Neuromuscular Blocking Drugs Flashcards
What is Chondrodendon tomentosum?
A vine from south america that can be used to make a deadly poison.
What are the two categories of non-depolarizing agents?
Isoquinoline derivatives
Steroid derivatives
Which drugs are isoquinoline derivatives?
Atracurium
Cisatracurium
D-Tubocurarine
What drugs are steroid derivatives?
Pancuronium
Rocuronium
Vecuronium
What is the name of the depolarizing agent?
Succinylcholine
What drugs are reversal agents?
Pyridostigmine
Neostigmine
physostigmine
sugammedex
What is the location and function of nicotinic receptors?
- Neuromuscular end plate, skeletal muscle
2. Autonomic ganglion cells
What is the basic structure of the nicotinic Ach receptor?
The Nicotinic Ach receptor is a transmembrane ligand gated Na+ channel that opens when bound to Ach.
What is the fundamental difference in the molecular mechanism of action between the depolarizing and the non-depolarizing NMBs?
The Non-depolarizing agents bind to the Ach binding sites on nicotinic receptors but prevent the channel from opening.
The depolarizing agents bind to the Ach binding site on nicotinic receptors both opening the channels and preventing the channels from closing again for repolarization.
What is the distribution and elimination of the Non-depolarizing NMBs (please name the drugs again)?
Non depolarizing NMBs:
Isoquinolines-Atracurium, Cisatracurium, D-Tubocurarine
Steroids- Pancuronium, Rocuronium, Vecuronium
Rapid initial distribution (Poor protein binding, highly ionized)
Slower elimination
What is special about the metabolism and elimination of atracurium?
Atracurium undergoes hepatic metabolism and Hoffmann elimination
What adverse effect is related to Atracurium metabolism?
Atracurium is matabolized mainly to laudanosine with is causally related to seizures.
What makes Cisatracurium somewhat better than atracurium?
Cisatracurium < dependence on hepatic inactivation, produces <
laudanosine, and releases < histamine
Cisatracurium has all the advantages of atracurium with fewer side effects.
Does succinylcholine have and extremely long or short duration of action? Why?
Succinylcholine has a very short duration of action (5-10 minutes) because it is rapidly hydrolyzed by buyrylcholinesterase in the liver and high capacity pseudocholinesterase in the plasma
Why must we be cautious when we prescribe succinylcholine?
There are many genetic variants of plasma cholinesterase which can drastically impact drug duration.
What can be done to overcome the heterogeneity of plasma cholinesterase?
The dibucaine test is used to identify abnormal variants of plasma pseudocholinesterase.
• Inhibits normal enzyme by 80% and abnormal enzyme by only 20%
What is the elimination route of Atracurium?
Spontaneous
What is the elimination route of Cisatracurium?
Mostly spontaneous
What is the elimination route of Tubocurarine?
Renal (40%)
Which of the Isoquinolines have the longest duration of action?
Tubocurarine (50+min) > Cisatracurium (25-44min) > Atracurium (20-35min)
What is the elimination route of pancuronium?
Renal (80%)
What is the elimination route of Rocuronium?
Hepatic (75-90%) + Renal
What is the elimination route of Vecuronium?
Hepatic (75-90%) + Renal
Compare the durations of the steroidal NMBs?
Pancuronium (35+min) > Rocuronium and Vecuronium (20-35min)
What are some off target actions of Atracurium?
Slight Histamine release
What are some off target actions of Cisatracurium?
None
What are some off target actions of Tubocurarine?
Weak ganglionic block
Moderate histamine release
What are some off target actions of pancuronium?
Moderate block of cardiac M receptor
What are some off target effects of Rocuronium?
Slight block of cardiac M receptors
What are some off target effects of vecuronium?
None
What are some off target effects of succinylcholine?
Stimulation of ganglia
Stimulation of Cardiac M receptors
Slight histamine release
What are some adverse effects of succinylcholine (Vol. I.)?
- Hemodynamic changes (arryth, HTN)
- Hyperkalemia with (burns, crush injuries, muscular dystrophies, prolonged immobiliztion)
- Prolonged neuromuscular blockade
- Increased intraoccular/intracranial pressure
What are some Adverse effects of succinylcholine (Vol. II.)?
- Muscle pain
- myoglobinuria
- Malignant hyperthermia
- Anaphylaxis
What is malignant hyperthermia?
Malignant hyperthermia is disease passed down through families that causes a fast rise in body temperature (fever) and severe muscle contractions when the affected person gets general anesthesia.
What things can trigger malignant hyperthermia?
- succinylcholine
2. all volatile anesthetic agents
What is the treatment for malignant hyperthermia?
- Dantrolene
- Stop giving trigger
- Avoid Calcium channel blockers
- Correct hyperkalemia and acidosis, Cool temp
What drug interactions are important to remember when dealing with NMBs?
- volatile anesthetics (malignant hyperthermia)
- Aminoglycosides (may enhance NM blockade)
- Local anesthetics (can also block NM junction)
- Other NM drugs
Why are anticholinergic co-administered with reversal agents?
because reversal agents are AchE inhibitors. Thus anticholinergics are given to limit the muscarinic effects of AchE inhibition.
What are the potential off target effects of the AchE inhibitors on the CV, pulmonary, cerebral, GI, genitourinary, and ophthalmic systems?
CV: Decreased HR, dysarrythmias
Pulmonary: Bronchospasm, increased secretions
Cerebral: Diffuse Excitation
GI: increased peristalsis and glandular secretions
Genitourinary: Increased bladder tone
Ophthalmologic: pupillary constriction
What is the MOA of sugammadex?
Sugammadex is a reversal agent that functions by encapsulating steroids like vecuronium and rocuronium. Does not work on none steroidal drugs.
What are the therapeutic uses for NMBs?
- adjuvant to surgical anesthesia
- short orthopedic proceedures
- Endotracheal intubation
How are NMBs administered?
IV
How are the effects of NMBs monitored?
Electrodes are placed along the length of a peripheral nerve (eg ulnar nerve) and the twitching of a muscle (eg adductor pollicis) innervated by that nerve is recorded.
