2 - Neuromuscular and Ganglionic Blockers

Question 1

Ganglionic blockers =

Answer 1

Nicotinic receptor antagonists

Question 2

Ganglionic blockers block what reflexes?

Answer 2

Baroreceptor

Pupillary

Question 3

____ is a ganglionic blocker for HoTN for surgery

Answer 3

Trimethaphan

Question 4

For tourettes, smoking cessation, and severe HTN

Answer 4

Mecamylamine

Question 5

endogenous tone of vascular smooth muscle

Answer 5

mild vasoconstriction

Question 6

Endogenous tone of all other ANS functions

Answer 6

P>S

Mild bradycardia

blockage = tachycardia

Question 7

Blockage of Ach transmission can occur either…

Answer 7

presyn or postsyn

Question 8

Drugs that block nicotinic receptors on skeletal muscle have ______

They are ______

Answer 8

Quaternary amine

peripherally restricted

Question 9

First clinically used NM blocker

Answer 9

Curare

D-tubocurarine = active alkaloid

Question 10

What is TOF ratio

Answer 10

the response of 4th twitch relative to the first

Question 11

TOF ratio = ____= 75% of receptors blocked

but…

Answer 11

0.25

but still near full muscular response

Question 12

Recovery to __ needed for extubation, ___ for full recovery

Answer 12

0. 7
1. 9

Question 13

____ twitch properly sedated

Answer 13

1-2

Question 14

What level of twich can be rapidly reversed when monitoring NM blockade

Answer 14

1 twitch

Question 15

Done redose if _____

Answer 15

no twitch

Question 16

Sequence of paralysis by NM block

Answer 16

1. Eye/speech
2. DIgits
3. Limbs
4. Intercostals
5. Diaphragm

Question 17

What happens as a result of persistent depolarizaiton of the muscle fiber?

Answer 17

Makes it more resistant to further stimulation by Ach

Question 18

• Succinylcholine duration
• metabolized to
• Use?
• CI’s?

Answer 18

• 5-10 m
• Metabolized to choline by BuChE
• Used in trauma care, (intubation), electroconvulsant therapy
• Avoid in HyperKalemia, cause of cardiac arrest

Question 19

Binding of SUX to receptor allows ____

Answer 19

Na influx

Question 20

Non-depolaizing NM blocker (curare-like)

Answer 20

Pancuronium (long acting, 180m)

Vecuronium + Atracurium (intermediate, 30m)

Trimethaphan (short acting i.v.)

Question 21

Benefit of curare like NMBs

Answer 21

Easily reversible

Question 22

Reversal agents for Non-depolarizing NMB’s

Answer 22

Neostigmine (interacts with Ach)

Sugammadex (interacts with pancoronium)

Question 23

AChe degrades Ach to

Answer 23

Choline and acetate

Question 24

Enyme that makes Ach

Answer 24

ChAT

Question 25

substrates for Ach production

Answer 25

AcetylCoA + Choline

Question 26

Plasmacholinesterase = Where? What molecules?

Answer 26

Butyrylcholinesterase (BuChE) In plasma **SUX**, Local **anesthetics** (procaine)

Question 27

AChE inhibitors = Have what groups? Mechanism?

Answer 27

* Carbamates * quaternary or tertiary amine groups * Temporary covalent modification to AChE =Reversible

Question 28

Tertiry amine AchE that enters CNS? Use?

Answer 28

Physostigmine used for ATROPINE OD, glaucoma, Alzheimers

Question 29

Neostigmine and Pyridostygmine properties Uses

Answer 29

Peripherally restricted, Quaternary amine M. gravis, NMB reversal, post-op ileus, bladder distension

Question 30

Quaternary amine that's orally available, has fewer sides and longer duration

Answer 30

Pyridostygmine

Question 31

Irreversible Covalently bonding Ach inhibitors Length of duration Use?

