Term
|
Definition
| naturally occuring alkaloid, lipid-soluble teritary amine |
|
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Term
| Since it's lipid soluble, where in a pregnany woman is nicotine found? |
|
Definition
across the placenta, in milk secretion
(plus throughout the body, including CNS) |
|
|
Term
| Why can nicotine activation lead to depolarizing blockade? |
|
Definition
|
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Term
|
Definition
1) intense autonomic stimulatio thru ganglia
2) CNS excitation with convulsions followed by depression
2) eventual skeletal muscle paralysis |
|
|
Term
| When is nicotine used pharmacologically? |
|
Definition
1) Tx of nicotine withdrawl
2) Improved cognition in Alzheimer's patients
3) Reduce Parkinson's incidence |
|
|
Term
| What allows for selective nAchR therapeutic manipulation? |
|
Definition
| different nicotinic subtypes at different locales |
|
|
Term
| What drug was the first partial nAchR agonist to be approved by FDA? |
|
Definition
|
|
Term
|
Definition
| aid in smoking cessasion by reducing pleasurable effects & cravings for tobacco |
|
|
Term
| Where is varenicline eliminated? |
|
Definition
|
|
Term
|
Definition
| negative neuropsychiatric SE |
|
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Term
| Patient is an African American 48 yo male experiencing irritability & insomnia. Formerly a heavy smoker (2 packs/day) but quit "cold turkey." Vital signs: tachycardia & hypertension. PE shows patient to be anxious & sweating. What is the basis for his complaint? How could he be treated. |
|
Definition
Undergoing nicotine withdrawl
Could be given nictotine or varenicline |
|
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Term
| Why are nAchR at the nmj given agonists as an adjunct to general anesthesia? |
|
Definition
| to produce controlled skeletal muscle relaxation |
|
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Term
| Why would nAchR agonists be given in mechanical ventillation, electroconvulsive therapy, or during an endoscopy? |
|
Definition
MV: suppress endogenous breathing
ECT: suppress muscle contractions
E: facilitate intubation |
|
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Term
| What are the 2 drug classification of skeletal muscle blocking drugs? |
|
Definition
1) Competitive antagonists
2) Depolarizing blockers (agonists) |
|
|
Term
Function
nAchR competitive agents |
|
Definition
| act as competitive antagonists at the nAchR on the motor end plate |
|
|
Term
Effect
nAchR competitive antagonist |
|
Definition
| reduce number of available nAchR for Ach to interact with => less responsive to nerve released Ach |
|
|
Term
| What are nAchR competitive antagonists competitive with? |
|
Definition
|
|
Term
| What can reverse the block caused my nAchR competitive antagonists? |
|
Definition
| increased amounts of Ach in synaptic cleft |
|
|
Term
| What can be used to increase Ach in the synpatic cleft to override nAchR competitive antagonists? |
|
Definition
anticholinesterase drugs
tetanic stimulation of motor nerves |
|
|
Term
| What 2 anticholinesterases can be used to increase Ach in the synpatic cleft to override nAchR competitive antagonists? (may be needed to reverse blockade when prolonged effects are delaying post-op recovery) |
|
Definition
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|
Term
| Why is atropine often given prior to neostigmine when it's employed for blockade reversal? |
|
Definition
| nAchR are the receptors needing unblocked, so when Ach is increased, we don't want extra stimulation of mAchR, thus atropine block. |
|
|
Term
| How do AMG antibiotics affect nAchR competitive antagonists? |
|
Definition
| Lead to longer paralysis since AMG reduces cytosolic calcium. |
|
|
Term
Structure
d-turbocurine (curare) |
|
Definition
| naturally occuring alkaloid |
|
|
Term
| What is the most common SE in d-TC? |
|
Definition
| BP drop, but gradual recovery by 10 min. |
|
|
Term
| What causes the Bp drop in d-TC use? |
|
Definition
1) autonomic ganglionic blockade => decreased SS tone to vasculature
2) release of histamine from mast cells by direct action => decreased vascular resistance |
|
|
Term
|
Definition
|
|
Term
| Where is d-TC metabolized/excreted? |
|
Definition
metabolized - liver
excreted - kidney (40% unchanged excretion) |
|
|
Term
| What synthetic agent is a potent isomer of former agent atracurium? |
|
Definition
|
|
Term
| Why does the nAchR competitive agonist cisatracurium have only mild hypotensive action? |
|
Definition
|
|
Term
| How is cisatracurium inactivated? |
|
Definition
|
|
Term
| Why can cistracurium be safely used in hepatic and renal failure patients? |
|
Definition
| not totally dependent on renal or hepatic excretion (since spontaneous breakdown & short half life) |
|
|
Term
What breakdown product of cisatracurium can cross the BBB?
