Blocking Drugs - 1 Flashcards
Drugs that affect skeletal muscle function include which two different therapeutic groups?
neuromuscular blockers
spasmolytics/antispasmodics
used during surgical procedures and in the intensive care unit (ICU) to produce muscle paralysis
Which drug?
neuromuscular blockers
those used to reduce spasticity in a variety of painful conditions
Which drug?
antispasmodics/spasmolytics
____________________ interfere with transmission at the neuromuscular end plate and lack central nervous system (CNS) activity
neuromuscular blocking drugs
How else can neuromuscular blocking drugs be used?
Adjuncts during general anesthesia to optimize surgical conditions and to facilitate endotracheal intubation in order to ensure adequate ventilation
NMB drugs structurally resemble which neurotransmitter?
acetylcholine
__________ is a depolarizing agent.
Succinylcholine is a depolarizing agent.
What are you the 2 major families of nondepolarizing agents and the drugs beneath them?
-
Drug class: Isoquinoline
- tubocuraine
-
Drug class: steroid derivatives
- pancuronium
Which domains on the nicotinic acetylcholine receptror (nAChR) line the channel pore?
M2
Where do the binding pockets for ACh occur?
α-β and the δ-α subunit interfaces
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?
Succinylcholine
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
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.
What are the names of the idoquinoline derivatives?
atracurium
cisatracurium
mivacurium
tubocuraine
What are the names of the steroid derivatives?
pancuronium
rocuronium
vecuronium
Which isoquinoline derivative has spontaneous elimination?
atracurium
Drugs that are excreted by the _________ typically have longer half-lives, leadring to longer durations of action (>35 minutes).
Drugs that are excreted by the kidney typically have longer half-lives, leadring to longer durations of action (>35 minutes).
Drugs eliminated by the________tend to have shorter half-lives and durations of action.
Drugs eliminated by the liver tend to have shorter half-lives and durations of action.
Rapid initial distribution phase followed by a slower elimination phase.
PK of which drugs?
NBDs
What is succinylcholine mainly used for?
Used clinically for rapid endotracheal intubation
Opens the ion channels causing depolarization and generation of a muscle action potential which results in brief contractions (fasiculations)
Which drug?
Succinylcholine
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?
Succinylcholine
MOA: Agonist at nicotinic acetylcholine (ACh) receptors, especially at neuromuscular junctions depolarizes
May stimulate ganglionic nicotinic ACh and cardiac muscarinic ACh receptors
Which drug?
Succinylcholine
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?
Succinylcholine
What are the 2 clinical applications of succinylcholine?
- placement of endotracheal tube at start of anesthetic procedure
- rarely, control of muscle contractions in status epilepticus
PK of Succinylcholine
Rapid metabolism by plasma cholinesterase: normal duration ~5 minutes
What are the 4 toxicities of succinylcholine?
arrhythmias
hyperkalemia
transient increased intra-abdominal, intraocular pressure
postoperative muscle pain
What are the 2 uses of non-depolarizing neuromuscular blockades Tubocuraine & Pancuronium?
Facilitate intubation
maintain skeletal muscle relaxation during surgery
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?
Non-depolarizing neuromuscular blockade: Tubocuraine and Pancuronium
How can the action of Tubocuraine and Pancuronium be overcome?
By increasing the amount of ACh in the synaptic cleft: administer cholinesterase inhibitors like neostigmine or pyridostigmine to shorten the duration of neuromuscular blockade
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?
Muscarinic receptor antagonists: atropine or glycopyrrolate
Benefit of coadministration: voids the bradydysrhythmias associated with agonism of the cardiac muscarinic receptors
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.
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.
What are the 2 drug interactions of non-depolarizing neuromuscular blockade?
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.
Competitive antagonist at nACh receptors, especially at neuromuscular junctions
MOA of which drug?
d-Tubocurarine
Prevents depolarization by ACh, causes flaccid paralysis
Can cause histamine release with hypotension
Weak block of cardiac muscarinic ACh receptors
Effects of which drug?
d-Tubocurarine
Like tubocurarine but lacks histamine release and antimuscarinic effects
Effects of which drug?
Cisatracurium
Prolonged relaxation for surgical procedures
Relaxation of respiratory muscles to facilitate mechanical ventilation in intensive care unit
Clinical Applications of which drug?
Cisatracurium
Prolonged relaxation for surgical procedures
Relaxation of respiratory muscles to facilitate mechanical ventilation in intensive care unit
Clinical Applications for which drug?
Cisatracurium
Renal excretion: duration: ~40–60 min
Toxicities:
Histamine release
Hypotension
Prolonged apnea
PK, Toxicities and Interactions of which drug?
d-Tubocurarine
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?
Cisatracurium
Hepatic metabolism
duration, ~20–35 min
Toxicities:
Like cisatracurium
Rocuronium
Anesthesia induced by inhalation of drug
Inhalation anesthesia
The alveolar concentration of an inhaled anesthetic that is required to prevent a response to a standardized painful stimulus in 50% of patients
Minimum alveolar anesthetic concentration (MAC)
A state of decreased awareness of pain, sometimes with amnesia
Analgesia
A state of unconsciousness, analgesia, and amnesia, with skeletal muscle relaxation and loss of reflexes
General anesthesia
What are the 4 stages of anesthesia?
Stage 1: Analgesia
Stage 2: Disinhibition
Stage 3: Surgical Anesthesia
Stage 4: Medullary Depression
the patient has decreased awareness of pain, sometimes with amnesia. Consciousness may be impaired but is not lost.
What stage of Anesthesia?
Stage 1: Analgesia
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?
Stage 2: Dishinibition
the patient is unconscious and has no pain reflexes; respiration is very regular, and blood pressure is maintained
What stage of Anesthesia?
Stage 3
the patient develops severe respiratory and cardiovascular depression that requires mechanical and pharmacologic support.
What stage of Anesthesia?
Stage 4: medullary depression
Neurophysiologic state produced by general anesthetics is characterized by what five primary effects
uunconsciousness
uamnesia
uanalgesia
uinhibition of autonomic reflexes
uskeletal muscle relaxation
Anesthetic drugs may do what 2 things?
- enhance inhibitory synaptic activity
OR
- Diminish excitatory activity
What 3 neurotransmitters do anesthetics target?
ACh
acetylcholine
GABAa, γ-aminobutyric acid-A
