Pharmacology Exam 3- Ganglionic Nicotinic Receptors

Front 1

nicotine elicits what responses (5)

Back 1

1) increased cardiac rate
2) increased vasoconstriction
3) decreased mucociliary mvmt in lungs
4) increased plasma levels of epinephrine from stimulus of adrenal medulla
5) stimulates CNS mildly

Front 2

cigarettes contain what types of chemicals (4)

Back 2

1) nicotine
2) aldehydes
3) nitrosamines
4) other alkylating agents

Front 3

lethal dose of nicotine (systemic?)

Back 3

40 mg

Front 4

acute nicotine intoxication autonomic effects (5)

Back 4

1) nausea, vomiting, diarrhea, abdominal pain
2) excess salivation
3) cold sweat
4) dizziness/headache
5) visual problems

Front 5

central stimulant effects from acute nicotine intoxication (5 steps)

Back 5

alertness-->tremors-->convulsions-->coma-->respiratory arrest

Front 6

acute nicotine intoxication muscle effect (3)

Back 6

muscle endplate depolarization-->blockade (desensitization)-->respiratory paralysis

Front 7

atria/sinoatrial node:
predominant tone
effect of ganglionic blockade

Back 7

parasympathetic
effect of blockade: blocks predominant tone. tachycardia

Front 8

ventricle:
predominant tone
effect of ganglionic blockade

Back 8

sympathetic
effect of blockade:
decreased contractile force

Front 9

sympathetic predominant organs

Back 9

blood vessels
ventricles
sweat glands

Front 10

ciliary muscle (eye):
predominant tone
effect of ganglionic blockade

Back 10

parasympathetic
blockade: focused for far vision (cycloplegia- paralysis of muscle)

Front 11

iris:
predominant tone
effect of ganglionic blockade

Back 11

parasympathetic (normally constricts pupils)
effect of blockade: mydriasis (dilation)

Front 12

blood vessels:
predominant tone
effect of ganglionic blockade (3)

Back 12

sympathetic
vasodilation, hypotension, decrease venous return (because blood is pooling in the veins due to dilation)

Front 13

ventricles:
predominant tone
effect of ganglionic blockade

Back 13

sympathetic
decreased contractile force

Front 14

sweat glands:
predominant tone
effect of ganglionic blockade

Back 14

sympathetic
thermoregulatory/nonthermoregulatory sweating decreased

Front 15

interrupting adrenergic control of arterioles results in...(3)

Back 15

1) vasodilation
2) decreased BP
3) increased peripheral blood flow to some vascular beds

Front 16

"symptoms" of sympathetic ganglionic blockade to vessels (5)

Back 16

1) orthostatic hypotension (blood rushing out to dilated vessels)
2) tachycardia due to baroreceptor reflex
3) decreased cardiac output
4) decreased total peripheral resistance
5) fainting
3)

Front 17

interruption of parasympathetic ganglionic transmission elicits (7)

Back 17

1) Tachycardia
2) Mydriasis (dilation)
3) Cycloplegia (far sight only)
4) Xerostomia (no saliva)
5) Urinary retention/constipation
6) Decreased GI tone, secretions, motility
7) Impaired sexual function due to no point/shoot

Front 18

Hexamethonium (structure, absorption, use, type of blocker, specificity)

Back 18

Structure: 2 Ach molecules put end to end. Quaternary amine with poor absorption.
Use: first effective drug for hypertension (not used anymore though)
Type of agent: classical nondepolarizing blocking agent (competitive)
Specificity: highly specific; minimal activity at NMJ/muscarinic sites

Front 19

High concentrations of nicotine in some insecticides elicit what response (as blockers)? Targets what receptors?

Back 19

Persistent depolarization of membranes in regions with N1 and N2 receptors

Front 20

Mecamylamine (structure, duration, MoA)

Back 20

Structure: secondary amine for better absorption from GI
Duration: 12 hours
MoA: non-depolarizing competitive antagonist of ganglionic nicotinic receptors (N1) (does it affect NMJ?)

Front 21

CNS side effects of Mecamylamine (crosses BBB) (5)

Back 21

Tremors
Confusion
Seizures
Mania
Depression

Front 22

Trimethaphan (structure, route of admin, duration, MoA)

Back 22

Structure: quaternary amine
Route: IV admin
Duration: minutes
MoA: non-depolarizing competitive antagonist of ganglionic nicotinic receptors (N1)

Front 23

What are ganglionic blocking agents typically used for? (4)

Back 23

1) Adjunct therapy (not first line anymore due to side fx) for hypertensive emergencies (severe hypertension)
2) Adjunct therapy for peripheral vascular disease (relieves vasoconstriction so better perfusion)
3) Lower arterial pressure to combat bleeding
4) Diagnose pheochromocytoma

Front 24

Trimethaphan is commonly used for what indication. What side effects (2) must be watched for?

