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Neuro Review by Minnie > PNP Minimodule Reveiw (39b - 42b) > Flashcards

PNP Minimodule Reveiw (39b - 42b) Flashcards

Bless Silinsky

1
Q

What are the therapeutic uses for neostigmine?

A

Neostigmine = cholinesterase inhibitor

  • Skeletal NMJ
    • Treat myasthenia gravis
    • Revers a non-depolarizing blocker after surgery
  • Autonomic (theoretically enhances transmission at the parasympathetic muscarinic receptor, but rarely used)
    • Glaucoma therapy
    • Treat urinary retention
    • Treat GI stasis
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2
Q

Which adrenergic receptors are activated by epinephrine?

What are the effects?

A

Epinephrine acts on all adrenergic receptors

  • α1 -> vasoconstriction
  • α2 -> inhibition of cellular functions
  • β1 -> stimulates the heart
  • β2 -> relax smooth muscle
    • Note: This effect is at odds with α1 vasoconstriction; α1 effect will prevail at high doses
  • β3 -> relax smooth muscle
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3
Q

What kind of drug is clonidine?

What is it used for?

A

Clonidine is a selective alpha-2 agonist (adrenergic)

Inhibits sympathetic outflow from CNS to periphery

  • Antihypertensive
  • Treat opioid withdrawal

Note: applies to other -onidines

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4
Q

Which agent cleaves synaptobrevin?

What is it used for?

A

Botox B

Used to treat muscle spasms in the neck (cervical dystonia)

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5
Q

What is the mechanism of rocuronium?

A

Nondepolarizing blocker at the NMJ

(post-synaptic agent)

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6
Q

What enzyme degrades ACh in the NMJ?

A

Cholinesterase

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7
Q

Which agent cleaves SNARE SNAP-25? What is the effect?

A

Botox A -> Reduced muscle contraction

  • Cleaves SNARE SNAP-25 near synaptotagmin’s Ca2+ binding site
  • -> If synaptotagmin cannot bind Ca2+, the vesicle cannot release ACh into the nerve terminal
  • -> Muscle twitch not initiated
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8
Q

What kind of drug is physostigmine?

What is it used for?

A

Reversible Cholinesterase inhibitor (indirect-acting parasympathomimetic)

Atropine poisoning

(Not a good antidote for irreversible anti-ChE poisioning!)

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9
Q

What are the contraindications for propranolol?

A
  • Asthma
    • Causes vasoconstriction and bronchoconstriction
  • Diabetes
    • Propranolol masks signs of hypoglycemis and decreases glycogenolysis
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10
Q

How is anticholinesterase toxicity treated?

A

Anticholinesterase toxicity is due to nerve gas or insecticide poisoning

  1. Decontaminate the patinet
  2. Give Atropine - blocks excessive muscarinic activity (autonomic)
  3. Give 2-PAM (or other -oxine) - reactivates ChE (skeletal muscle)
    - Lifts the phosphoryl group from ChE, must be used quickly
  4. Artificial respiration
  5. Anticonvulsants
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11
Q

Effect on the GI tract (muscle wall) of:

  • Sympathetic stimulation:
  • Parasympathetic stimulation:
A
  • Sympathetic stimulation: Relaxation
    • ​Not ideal to poop yourself during fight or flight response
  • Parasympathetic stimulation: Contraction
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12
Q

What is the effect of inhibiting Uptake-1?

A
  • Increased NE effect -> adrenergic receptor activation
    • NE stays in the nerve terminal longer
  • Tyramine has no effect
    • Cannot get into the nerve terminal
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13
Q

Which drug is used to treat premature labor?

A

Terbutaline

(injectable beta-2 agonist)

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14
Q

After a patient has received vecuronium or rocuronium as a neuromuscular blocker during surgery, what result from the “train of 4” indicates that:

  • 80% of receptors are blocked?
  • 90% of receptors are blocked?
A
  • 80% of receptors are blocked = 2/4 twitches
    • Twitch, twitch, no, no
  • 90% of receptors are blocked = 1/4 twitches
    • ​Twitch, no, no, no
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15
Q

What is the general effect of alpha-2 receptors in the CNS?

A

Alpha-2 activation reduces sympathetic tone

Example: Clonidine in the CNS activates alpha-2 receptors ->

  • Decreased beta-1 action in the heart
  • Decreased release of of NE from nerve terminal sthat innervate the heart
  • Decreased alpha-1 vasoconstriction in the blood vessels
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16
Q

What kind of drug is propranolol?

What is it used for?

A

Nonselective beta-1 and beta-2 blocker

Also blocks renin release

Used to treat:

  • Hypertension
  • Arrhythmia
  • Angina
  • Pheochromocytoma
  • Stage fright
  • Prophylaxis for migraine headaches
  • Acute phase of thyrotoxicosis
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17
Q

Which anticholinergic is used for anti-ChE poisoining?

A

Atropine

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18
Q

What are the autonomic responses to tactile or visual sexual stimulation?

A

Parasympathetic response

Erection and mucous secretion (both male and female)

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19
Q

How is NE (sympathetic) signaling terminated?

A

Reuptake into the nerve terminal by Uptake 1

  • High affinity, low capacity
  • Inhibited by tricyclic antidepressants, cocaine, ritalin

Alternative pathway: reuptake into the effector cell

  • Low affinity, high capacity
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20
Q

Which drugs may be used for intubation in the early stage of anesthesia?

A

Succinylcholine (depolarizing)

Rocuronium (nondepolarizing)

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21
Q

List the components of the fusion machine

A
  • 3 SNARE proteins that anchor the vesicle to the nerve plasma membrane
    • Syntaxin (Plasma membrane)
    • SNAP-25 (Plasma membrane)
    • Synaptobrevin (Vesicular)
  • One Ca2+ sensing protein
    • Synaptotagmin (Vesicular)
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22
Q

What kind of drug is dobutamine?

What is it used for?

A

Selective Beta-1 agonist

Low doses selectively increase the force of cardiac contraction without increasing heart rate

  • Acute heart failure
    • Increase cardiac output
    • Bridge to heart transplant
  • Stress EKG
    • High doses increase HR for patients who cannot exercise
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23
Q

What kind of drug is phentolamine?

What is it used for?

A

Nonselective reversible alpha blocker

  • Treat hypertension:
    • Crisis due to tyramine/MAO inhibition
    • Paroxysms in pheochromocytoma

(Competitive antagonist)

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24
Q

Describe the differences in observed muscle twitches with depolarizing vs. nondepolarizing neuromuscular blockers

A
  • Depolarizing blocker
    • Smaller amplitude, but no decline with sustained stimulation
  • Nondepolarizing blocker
    • Neuromuscular depression: repetitive stimulation results in progressive decline in twitch amplitude
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25
Q

What innervates eccrine sweat glands?

