Blocking Drugs - 1

Question 1

Drugs that affect skeletal muscle function include which two different therapeutic groups?

Answer 1

neuromuscular blockers

spasmolytics/antispasmodics

Question 2

used during surgical procedures and in the intensive care unit (ICU) to produce muscle paralysis

Which drug?

Answer 2

neuromuscular blockers

Question 3

those used to reduce spasticity in a variety of painful conditions

Which drug?

Answer 3

antispasmodics/spasmolytics

Question 4

____________________ interfere with transmission at the neuromuscular end plate and lack central nervous system (CNS) activity

Answer 4

neuromuscular blocking drugs

Question 5

How else can neuromuscular blocking drugs be used?

Answer 5

Adjuncts during general anesthesia to optimize surgical conditions and to facilitate endotracheal intubation in order to ensure adequate ventilation

Question 6

NMB drugs structurally resemble which neurotransmitter?

Answer 6

acetylcholine

Question 7

__________ is a depolarizing agent.

Answer 7

Succinylcholine is a depolarizing agent.

Question 8

What are you the 2 major families of nondepolarizing agents and the drugs beneath them?

Answer 8

• Drug class: Isoquinoline
  
  • tubocuraine
• Drug class: steroid derivatives
  
  • pancuronium

Question 9

Which domains on the nicotinic acetylcholine receptror (nAChR) line the channel pore?

Answer 9

M2

Question 10

Where do the binding pockets for ACh occur?

Answer 10

α-β and the δ-α subunit interfaces

Question 11

This drug occupies the receptor AND blocks the channel.

Normal closure of the channel gate is prevented and the blocker may move rapidly in and out of the pore.

This drug may desensitize the end plate by occupying the receptor and causing persistent depolarization.

Which drug is this?

Answer 11

Succinylcholine

Question 12

An additional effect of drugs on the end plate channel may occur through changes in the _____________ surrounding the channel.

General anesthetics and alcohols may impair ________________ by this mechanism

Answer 12

An additional effect of drugs on the end plate channel may occur through changes in the lipid environment surrounding the channel.

General anesthetics and alcohols may impair neuromuscular transmission by this mechanism.

Question 13

What are the names of the idoquinoline derivatives?

Answer 13

atracurium

cisatracurium

mivacurium

tubocuraine

Question 14

What are the names of the steroid derivatives?

Answer 14

pancuronium

rocuronium

vecuronium

Question 15

Which isoquinoline derivative has spontaneous elimination?

Answer 15

atracurium

Question 16

Drugs that are excreted by the _________ typically have longer half-lives, leadring to longer durations of action (>35 minutes).

Answer 16

Drugs that are excreted by the kidney typically have longer half-lives, leadring to longer durations of action (>35 minutes).

Question 17

Drugs eliminated by the________tend to have shorter half-lives and durations of action.

Answer 17

Drugs eliminated by the liver tend to have shorter half-lives and durations of action.

Question 18

Rapid initial distribution phase followed by a slower elimination phase.

PK of which drugs?

Answer 18

NBDs

Question 19

What is succinylcholine mainly used for?

Answer 19

Used clinically for rapid endotracheal intubation

Question 20

Opens the ion channels causing depolarization and generation of a muscle action potential which results in brief contractions (fasiculations)

Which drug?

Answer 20

Succinylcholine

Question 21

This drug is not hydrolyzed efficiently by junctional AChE

Persists at the nAChR resulting in sustained local muscle endplate depolarization

Causes the voltage-gated Na channel to remain in the inactive state for a prolonged period

Becomes refractory to further presynaptic release of Ach, and flaccid paralysis results

Which drug?

Answer 21

Succinylcholine

Question 22

MOA: Agonist at nicotinic acetylcholine (ACh) receptors, especially at neuromuscular junctions depolarizes

May stimulate ganglionic nicotinic ACh and cardiac muscarinic ACh receptors

Which drug?

Answer 22

Succinylcholine

Question 23

Initial depolarization causes transient contractions, followed by prolonged flaccid paralysis

Depolarization is then followed by repolarization that is also accompanied by paralysis

Effects of which drug?

Answer 23

Succinylcholine

Question 24

What are the 2 clinical applications of succinylcholine?

Answer 24

1. placement of endotracheal tube at start of anesthetic procedure
2. rarely, control of muscle contractions in status epilepticus

Question 25

PK of Succinylcholine

Answer 25

Rapid metabolism by plasma cholinesterase: normal duration ~5 minutes

Question 26

What are the 4 **toxicities of succinylcholine**?

Answer 26

arrhythmias hyperkalemia transient increased intra-abdominal, intraocular pressure postoperative muscle pain

Question 27

What are the 2 uses of **non-depolarizing neuromuscular blockades Tubocuraine & Pancuronium?**

Answer 27

**Facilitate intubation** **maintain skeletal muscle relaxation** during surgery

Question 28

competitively inhibit normal channel activation preventing muscle cell depolarization, causing flaccid paralysis Small rapidly moving muscles of the **face and eyes are affected first** followed by **fingers, toes, extremities, trunk, intercostals** and **lastly the diaphragm** MOA of which drug?

