ANS - Cholinergic Agonists and Antagonists

Question 1

Parasympathomimetic Agents are drugs that produce _________ effects. These drugs can be divided into two major groups?

Answer 1

parasympathomimetic
1. Direct-acting agents
2. Cholinesterase inhibitors

Question 2

Question 3

Direct-acting parasympathomimetic agonists consist of: ______ esters, including ____ and numerous ______ esters, and ________ alkaloids

Answer 3

Choline, ACh, synthetic, cholinomimetic

Question 4

Direct-acting agonists:
- act ____ on receptors and do not depend upon endogenous ___ for their effects
- agonists contain ____ groupings that allow interaction with the receptor

Answer 4

directly, ACh, structural

Question 5

List primary choline and cholinomimetic alakloids

Question 6

Nicotinic (NN) receptors
1. These receptors were named according to the alkaloids ______ and ______ that were identified to be agonists at the respective receptors.
2. NN receptors are present on _________ neurons in autonomic ganglia (?).They are also present on adrenal medullary ______ cells and mediate neurotransmission from _______ SNS neurons to adrenal medullary ______ cells
3. NN receptors are widely distributed in the CNS and are present in _______ tissues

Answer 6

nicotine, muscarine, postganglionic, intramural, prevertebral, and paravertebral, chromaffin, preganglionic, chromaffin, nonneuronal

Question 7

Nicotinic muscle (NM) receptors are involved in the signal ______ at the _______ junction (_____ nervous system)
* NN receptors are ____-gated ion channels and contain ___ homologous subunits
* Activation of these receptors initiates a rapid ____ in cellular ______ to selective cations (?):

Cholinergic Receptors
Nicotinic (NN) receptors
➢ Cell membrane depolarization
➢ Excitation of postganglionic ANS neurons
➢ Excitation adrenal medullary chromaffin cells
➢ Excitation of skeletal muscle fibers

Answer 7

transmission, neuromuscular, somatic, ligand, five, increase, permeability, Na+ and Ca2+

Question 8

Cholinergic Receptors
–> Muscarinic Receptors
* Muscarinic receptors are located predominately at _______ target sites innervated by _______ _____ nerves such as:?
* ____ suptypes have been identified (M1-M5)
* Muscarinic receptors are ___-_____ _____ receptors (GPCRs)
* Receptor subtypes M1, M3, and M5 couple through ?. M2 and M4 receptor subtypes couple ?
* Specificity in the intracellular response profiles following activation of specific muscarinic receptors are the result of ?

Answer 8

postsynaptic, postganglionic, parasympathetic, Heart, glands, urinary bladder, and gastrointestinal tract, Five, G-protein-coupled, G-protein Gq/11, Gi and G0, G-protein-mediated effect

Question 9

_____ is the neurotransmitter released at sympathetic and parasympathetic ganglia

Answer 9

ACh

Question 10

What are the effects of cholinergic receptor stimulants on the eye? Which muscles are involved?

Answer 10

Question 11

What are the effects of cholinergic receptor stimulants on the glands? Which muscles are involved?

Answer 11

Question 12

What are the effects of cholinergic receptor stimulants on the lungs? Which muscles are involved?

Answer 12

Question 13

What are the effects of cholinergic receptor stimulants on the heart? Which muscles are involved?

Answer 13

Question 14

What are the effects of cholinergic receptor stimulants on the blood vessels? Which muscles are involved?

Answer 14

Question 15

What are the effects of cholinergic receptor stimulants on the GI tract? Which muscles are involved?

Answer 15

Question 16

What are the effects of cholinergic receptor stimulants on the urinary bladder? Which muscles are involved?

Answer 16

Question 17

–> ACh a Prototypical Cholinergic Agonist
ACh is the _______ _______ _____ and helps understand the pharmacological effects of other cholinomimetic drugs.
- ACh is not used _____
1. Muscarinic and nicotinic receptors are located at numerous tissues → no ___ response can be achieved
2. Its duration of action is ____ → ACh is rapidly ______ by the cholinesterases.