Back 24

Lower arterial pressure to combat bleeding during surgery (because of short duration)
Side fx: hypotension and brain anoxia

Front 25

How are ganglionic blocking agents used to diagnose pheochromocytoma?

Back 25

If tumor is present in adrenal medulla, blocking stimulation of it will result in a large drop in arterial pressure because you lose more epinephrine than a normal person would due to tumor secreting epinephrine.

Front 26

Rate of Ach Synthesis is controlled by…

Back 26

Activity of choline transport system

Front 27

Distinguishing feature of NMJ receptors

Back 27

Localization of N2 receptors/end plate in middle of muscle fiber

Front 28

Asynchronous vs. synchronous release effects of Ach at NMJ

Back 28

Asynchronous: elicits localized motor end plate potential but does not trigger muscle contraction
Synchronous: reaches threshold level of Ach needed and elicits muscle contraction

Front 29

Ephedrine adjunct therapy with neostigmine: describe

Back 29

Increase strength of muscle contraction with neostigmine, which is an AchE inhibitor (increases conc. of Ach in NMJ allowing reach-age of threshold potential). Mechanism not known.

Front 30

Myasthenia gravis

Back 30

Autoimmune disease that attacks Ach receptors; they are destroyed so Ach is degraded by AchE before it can elicit contraction.

Front 31

Effects of denervation of smooth/skeletal muscle (due to degenerative process or trauma)- what is this process called

Back 31

Threshold level of Ach needed is significantly reduced (denervation supersensitivity)

Front 32

What is responsible for denervation supersensitivty (what allows it to happen) (2) Does it persist of muscle is reinnervated?

Back 32

1) Redistribution of N2 receptors across end plate
2) Increased numbers of N2 receptors
3) No.

Front 33

Muscle atrophy due to denervation of smooth vs. skeletal muscle

Back 33

Skeletal muscle atrophies but smooth muscle doesn’t

Front 34

Mechanism of action of non-depolarizing inhibitors. What happens to the Ach?

Back 34

Blocks Na+ channel (nicotinic ligand gated ion channel) so ligand cannot bind and open channel. Ach which cannot bind will then be hydrolyzed by AchE.

Front 35

What happens if you add AChE inhibitor to non-depolarizing inhibitors?

Back 35

AChE inhibitor allows for Ach to accumulate and the increase in conc. allows it to compete off the non-depolarizing inhibitors.

Front 36

Physiological effect on muscle of using non-depolarizing NMJ inhibitors (how is action lost) (2)

Back 36

1) Muscle weakness/total flaccid paralysis
2) Lost from peripherals to core, with diaphragm/intercostal muscles lost last

Front 37

All neuromuscular blockers have this structure in common

Back 37

Quaternary amine group- so it can’t cross BBB (also has poor lipid solubilty)

Front 38

NMJ blockers clinically used for what purpose (general, and then 4 specific ones)

Back 38

General: muscle relaxant (adjunct during surgery, often)
1) Muscle relaxant for intracavitary surgery
2) Facilitate tracheal intubation
3) Control ventilation in pt with ventilation failure
4) Treatment of convulsions

Front 39

General considerations before using NMJ blocker (4)

Back 39

1) Check respiration
2) Ensure adequate ventilation
3) No bronchial airway obstruction (all this breathing checking is to ensure that blockade of NMJ/paralysis won’t suffocate pt)
4) No CO2 accumulation

Front 40

Depolarizing blocker MoA (specify what type of inhibitor)

Back 40

Na+ channel is locked non-competitively in open position by depolarizing blocker. Can’t reset.

Front 41

Factors to consider in selecting NMJ blocker for pt (2)

Back 41

1) Needed duration
2) CV problems or no CV problems?
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Front 42

Long acting NMJ blockers (4) (and specify duration)

Back 42

1) D-Tubocurarine
2) Pancuronium
3) Doxacurium
4) Pipecuronium
>90 minutes

Front 43

Intermediate acting NMJ blockers (and specify duration) (4)

Back 43

1) Atracurium
2) Vecuronium
3) Gallamine
4) Rocuronium
30-90 minutes

Front 44

Short acting NMJ blocker (1) (and specify duration)

Back 44

Mivacurium (10-30 min)

Front 45

Benzylisoquinolones- downside and upside

Back 45

Category of NMJ non-depolarizing blockers that are devoid of cross-reactivity of nicotinic receptors- thus no vagolytic(inhibit vagal/ganglionic blocking activity but have some histamine release (why?)

