Reversal Agents Flashcards
T/F: PNS postganglia secrete epinephrine
False: secrete ACh.
Where does PNS originate from?
Craniosacral origin (III, V, VII, X).
Where is the highest concentration of acetylcholinesterases?
In between the synapses.
What are the two types of cholinergic receptors?
Nicotinic and muscarinic
What does SNS stimulation of bronchial smooth muscle cause? PNS?
SNS causes relaxation.
PNS causes normal activity to contraction
What does SNS stimulation cause on gallbladder? PNS?
SNS= relaxation.
PNS=Contraction.
What does SNS stimulation cause on urinary bladder? PNS?
SNS=smooth muscle relaxation and sphincter contraction.
PNS=Smooth muscle contraction and sphincter relaxation
What does SNS stimulation cause on GI tract? PNS?
SNS=Dec motility/secretions, sphincter constriction.
PNS=Inc motility/secretion and sphincter relaxation
What is gluconeogenesis?
Making new glucose
SNS or PNS cause miosis?
PNS=miosis
SNS=mydriasis
SNS or PNS decrease beta cell secretion of pancreas?
SNS= want more glucose available so insulin will decrease
What is down regulation?
Extended exposure to agonists reduces the number, but not their response. (results in tachyphylaxis)
What is tachyphylaxis?
Rapidly diminishing response to successive doses of a drug, rendering it less efective.
What is up regulation?
Chronic depletion of catecholamines or use of antagonists increases the number of receptors, but not their sensitivity. May account for withdrawal syndrome with beta blockers.
What is sequestration?
Occurs slowly. Movement of receptors from the cell surface to intracellular compartments.
What does pheochromocytoma cause?
Uncontrolled release of catecholamines due to an adrenal gland tumor. Constant SMS stimulation
What causes the adrenal medulla to release hormones?
Release triggered by ACh at cholinergic fibers due to calcium ion influx.
What are the two classes of anticholinesterase drugs?
Tertiary amines and Quaternary ammoniums.
Which class of anticholinesterase drugs enters the CNS more easily?
Tertiary amines
What is an example of a tertiary amine anticholinesterase drug?
Physostigmine
What is an example of a quaternary ammonium anticholinesterase?
Edrophonium.
Neostigmine.
Pyridostigmine.
Which anticholinesterase class is more lipophilic?
tertiary amines like physostigmine.
What is the general idea behind giving anticholinesterase drugs as reversal of ND-NMBAs?
Attempting to increase the amount of acetylcholine so it “bullies” off the drug.
What are the three actions performed by anticholinesterase drugs?
- Enzyme Inhibition.
- Presynaptic effects.
- Direct effects.
What action is the primary action of anticholinesterase drugs?
Enzyme inhibition: Inhibites acetylcholinesterase
T/F: Anticholinesterase is a competitive agonist?
False: it is a competitive antagonist
By inhibiting acetylcholinesterase, anticholinesterase drugs increase availability of acetylcholine at what three sites?
- Neuromuscular junction.
- Muscarinic receptors.
- Autonomic ganglia
Which drug forms a reversible electrostatic attachment ?
Edrophonium.
T/F:Even at greater than clinical doses, anticholinesterase drugs have not been reported to produce neuromuscular blockade?
False; they do
What are the three classifications for anticholinesterase drugs?
- Reversible inhibition.
- Formation of carbamyl esters.
- Irreversible inhibition.
Which drug would be considered a reversible inhibitory anticholinesterase?
Edrophonium: Electrostatic attachment to the anionic site.
What is the most important determinant of potency for anticholinesterase drugs?
Affinity for receptor
What is the onset of different anticholinesterase drugs?
Edrophonium- 1-2 min.
Neostigmine 7-11min
Pyridostigmin 16 min.
Why does edrophonium have such a fast onset?
Electrostatic attachment
What is the duration of action for anticholinesterase drugs?
60-120 mins
What is the influence of age on neostigmine dose?
dose in Infants
What are the muscarinic effects of anticholinesterase drugs?
bradycardia, salivation, bronchoconstriction, miosis, hyperperistalsis, increase risk of PONV.
T/F: Edrophonium produces marked and prolonged inhibition of plasma cholinesterase?
False: neostigmine and pyridostigmine.
Which drug is used for treatment of myasthenia gravis?
pyridostigmine.
How does pyridostigmine treat myasthenia gravis?
Increases ACh at the neuromuscular junction.
Does the reversal of NMB by anticholinesterase drugs act presynaptically or postsynaptically?
Both
What must first occur before administration of anticholinesterase for NMB reversal?
Must be spontaneously recovering from NMB.
What type of drug is given simultaneously with an anticholinesterase drug to block muscarinic effects?
Anticholinergic.
Do you want the anticholinergic or the anticholinesterase drug to have a faster onset and why?
Anticholinergic.