Why? |
|
Definition
| laudanosine - it's lipid soluble |
|
|
Term
| Why has cisatracurium (the cis isomer of atracurium) replaced atracurium? |
|
Definition
| more potent therefore less drug is needed => less laudanosine produced |
|
|
Term
| What nAchR competitive antagonist is selective for nmj & has a long duration of action? |
|
Definition
doxacurium
(no longer used) |
|
|
Term
| What nAchR competitive antagonist has the shortest duration of action? |
|
Definition
Mivacurium
(no longer used) |
|
|
Term
| What are the 3 steroid-based nAchR competitive antagonists? |
|
Definition
1) Pancuronium
2) Vecuronium
3) Rocuronium |
|
|
Term
| Which steriod-based nAchR competitive antagonist has a long duration & is eliminated by the kidneys? |
|
Definition
|
|
Term
| Which steroid-based nAchR competitive antagonist has the fastest onset? |
|
Definition
|
|
Term
| How is vercuronium different from pancuronium? |
|
Definition
| intermediate duration of action & eliminated by liver to bile |
|
|
Term
| Why does pancuronium produce tachycardia? |
|
Definition
| has some additional antagonistic activity at M2 receptors |
|
|
Term
| How is rocuronium eliminated? |
|
Definition
|
|
Term
| What 6 things can potentiate the competitive nmj blocking agents? |
|
Definition
1) general anesthetics
2) AMG
3) electrolyte imbalance
4) polypeptide Abx
5) advanced age
6) pathologies |
|
|
Term
| What is the nAchR depolarizaing blocking agent? |
|
Definition
|
|
Term
| Where is succinylcholine a long-lasting agonist? |
|
Definition
| nmj (some rapid onset & very short duration at most AchR) |
|
|
Term
| What metabolizes succinylcholine? |
|
Definition
|
|
Term
| What is succinylcholine metabolized to? |
|
Definition
|
|
Term
What happens if a patient is heteozygous for atypical pseudocholinesterases?
homozygous? |
|
Definition
heterozygous: degrade succinylcholine slowly
homozygous: unable to hydrolyze succiylcholine at all => renal excretion becomes only route of drug termination |
|
|
Term
| How is biodegradation of succinylcholine resumed to normal in patients homo- or hetero- zygous for atypical pseudocholinesterases? |
|
Definition
| administration of plasma containing normal pseudocholinesterases |
|
|
Term
| Why aren't BP changes detected in succinylcholine administration? |
|
Definition
1) histimine released => BP change
2) mild ganglionic stimulation => mask of histamine effect |
|
|
Term
| Why can succinylcholine lead to cardiac arrest? |
|
Definition
| it can produce significant release of potassium into blood (hyperkalemia) |
|
|
Term
| When is succinylcholine usually administered? |
|
Definition
| to assist in intubation after anesthesia via relaxing of the laryngeal muscles |
|
|
Term
| Why is succinylcholine only used in emergency situations of intubation need in children? |
|
Definition
| reports of cardiac arrest |
|
|
Term
|
Definition
| potent nAchR agonist at nmj => sustained binding since metabolism occurs at nmj. This leads to 2 phases on pharmacologic response |
|
|
Term
| When can succinylcholine cause phase I depolarizing blockade? |
|
Definition
| single dose/short infusion |
|
|
Term
| When can succinylcholine cause phase II? |
|
Definition
| longer infusions or re-administered in frequent intervals => sustained paralysis |
|
|
Term
| When does phase I nicotinic nmj junction with polarizing agents occur? |
|
Definition
| within seconds following IV administration |
|
|
Term
| What is phase I nicotinic nmj junction with polarizing agents |
|
Definition
| gradual depolarization of the motor end plate |
|
|
Term
| What is phase I nicotinic nmj junction with polarizing agents |
|
Definition
| gradual depolarization of the motor end plate |
|
|
Term
| What does succinycholine do to cause motor end plate depolarization? |
|
Definition
| opens Na+ & K+ channels as Ach opens them as well, but succinylcholine causes slower distribution to the synapse => membrane potential decreases past threshold => Ach threshold is blocked (therefore blockage of nmj) |
|
|
Term
| What causes muscle fasiculations in upper thorax, limnbs & neck after succinylcholine amdinistration? |
|
Definition
| direct action on motor end plate occuring asynchronously as each fiber reaches threshold as it's depolarized |
|
|
Term
| How are fasciculations avoided in succinylcholine use? |
|
Definition