What do they control?

A

Sympathetic cholinergics

Sweating for temperature regulation

(apocrine sweat glands that respond to sex and stress are not innervated; they respond to EPI released from the adrenal medulla)

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26
Q

What kind of drug is parathion?

What is it used for?

How is it metabolized?

A

Irreversible cholinesterase inhibitor

  • Used as an insecticide
  • Metabolized by CYP3A4
    • Not great for us; malathion is safer because it is metabolized by carboxylases, leaving CYP3A4 to do its thing
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27
Q

Describe the effect of intracardiac epinephrine on BP, HR, and SV

A

Increased BP, HR, and SV

  • Beta-1 effect = direct action at the SA node
    • Increase HR, SV
    • Increased SV -> Increased BP
    • No beta-2 effect on peripheral vessels with intracardiac Epi
  • Alpha-1 effect in the heart
    • Vasoconstriction, further increases in BP
  • Reflex bradycardia kicks in as the dose of Epi begins to wane

Key: direct beta-1 effect wins at first, but as Epi wears off, the barostatic reflex takes over to decrease HR (reflex bradycardia)

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28
Q

What enzymes metabolize norepinephrine?

Why do we need these enzymes?

A
  • MAO
    • In nerve terminal and effector cells
  • COMT
    • In the effector cell
    • Works on NE and Epi

Even though NE signal termination is via Uptake-1, MAO is necessary to metabolize exogenous amines (ex: tyrosine from diet)

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29
Q

What is the effect of Lambert-Eaton Myasthenic Syndrome (LEMS) on the neuromuscular junction?

A

Decreased ACh release -> Difficulty initiating muscle contraction

  • This is a presynaptic deficit due to fewer P/Q type Ca2+ channels in the nerve ending
  • This results in:
    • Smaller EPPs
    • No change in MEPPs
    • Normal response to exogenous ACh

vs. Myasthenia Gravis, a post-synaptic deficit that results in smaller EPPs, MEPPs, and no response to exogenous ACh

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30
Q

What kind of drug is cevimeline?

What is it used for?

A

Direct parasympathomimetic

(Directly activates parasympathetic muscarinics)

Used to treat patinets with Sjogren’s syndrome

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31
Q

Effect on the spleen of:

  • Sympathetic stimulation:
  • Parasympathetic stimulation:
A
  • Sympathetic stimulation: Contraction
  • Parasympathetic stimulation: no direct effect
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32
Q

Which catecholamine antagonists can be used to treat pheochromocytoma?

A
  • Phenoxybenzamine (management)
  • Phentolamine (hypertensive paroxysms)
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33
Q

What is the effect of Botulinum Toxin Type A on the NMJ?

Describe the mechanism

A

Decreased muscle contraction

  • Presynaptic mechanism - irreversible
  • Botox A cleave SNARE SNAP-25 near the Ca2+ binding site of synaptotagmin
  • As a result, Ca2+ cannot bind to and activate the fusion machinery
  • ACh cannot be released
  • Decreased EPP, MEPP unchanged
    • Resembles LEMS
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34
Q

What is the result of beta-2 activation?

A

Relaxation of smooth muscle

-> Decreased TPR, BP

Note: NE does not act on beta-2 receptors

NE acts on alpha-1 receptors, increases TPR, BP

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35
Q

What is the treatment for botulinum toxicity?

A
  • If the toxin is circulating
    • Heptavalent antitoxin
  • If the toxin is bound or internalized into the nerve endings:
    • Artificial respiration
    • (it’s too late for the antitoxin to work)
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36
Q

Effect on the bronchioles of:

  • Sympathetic stimulation:
  • Parasympathetic stimulation:
A
  • Sympathetic stimulation: Dilation
  • Parasympathetic stimulation: Constriction
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37
Q

What is the effect of beta-3 activation?

A

Bladder relaxation

Fat cell stimulation

Note: NE, Epi, ISO are all nonspecific beta-3 agonists

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38
Q

What are nondepolarizing NMJ blockers used for clinically?

A

Muscle relaxant for the duration of surgery

Orthopedic manipulations

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39
Q

What are the clinical uses of succinylcholine?

A
  • Early phase of anesthesia for intubation
  • Emergency intubation

**Not to be used for the duration of surgery**

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40
Q

What kind of drug is sarin?

A

Irreversible cholinesterase inhibitor

Sarin = nerve gas

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41
Q

What are the clinical indications for cholinesterase inhibitors?

A

Myasthenia Gravis

Overcome inhibition due to nondepolaring block (after surgery)

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42
Q

Effect on the GI tract (sphincter) of:

  • Sympathetic stimulation:
  • Parasympathetic stimulation:
A
  • Sympathetic stimulation: Constriction
    • Would be bad if we pooped ourselves during fight or flight response
  • Parasympathetic stimulation: Relaxation
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43
Q

List 3 selective beta-1 blockers and their uses

A
  • Metoprolol
    • “propranolol but for asthmatics”
    • Treat HTN, arrhythma, angina, etc
  • Betaxolol
    • “Timolol but for asthmatics”
    • Treat glaucoma (decrease AH production)
  • Labetalol
    • Hypertensive crisis
    • Pheochromocytoma
    • HTN in pregnancy
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44
Q

What is the mechanism of Botox B?

A

Cleaves synaptobrevin

(synaptobrevin is part of the fusion machinery that primes the ACh vesicle to release its contents into the NMJ)

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45
Q

Under what conditions does ACh secreted by the post synaptic parasympathetic neuron activate the nicotinic receptor in the parasympathetic ganglion?

A

If the patient has had an irreversible cholinesterase inhibitor

  • -> ACh overload; ACh is not being hydrolyzed by ChE, and it builds up and begins to activate the post-ganglionic neuron
  • -> Positive feedback loop

Additionally, skeletal muscle begins acting like it’s in a Phase I-Phase II block at the NMJ

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46
Q

What kind of drug is diisopropylphosphorofluoridate (DFP)?

A

Irreversible cholinesterase inhibitor

Used as pesticide or nerve gas

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47
Q

Effect on the piloerectors of:

  • Sympathetic stimulation:
  • Parasympathetic stimulation:
A
  • Sympathetic stimulation: contraction
  • Parasympathetic stimulation: No direct effect
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48
Q

What is the action of nicotine at the NMJ?

A

Depolarizing blocker

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49
Q

What components achieve the effect on the right?