Answer 17

prototypical, cholinergic, agonist, therapeutically, selective, short, inactivated

Question 18

What are the effects of Ach on the cardiovascular system?

Answer 18

Question 19

What are the effects of Ach on nonvascular smooth muscle?

Answer 19

Question 20

What are the effects of Ach on the gastrointestinal system?

Answer 20

Question 21

What are the effects of Ach on the CNS?

Answer 21

Question 22

What are the effects of Ach on the adrenal medulla?

Answer 22

Question 23

Label the table accordingly.

Answer 23

Question 24

Receptor Activating Properties
* The pharmacological effects of the primary choline derivates are similar to the _______ effects produced by ACh administration
* The physiological response profiles produced by different choline esters are not ____ and vary in relative _____ for one organ system to another

Answer 24

parasympathomimetic, identical, selectivity

Question 25

Clinical Uses
There are ____ clinical indications for the use of cholinergic agonists in veterinary medicine.
1. Bethanechol
* It is resistant to _____ by cholinesterase
* It has been used to promote _______ contraction in ______ dogs and cats
* Bethanechol is used to promote ____ muscle contraction for treatment of _______ sphincter ______
2. Carbachol
* Carbachol is used topically to produce _____ in ophthalmology. Its use is specially at the end of ______ surgery

Answer 25

few, hydrolysis, bladder, paraplegic, detrusor, detrusor, dyssynergia, miosis, cataract

Question 26

Cholinomimetic Alkaloids
Pilocarpine, muscarine, and arecoline
* Are ____ alkaloids
* Are selective _________ agents
* Evoke their effects by direct activation of ______ receptors
—> Target organ effects of pilocarpine
* It stimulates flow of secretion from ______ glands including?
* It causes contraction of GI _____ muscle
Increases smooth muscle ___ and _____ activity
* It has an important constrictor effect on the ____
–> Target organ effects of arecoline?

Answer 26

plant, parasympathomimetic, muscarinic, exocrine, Salivary mucous, gastric, and digestive pancreatic secretions, smooth, tone, peristaltic, pupil
Glands, smooth muscles, and myocardium

Question 27

Cholinomimetic Alkaloids
Clinical uses

1. _______ is available as a 1%, 2%, and 4% ophthalmic solution
2. Topical pilocarpine causes ______ and lowers the _______ pressure in glaucoma
3. Used for the treatment of ________ ____ (KCS) in dogs
4. A _____ pilocarpine solution (0.125% or 0.25%) can be applied _____ to the eye to
   stimulate ___ production
5. Pilocarpine can cause local ______ and inflammation of the _____ tract
6. With repeated use, pilocarpine may cause ______ effects such as?

Answer 27

Pilocarpine, miosis, intraocular, keratoconjunctivitis sicca, dilute, directly, tear, irritation, uveal, systemic
vomiting, diarrhea, and increased salivation

Question 28

Cholinesterase Inhibitors (indirect-Acting) _____ or ______ acetylcholinesterase (AChE), increasing the level of synaptic _____
* The action of ACh will be _____ at all cholinergic receptors. The scope of activity is not limited to ________ (muscarinic) effects but can include _______ actions throughout the body
* Cholinesterase Inhibitors also cause _______ of Ach activity at ____ sites

Answer 28

Inactivate, inhibit, ACh, enhanced, parasympathomimetic, choinomimetic, intensification, nicotinic

Question 29

Parasympathomimetic Agents
Drugs that produce parasympathomimetic effects can be divided into two major groups:

1. Which parasympathetic agents are Reversible?
2. Which parasympathetic agents are Irreversible?

Answer 29

1. Direct-acting agents
2. Cholinesterase inhibitors
3. Physostigmine, neostigmine,
   pyridostigmine, edrophonium
4. Organophosphates

Question 30

Question 31

Cholinesterase Inhibitors (indirect-Acting)
Anticholinesterase (anti-AChE) agents prevent the ______ of ACh via the three following mechanisms:

Answer 31

hydrolysis
* Reversible AChE inhibition
* Carbamylation of AChE
* Phosphorylation of AChE