Answer 31

Organophosphates \>week in duration Treatment for glaucoma

Question 32

Other Irrev. covalent Ach Inhibitors

Answer 32

Nerve gases = **Soman/Sarin** Insecticides = **Malathion** (prodrug), **Parathion**, **Diazinon**

Question 33

Insecticides are \_\_\_\_\_\_\_

Answer 33

rapidly inactivated in mammals

Question 34

Antidote for ACHE poisioning | (antidote for...)

Answer 34

Pralidoxime Chloride (2-PAM) (antidote for pesticide or nerve gas poisoning) \*should give within 2-3 hours of exposure

Question 35

Symptomatic treatment of ACHE poisioning (as opposed to antidote) benefit of using this?

Answer 35

Atropine fast onset

Question 36

Treatment of ACHE poisoning involves \_\_\_\_\_\_\_\_

Answer 36

combination of Pralidoxime + Atropine

Question 37

Symptoms of ACHEI poisoning

Answer 37

DUMBBELLS M3 = Diarrhea, Urination, Miosis, Bronchospasms...Lacrimation, Sweating, Salivation M2 = Bradycardia Nm = Permanent depol of diaphragm is fatal (atropine wont help)

Question 38

ACHEI poisoning is more frequent with \_\_\_\_\_\_

Answer 38

farmers

Question 39

_Edrophonium (Tensilon)_ Binding DoA Use?

Answer 39

Binds non-covalently Short acting (5-10 minutes) Used to Dx Myasthenia Gravis

Question 40

M. gravis etiology

Answer 40

ABs block Nicotinic Ach receptors at the postsynaptic junction (NMJ)

Question 41

In M. gravis, Edrophonium improves \_\_\_\_\_ Treatment includes

Answer 41

Muscle strength Tx = neostigmine/pyridostigmine

Question 42

Lambert Eaton Mg etiology Treatment?

Answer 42

ABs against vg Calcium channels Excercise improves muscle strength Edrophonium has NO EFFECT

Question 43

Edrophonium is good at determining the difference between ___ and \_\_\_

Answer 43

Cholinergic crisis and MG CC = no effect, small decrease in muscle strength

Question 44

CI's to using Parasympathomimetic drugs?

Answer 44

1. **Asthma** and **COPD** (bronchoconstrict) 2. **Coronary deficiency** (lower HR) 3. Peptic **ulcer** (acid secretion increased) 4. **Obstruction** of UT or GIT 5. **Epilepsy** (M1Rs, CNS penetrable drugs like pilocarpine)

Question 45

Parkinsons etiology * Reduction in ___ and\_\_\_\_

Answer 45

Dementia with lewy bodies * Reduction in neocortical choline acetyltransferase (**ChAT**) * Rediuction in **AchE activity** in posterior regions and thalamus

Question 46

Other region implicated in Parkinson's

Answer 46

Nucleus Basalis of Meynert

Question 47

Alzheimers = ____ of brain, \_\_\_ of sulci/\_\_\_\_ of gyri Improper proccessing of ___ leads to what??

Answer 47

_Atrophy_ _wide_ sulci, _narrow_ gyri Improper processing of _Beta amyloid precursor protein_ (b-APP) leads to toxic form that promotes **apoptosis**

Question 48

Toxic form of beta amyloid

Answer 48

b-A42

Question 49

Alzheimers Tx * MOA * Binding * but...

Answer 49

**Donepezil** (aricept) * Bind to anionic site and block ACh binding * Reversible, non-covalent * Does NOT SLOW PROGRESSION of the disease

Question 50

Rivastigmine MOA Function Sides Replacement?

Answer 50

Reversible carbamate ACHEI increases cholinergic function Sides = Nausea, vomit, anorexia, weight loss. Replacement = Eptastigmine

Question 51

Galamthamine MOA From where? May be a \_\_\_\_ Pharmacokinetics?

Answer 51

Reversible Competitive ACHEI From daffodil May be a nicotinic receptor agonist **Inhibits P450 (3A4, 2D6)**

Question 52

Rivastigmine and Galanthamine caveat

Answer 52

Lost effectiveness as disease progresses