  • # 1 (nerve):
  • # 2 (neurotransmitter):
  • # 3 (parasympathetic or sympathetic?):

What is the effect?

A
  • # 1 (nerve): Oculomotor nerve
    • ​Synapses with parasympathetics in the ciliary ganglion
  • # 2 (neurotransmitter): ACh
  • # 3 (parasympathetic or sympathetic?): Parasympathetic

The release of ACh causes the sphincter pupilae (blue) to constrict, resulting in miosis

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50
Q

What mechanisms are at play during a Phase II block at the NMJ?

A

Phase II Block = Block by desensitization

  • ACh cannot bind to the nicotinic receptor because SUX is still occupying it, and it is desensitized to ACh
    • However, the channel is le tired and is no longer letting ions through. This allows the membrane to repolarize, and voltag-gated Na+ channels to recover

Note: in a phase 1 block, the nonspecific cation channel stays open, resulting in persistent depolarization that prevents the voltage-gated Na+ channels to recover

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51
Q

What kind of drug is Latanoprost? (and other -prosts)

What is it used for?

What are the side effects?

A

Prostaglandin analogues

  • Increases aqueous humor outflow through the uveal-scleral route

Side effects:

  • Irreversible darkening of the iris and eyelashes
  • Growth of eyelashes and eyebrows
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52
Q

Which adrenergic receptors are activated by norepinephrine?

What are the effects?

A

Norepinephrine acts on all adrenergic receptors except β2

  • α1 -> vasoconstriction
  • α2 -> inhibition of cellular functions
  • β1 -> stimulates the heart
  • β3 -> relax smooth muscle
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53
Q

What are the contraindications for succinylcholine?

A
  • Arrhythmia
  • Liver disease or genetic cholinesterase deficiency

**Never use for the duration of surgery**

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54
Q

Effect on the Urinary bladder (sphincter/trigone) of:

  • Sympathetic stimulation:
  • Parasympathetic stimulation:
A
  • Sympathetic stimulation: Contraction
  • Parasympathetic stimulation: Relaxation
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55
Q

There are two “correct” sequences for the use of neuromuscular agents during surgery

Describe them

A

Typical:

  • Succinylcholine for intubation
  • Vecuronium
    • 2/4 twitches in “train of 4” => 80% of receptors are blocked
  • Neostigmine for recovery
    • Recovery is complete when 4/4 twitches in the “train of 4” are observed

Alternative:

  • Rocuronium infusion for intubation and duration of surgery
    • 1/4 twitches in “train of 4” => 90% of receptors are blocked
  • Sugammadex for recovery
    • Recovery is complete when 4/4 twitches in the “train of 4” are observed
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56
Q

What is the rate limiting step of the synthesis of catecholamines?

A

Tyrosine -> DOPA

Catalyzed by tyrosine hydroxylase

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57
Q

What are the contraindications for bethanechol?

A

To stay HAPII when using Bethanechol, remember to avoid giving it to people with:

  • Hyperthyroid -> arrhythmia
  • Asthma
  • Peptic ulcers (increases gastric acid secretion)
  • Intestinal or bladder obstruction
  • IV or IM administration -> shock

Remember: Bethanechol = direct parasympathomimetic

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58
Q

What kind of drug is mirabegron?

What is it used for?

A

Selective beta-3 agonist

Used to treat overactive bladder

  • As effective as muscarinic antagonists, but without the anti-muscarinic side effects
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59
Q

How will the following deficits affect EPPs and MEPPs in the NMJ?

  • Presynaptic deficit
  • Postsynaptic deficit
A
  • Presynaptic deficit
    • EPP - smaller
    • MEPP - no change
    • Spontaneously released ACh vesicles still have an effect on the post-synpatic membrane (MEPP); the issue is that there is a problem with the coordinated release of a large number of ACh vesicles (decreased EPP)
    • *Exception: black widow spider venom -> barrage of MEPPs, summing to EPPs
  • Postsynaptic deficit
    • EPP - smaller
    • MEPP - smaller
    • Neither spontaneous or coordinated ACh vesicle release will have an effect on the non-working post-synaptic membrane
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60
Q

Describe the effect of inhibiting Uptake-1

A

Increased NE signaling (mostly sympathetic)

  • Note: eccrine sweating will not increase; this is mediated by sympathetic cholinergics
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61
Q

Describe the signs and symptoms of anticholinergic toxicity

A

Anticholinergic toxicity = atropine poisoning

  • Dry as a bone
    • Decreased secretions
    • Urinary retention
  • Hot as a stove
    • Decreased sweating due to blocked sympathetic cholinergics
  • Red as a beet
    • Cutaneous vasodilation due to histamine release
    • Compensatory due to increased temperature
  • Blind as a bat
    • ​Mydriasis
    • Cycloplegia (cannot constrict cilliary body to accomodate)
  • Mad as a hatter
    • Delerium
    • Hallucinations
    • Coma
    • Death eventually

Treat with gastric lavage, activated charcoal, physostigmine

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62
Q

What are the therapeutic uses of isoproterenol?

A

Not widely used, but can work on:

  • Bradycardia
  • Asthma
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63
Q

What kind of drug is pyridostigmine?

What is it used for?

A

Cholinesterase inhibitor -> enhances transmission at parasympathetic muscarinics and skeletal NMJ

(Indirect-acting parasympathomimetic)

  • Useful at bedtime to treat myasthenia gravis
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64
Q

Which adrenergic agent has this effect?

A

Isoproterenol

  • Beta-2 receptors activated -> vasodilation
  • Decrease diastolic pressure due to decreased TPR
  • Beta-1 receptors activated -> increase systolic pressure
    • Effect on heart muscle contractility
  • Beta-1 direct simulation + reflex to decreased TPR -> tachycardia
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65
Q

What kind of drug is an -afil?

(sildenafil, vardenafil, tadalafil, avanafil)

What are they used for?

A

PDE-5 inhibitors

Inhibit cGMP degradation -> increased smooth muscle relaxation -> blood flow to corpus cavernosum

Used to treat erectile dysfunction

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66
Q

Which nondepolarizing blockers are used clinically?

A
  • Vecuronium
  • Rocuronium
    • Faster acting than vecuronium

Both have intermediate duration, no CV effects, and do not cause histamine release

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67
Q

What kind of drug is malthion?

What is it used for?

How is it metabolized?

A

Irreversible cholinesterase inhibitor

  • Used as an insecticide
  • Metabolized by carboxylases (higher animals only)
    • Safer than parathion, which is metabolized by CYP3A4
    • Can still produce SLUD syndrome in high doses
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68
Q

What kind of agent is chloropyrifos?