Question 32

Cholinesterase Inhibitors (indirect-Acting)
AChE has ____ active sites that recognize specific parts of ACh molecule:
1. An _____ (______ charged) region where electrostatic binding occurs with the _____ nitrogen of the choline moiety
2. An ____ site where the ____ portion of the acetyl ester binds to it by ____ binding
- _______, ________ and other carbamate derivates interact with the anionic and esteratic site of the enzyme.
- Neostigmine and physostigmine are believed to be _____ in a manner similar to but much ____ than that of ACh

Answer 32

two, anionic, negatively, cationic, esteratic, carboxyl, covalent, Neostigmine, physostigmine, hydrolyzed, slower

Question 33

Cholinesterase Inhibitors (indirect-Acting)
–> Reversible Inhibitors
1. Name the reversible inhibitors?
2. The physiological responses produced by these drugs are similar to ?

Answer 33

1. Physostigmine, neostigmine, edrophonium, pyridostigmine
2. direct-acting parasympathomimetic agents

Question 34

What are the effects of Phyostigmine and/or neostigmine on the GI tract?

Answer 34

for last box: B1 receptors are the most important

Question 35

What are the effects of Phyostigmine and/or neostigmine on the eyes?

Answer 35

Question 36

What are the effects of Phyostigmine and/or neostigmine on the skeletal muscle?

Answer 36

Question 37

What are the effects of Phyostigmine and/or neostigmine on the other effects?

Answer 37

Question 38

Cholinesterase Inhibitors (indirect-Acting)
–> Clinical uses
1. (4) can be used to reverse the effects of nondepolarizing neuromuscular blocking drugs in voluntary muscles
2. AChE inhibitors are used in the therapy of dogs (but rarely ____), with ______ ____ (MG)
3. Edrophonium can be used as an initial screening test for dogs with suspected ___ ( ______ absence or _____ autoimmune diseases resulting in deficiency of AChRs)
4. ______ _____ are the most used AChE inhibitors for MG.
5. _______ is preferred → longer duration and lower adverse GI effects

Adverse effects
Are related to the muscarine effects of excess ACh –> ?

Answer 38

Physostigmine, neostigmine, pyridostigmine, edrophonium, cats, myasthenia gravis, MG, congenital, acquired, Neostigmine, pyridostigmine, Pyridostigmine, Increased GI motility, diarrhea, salivation, and bradycardia

Question 39

Cholinesterase Inhibitors (indirect-Acting)
–> Irreversible Inhibitors
Organophosphorus compounds
* Organophosphates _____________ phosphorylate the ________ site of AChE throughout the body.
________________ ACh is not inactivated
* Organophosphate poisoning produces diffuse _______________ effects → typical
parasympathomimetic actions:
➢ Profuse _________
➢ ___________
➢ ____________
➢ _______________ of GI tract
➢ _____________
➢ ____________
➢ ________________
➢ Severe _________________
➢ Excess ___________ secretion

Answer 39

Cholinesterase Inhibitors (indirect-Acting)
–> Irreversible Inhibitors
Organophosphorus compounds
* Organophosphates irreversibly phosphorylate the esteratic site of AChE throughout the body.
Endogenous ACh is not inactivated
* Organophosphate poisoning produces diffuse cholinomimetic effects → typical
parasympathomimetic actions:
➢ Profuse salivation
➢ Vomiting
➢ Defecation
➢ Hypermotility of GI tract
➢ Urination
➢ Bradycardia
➢ Hypotension
➢ Severe bronchoconstriction
➢ Excess bronchial secretion

Question 40

Cholinesterase Inhibitors (indirect-Acting)
–> Irreversible inhibitors - Organophosphorus compounds
* Organophosphates produce skeletal muscle _______, ______, and subsequently, muscle _____ occurs. These effects are due the _______ excessive stimulation of the ______ receptors
* Convulsions and frequently death are seen in ______ poisoning caused by penetration of the agent into the ____
- _______ (?) causes an effective removal of the phosphate group from the enzyme (reactivated).