| Prior treatment with low-dose non-depolarizing agent s.a. rocuronium (but then increased doses of succinylcholine will be needed) |
|
|
Term
| What would intensify phase I deploarizing blockade? |
|
Definition
1) stimulation of motor nerves
2) administration of neostimine or edrophonoium
(i.e. further reduction of membrane potential) |
|
|
Term
| What is the pharmacological antagonist for phase I depolarizing blockade? |
|
Definition
|
|
Term
| How is succinylcholine overdose treated? |
|
Definition
| ventilation breathing supposrt until effects wear off |
|
|
Term
| What happens to the membrane potential in phase II blockade? |
|
Definition
| repolarizes, though transmission failure still present |
|
|
Term
| How does phase II blockade resemble competitive antagonism? |
|
Definition
| tetanic stimulation of motor nerve will result in improved but weak muscular contractions & tone |
|
|
Term
| What will neostigmine or endrophonium do during phase II bloackade? |
|
Definition
| breathing & normal tonus can be partially restored |
|
|
Term
|
Definition
unclear
may be due to block of channel pore by drug or due to gradual accumulation of metabolite of succinylcholine that may act as a competitive antagonist |
|
|
Term
| Why is phase II associated with mixed/dual blockade? |
|
Definition
| not all end plates reach phase II at the same time |
|
|
Term
Structure
all skeletal muscle relaxants |
|
Definition
|
|
Term
| How must all skeletal muscle relaxants be administered? |
|
Definition
| parenterally (usually IV) |
|
|
Term
| Do skeletal muscle relaxants cross the BBB? |
|
Definition
|
|
Term
| Why is use of nAchR nmj blockage by itself during surgery unethical? |
|
Definition
| they provide no anesthetic effect |
|
|
Term
| What are the 5 most sensitive muscles in decending order (most to least) to nAchR nmj blockage? |
|
Definition
1) digits
2) neck & limbs
3) abdomen
4) thorax
5) diaphragm |
|
|
Term
| How are nAchR nmj relaxant agents chosen? |
|
Definition
| duration of action & safety |
|
|
Term
| Which 2 nAchR muscle relaxants are long duration? |
|
Definition
|
|
Term
| Which nAchR muscle relaxant has massive histamine realease? |
|
Definition
|
|
Term
| What 3 nAchR muscle relaxants have no histamine release? |
|
Definition
Pancuronium
Rocuronium
Vercuronium |
|
|
Term
| Which 2 nAchR muscle relaxants have no significant adverse effects? |
|
Definition
|
|
Term
| Which nAchR muscle relaxant causes hyperkalemia? |
|
Definition
|
|
Term
| What nAchR muscle relaxant causes CNS excitement? |
|
Definition
|
|
Term
| Which nAchR muscle relaxant causes tachycardia? |
|
Definition
|
|
Term
| Which nAchR muscle relaxant causes weak ganglionic blockade? |
|
Definition
|
|
Term
| How are the effects of skeletal muscle relaxants monitored? |
|
Definition
| transdermal stimulation of nerves to hand & record evoked twitches |
|
|
Term
| Which 2 nAchR muscle relaxants have rapid onset? |
|
Definition
Rocuronium
Succinylcholine |
|
|
Term
| Which nAchR muscle relaxant has a very short duration of action? |
|
Definition
|
|
Term
| What nAchR muscle relaxant is eliminated by spontaneous breakdown? |
|
Definition
|
|
Term
| Which nAchR muscle relaxant is eliminated by pseudochoinesterase? |
|
Definition
|
|
Term
| What 2 nAchR muscle relaxants are eliminated mostly by liver/bile? |
|
Definition
|
|
Term
| What 3 nAchR muscle relaxants have intermediate duration of action? |
|
Definition
Cisatracurium
Rocuronium
Vercuronium |
|
|
Term
| What 2 nAchR muscle relaxants have small histadine release? |
|
Definition
Cisatracurium
succinylcholine |
|
|
Term
| What 2 nAchR muscle relaxants are mainly eliminated by the kidney? |
|
Definition
|
|
Term
| 7 yo girl has been admitted thru ER with intense abdominal pain & vomiting. PE reveals RLQ tenderness. Abdominal ultrasonography is consistent with appendicitis. Which skeletal muscle relaxant would be appropriate as an adjunct to general anethesia? |
|
Definition
| Any except succinylcholine (don't give to children) |
|
|
Term
| What are the non-cholinergic muscle relaxant? |
|
Definition
|
|
Term
|
Definition
| blocks Ca2+ from sarcoplasma reticulum of skeletal muscle |
|
|
Term
| What are 2 uses of dantolene? |
|
Definition
1) spasticity type diseases
2) as an adjunct to anesthesia to treat malignant hyperthermia since no effect on Ach release |
|
|