What is it used for?

A

Irreversible cholinesterase inhibitor

  • ​WIDELY used as an insecticide
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69
Q

What is the affect of aminoglycoside antibiotics at the NMJ?

Describe the mechanism

A

Decresed muscle contraction

  • Presynaptic mechanism
  • Aminoglycosides inhibit Ca2+ entry into the nerve ending
  • This prevents activation of the fusion machinery, resulting in decreased ACh release
  • Smaller EPP, no change in MEPP
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70
Q

What change in the structure of ACh results in specificity for muscarinic receptors?

A

Methylation of the beta carbon

  • Allows cholinergic agents to specifically target parasympathetic pathways, rather than cross-reacting with nicotinic pathways (ganglionic, skeletal NMJ)
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71
Q

What kind of drug is edrophonium?

What is it used for?

A

Short-acting, reversible cholinesterase inhibitor; too short to have any value for treatment

Used to test for myasthenia gravis

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72
Q

This image (bottom half) is characteristic of what kind of neuromuscular blocker?

A

Phase I block of a depolarizing blocer

(Succinylcholine, Acetylcholine)

  • All twitches are smaller than normal muscle
  • There is no decline with repeated twitches
    • Unless it progresses to a phase II block - then we see decline
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73
Q

Does the bottom half of this image show a patient with Myasthenia Gravis or LEMS?

A

LEMS

  • Huge muscle twitch with repetitive stiulation
  • This increased facilitation is diagnostic of LEMS
74
Q

What is the effect of atropine on HR and BP?

A

Increase HR, inrease BP

  • Atropine is a parasympathetic antagonist (anti-muscarinic)
  • Decreased parasympathetic signaling -> increased effect of sympathetic signaling
75
Q

Describe the mechanism of action of tyramine

A

Tyramine is an indirect-acting sympathomimetic amine

(Increases sympathetic response but doesn’t activate adrenergic receptors)

  • Gets into nerve terminal via Uptake-1
    • Uptake-1 inhibitors block effects
    • MAO inhibitors potentiate effects -> increased sympathetic response
  • Kicks NE out of the nerve terminal
  • Released NE acts on effector cells
76
Q

What is the drug of choice to treat hypertension in pregnancy?

A

Labetalol

77
Q

Which neruomuscular blockers can be used for the duration of surgery?

A
  • Vecuronium
  • Rocuronium
    • Faster acting than vecuronium
78
Q

What is the treatment for anticholinergic toxicity?

A

All of the following

  • Gastric lavage
  • Activated charcoal
  • Antidote: physostigmine
    • Cholinesterase inhibitor
    • Can cross the blood-brain barrier to counteract CNS effects
79
Q

What kind of drug is timolol?

What is it used for?

A

Non-selective beta blocker (beta-1 and beta-2)

  • Used to treat glaucoma
    • Blocks secretion of aqueous humor

Note: use betaxolol for asthmatics (selective beta-1 blocker)

80
Q

What components achieve the effect on the right?

  • # 1 (neurotransmitter):
  • # 2 (sympathetic or parasympathetic):

What is the effect?

A
  • # 1 (neurotransmitter): Norepinephrine
  • # 2 (sympathetic or parasympathetic): Sympathetic

The release of NE from the sympathetic nervous system causes the radially arranged fibers of the pupil dilator to constrict, which yanks the pupil open -> dilation (mydriasis)

81
Q

Effect on the Urinary bladder (muscle wall/fundus) of:

  • Sympathetic stimulation:
  • Parasympathetic stimulation:
A
  • Sympathetic stimulation: Relaxation
  • Parasympathetic stimulation: Contraction
82
Q

Effect on the eccrine sweat glands of:

  • Sympathetic stimulation:
  • Parasympathetic stimulation:
A
  • Sympathetic stimulation: secretion (due to sympathetic cholinergics)
  • Parasympathetic stimulation: no direct effect
83
Q

Which anticholinergic is given after surgery with neostigmine to prevent excessive muscarinic effects of neostigmine?

A

Glycopyrrolate

84
Q

Effect on the Heart Rate of:

  • Sympathetic stimulation:
  • Parasympathetic stimulation:
A
  • Sympathetic stimulation: Acceleration
  • Parasympathetic stimulation: Relaxation (slowing)
85
Q

Which beta blocker is best to treat heart failure?

A

Carvidelol

  • Beta block
    • Decrease adverse effects of sympathetic stimulation
    • Decrease afterload, increase CO
  • Alpha-1 block
    • Increase CO
    • Also Ca2+ channel block and antioxidant
86
Q

What causes physiologic neuromuscular depression?

A
  • ATP packaged with ACh into the same vesicle; they are released together
  • ATP is degraded to adenosine
  • Adenosine acts on A1 adenosine receptor on the nerve terminal
  • -> inhibition of Ca2+ entry
  • => decreased ACh release

A negative feedback loop!

87
Q

This image is characteristic of what kind of neruomuscular blocker?

A

A non-depolarizing blocker

(vecuronium, rocuronium)

  • Neuromuscular depression aka “rundown,” where the amplitude of the twitch gets smaller
  • Can also see this in Phase II block from a depolarizing blocker, or in myasthenia gravis
88
Q

What is the mechanism of vecuronium?

A

Nondepolarizing blocker at the NMJ

(post-synaptic agent)

89
Q

What are the contraindications for imidazoline

(and other -azoline drugs?)

A
  • Kids - severe depressant affects
  • Everyone - Do not use for more than 3 days - structural damage to nasal mucosa
    • Due to alpha-2b mediated constriction of arterioles

Recall: -azoline or -ozoine drugs are alpha-1 agonists w/alpha-2 effect at high doses; used as nasal spray or eye drops

90
Q

Describe the mechanism of action of amphetamines

What is their effect?

A

Amphetamines are indirect-acting sympathomimetic amines

  • Increases sympathetic tone

Note: Effects blocked by Uptake-1 inhibitors, potentiated by MAO inhibitors

91
Q

What is the mechanism of sugammadex?

A

Chelates vecuronium or rocuronium after surgery - Captures it in the donut

This results in rapid recovery (much faster than a cholinesterase inhibitor)

92
Q

What is the effect of Mg2+ on the NMJ?

Describe the mechanism

A

Mg2+ decreases muscle contraction

  • Presynaptic mechanism
  • Competes with Ca2+ in the nerve ending, resulting in less Ca2+ entry
  • Less Ca2+ into the nerve ending -> Decreased ACh release
93
Q

What drug is used to treat severe hypotension in the ICU?