Answer 40

fasciculations, twitching, paralysis, persistent, nicotinic, organophosphate, CNS, Pralidoxime (pyridine-2-aldoxime-methiodide, 2-PAM)

Question 41

–> Muscarinic Receptor Antagonists
Muscarinic receptor antagonists (MRA) block the effect of ___ and related _______ receptor agonists from binding to and activating ______ receptors (antimuscarinic agents)
Example of this is ______, a _______ _____ blocking agent
* It is an alkaloid extracted from _____ ______
- Antimuscarinic drugs are considered _____ for different muscarinic receptor subtypes
- It is difficult to achieve a _____ action on targeted structures without concurrently inducing side effects on other more ______ sites

Answer 41

ACh, cholinergic, muscarinic, Atropine, prototypical muscarinic, Atropa Belladonna, nonspecific, selective, susceptible

Question 42

Know this table

Answer 42

ABP = arterial blood pressure
Atropine also can activate other tissues?; can activate cardio, GI, etc. when you want to treat a specific thing, you need to use a drg that cna target specifically

Question 43

Clinical uses - Muscarinic Receptor Antagonists
Muscarinic receptor antagonists can be used as __________. ___ or abolish GI ________ or
___ _______ of the uterus, urinary bladder, ureter, bile duct, and bronchioles
* ________ drugs are not as effective as EPI or other adrenergic amines in _____ the bronchioles, but atropine is effective in antagonizing excessive _______ stimulation
* Atropine is used to treat ________. Atropine may be administered as a ______ test to determine the _______ of a bradyarrhythmia to an anticholinergic drug
* Atropine is used to facilitate ________ examination of internal ocular structures. Atropine is available as a __% ophthalmic solution (potent mydriatic and cycloplegic)
* Atropine is used commonly in the treatment of iridocyclitis because of its long duration of action
Atropine is used to counter anti-cholinesterase overdose or toxicity

Answer 43

antispasmodics, ↓, hypermotility ↓ hypertonicity, Antimuscarinic, dilating, cholinergic, bradyarrhythmias, diagnostic, responsiveness, ophthalmoscopic , 1

Question 44

Adverse effects of Muscarinic Receptor Antagonists
* Excessive _____ and _____ (after topical application) is more likely to occur with use of solution compared to the ______ formulation
* Atropine can cause an increase in ______ pressure and can decrease ____ production. It should be avoided in patients with ______ or ?

Answer 44

salivation, vomiting, ointment, intraocular, tear, glaucoma, keratoconjunctivitis sicca

Question 45

Muscarinic Receptor Antagonists - Examples:
–> Glycopyrrolate
* The antimuscarinic effects of this antagonist are similar to _____
* It has a lower risk of marked _______ when compared to atropine
* In dogs glycopyrrolate decreases the _____ and _____ of gastric secretions
* It reduces intestinal _____
* It reduces and controls excessive secretions of the ____ tract
* Glycopyrrolate penetrates the ____ less effectively than atropine

–> N-butylscopolamine bromide (NBB)
* The antimuscarinic effects are similar in action to ___
* Used for the treatment (IV injection) of ______ ____ in horses
* It is associated with fewer _____ side effects
* It is a preferred treatment for ______ obstruction in horses

Answer 45

atropine, tachyarrhythmias, volume, acidity, motility, respiratory, BBB, atropine, spasmodic colic, systemic, airway

Question 46

Muscarinic Receptor Antagonists - Example
–> Methantheline, propantheline, methylatropine
* These compounds don not cross the ___ to an appreciable extent
* They are considerably less effective than atropine as ______ to organophosphates
* Propantheline has been used in dogs with _____ ____ that develop significant ______ side effects (response to pyridostigmine)
* In small animals, propantheline is used _____ as an antispasmodic/antisecretory agent in the treatment of ?
* In horses, propantheline has been administered IV to reduce colonic _______ and to relax the _____ (easier rectal examination and surgery)

Answer 46

BBB, antagonists, myasthenia gravis, muscarinic, orally, diarrhea, colitis, and acute irritable bowel syndrome, peristalsis, rectum