Answer 28

Non-depolarizing neuromuscular blockade: **Tubocuraine and Pancuronium**

Question 29

How can the action of Tubocuraine and Pancuronium be overcome?

Answer 29

By increasing the amount of ACh in the synaptic cleft: administer cholinesterase inhibitors like **neostigmine or pyridostigmine** to shorten the duration of neuromuscular blockade

Question 30

Which class of drugs are usually co-administered with cholinesterase inhibitors? What are the names of these drugs? What is the benefit of this coadministration?

Answer 30

Muscarinic receptor antagonists: atropine or glycopyrrolate Benefit of coadministration: **voids the bradydysrhythmias** associated with agonism of the cardiac muscarinic receptors

Question 31

T/F: high doses of non-depolarizing agents can block the ion channels of the end plate resulting in **increased** ability of cholinesterase inhibitors to reverse neuromuscular blockade.

Answer 31

False: high doses of non-depolarizing agents can block the ion channels of the end plate resulting in **decreased** ability of cholinesterase inhibitors to reverse neuromuscular blockade.

Question 32

What are the 2 drug interactions of non-depolarizing neuromuscular blockade?

Answer 32

Aminoglycosides: **gentamicin and tobramycin** inhibit acetylcholine release from cholinergic nerves by competing with calcium ions. They act synergistically to enhance neuromuscular blockade Calcium channel blockers: **verapamil, and dihydropyrodinesal** enhance the neuromuscular blocking effects of non-depolarizing agents.

Question 33

Competitive antagonist at nACh receptors, especially at neuromuscular junctions MOA of which drug?

Answer 33

d-Tubocurarine

Question 34

Prevents depolarization by ACh, causes flaccid paralysis Can cause histamine release with hypotension Weak block of cardiac muscarinic ACh receptors Effects of which drug?

Answer 34

d-Tubocurarine

Question 35

Like tubocurarine but lacks histamine release and antimuscarinic effects Effects of which drug?

Answer 35

Cisatracurium

Question 36

Prolonged relaxation for surgical procedures Relaxation of respiratory muscles to facilitate mechanical ventilation in intensive care unit Clinical Applications of which drug?

Answer 36

Cisatracurium

Question 37

Prolonged relaxation for surgical procedures Relaxation of respiratory muscles to facilitate mechanical ventilation in intensive care unit Clinical Applications for which drug?

Answer 37

Cisatracurium

Question 38

**Renal excretion:** duration: ~40–60 min **Toxicities:** Histamine release Hypotension Prolonged apnea PK, Toxicities and Interactions of which drug?

Answer 38

d-Tubocurarine

Question 39

Not dependent on renal or hepatic function •duration: **~25–45 min** **Toxicities:** Prolonged apnea but less toxic than atracurium PK, toxicities and interactions of which drug?

Answer 39

Cisatracurium

Question 40

**Hepatic metabolism** duration, **~20–35 min** **Toxicities:** Like cisatracurium

Answer 40

Rocuronium

Question 41

Anesthesia induced by inhalation of drug

Answer 41

Inhalation anesthesia

Question 42

The alveolar concentration of an inhaled anesthetic that is required to prevent a response to a standardized painful stimulus in 50% of patients

Answer 42

Minimum alveolar anesthetic concentration (MAC)

Question 43

A state of decreased awareness of pain, sometimes with amnesia

Answer 43

Analgesia

Question 44

A state of unconsciousness, analgesia, and amnesia, with skeletal muscle relaxation and loss of reflexes

Answer 44

General anesthesia

Question 45

What are the 4 stages of anesthesia?

Answer 45

Stage 1: **Analgesia** Stage 2: **Disinhibition** Stage 3: **Surgical Anesthesia** Stage 4: **Medullary Depression**

Question 46

the patient has decreased awareness of pain, sometimes with amnesia. Consciousness may be impaired but is not lost. What stage of Anesthesia?

Answer 46

Stage 1: Analgesia

Question 47

the patient appears to be delirious and excited. Amnesia occurs, reflexes are enhanced, and respiration is typically irregular; retching and incontinence may occur. What stage of Anesthesia?

Answer 47

**Stage 2: Dishinibition**

Question 48

the patient is unconscious and has no pain reflexes; respiration is very regular, and blood pressure is maintained What stage of Anesthesia?

Answer 48

Stage 3

Question 49

the patient develops severe respiratory and cardiovascular depression that requires mechanical and pharmacologic support. What stage of Anesthesia?

Answer 49

Stage 4: medullary depression

Question 50

Neurophysiologic state produced by general anesthetics is characterized by what five primary effects

Answer 50

uunconsciousness uamnesia uanalgesia uinhibition of autonomic reflexes uskeletal muscle relaxation

Question 51

Anesthetic drugs may do what 2 things?

Answer 51

1. enhance inhibitory synaptic activity OR 2. Diminish excitatory activity

Question 52

What 3 neurotransmitters do anesthetics target?

Answer 52

ACh acetylcholine GABAa, γ-aminobutyric acid-A