CHAPTER 5: CHOLINERGIC ANTAGONISTS- GANGLIONIC BLOCKERS/NMBs

Question 1

Ganglionic blockers specifically act on

Answer 1

nicotinic receptor of parasymp and symp autonomic ganglia

Question 2

ganglionic blockers block what?

Answer 2

block entire OUTPUT of ANS at the nicotine receptor

Question 3

effects of ganglionic blockers

Answer 3

effects the tone of a given organ system:
vasodilation, atony of bladder and GI tract, cycloplegia, xerostomia, tachycardia

Question 4

is ganglionic blockade used therapuetically?

Answer 4

NO. rarely used therapeutically, used in experimental pharm

Question 5

Ganglionic blocker- NICOTINE

Answer 5

poison with undesired action
- depending on dose, depolarizes autonomic ganglia, so first stimulation then paralysis of ALL ganglia

Question 6

Nicotine- stimulatory effects

Answer 6

occur from inc release of neurotransmitter—-> effects both symp and parasymp ganglia
-mixed effects since it doesn’t have selectivity

Question 7

Nicotine- higher doses

Answer 7

HIGH doses, BP falls bc of ganglionic blockade
-activity in GI and bladder musculature stops

Question 8

Neuromuscular Blockers (NMBs)

Answer 8

these drugs block cholinergic transmission between motor nerve ending and the nicotinic receptors on skeletal muscles. (Nm)

Question 9

NMB 2 types

Answer 9

have chemical similarities to ACh
-antagonists (nondepolarizing)
-agonists (depolarizing)
AT receptors on endplate of the NMJ

Question 10

NMB uses

Answer 10

clinically useful to facilitate rapid intubation
-during surgery for endotracheal intubation and complete muscle relaxation at lower anesthetic doses

Question 11

NMB’s- 5 of them

Answer 11

cisatracurium, pancuronium, rocuronium, vecuronium, succinylcholine

Question 12

which NMB’s are depolarizing/non depolarizing?

Answer 12

the drugs that end in ONIUM/URIUM are NON-DEPOLARIZING
- others are depolarizing (succinylcholine)

Question 13

Nondepolarizing NMBs are

Answer 13

antagonists of the nicotinic receptor at neuromuscular junctions (NMJ)
- they work to block the ACh from binding to the nicotinic receptor, instead the drug binds, closing the channel, and not allowing Na+ to pass through (so it doesn’t depolarize)

Question 14

NMB receptor is a

Answer 14

ligand gated ion channel

Question 15

Nondepolarizing NMB- mechanism of action
-low and high dose

Answer 15

LOW: prevent binding of ACh, prevent depolarizing in muscle cell, INHIBIT muscular contraction (Induce paralysis)

HIGH: block pore of ion channels of endplate, weaken neuromuscular transmission, and reduce ability of AChE inhibitors to reverse actions of non depolarizing muscle relaxants
(NMB goes in channel and BLOCKS IT)

Question 16

how do we overcome low dose action of nondepolarizing NMB?

Answer 16

increase conc of ACh in snynaptic gap
- ex) cholinesterase inhibitors (neostigmine and edrophonium) block the AChE enzyme

Question 17

example of using edrophonium/neostigmine (nondepolarizing NMB)

Answer 17

used by anesthesiologists to shorten duration of neuromuscular blockade and inc muscle tone after surgery

Question 18

Nondepolarizing NMB- actions
firs to last

Answer 18

muscles relax from HEAD to TOE
1st- face and eye
2nd- fingers
3rd- limbs, neck, trunk muscles
4th- intercostal muscles
5th- diaphragm muscles

Question 19

how do the muscles recover after nondepolarizing NMBs

Answer 19

recover in reverse manner (TOE to HEAD)

Question 20

Nondepolarizing NMBs- therapeutic uses/indications

Answer 20

adjuvant drugs in anesthesia during surgery to relax skeletal muscle
-facilitate intubation during ortho surgery

Question 21

Non Depolarizing NMB- pharmacokinetics and side effects

Answer 21

kinetics:
-INEFFECTIVE ORALLY, injected IV
- charged (+) so it doesn’t cross BBB easily, poor absorption orally

side effects:
-safe with minimal side effects
-caution for malignant hyperthermia

Question 22

does liver dysfunction affect the metabolism of nondepolarizing NMBs?

Answer 22

NO! Drugs are metabolized in the bile and primarily excreted in urine and UNCHANGED when excreted

Question 23

Malignant Hyperthermia

Answer 23

muscle metabolism not working properly in reaction to anesthetic meds
-result in high body temp, rapid heart rate, death if not treated immediatel

Question 24

MH antidote?

Answer 24

dantrolene

Question 25

Depolarizing NMB’s are

Answer 25

agonists of the nicotinic receptor at the neuromuscular junctions
-bind and activate ACh receptor
-SUCCINYLCHOLINE

Question 26

Depolarizing NMB’s work by

Answer 26

depolarizing plasma membrane of muscle fiber, SIMILAR to ACh action

Question 27

Depolarizing NMB’s allow

Answer 27

passage of Na+ through the channel/depolarization

Question 28

depolarizing NMB- degradation

Answer 28

more resistant to degradation by AChE and can persistently depolarize muscle fibers

Question 29

depolarizing NMB- phases

Answer 29

PHASE I- depolarization
PHASE II- repolarization and desensitization of receptors
second phase is due to continuous stimulation which causes opposite effect/paralysis of receptors

Question 30

depolarizing NMB- duration of action

Answer 30

SHORT, but amount that regulates muscles is enough to provide its action

Question 31

depolarizing NMB- Succinylcholine
ACTION

Answer 31

bind to nicotinic receptor at NMJ, result is muscle paralysis, respiratory muscles paralyzed LAST

Question 32

Succinylcholine- therapeutic uses/indications

Answer 32

useful for rapid endotracheal intubation during induction of anesthesia

Question 33

Succinylcholine- pharmacokinetics

Answer 33

injected IV
-brief duration of actions (minutes) results from redistribution and hydrolysis by plasma cholinesterase

Question 34

Succinylcholine- adverse effects

Answer 34

-malignant hyperthermia
-apnea due to paralysis of the diaphragm
-hyperkalemia (inc of K)

may have contraindication with drugs that also cause apnea

Question 35

apnea

Answer 35

problems breathing

Question 36

hyperkalemia

Answer 36

increase of K, causes electrolyte imbalance