Question 47

Neuromuscular Blocking Agents
Are agents used in clinical medicine act by interfering with the action of _______ neurotransmitter.
ACh on the ______-_______ receptor at the neuromuscular junction (NMJ)
* Neuromuscular blocking (NMB) drugs originated with the discovery of ______. In 1856, Claude Bernand showed that curare causes _____ by blocking neuromuscular
transmission
* NMB agents possess _____ _____ groups that allow interaction with the nicotinic
cholinergic receptors.
* Curare is a mixture of _______ occurring ____ found in various South American ___ and used as ____ poison by South American
Indians → Death by paralysis of _____ muscles
* The most important component is _______

Answer 47

endogenous, nicotinic, cholinergic, curare, paralysis, chemical, structural, naturally, alkaloids, plants, arrow, respiratory, tubocurarine

Question 48

Neuromuscular Blocking Agents
NMB drugs are classified as _______, ________ and ________ agents
* Competitive nondepolarizing agents:
Competitive nondepolarizing NMB agents occupy the receptor so that ACh _____ access its binding site and upon binding these drugs ____ to trigger _______ ion movement, resulting in muscle _______
* Depolarizing agents:
Depolarizing agents act in a more complicated manner initially causing membrane ________
(muscle _______), before _____ and muscle ______ occur.

Answer 48

competitive, nondepolarizing, depolarizing, cannot, fail, transmembrane, paralysis, depolarization, fasciculation, blockade, paralysis

Question 49

Answer 49

Diagram explaining the most important points regarding the neuromuscular junction.
Motor axon pictured
Right side: physiological processes involved
Local anesthetics: stabilize membrane effect
Hemich= block choline uptake, which is important for synthesis of AcH (we need choline to synthesize Acetylcholine).

Question 50

Neuromuscular Blocking Agents - Physiological Aspects
* The ACh released into the ______ _____ binds to ______ receptors
* The exclusively _______ ______ receptors located on the plasma membrane surface of the muscle cell are clustered in ____ density
* It requires the activation of a ____ number of _______ _______ receptors to excite a _____
muscle fiber → muscle ______
* A single synaptic vesicle contains → ______-______ molecules of ACh. A single action potential may trigger the fusion of ___-____ vesicles
* The relative ratio of binding site for ACh on the ______ _____ receptor to AChE binding sites at the ____ is ~10: 1.

Answer 50

synaptic cleft, specialized, nicotinic cholinergic, high, large, nicotinic cholinergic, single, contraction, 7,000-12,000, 40-300, nicotinic cholinergic , NMJ

Question 51

Nicotinic cholinergic receptor
* Contains __ subunits: ?
* Receptors have two ____ ( _____ charged)
* ___ ACh molecules must bind to receptor to
induce a conformation change
* The central transmembrane channel of the receptor represents the membrane for ____ ______ instigated by ____ activation of the receptor
* Large movement of ____ inside into the cells and smaller movement of ___ out (depolarization)
* Agonist and antagonist binding sites are restricted to __-subunits

Answer 51

5, α1, α2, β, δ, γ (ε), anionic, negatively, 2, ion fluxes, agonist, Na+, K+, α

Question 52

Neuromuscular Blocking Agents

Answer 52

Nicotinic receptors:
Contains 5 subunits
Epsilon in parenthesis because in adult cells, this delta subunit is changed into epsilon subunit.
Build a special pore for the sodium movement into cells?
Pore for ion fluxes and the amount of molecules that should bind to these receptors are 2 and they only bind to alpha 1 and 2 binding sites.

Question 53

Answer 53

Different chemical structures of these drugs.
Look at difference between structures. Very important differences because the agents are also

Question 54

➢ Occupation of the _______ charged binding sites on the receptor by _______ _____ stabilizes the receptor → Membrane channel is ___ activated
➢ Depolarizing agents allow ____ channel activation and ___ flow but it will result in a ______ interruption in ion flow through the receptor.