A

Norepinephrine

94
Q

What kind of drug is pilocarpine?

What is it used for?

A

Direct parasympathomimetic

(directly activates parasympathetic muscarinic receptors)

Used to treat:

  • Glaucoma
    • Narrow angle: give pilocarpine pre-surgery
    • Open angle: give pilocarpine to tone the trabecular meshwork. Rarely used alone
  • Sjogren’s
    • Treats dry mouth, but usually cevimeline is used instead
95
Q

What kind of drug is a -stigmine?

A

Cholinesterase inhibitor

Can act at the skeletal NMJ or parasympathetic muscarinic synapse

96
Q

Which adrenergic agent has this effect?

A

Epinephrine (low dose)

  • Beta-2 effect wins -> vasodilation -> decrease TPR
  • Beta-1 effect -> increase in systolic BP, but little to no increase in mean blood pressure
    • No change in BP = no reflexive changes to HR
    • Can see direct effect of drug on the heart: Beta-1 effect
    • Increase SV
    • Increase HR

Note: at this dose, EPI does not have significant vasopressor effects

97
Q

Which agents are first line to treat glaucoma?

A
  • Timolol
    • Nonselective beta blocker
    • Blocks secretion of aqueous humor
    • Better than pilocarpine b/c fewer side effects
  • Latanoprost
    • PGF2-alpha receptor agonist
    • Increases AH outlflow via uveal-scleral route
98
Q

What kind of drug is a -terol?

What are the uses of -terols?

A

Selective beta-2 receptor agonist

  • Short-acting (SABA)
    • Rescue inhaler (albuterol)
  • Long-acting (LABA)
    • Asthma management (salmeterol, formoterol)
    • ***Never give LABA alone, must pair with inhaled corticosteroid**
99
Q

What kind of drug is terbutaline?

What is it used for?

A

Selective beta-2 agonist

  • Uterine relaxation to treat premature labor

Note: must be given for parenterally; this is the only injectable beta-2 receptor agonist

100
Q

What are the signs and symptoms of anticholinesterase poisioning?

A

Phase I/Phase II skeletal muscle block at NMJ + SLUD syndrome

  • Salivation, sweating
  • Lacrimation
  • Urination
  • Defecation

Also: dyspnea, bradycardia, miosis, emesis

Basically, the results of a ton of parasympathetic innervation

This can result from reversible or irreversible (organophosphorous) cholinesterase inhibitors

101
Q

How do alpha-2 blockers affect the erectile response?

Describe the mechanism

A

Normally, activation of alpha-2 receptors inhibits Ca2+ entry into the parasmpathetic nerve ending, thus preventing neurotransmitter release

Alpha-2 blockers inhibit the inhibition, resulting in parasympathetic stimulation to the corpus cavernosum

-> increased erectile response

  • Alpha-2 blockers inhibit the inhibition of Ca2+ entry into the parasympathetic nerve ending
  • Increased NO synthesis in the nerve ending
  • NO diffuses into the cavernosal smooth muscle cell
  • NO stimulates guanalyl cyclase
  • Increased cGMP
    • Degraded by PDE-5 (drug target!)
  • cGMP activated PKG
  • Phosphorylation of things
  • Smooth muscle relaxation -> increased blood flow
102
Q

What kind of drug is guanfacine?

A

Selective alpha-2 agonist

(Limits sympathetic outflow from CNS to periphery)

103
Q

-azoline and -ozoline drugs are selective, but can activate alpha-2b receptors at high doses

What is the clinical significance?

A
  • Alpha-1 receptors are found on venous capacitance vessels in the nasal mucosa. When they are activated, the venous capacitance vessels constrict, thus reducing the fluid reservoir for mucous production and secretion :)
  • Alpha-2b receptors are found on arterioles in the nasal mucosa. Prolonged use of imidazoline (and other -azolines) activates these receptors, thus constricting the arterioles and cutting off nutrient delivery. This can result in permanent tissue damage
104
Q

What is the result on repetitive muscle activation in:

  • LEMS:
  • Myasthenia gravis:
A

Repeated muscle stimulation leads to…

  • LEMS
    • Increased strength of contraction
    • Even though there are fewer Ca2+ channels in the nerve ending, repeated stimulation keeps these channels open, allowing for the release of ACh vesicles into the NMJ
  • Myasthenia gravis
    • Early muscle fatigue
    • Due to fewer ACh receptors in the NMJ
105
Q

How does the effect of ACh on the heart vary depending on the dose of ACh?

A
  • Low dose
    • ACh decreases blood pressure, little direct effect on the heart
    • Reflex tachycardia wins, resulting in increased heart rate
  • High dose
    • ACh decreases blood pressure, but also affects the SA node
    • Reflex tachycardia is overpowered by the direct effects of ACh on the heart, resulting in decreased heart rate
106
Q

What kind of drugs end in -tropium?

What are they used for?

A

Inhaled muscarinic antagonists

  • Ipratropium
    • SABA, acts on post-synpatic M3 receptors in the bronchioles
    • But also acts on pre-synpatic M2 receptors, signaling for ACh release - this is not great
  • Tiotripium
    • LABA, selective for post-synpatic M3 recepotrs in the bronchioles
    • No negative feedback, better for long-term use
107
Q

What kind of drug is atropine?

What is it used for?

A

The protoypical muscarinic antagonist (anticholinergic)

(Effects mimic sympathetic stimulation)

Used to treat:

  • Anti-cholinergic toxicity
  • GI spasm
  • Frequent urination
  • HR during stage 2 of spinal anesthesia (atropine increases HR)
108
Q

What is the mechanism of drugs that end in -curonium?

What are they used for?

A

Nondepolarizing blockers at the NMJ

Muscle relaxant for the duration of surgery

(Rocuronium can also be used for intubation)

109
Q

Effect on the Fatty Depts of:

  • Sympathetic stimulation:
  • Parasympathetic stimulation:
A
  • Sympathetic stimulation: Fatty acids released
    • ​So we can use them to fight or fly away
  • Parasympathetic stimulation: None
110
Q

Effect on the Blood Vessels of:

  • Sympathetic stimulation:
  • Parasympathetic stimulation:
A
  • Sympathetic stimulation:
    • Skeletal Muscle and Liver: Dilation (Epi from adrenal medulla on beta-2)
    • Everywhere else: Constriction (alpha-1)
  • Parasympathetic stimulation:
    • No direct effect
111
Q

Effect on the sex organs of:

  • Sympathetic stimulation:
  • Parasympathetic stimulation:
A
  • Sympathetic stimulation: vasoconstiction, semen discharge
    • But does the female orgasm exist?? Who could possibly know, I guess it will remain a mystery ¯_(ツ)_/¯
  • Parasympathetic stimulation: dilation -> erection
112
Q

What is the action of neostigmine at the NMJ?