To minimize bradycardia.
At what percent of twitch height recovery would you administer reversal ?
> 10%
What can inhibit or prevent antagonism of neuromuscular blockade?
Antibiotics (aminoglycosides).
Hypothermia.
Resp Acidosis.
Hypokalemia and metabolic acidosis.
Physostigmine reverses what 4 things?
- Anticholinergic OD.
- Opiods (not the analgesia).
- Benzodiazepines.
- Anesthetics
What are some secondary uses for physostigmine?
Glaucoma, Alzheimer’s disease, Chronic Fatigue Syndrome, Diagnosis and management of cardiac arrhythmias, postop analgesia, postop shivering.
What are two examples of naturally occuring tertiary amines anticholinergic?
Atropine and scopolamine.
What is an example of a quaternary ammonium anticholinergic?
Glycopyrrolate.
Which has the ability to cross the blood brain barrier - glycopyrrolate, atropine, scopolamine?
Atropine and scopolamine (they are tertiary amines).
Anticholinergic drugs come in racemic mixtures that are left or right antiomers?
Left- levo-antiomers.
What structurally binds to the receptor on an anticholinergic drug?
The positively charged nitrogen.
Are anticholinergic drugs competive/noncompetitive? Antagonist/agonist?
Competitive antagonists.
What is the main mechanism of action of anticholinergic drugs?
Reversibly binds to muscarinic receptors (through competitive antagonism) which prevents ACh from binding.
How many muscarinic subtypes are there?
5 (M1, M2, M3, M4, M5).
What does acetylcholine do once it binds to a muscarinic cholinergic receptor?
Binds to one of the M1-M5 receptor subtypes. Causes second messengers to be sent and boosts the signal of M1-M5 to the appropriate site of action.
Which muscarinic receptor subtype has clinical effects on the heart and what does it do?
M2. Causes bradycardia
Why does M2 stimulation via ACh cause bradycardia?
Decreases/inhibits Ca++
Which muscarinic receptor subtypes are most susceptible to effects of drugs?
M3>M2, M1.
Why should small (subclinical) dosing of anticholinergics be avoided?
Can produce bradycardia due to direct agonist effects.
What is the onset and duration of atropine?
1 minute.
30-60mins.
What is the onset and duration of glycopyrrolate?
2-3mins.
.
30-60mins
What are all the uses of anticholinergic drugs?
Preop for sedation/antisialagogue,/ prevent vagal reflexes. Treat reflex-mediated bradycardia. Combined with anticholinesterase drugs. Bronchodilation. Prevent motion-induced nausea.
Which anticholinergics can be used for their sedative effects?
Scopolamine.
Atropine.
Since atropine has mydriatic effects, which patients should it be avoided in?
Glaucoma. Increased IOP
Which anticholinergic drugs have more potent antisialagogue effects?
Scopolamine 3x more potent and glycopyrrolate 2x more potent than atropine.
Which anticholinergic is the drug of choice for intraoperative bradycardia?
Atropine.
What is atropine’s MOA when given for bradycardia?
Blocks effects of ACh on the SA node.
Which age patients have the most profound response to atropine for bradycardia?
Young adults
What are examples of anticholinergics that ause bronchodilation specifically?
Ipatropium/atrovent/duoneb.
Which muscarinic receptor subtype is involved in bronchodilation?
M3
Scopolamine must be given how many hours before noxious stimuli?
4 hours prior.
How long should scopolamine stay on as transdermal patch after surgery?
24 hours
What is Central Anticholinergic Syndrome?
When scopolamine and atropine enter the CNS and cause Restlessness and hallucinations to somnolence and unconsciousness.
What are symptoms of anticholinergic overdose?
(can’t see, cant pee, cant spit, cant shit).Dry mouth, blurred vision, photophobia, tachycardia, dry/flushed skin,
What is treatment of anticholinergic overdose?
Physostigmine 15-60mcg/kg IV
Why did the FDA initially not approve suggamedex?
Bleeding and anaphylactic complications
Which NMBAs does suggamedez reverse?
Vecuronium and rocuronium.
What is suggamedex dose if 1-2 post-tetanic counts and there is not response to TOF?
4mg/kg
What is suggamedex dose if reappearance of the second twitch response to TOF?
2mg/kg
What is suggamedex dose for rapid reversal of roc bolus dose?
16mg/kg
What are side effects of suggamedex?
0.3% anaphylaxis. Bradycardia. Bleeding/coagulopathies. N/V, pain, hypotension, headache. Not recommended for use in severe renal impairment. BC pills have reduced efficacy.
What is a Cochrane Review?
A bunch of smaller studies combined to strengthen an argument.
What did the Cochrane Review 2017 determine?
- Suggamedex will reverse deep blockade.
2. Neostigmine really only works on spontaneously reversing patients (not DEEP blockade.