Answer 54

negatively, competitive agents, not, initial, ion, persistent

Question 55

Neuromuscular Blocking Agents- Pharmacological considerations
_________ and ______ (fish and shellfish poisons)
* __ permeability of excitable membranes to ____ (but not to ____)
* No generation of axonal action potentials → muscle ______

Local anesthetics
* Inactivate ____/_____ channels → propagation of AP is _____
Hemicholinium
* Interferes with the choline _______ into _______ neurons
* No current ______ application. It is used in ______ application

Answer 55

Tetrodotoxin, saxitoxin, ↓ , Na+, K+, paralysis, Na+/K+, halted, reuptake, cholinergic, clinical, research

Question 56

Neuromuscular Blocking Agents

Answer 56

Cholinergic transmission steps
Red arrows indicate which drugs interfere with step in cholinergic transmission.

Question 57

Neuromuscular Blocking Agents- Pharmacological considerations
–> Botulinum toxin (Clostridium botulinum)
* Ingestion in ? is often fatal
* Interferes with ______ of synaptic vesicles with plasma membrane
* Prevents ACh release into the ____ → muscle ______
–> Cholinesterase inhibitors
* Decrease the activity of _____. Endogenous ACh accumulates at ___ receptors
* In case of overdose → muscle _______, _____, and eventually ____

Answer 57

cattle/horses/poultry/waterfowl, fusion, NMJ, paralysis, AChE, N , fasciculations, spasms, apnea

Question 58

Question 59

Neuromuscular Blocking Agents
Pharmacological considerations
–> Aminoglycoside antibiotics
* Examples include?
* Inhibit release of ACh from ____ nerves.
decrease availability of ___ at axonal terminal
* decrease _____ of the postsynaptic membrane to ACh
–> ________ ions
* Interfere with release of ____ by competing for _______ mechanisms responsible for mobilization of ____ into
the nerve
*____ sensitivity of postsynaptic membrane to ACh

Answer 59

Neomycin, streptomycin, kanamycin, gentamycin, motor, Ca2+, sensitivity, Magnesium, Ach, transport, Ca++, ↓

Question 60

Question 61

Answer 61

Different kind of neuromuscular blocking agents
Red = depolarizing. Noncompetitive Non-depolarizing agent = Succinylcholine = only NBA used in Vet Med.

Green = competitive non-depolarizing agents; not used in vet med

Onset, duration, and elimination differ. Most elimination is via hydrolysis in plasma (cholinesterase). Do not need enzymes in order for elimination to occur. Most important factors that can interfere are the pH and temperature.

Question 62

Neuromuscular Blocking Agents- Competitive nondepolarizing agents
* Nondepolarizing NMB agents compete with ACh for available _______ _____ receptors
* The historical prototype of this group of drugs is __-_______. Today, d-tubocurarine is
not used _____ and has long been replaced with _____ acting agents:
➢ Atracurium
➢ Cisatracurium
➢ Mivacurium
➢ Doxocurium
➢ Pancuronium
➢ Vecuronium
➢ Rocuronium
➢ Gantacurium
Although d-tubucurarine binds to cholinergic receptors in the same region as ACh, d-tubucurarine does not exhibit _______ _______ properties → It does not cause a _______ ____-plate potential

Answer 62

nicotinic cholinergic, d-tubocurarine, clinically, similarly, receptor-activating, motor end

Question 63

Neuromuscular Blocking Agents
Competitive nondepolarizing agents
* Nondepolarizing NMB agents are classified as _______ or ____ molecules
* Two groups of synthetic pachycurares contain the drugs in common use in medicine today: (3)?

Answer 63

pachycurares, bulky,
1. Benzylisoquinoliniums
2. Aminosteroids
3. Asymetric mixed-onium chlorofumarates (new class)

Question 64

Neuromuscular Blocking Agents

Answer 64

Three different classes represent the drugs
1. Benzylisoquinoliniums
2. Aminosteroids
3. Asymetric mixed-onium chlorofumarates (new class)

Question 65

Neuromuscular Blocking Agents
Competitive nondepolarizing agents: benzylisoquinolinium compounds
–> Atracurium
* It has been widely used across a variety of species including dogs, cats, horses
* Atracurium produces muscle _____ during ____ procedures
* It facilitates _______ intubation
* Atracurium can be used safely in patients with significant ____ or ____ insufficiency. Why?
* Intraurethral adm. in male cats with urethral plugs __ ______ removal
* At usual doses, atracurium exhibits minimal _______ effects
* Physiologic __ and _____ can affect its elimination
–> Cisatracurium
* It is a ___-______ of atracurium
* It has a similar _____ and _____ effects to atracurium