A

Neostigmine is a cholinesterase inhibitor

  • -> More ACh in the NMJ
  • -> Enhanced transmission/muscle contraction
113
Q

What categories of drugs are contraindicated when used with sildenafil?

A
  • Nitrates -> hypotension
  • Alpha-1 blockers that block alpha-1b receptors
    • Ex: the -azosins (for benign prostatic hypertrophy)
114
Q

Which anticholinergic is used to prevent motion sickness?

A

Scopolamine

115
Q

Effect on the eye (pupil) of:

  • Sympathetic stimulation:
  • Parasympathetic stimulation:
A
  • Sympathetic stimulation: Dilation (mydriasis)
  • Parasympathetic stimulation: Constriction (Miosis)
    • Also accomodation for close-up vision
116
Q

What kind of drugs inhibit sympathetic outflow from the CNS to the periphery?

A

Alpha-2 agonists

(ex: clonidine)

117
Q

How are beta blockers metabolized?

A
  • Phase I
    • CYP2D6
    • Also CYP2D19 for propranolol
  • Phase II
    • Glucuronidation or sulfation
118
Q

What is the fastest onset neuromuscular blocker?

What is it used for?

A

Succinylcholine

  • Early phase of anesthesia for intubation
  • Emergency airway

**Do not use for the duration of surgery**

119
Q

What kind of drug is bethanechol?

What is it used for?

A

Direct-acting parasympathomimetic (directly activates parasympathetic muscarinic receptors)

  • GI: Treats adynamic ileus
    • Relaxes sphincter, constricts body wall
  • GU: Treats urinary retention
    • Relaxes sphincter, increases tone in the detrusor
120
Q

How does Myasthenic Gravis affect the NMJ?

A

Muscular contraction in reduced due to destruction of ACh receptors in the post-synaptic membrane

  • Smaller EPPs
  • Smaller MEPPs
  • Decreased response to exogenous ACh

All are decreased in parallel

vs. LEMS, a presynaptic deficit, where only EPPs are smaller; MEPPs and response to exogenous ACh are maintained

121
Q

Which adrenergic agent has this effect?

A

Norepinephrine

  • Alpha-1 receptors activated -> vasoconstriction -> increase TPR
    • Beta-2 receptors are not sensitive to NE
  • Increase in systolic and diastolic pressure
  • Reflex bradycardia
122
Q

Describe the 3 mechanisms by which ACh affects the SA node

A

ACh acts on the SA node to decrease heart rate by:

  1. Increasing K+ conductance. This hyperpolarizes the membrane and makes the SA node cells less excitable
  2. Inhibiting If during phase 4
  3. Inhibiting L-type Ca2+ channels during phase 0

BUT: even though this is the direct effect of ACh on the SA node, the effect of ACh on the HR may vary, if there is also reflex tachycardia due to the vasodilitory effect of ACh on blood vessels

Picture shows normal SA node activity

123
Q

What is the major effect of alpha-2 receptors?

A

Inhibition of cellular processes

124
Q

What are the effects of ACh on blood vessels?

Describe the mechanism

A

ACh -> Vasodilation -> decreased TPR and BP

(Note: this results in reflex tachycardia, even though the direct effect of ACh on the heart is to decrease SA node firing)

  • ACh bind to receptors in the endothelium of blood vessels (not the smooth muscle)
  • -> Activates PLC
  • -> Ca2+ released from the ER, activates Nitric Oxide synthase
  • -> NO diffuses to the smooth muscle cell
  • -> Activates guanylate cyclase, increases cGMP
  • -> Activates PKG
  • -> Phosphorylation
  • -> Relaxation of smooth muscle
  • -> Vasodilation
125
Q

What mechanisms are at play during a Phase I Block at the NMJ?

A

Phase I = block by depolarization

Achieved by depolarizing blockers (SUX or ACh)

Phase I Block: after SUX has bound to the nicotinic receptor and caused depolarization:

  • ACh cannot bind to the nicotinic receptor because SUX is still occupying it
  • The membrane is persistently depolarized, with no driving force for ion flow. The receptor channel has been open for too long!
  • Voltage-gated Na+ channels are inactivated (and cannot recover due to persistent depolarization)

Note: In a Phase II block, the nonspecific cation channel closes, allowing the membrane to repolarize and voltage-gated Na+ channels to recover. Signal is still blocked by SUX bound to the receptor + desensitization of the receptor to ACh

126
Q

What is the effect of high doses of Epi on blood pressure?

How can this effect be reversed?

A

High dose Epi acts on alpha-1 receptors causing vasoconstriction, which increases blood pressure

Inhibiting the alpha-1 receptor (ex: ergotoxin) halts the alpha-1 effect, unmasking the beta-2 vasodilatory effect; decreased TPR leads to decreased blood pressure

127
Q

Why shouldn’t selective alpha-1 agonists be used for nasal decongestion for more than 3 days?

A
  • Alpha-1 agonists work to reduce nasal decongestion because they activate alpha-1 receptors on venous capacitance vessels
  • Constriction of the venous capacitance vessels decrease the fluid reservoir for secretions, thus relieving nasal decongestion

BUT

  • Prolonged interruption of venous flow causes the release of local metabolites that dilate the venous capacitance vessels; the alpha-1 agonist is no longer effective
    • Applies to phenylephrine and the -azolines

ALSO: prolonged use of -azolines leads to…

  • Activation of alpha-2b receptors on the arterioles of the nasal mucosa
  • -> arteriole constriction, decreased nutrient delivery, permanent damage
128
Q

What kind of drug is ephedrine (or pseudoephedrine)?

What is it used for?

A

Mixed (direct and indirect) acting sympathomimetic amine

  • OTC nasal decongestant (alpha-1)
  • OTC anti-asthma prep (beta-2)
129
Q

Which adrenergic receptors are activated by isoproterenol (ISO)?

What are the effects?

A

ISO acts only on beta receptors

  • β1 -> stimulates the heart
  • β2 -> relax smooth muscle
  • β3 -> relax smooth muscle
130
Q

Effect on the Liver of:

  • Sympathetic stimulation:
  • Parasympathetic stimulation:
A
  • Sympathetic stimulation: Glycogenolysis, gluconeogenesis
  • Parasympathetic stimulation: Glycogen synthesis
131
Q

Where are beta-3 receptors found?

