Muscarinic blockers and Neuromuscular blockers Flashcards
1
Q
Pharmacologic definitions
A
- Intrinsic activity: effect when a drug binds w/ receptor, =1 is agonist, =0 is antagonist
- Potentiation: 2 drugs administered together and their effect together are greater than the sum of their effects separately (i.e. methacholine + CEI)
- Summation: 2 drugs administered together and their effect together is equal to the sum of their effects separately (i.e. carbachol + bethanechol)
2
Q
Actions of muscarinic blockers 1
A
- Prevent the action of para/post neurons on their targets, so the sym/post will effects will dominate (indirect sympathomimetic)
- Affects on tissues: dilates pupils (mydriasis, miosis is constricted pupils), prevents gland secretion, tachycardia, dilation of bronchioles, inhibits GI/bladder
- There is NO direct effect on BP from changes in vasoconstriction b/c there is no para/post input onto blood vessels to block
3
Q
Actions of muscarinic blockers 2
A
- However, HR will still increase, which increases CO which will increase BP (indirect BP increase from increased sum/post on heart)
- The baroreceptors will sense this change in BP and decrease the sympathetic input on heart to slow heart and decrease force of contraction, also reduces symp input on blood vessels and causes vasodilation
- These effects reduce BP back to normal levels, and since all of this happens in an instant, there is no observed change in BP from muscarinic blockers
4
Q
Atropine
A
- Broad spectrum muscarinic blocker than binds all (5) types of muscarinic receptors, and doesn’t bind to nicotinic receptors
- Binds in a competitive fashion, thus enough muscarinic agonist can compete it out for receptor binding
- Atropine’s actions are all of the general actions of muscarinic blockers, does cross BBB
- Main therapeutic uses: pre-anesthetic (dilation of bronchioles and inhibition of bronchial secretion), Rx of bradycardia (causes tachycardia, side effect is angina), Rx of hyperhydrosis (inhibits the muscarinic receptors on the sweat glands, even though they are innervated by symp)
5
Q
Atropine poisoning
A
- Inhibited sweat glands and effect on hypothalamus increases body temp; hyperthermia (hallucinations)
- Dried lacrimal/salivary glands
- Blurred vision, photophobia (no light reflex)
- Tachycardia
- Constipation and difficulty urinating
- Most dangerous: hyperthermia
6
Q
Antidote of atropine poisoning
A
- Usually none is required, since its metabolized in liver (T1/2 is 4 hrs)
- If it must be Rx, best thing to use is CEI that can cross the BBB (tertiary amine; physostigmine) so that it can increase Ach in synapse and outcompete the atropine
7
Q
Other muscarinic antagonists
A
- Dicyclomine: used to Rx overactive GI system
- Fesoterodine: used to Rx overactive bladder
8
Q
Botox vs atropine poisoning
A
- Botox acts on cholinergic nerves to prevent the release of Ach-filled synaptic vessels
- Occurs in para sympathetic nerves and in NMJ
- Used to paralyze muscles that cause wrinkles
- Differentiating botox poisoning from atropine poisoning: both will show mydriasis (dilated pupil) and dry mouth
- But there will be skeletal muscle weakness in botox poisoning and not in atropine poisoning (only affects muscarinic)
- Also, death from botox due to respiratory paralysis but death from atropine due to hyperthermia
9
Q
Neuromuscular blockers (NMBs) vs anesthetics
A
- NMBs are used w/ anesthetics, to help prevent movement during surgery, but do no anesthetize
- Anesthetics blocks some of the pain but blocks all memory of the pain
- NMBs also used to facilitate intubation
- 2 types: depolarizing and non-depolarizing
10
Q
Non-depolarizing NMBs
A
- These bind to the nAchR in NMJ and prevent Ach binding, thereby preventing depolarization of the muscle (competitive antagonists, can be outcompeted)
- There is some electrical activity at end plate (not all nAchR receptors blocked), but not enough to trigger AP
- Drugs of this category include tubocurarine, atracurium, pancuronium, doxacurium, and mivacurium
- These are different based on their T1/2s, with tubocurarine lasting the longest (80-120 min), atracurium lasting 30-40 min, and mivacurium lasting only 12-18 min
11
Q
Reversing the effects of non-depolarizing NMBs
A
- Giving a CEI will increase the Ach levels in synapses, allowing Ach to outcompete the NMB
- Tertiary CEIs (can cross BBB) like physostigmine only have CEI actions
- But quaternary (don’t cross BBB) CEIs like neostigmine, pyridostigmine, and edrophonium not only act as CEIs but that also have agonistic affects on nAchR (not mAchR)
- Therefore, if you want to reverse the affects of a NMB quickly, its best to give a quaternary CEI since it will not only increase Ach but will also bind to the nAchR and stimulate it
12
Q
Depolarizing NMB: succinylcholine
A
- Succinylcholine (SC) is 2 acetylcholine molecules joined end-end
- SC is hydrolyzed by CE (the nonspecific, serum CE)
- Acts by competitively binding to and activating the nAchR at the NMJ
- Initially this depolarizes the muscle, but soon after depolarization there is a block that prevents further depolarization and repolarization
- This prevents further muscle contractions
- The initial depolarization causes fasciculations
13
Q
Contraindications of succinylcholine
A
- SC causes K to be released from the skeletal muscle (increases serum K)
- Pts w/ burn injuries respond w/ a hyper release of K, which can causes arrhythmias, cardiac arrest, and death
- Thus SC is contraindicated in burn victims
14
Q
Reversing SC action on NMJ
A
- CEIs will not help to reverse SC affects, since cholinesterase is the nz that breaks down SC
- This means that CEIs will inactivate the nz that inactivates SC, which prolonging its effects and increases its T1/2
- To reverse the action of SC, we should give a nAchR agonist to kick off the SC from the receptor (which protects it from CE) so it can be degraded
15
Q
Reversing SC action on NMJ
A
- CEIs will not help to reverse SC affects, since cholinesterase is the nz that breaks down SC
- This means that CEIs will inactivate the nz that inactivates SC, which prolonging its effects and increases its T1/2
- To reverse the action of SC, we should give a nAchR agonist to kick off the SC from the receptor (which protects it from CE) so it can be degraded