Answer 65

relaxation, surgical, endotracheal, renal, hepatic, (Why? = Don’t really need to be eliminated to be metabolized in the liver or kidneys)↑ , obstruction, cardiovascular, pH, temperature, cis-isomer, duration, clinical

Question 66

• Vencuronium is indicated as an _____ to general anesthesia to produce muscle ______
• Vecuronium is _____ metabolized (_____). Prolonged recovery times may result in patients with significant _____ or _____ disease.
  *Very minimal _____ effects caused by vecuronium. Its potency appears to be lower in ______ than in other species

Answer 66

adjunct, relaxation, partially, hepatic, renal, hepatic, cardiac, horses

Question 67

• Pancuronium was the first _______ to be introduced as a NMB agent. Use today is ____. ______, ______, and ______ are generally preferred
• Pancuronium produces muscle _______ during surgical procedures. It facilitates _______ intubation
• The effects of pancuronium on the cardiovascuar system are ______ among species (blocks cardiac ______ receptors)

Answer 67

aminosteroid, rare, Vecuronium, rocuronium, atracurium, relaxation, endotracheal, inconsistent, muscarinic,

Question 68

Competitive nondepolarizing agents: asymetric mixed-onium chlorofumarates
–> Gantacurium
* Gantacurium has an ______ duration of action. It is degraded in _____ by ___ sensitive chemical hydrolysis
* At clinical doses, cats and dogs do not appear to have appreciable _____ effects
* Recovery is accelerated with ____ inhibitors

Answer 68

ultrashort, plasma, pHs, cardiovascular, AchE

Question 69

Depolarizing Agents
–> Succinylcholine
* Succinylcholine is the only ______ neuromuscular blocking agent available for use within veterinary medicine
* It has a ____ onset of action and ____ duration. Because of the short duration frequent _____ or a ______-rate infusion is required
* Its use in ____ animal patients has been limited. _____ of dogs and cats does not routinely exhibit excessive _______
* Succinylcholine like Ach, stimulates ______ receptors at the NMJ
* It elicits a _____ depolarization of the neuromuscular ___-plate
The mechanism of depolarizing has been described as _____:
1. _____ ___ block
2. _____ ___ block

Answer 69

depolarizing, rapid, short, redosing, constant, small, Larynx, laryngospasm, cholinergic, prolonged, end, biphasic, Phase I , Phase II

Question 70

Succinylcholine
1. Phase I block
* The ________ _____ channel associated with the NM is _____ → the receptor is _____
* The depolarization by succinylcholine resulting in an ___ and persistent permeability to ___ and ____
* Its depolarizing action is clinically characterized by ____
* Succinylcholine causes a persistent alteration because it is not ______ and must _____ diffuse ___ from the NMJ
2. Phase II block
* Over time, the nonselective cation channel ____ and ______ occurs, rendering the
neuromuscular junction _____ to depolarization → _______ _____

Answer 70

nonselective, cation, opened, depolarized, ↑, Na+, K+, fasciculations, hydrolized, slowly, away, closes, repolarization, resistant, flaccid paralysis

Question 71

Clinical use
Muscle paralysis proceeds at different ____ in different body ______ after administration of
a NMB agent
* ______ muscles, _____ muscle, and those of the ____ and ____ are affected first (0.25-1
min.) after injection
* Subsequently, muscles of the ____ are paralyzed, then the ____ and _____ muscles
(____)
* ______ muscles, ______ muscles, and the ______ are then paralyzed (in this order)
* Recovery usually proceeds in the ______ of this sequence
* Use doses of NMB agents adequate to paralyze ______ muscle but insufficient to affect the _____. Respiratory _______ may still occur!
It is imperative that apparatus for administering _______ ventilation is available when NMB agents are used

