Flashcards in Nicotinic cholinergics Deck (34):
When can nicotine be poisonous and why do these people normally not die?
In children, who eat cigarette butts off their parents floor.
Generally, the emetic action of nicotine limits the amount absorbed
What are the symptoms of nicotine poisoning?
Activation -> depolarizing blockade
1. Autonomic stimulation via the ganglia
2. CNS excitation with convulsions, followed by depression (from blockade)
3. Skeletal muscle paralysis from excessive stimulation
What is varenicline and how is it used? What is its rare side effect?
Partial nicotinic receptor agonist, used in smoking cessation
Rare side effect: suicide
How have neuromuscular junction ACh blockers revolutionized anesthesia?
Lower doses need to be used of general anesthesia, so patients don't die. Can just immobilize their muscles and use enough to mentally sedate them
What is the prototype competitive antagonist for nicotinic ACh receptors? What type of blockade is this?
How can these agents be counteracted?
Agents can be counteracted by increasing ACh in the cleft to outcompete (Achase inhibitors)
Before giving neostigmine for depolarizing blockade reversal, what is given first?
Atropine -> prevents the bradycardia, urination, and defecation associated with muscarinic ACh receptors (nicotinic at NMJ will still be reactivated)
What is the main reason why tubocurarine is not used anymore, and what is the mechanism?
Rapid and transient fall in blood pressure for 2 reasons:
1. Sympathetic ganglion blockade reduces sympathetic tone of vascular system
2. d-TC stimulates histamine release from mast cells, which decreases peripheral resistance
What is cisatracurium and why is it much more attractive of an option than d-TC?
Competitive nAChR antagonist, but only has mild hypotensive actions.
Much more attractive: spontaneously broken down with short half-life and thus safely used in patients with hepatic and renal failure
What is the side effect of concern with cisatracurium?
One of its breakdown products crosses the BBB and can cause seizures (CNS excitation)
What is pancuronium used for? In what way is it cross-reactive?
It is a nAChR competitive antagonist, with some M2 cross-reactivity (causes tachycardia)
Used in lethal injection
What drug is structurally similar to pancuronium and why is it more attractive? How is it metabolized?
Vecuronium -> eliminated in bile (steroid-based, just like pancuronium, but pancuronium is eliminated renally)
More attractive because there is no M2 cross-reactivity
What is Rocuronium used for and how is it similar to pancuronium and vecuronium?
Similar in that it's steroid based -> eliminated in bile
Used for rapid-sequence intubation instead of Succinylcholine -> fastest onset of all three
What drug causes depolarizing blockade of NMJ? What is its time-table? What type of drug is it?
Succinylcholine - agonist at NMJ, less than 1 minute onset of action, short duration
Drug type: competitive agonist (depolarizing blockade)
How is succinylcholine metabolized and why is this a problem in some people?
Metabolized by plasma pseudocholinesterases after it diffuses out of the neuromuscular junction.
Some people have atypical plasma cholinesterases and if you are homozygous for this you will need a plasma transfusion which has this enzyme.
Takes longer if heterozygous
Why should succinylcholine not be used in children?
May have an undiagnosed muscular dystrophy which upregulates nACh receptors, which can lead to an oversized response
-> main side effect is increase in blood potassium due to significant depolarization
Given the main side effect of succinylcholine, what other patient populations should its use be avoided in?
extensive burns, trauma, people with K+ sparing diuretics or digitalis, or people with renal failure
-> all conditions where you would have high plasma levels of K+
-> Can cause cardiac arrest
What is Phase 1 depolarizing blockade, and what can be used to antagonize it?
Slow increase in RMP to 0, above threshold, at which time the motor end plate is excited and causes at most one fasciculation before just staying depolarized
Nothing can antagonize it (acetylcholinesterases just make it worse)
What is succinylcholine used for?
In emergency situations to facilitate intubation, or to relax neck and vocal cords so intubation can be done prior to general anesthesia
What is pre-curarization?
Administration of rocuronium (non-depolarizing agent) prior to succinylcholine to prevent fasciculations
-> makes no sense in how it works
What is phase 2 depolarizing blockade?
Prolonged use of succinylcholine will allow membrane to repolarize, and can actually be partially reversed via neostigmine (so weird, don't know the mechanism)
What type of amines are the skeletal muscle relaxants and how they administered?
All quaternary amines -> administered via IV (parenteral)
Do not cross BBB or placenta because of this
What muscles are most and least affected by skeletal muscle blockade?
Most affected: digits, followed by neck & limbs
Least affected: Diaphragm and thorax -> but we still always intubate when we administer
Is histamine release affected by cisatracurium and succinylcholine?
Not affected by pancuronium, rocuronium, or vecuronium
How is dTC metabolized?
Eliminated in the kidney -> same as pancuronium
What is the mechanism of action of dantrolene and what is it used for?
Blocks Ca+2 release from SR in skeletal muscles.
1. Treatment of malignant hyperthermia (which is caused by muscle spasm in anesthesia)
2. UMN spasticity in those wheelchair bound (will still keep them in wheelchair)
What is the mechanism of action of baclofen and who is it given to?
GABA-B agonist, anti-spasmodic which is relatively non-sedating and does not produce as much generalized weakness as dantrolene
What anti-spasmodic works as an atypical alpha-2 agonist? (pre- and post-synaptic nerve inhibition)
What is the MoA of Riluzole and what is it used for?
Inhibits glutamate signaling -> antispasmodic
Used to prolong life in ALS patients
What is the name of the spasmolytic most frequently given as an anti-spasmodic by everyone? Mechanism of action unknown, but is definitely anti-muscarinic and sedative
What is the acetylcholine receptor primarily responsible for hyperpolarization?
M2 - Gi pathway
What causes the slow excitation (EPSP) via acetylcholine?
Typically M1 receptors, or peptides.
The nicotinic receptor is very fast
What is the mechanism of action of Mecamylamine? Is it a tertiary or quaternary amine?
Works via competitive antagonism of nAChR's in postganglionic cell dendrites
It is actually a SECONDARY amine -> only one
What is the primary reason ganglionic blocking drugs are not used?
Orthostatic hypotension -> due to lack of sympathetic tone in veins which prevent pooling of blood, along with a ton of different cholinergic atropine-like effects + impotence