Neuromuscular Blocking Agents

Front 1

Why do ACh receptors at the NMJ need to be blocked particularly well

Back 1

Many spare receptor

Front 2

ACh receptor is a:

Back 2

Ligand gated ion channel

Front 3

Denervation of a muscle causes:

Back 3

more ACh receptors to be added extrajunctionally

Front 4

Structure of an AChR

Back 4

Pentameric, 2 alpha, beta, delta, epsilon

Front 5

Pentameric AChR:
Binding, activation, and deactivation mechanism

Back 5

Both alpha subunits need to bind ligand in order to open channel. After two AChh bind, it becomes open, and then desensitzed with both ACh still bound. Finally the ACh releases and leave the empty, closed receptor.

Front 6

The only depolarizing NMJ blocker is?

Back 6

Succinylcholine

Front 7

SUX mechanism of depolarizing blocking

Back 7

It binds the receptor, and opens the receptor. Once it opens allows current through, and then desensitizes (closes) the receptor, it cannot be metabolized and holds the receptor in the insensitive state for a long time. This depolarizes first, and then desensitizes. Works because it has longer residence time on the receptor, and because it cannot be metabolized well by cholinesterases.

Front 8

SUX is useful ONLY because of its pharmacokinetic profile which is;;;;

Back 8

Rapid onset (45 sec to 1 min)
Short duration (5-10 min)

Front 9

Metabolism of SUX?
Mutation which changes this and its consequences?

Back 9

Diffusion away and then hydrolysis by butyrylcholinesterae.

Mutant butyrylcholinesterase that cannot hydrolyze SUX. This leds to the need for renal elimination which takes hours.

Front 10

Three conditions which will double active time of SUX

Back 10

1) Liver DIsease
2)Pregnancy
3) Renal Failure

Front 11

Clinical Use of SUX

Back 11

ET intubation (relaxes jaw quickly)
Brief Muscle Relaxation (short surgeries)

Front 12

Six Side effects of SUX and their clinical etology.

Back 12

1) Muscle pain (random muscle fiber contration)
2)Bradycardia in kids or with second dose (muscarinic activation)
3)Hyperkalemia (see devoted flashcard)
4) Masseter Muscle Contraction (lags behing recovery of other muscles)
5)INcreased pressure in closed spaces due to random muscle contraction (intracranial [diaphragmatic presure transmit upwards], intraocular, Gastric)
6) Malignant Hyperthermia- Only happens when SUX paired with volatile anesthetics

Front 13

SUX can induce Hyperkalemia-- why?

Back 13

DEpolarization normally allows outflow of small amount of K+ from the cell. Denervated muscles have upregulated their AChR extraunctionally to a huge degree and when thee are activated, there can be massive K+ efflux. Happens in Burns, muscle/tissue trauma)

Front 14

Absolute Contraindications to SUX

Back 14

1) family history of Malignant Hyprthermia
2) Major denervation (okay if within last 24 hrs- havent yet upregulated AChR)

Front 15

4) Relative Contraindications to SUX

Back 15

1)Children- Bradycardia, masseter muscle spasm
2) patients with known history of atypical AChE
3) High IOP or ICP
4) Existin Hyperkalemia

Front 16

3 classes of non-depolarizing NMJ blockers

Back 16

1) curare-like alkaloids
2) Benzylisoquinoliniums
2)Ammonio-steroids

Front 17

Mechanism of Non-depolarizing NMJ blockers

Back 17

Competitive antagonist of ACh at AChR

Front 18

Route of adminitration of Non-depolarizing NMJ blockers

Back 18

IV for all

Front 19

Only 3 Non-depolarizing NMJ blockers not dependant upon renal or hepatic metabolism

Back 19

mivacurium, atricurium, cis-atricurium

Front 20

Drugs which inhibit metabolism of Non-depolarizing NMJ blockers

Back 20

Aminoglycosides, tetracyclin

Front 21

Drug which increases metabolism of Non-depolarizing NMJ blockers

Back 21

Phenytoin

Front 22

Choice of Non-depolarizing NMJ blockers is based primarily on...

Back 22

Pharmacokinetics

Front 23

Side effects of Non-depolarizing NMJ blockers

Back 23

Minimal

Histamine release (mivicurium)
Tachycardia (pancuronium)- can be good soemtimes

Front 24

Characteristic of Non-depolarizing NMJ blockers on electrical monitoring of sequential nerve transmissions

Back 24

Will see a fade in amplitude on successive stimulations.

Front 25

AChE inhibitors- Edrophonium mechanism

Back 25

binds to active site with charged amine. There is nothing to hydrolyze though, so it sits on the enzyme for a long time. Slow off rate.

Front 26

AChE inhibitor- Neostigmine mechanism

Back 26

carbamoylates the enzyme which slows it down,

Front 27

AChE inhibitor- DFP mechanism

Back 27

phosphorylate enzyme serine which causes it to inactivate totally. Cannot be reactivated.

Front 28

AChE Inhibitor which can be absorbed PO?

Why cant others?

Back 28

Physostimgine


They are quaternary ammonium compounds

Front 29

Example of a poison that is an AChE inhibitosr

Back 29

Organophosphorus

Front 30

Physiological Effects of AChE Inhibitors
7 systems

Back 30

NMJ – muscle fiber fibrillation then depolarizing block if prolonged or high level (due to desensitization)
GI – increase in GI tone, motility, secretion
Ocular – miosis (pupillary constriction)
Salivation, lacrimation, sweating, urination
Pulmonary – increased bronchiolar tone, secretion
CV – usually bradycardia/hypotension
CNS – stimulation possibly seizures

Front 31

Sites Where ACh acts and AChE has an effect

Back 31

NMJ,
autonomic ganglia,
muscarinic R
Neuronal nicotinic R

Front 32

Treatment of AChE Inhibitor toxicity?

And specifically for Organic phosphate poisoning

Back 32

supportive
Atropine
Pralidoxime (for organic phospate poisoning

Front 33

Uses of AChE inhibitors
Reversal of:

Back 33

1)Reversal of Non-depolarizing (competitive antagonist) neuromuscular blockade)

Front 34

Uses of AChE inhibitors:
Urinary/GI
Due to effect on what receptor

Back 34

Uriniary bladder atony and paralytiic ileus
due to muscarinic effects

Front 35

Uses of AChE inhibitors:
Opthalmic

Back 35

Reduces IOP

Front 36

Uses of AChE inhibitors:
Neural Diseases?
By actions on what receptors

Back 36

Alzheimer's (actions on CNS Nn receptors)
Treats Myasthenia Gravis (NMJ)
Also diagnostic for MG with Tensilon test

Front 37

Uses of AChE inhibitors:
Outside of body (2)?

Back 37

Insectisides
Nerve Gas

Front 38

SUX used ONLY for two things...

Back 38

1) to facilitate intubation
2) muscle relaxation for short procedures

Front 39

uses of AChE inhibitors?

Back 39

reversal of non-depolarizing muscle relaxants.