Answer 71

rates, regions, Extraocular, facial, head, neck, limbs, deglution, laryngeal, glottis, Abdominal, intercostal, diaphragm, reverse, ambulatory, diaphragm, insufficiency, mechanical

Question 72

Clinical use of NMB agents
* To facilitate _____ intubation (TI). TI may be performed in a ______ animal immediately
after a _____ dose of NMB agent has taken effect. Prior administration of _____ or ______ is advisable!
Purpose?
* To increase muscle ______ to facilitate surgical access to _____ anatomic regions
* To evoke muscle ______ to facilitate ______ manipulations
* To help improve _____ positioning for surgery
* To reduce the amount of general ______ required

Answer 72

tracheal, unanesthetized, paralyzing, sedation, tranquilization, relaxation, difficult, relaxation, orthopedic, ocular, anesthesic

Question 73

Margin of safety
It has been estimated that a relatively ____ percentage of the cholinergic receptors must be occupied by a NMB before muscle ____ fails
* In the cat diaphragm, muscle twitch is not affected until about __% of the receptors are blocked by __-______. Twitch is completely abolished until about ___% of the receptors are occupied.
* For recovering from the effects (diaphragm) only a small % (5% in ____, 18% in ____) need to be be free
* As a patient regains some control of voluntary muscles, spontaneous respiration returns and may seem completely normal….BUT
Only a small % of the postsynaptic receptors are available for interaction with ACh → this small
fraction is responsible for maintaining muscle contraction

Answer 73

large, twitch, 80, d-tubocurarine, 90, dogs, cats

Question 74

Clinical reversal of neuromuscular paralysis
* The first step should be to initiate (or to continue) ______ pressure ventilation (PPV). Ventilation will allow adequate time for the drug to be _______.
* To ______ administration of the involved NMB agent
* Avoid to use other drugs that may _______ interact with NMB agents
* Use drugs for ______ of neuromuscular blockade. There are two classes of drugs use for this purpose:

Answer 74

positive, metabolized, withdraw, synergistically, reversal

AChE inhibitors, and the cyclodextrin, suggammadex

Question 75

Clinical reversal of neuromuscular paralysis: Acetylcholinesterase inhibtors
* AChE inhibitors → They ______ neuromuscular blockade by ______ the enzyme _____ which is responsible for the ______ of ACh into _____ and _____ _____.
* Which AChE inhibitors reverse the action of nondepolarizing NMB drugs?
* AChE inhibitors are not effective for _____ of depolarizing NMB agents → ______
* Several human AChE inhibitor products come premixed with an ______

_________ has the most rapid onset of action followed by ______ and then ______.

Answer 75

reverse, inhibiting, AChE, hydrolysis, choline, acetic acid
edrophonium, neostigmine, and pyridostigmine

reversal, succinylcholine, anticholinergic

Edrophonium, neostigmine, pyridostigmine,

Question 76

The muscarinic effects of edrophonium are mild compared to _________ or __________.

Answer 76

neostigmine, pyridostigmine

Question 77

_________ is the drug most commonly selected for neuromuscular reversal in veterinary medicine

Answer 77

Edrophonium

Question 78

Clinical reversal of neuromuscular paralysis: cyclodextrin, suggammadex
* __________ is the first selective relaxant binding agent (SRBA). It is a ________ ______ _____ that when administered, tightly encapsulates _______-base _______ NMB agents.

Answer 78

Suggammadex, modified gamma cyclodextrin, aminosteroid, nondepolarizing

Question 79

• The cyclodextran structure has a _______ cavity and a _______ exterior. _________ interaction trap the NMB agent in the ________ cavity → this _____ soluble guest-host complex is readily available for _______.

Answer 79

hydrophobic, hydrophilic, Hydrophobic, cyclodextrin, water, elimination

Question 80

What are the effects of cholinergic receptor stimulants on the urinary bladder? Which muscles are involved?

Question 81

_________ is the drug most commonly selected for neuromuscular reversal in veterinary medicine

Answer 81

Edrophonium

Question 82

Don’t forget to do the MCQ associated with these lectures.