A

Brown and white fat cells

Urinary bladder

(Target for overacitve bladder)

132
Q

How does ACh affect the AV node?

A

ACh decreases AV node conduction by increasing K+ conductance

  • K+ hyperpolarizes the membrane, making cells of the AV node less excitable
133
Q

Which agents overcome inhibition due to nondepolarizing blockers?

A
  • Cholinesterase inhibitors (-stigmines)
  • Sugammadex (by chelating the drug)
134
Q

Which protein is cleaved by Botox A?

What is the result?

A

SNARE SNAP-25

  • Part of the fusion machine that primes vesicles in the nerve ending to release ACh
  • The locus that Botox A cleaves is very close to the Ca2+ binding site of synaptotagmin - Cleavage of SNARE SNAP-25 results in decreased affinity of this binding site for Ca2+
    • Synaptotagmin binds Ca2+ -> activates the fusion machine
  • -> Decreased fusion machinery activation
135
Q

What is the mechanism of methacholine?

What is it used for?

A

Methacholine directly activates parasympathetic muscarinic receptors in the bronchioles (specific)

  • This results in bronchoconstiction
  • It is used in the challenge test for bronchiole asthma
136
Q

What is the effect of beta-1 activation?

A

Stimulation of the heart

-> Increased HR, SV

137
Q

What kind of drug is glycopyrrolate?

What is it used for?

A

Muscarinic antagonist (anticholinergic)

  • Give during recovery from surgical procedure to prevent excessive muscarinic effects while neostigmine is reversing the non-depolarizng blocker used during surgery
138
Q

What kind of drug are the -onidine drugs?

A

Selective alpha-2 agonists

Limit sympathetic outlflow from the CNS to the periphery

Clonidine, apraclonidine, brimonidine

139
Q

Which anti-cholinergics are used to treat overactive bladder?

Are they effective?

A

-terodines and -fenacins

  • Tolterodine
  • Fesoterodine
  • Solifenacin
  • Darifenacin
  • Oxybutynin

But - they aren’t very effective because overactive bladder is usually caused by excess P2X ATP receptors

140
Q

What kind of drug is carvedilol?

What is it used for?

A

3rd generation beta-blockers

Beta block, alpha-1 block, Ca2+ channel block

Drug of choice for mild-moderate heart failure

141
Q

In general, what is the effect of alpha-2 adrenergic receptor activation?

Inhibition?

A
  • Activation of alpha-2 receptors inhibits excitable cells
  • Inhibition of alpha-2 receptors removes the inhibition, resuling in excitement
142
Q

What agents reduce Ca2+ entry into the nerve terminal?

What is the result?

A
  • Mg2+ and other polyvalent cations
  • Aminoglycoside antibiotics
  • LEMS

Ca2+ cannot enter the nerve terminal to initiate ACh release

This is a presynaptic deficit: Decreased EPP, normal MEPP

143
Q

What is the effect of hemicholinium on the NMJ?

A

Smaller amplitude MEPPs

  • Hemicholinium is a presynpatic agent that blocks choline uptake by the choline transporter, resulitng in less ACh per vesicle
  • This makes it difficult to initiate a muscle twitch
144
Q

What kind of drug is alpha-methyldopa?

What is it used for?

A

Selective alpha-2 agonist

  • Can treat HTN during pregnancy
    • But not at Northwestern! Use labetalol instead
145
Q

What is the mechanism of pancuronium?

A

Nondepolarizing blocker at the NMJ

(post-synaptic agent, not used clinically)

146
Q

What are the side effects of clonidine?

A
  • Alpha-2b receptor stimulation
  • Sedation
  • Constipation
  • Sexual dysfunction

Remember: clonidine is a selective alpha-2 agonist. Activation of alpha-2 receptors inhibits sympathetic outflow from the CNS to the periphery

147
Q

What is the effect of black widow spider venom in the NMJ?

Describe the mechanism

A

WAY increased muscle contraction

  • Presynaptic mechanism
  • Venom forms a Ca2+ channel in the nerve terminal
  • -> Storm of vesicle fusion and ACh release
  • -> Barrage of MEPPs on top of EPPs - very painful!!
    • The muscle is stimulated even after it has fired an action potential
148
Q

What kind of drug is an -azoline?

What is it used for? (2)

A

Selective alpha-1 adrenergic agonist at low doses

Also alpha-2 agonist at high doses

Long-acting (not substrates for MAO or COMT)

  • Nasal spray - decongestion
  • Eye drops - reduces redness
149
Q

What is the effect of dobutamine on the heart?

A

Low doses increase CO without affecting HR

Higher doses increase HR (used for stress EKG)

Dobutamine is a selective beta-1 agonist

150
Q

Which anticholinergics are used to block secretions?

Which secretions?

A

Atropine and glycopyrrolate

Can be used to block:

  • Respiratory secretions (cold medicine)
  • Acid secretion (not used for this b/c PPIs are better)
  • Autonomic effects of neostigmine (used after surgery, while neostigmine is reversing the nondepolarizing block)
151
Q

What is the effect of adrenergic stimulation on the heart?

A

Activates beta-1 receptors

-> increased HR, SV

152
Q

What are the side effects of succinylcholine?

A
  • Malignant hyperthermia
  • Bradycardia (especially in children)
  • CV collapse if there are new nicotinic receptors along the muscle surface
    • -> high serum potassium precedes collapse
    • Especially in burn patients

**do not use for the duration of surgery**

153
Q

What is the mechanism of tubocurarine?

A

Nondepolarizing blocker at the NMJ

(post-synaptic agent, not used clinically)

154
Q

What kind of drug is phenylephrine?

What is it used for? (3)

A

Selective alpha-1 adrenergic agonist

  • Nasal decongestion
  • Pupillary dilation
  • Increase BP during surgery
155
Q

What are the side effects of sugammadex?

A

Hypersensitivity reaction

Encapsulates other steroids (hormonal birth control!!)

156
Q

Is this image characteristic of a patient with Myasthenia Gravis or LEMS?

A

Myasthenia Gravis

Post-synaptic deficit; Looks like inhibition due to a nondepolarizing neuromuscular blocker

157
Q

Which anticholinergics might be used on the bronchioles?

Why?

A
  • Ipratropium - 1st line for COPD
    • Short-acting muscarinic antagonist at M3 receptors
    • Not for long-term use b/c it also blocks presynaptic M2 receptors, signaling for the release of more ACh
  • Tiotropium - maintenence inhaler for asthma
    • Long-acting muscarinic antagonist
    • More effective than ipratropium becaues it only blocks M3 receptors
158
Q

What is thte mechanism of action (in general) of -stigmine drugs?

