntary activity of the smooth muscles and glands of our organs, and is further divided into the sympathetic and parasympathetic nervous systems.

Parasympathetic neurons in the central nervous system project preganglionic fibers towards parasympathetic ganglia, which are collections of neurons near the organ they are supposed to affect.

From there, postganglionic fibers project towards the target cell.

Both the preganglionic and postganglionic neurons release the neurotransmitter acetylcholine.

Acetylcholine released from preganglionic fibers acts on nicotinic receptors on the postganglionic neurons.

And acetylcholine released from postganglionic neurons acts on muscarinic and nicotinic receptors on target organs.

Nicotinic receptors are coupled to ion channels that let sodium in and potassium out, causing depolarization.

Muscarinic receptors are G-protein coupled receptors, which means they trigger secondary messenger proteins that activating a cascade of enzymes inside the cell.

The physiologic effects of the muscarinic and nicotinic stimulation can be remembered with the mnemonic: DUMB HAVES, so defecation; urination; muscle excitation; bronchospasm; heart bradycardia; autonomic ganglia stimulation; vasodilation; eye miosis, which is constriction of the pupil, and eye accommodation, which is contraction of the ciliary muscles of the iris to facilitate looking at near objects; and secretions from the lacrimal, salivary, and sweat glands, as well as the glands in the GI tract.

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