Week 1 Flashcards
In an experiment, you observe decreased EPPs, but the MEPPs are NOT decreased in amplitude. With which neuromuscular junction disorder would you see the same phenomenon?
Lambert-Eaton Myasthenic Syndrome (LEMS)
The problem is a lower quantity of MEPPs (amount of ACh released) resulting in decreased EPP. However, each ACh that IS released can still evoke the same amplitude MEPP.
Lecture: Overview of the NMJ and Presynaptic Agents
Objective 4: Describe the sites of neuromuscular deficits in Lambert-Eaton Myasthenic Syndrome (LEMS) and Myasthenia Gravis (MG).
Presynaptic vesicles are released when Ca2+ is sensed by which protein?
Synaptotagmin
Lecture: Structural Correlates of Secretion
Objective 1: Identify the target site for Botulinum Toxin Type A in motor nerve terminals and explain why this toxin reduces the calcium-sensitivity of neurotransmitter release
A patient who was recently badly burned in a house fire is under your care. If you need to perform a procedure, which type of neuromuscular blocker should you avoid?
Succinylcholine (a depolarizing blocker). Burn patients can have many new ACh receptors along their muscles, predisposing them to a large release of K+ when the muscle is depolarized. This electrolyte abnormality can lead to cardiac collapse.
Lecture: NMJ Postsynaptic Agents
Objective 4: List the uses and contraindications of the clinically-used non-depolarizing and depolarizing blocking drugs (use the Drug List to guide your studying) as well as how neuromuscular block can be reversed.
You notice a progressive decrease in twitch amplitude in a Train of Four while observing a patient where Succinylcholine is being used. Is there any cause for concern? Why?
Yes. The patient is now in Phase II of a depolarizing block. During this phase, the ACh receptors cannot respond to ACh and the patient will most likely need to be kept on a ventilator until the block resolves.
Lecture: NMJ Clinical Aspects
Objective 1: Describe the effects of depolarizing and non-depolarizing neuromuscular blockers on nerve-evoked muscle twitches as assessed during surgical procedures.
Your patient’s blood pressure falls suddenly and their HR jumps up by 30bpm. This reflex is a result of decreased stretch at what structures to increase release of which substance?
Decreased stretch sensed by the baroreceptors in the aortic arch and carotid sinus lead to increased NE released to cause reflex tachycardia
Lecture: Overview ANS drug targets
Objective 3: Explain how autonomic reflexes can occur in: the brain (the barostatic reflex), the spinal cord (micturition in the newborn) and in the isolated the gastrointestinal tract (via the enteric nervous system=the third or “forgotten” division of the ANS)
You are reversing a neuromuscular block at the end of surgery with neostigmine and decide to add on Glycopyrrolate. What class of drug is glycopyrrolate and why are you using it?
Anti-muscarinic agent.
Neostigmine will increase the amount of available ACh in all synapses, resulting in stimulation of both nicotinic (good for reversing the block) and muscarinic receptors (off-target effects).
Lecture: Cholinergic agents
Objective 5: List the important properties, therapeutic uses, and side effects of the clinically-used muscarinic antagonists (using the Drug List as a guide) and relate these properties to the predicted effects of blockade of the parasympathetic nervous system.
Your patient was recently working in the garden when he began to notice that his vision was blurry. He presents at the Emergency Room with excessive drooling and confusion. You begin to suspect exposure to which class of autonomic agent? What is their mechanism of action?
Parasympathomimetic. He has most likely been exposed to an organophosphate which will irreversibly bind to AChE, increasing the amount of ACh remaining in the synpase.
Lecture: Cholinergic Agents
Objective 4: Describe the symptoms and treatment of poisoning by irreversible cholinesterase inhibitors.
Which enzyme converts Tyrosine into DOPA? Next, what is the product of the reaction catalyzed by DOPA decarboxylase?
Tyrosine hydroxylase converts tyrosine into DOPA.
Norepinephrine is produced by DOPA decarboxylase.
Lecture: Overview of Sympathetic Transmission and Alpha and Beta Receptors
Objective 2: Identify the broad principles of catecholamine synthesis, keeping in mind that other amine transmitters to be discussed in this and later modules (e.g. serotonin) follow a similar synthetic pattern (amino acid hydroxylation followed by decarboxylation).
Your patient has resistant hypertension and is started on a drug which reduces sympathetic tone. What drug is this and what receptor does it act on?
Clonidine. This is an alpha 2 agonist.
Lecture: Adrenergic agents – Alpha & Beta Agonists
Objective 5: 5. Identify the important agonists that act directly on alpha-1, alpha-2, beta-1, beta-2 and beta-3 sites.
An elderly gentleman requests a change in medication to treat his benign prostatic hypertrophy as his current one makes him feel dizzy when he stands up quickly. What class of drug is he currently on? Why does he feel dizzy?
He’s on a nonselective alpha 1 blocker (ex. Prazosin, Terazosin) which can act on blood vessels as well as the bladder neck. He’s experiencing the orthostatic hypotension which could be avoided with the use of a specific alpha 1a blocker like tamsulosin.
Lecture: Adrenergic agents – Antagonists at Alpha & Beta Receptors
Objective 9: 9. Review the properties and clinical uses of the important alpha blockers (including those that selectively block alpha-1A over alpha-1B receptors) and beta blocking agents (including the three generations of beta blockers).