A
  • stigmines reversibly inhibit cholinesterase by adding a carbamyl to ChE’s esteric site. This prevents it from binding and hydrolyzing ACh
  • ChE can hydrolyze the carbamyl group (like it does to ACh), but it does so SLOWLY, thus tying up all of the enzymes and leaving ACh to do its thing
  • Recall that organophosphorous agents irreversibly inhibit cholinesterase via phosphorylation*
159
Q

What is the mechanism of the irreversible cholinesterase inhibitors?

A

Phosphorylates cholinesterase at the esteric site

This prevents it from binding and hydrolyzing ACh, resulting in ACh overload

Recall: reversible cholinesterase inhibitors (-stigmines) add a carbamyl group here; ChE can hydrolyze the carbamyl (thus reversing the effect), but this happens slowly, so the drug can act

160
Q

Effect on the salivary glands of:

  • Sympathetic stimulation:
  • Parasympathetic stimulation:
A
  • Sympathetic stimulation: secretion (viscous)
  • Parasympathetic stimulation: secretion (watery)
161
Q

What kind of drug is yohimbine?

What is it used for?

A

Selective alpha-2 antagonist

  • -> CNS stimulation
    • alpha-2 activation is inhibitory;
      blocking the inhibitor -> excitation
  • Used to treat impotence in diabetics
162
Q

What kind of drug is an -osin?

What are they used for?

A

Selectiva alpha-1a antagonist

Treat benign prostatic hypertrophy without side effect of orthostatic hypotension

(tamsulosin, alfuzosin, silodosin)

Side effect: no ejaculation

(Does not act on alpha-1b)

163
Q

What kind of drug is phenyoxybenzamine?

What is it used for?

A

Nonselective, irreversible alpha blocker

  • Management of pheochromocytoma
    • Adrenal medulla tumor -> Epi secretion
    • Phenyoxybenzamine can help reduce Epi effects

Side effects are predictable based on what happens when alpha receptors are blocked

164
Q

What kind of drugs are -fenacins?

What are they used for?

A

Muscarinic antagonists (anticholinergics)

Used to treat overactive bladder, but not very effective

(Solifenacin, Darifenacin)

Also the -terodines and oxybutynin

165
Q

Which anticholinergic may be used to increase heart rate?

When would we want to use this agent?

A

Atropine

  • General anesthesia
  • Spinal anesthesia if “high total spinal” occurs
    • High total spinal = NMJ blocker inhibits the cardioaccelerator
    • Use atropine to prevent drop in HR
166
Q

What kind of drug is labetalol?

What is it used for?

A

Selective beta-1 blocker that also blocks alpha-1

Used to treat:

  • Hypertensive crisis
  • Pheochromocytoma
  • HTN during pregnancy

Blocking beta-1 slows HR

Blocking alpha-1 lowers BP

(3rd generation beta blocker)

167
Q

What is the effect of tetrodotoxin (TTX) on the NMJ?

Describe the mechanism

A

Decreased muscle contraction

  • Postsynaptic mechanism
  • TTX inhibits Na+ conductance in the muscle cell
  • This blocks the initiation of Na+ dependent action potentials
    • Although ACh can successfully open the nonspecific cation channel, the resultant depolarization cannot open voltage-gated Na+ channels that are responsible for generating the action potential in the muscle cell
  • MEPP, EPP remain normal
168
Q

Which drugs can be used to reverse depolarizing blockers?

A

None!

169
Q

What kind of drug is a -azosin?

What are they used for?

What is a cmmon side effect?

A

Selective alpha-1 receptor blocker

  • Treat benign prostatic hypertrophy

(prazosin, terazosin)

Side effect = orthostatic hypotension due to inhibition of alpha-1b (blood vessel) receptors as well as alpha-1a; to treat BPH without orthostatic hypotension, use -osins, selective alpha-1a receptor

170
Q

In the NMJ, which protein binds Ca2+ to activate the fusion machine?

A

Synaptotagmin

171
Q

What kind of drug is nebivolol?

What is it used for?

A

3rd generation beta blocker

  • Beta-1 block at low doses
  • NO potentiation

Used to treat HTN and left ventricular failure

172
Q

Effect on the contractile force of the heart of:

  • Sympathetic stimulation:
  • Parasympathetic stimulation:
A
  • Sympathetic stimulation: Increased
  • Parasympathetic stimulation: No effect*
    • *Unless there is a lot of sympathetic tone preceding the parasympathetic stimulation; then a decrease is observed
173
Q

What kind of drug is scopolamine?

What is it used for?

What are the side effects?

A

Muscarinic antagonist (anti-cholinergic)

Most commonly used to treat motion sickness

Like atropine, but with more CNS depressive effects:

  • Amnesia
  • Sedation (blocks CNS cholinergic sites responsible for diffuse arousal)
174
Q

What are the autonomic responses to coition (physical sexual stimulation)?

A

Sympathetic response

Smooth muscle contraction, secretion

175
Q

After surgery is completed and the patient is recovering, how many of the “train of four” must produce a twitch if the patient’s neuromuscular function is recovered?

A

All 4

176
Q

What kind of drugs are -terodines?

What are they used for?

A

Muscarinic antagonists (anticholinergics)

Used to treat overactive bladder, but not very effective

(Tolterodine, Fesoterodine)

Also -fenacins and oxybutinin

177
Q

What kind of drug is Midodrine?

What is it used for?

What are the side effects?

A

Selective alpha-1 adrenergic agonist

  • Treat orthostatic hypotension (wonderdrug!)
  • Increase BP in severe liver or kidney disease

Side effects: piloerection, urinary retention

178
Q

What is the effect of inhibiting MAO?

A
  • Endogenous NE effect is unchanged
    • NE signal is terminated by Uptake-1
  • Increased tyramine effect
    • Causes increased NE release
    • Increased adrenergic activation
    • Can lead to hypertensive crisis

Recall: tyramine is an indirect-acting sympathomimetic amine; it gets into the nerve terminal via Uptake-1 and causes increase NE release. Tyramine is metabolized by MAO

179
Q

Which reversibe cholinesterase inhibitor can cross the blood-brain barrier?

Why is this important?

A

Physostigmine

Can be used to treat CNS cholinergic toxicity

180
Q

Epinephrine acts on α1 receptors to cause?

A

vasoconstriction in blood vessels to the skin, gi sphincters, kidneys, and the brain.

181
Q

Epinephrine acts on α2 receptors to cause?

A

inhibition of cellular functions

Neuro Review by Minnie (8 decks)

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