Front 46

Ammonio steroids- what are they? 1 upside, 2 downsides

Back 46

Category of NMJ non-depolarizing blockers that have virtually no histamine release, but some cross reactivity with N1 receptors (vagal blockadetachycardia) and muscarinic blockade.

Newer agents don’t have tachycardia though.

Front 47

3 Ammonio steroid drugs

Back 47

1) Pancuronium
2) Vecuronium
3) Rocuronium
(-CURONIUM)

Front 48

Newer NMJ non-depolarizing agent properties (2)

Back 48

1) Shorter acting
2) Diminished side fx involving vagal blockade, ganglionic blockade, histamine release

Front 49

The only depolarizing NMJ blocker (what is it, type of inhibitor)

Back 49

Succinylcholine; mimics acetylcholine (similar names) and binds noncompetitively

Front 50

Succinylcholine is hydrolyzed by what enzyme?

Back 50

Plasma ChE (NOT AchE)

Front 51

2 phases of depolarizing NMJ blocker (describe what happens in each phase both physiologically and physically)

Back 51

Phase I: (depolarizing) depolarizes membrane and stays depolarized. Unresponsive to later impulses due to not resetting. Results in flaccid paralysis because there is no repriming and you can’t maintain a normal muscle tone.
Phase II: (desensitizing) membrane repolarizes after sustained exposure to succinylcholine. However it is resistant to further depolarization.

Front 52

ChE inhibitors effect on depolarizing NMJ blockers

Back 52

Augment effect (more Ach = faster it desensitizes?)

Front 53

Succinylcholine: local vs. systemic activity

Back 53

Systemic activity is short lived due to wide spread plasma ChE

Localized end-plate activity lasts longer because there is not as much plasma ChE there.

Front 54

Some issues with succinylcholine (regarding cardiac muscle and eyes) (2)

Back 54

1) Excessive loss of K+ from skeletal muscle can lead to catastrophic cardiac arrest
2) Contraction of extraocular muscles can lead to eye dmg if pt has glaucoma as this increases pressure

Front 55

Patients with these conditions are susceptible to cardiac problems (due to loss of K+) when taking succinylcholine (4)

Back 55

1) CHF
2) Burns/trauma
3) Spinal cord injury
4) Muscular dystrophies

Front 56

On rare occasions, depolarizing agents may have what effect on phase II?

Back 56

Prolong it (prolonged inhibition of NMJ)

Front 57

Why does O-P intoxication prolong phase II of depolarizing agents?

Back 57

It inhibits AchE and plasma ChE too, so you get prolonged activity of succinylcholine

Front 58

Genetic mutation of plasma ChE can result in what effect on depolarizing agents?

Back 58

Prolongation of phase II due to not having enough functional plasma ChE to degrade succinylcholine.

Front 59

Contraindications of NMJ blockers (3)

Back 59

1) Respiratory issues
2) Other drugs (like anesthesia) that can modify activity of NMJ blockers
3) Impaired renal function- can’t clear some NMJ blockers effectively

Front 60

NMJ blockers used as muscle relaxants adjunct to anesthesia (4)

Back 60

1) Curare
2) Atracurium
3) Mivacurium
4) Succinylcholine

Front 61

Curare a.k.a Tubocurarine (Type of inhibition, AchE inhibitor effect, plasma ChE effect, duration, ganglionic inhibition/release of histamine?)

Back 61

Type of inhibition: competitive
Action reversed by AchE inhibitors: Yes
Hydrolysis by plasma ChE: No (hence long duration)
Duration: 80-120 min
Ganglionic inhibition/release of histamine: Yes

Front 62

Atracurium (Type of inhibition, AchE inhibitor effect, plasma ChE effect, duration, ganglionic inhibition/release of histamine?)

Back 62

Type of inhibition: competitive
Action reversed by AchE inhibitors: Yes
Hydrolysis by plasma ChE: Yes
Duration: 30-60 min
Ganglionic inhibition/release of histamine: No

Front 63

Mivacurium (Type of inhibition, AchE inhibitor effect, plasma ChE effect, duration, ganglionic inhibition/release of histamine?)

Back 63

Type of inhibition: competitive
Action reversed by AchE inhibitors: Yes
Hydrolysis by plasma ChE: Yes
Duration: 12-18 min
Ganglionic inhibition/release of histamine: No

Front 64

Succinylcholine (Type of inhibition, AchE inhibitor effect, plasma ChE effect, duration, ganglionic inhibition/release of histamine?)

Back 64

Type of inhibition: depolarizing
Action reversed by AchE inhibitors: No- inhibition is augmented
Hydrolysis by plasma ChE: Yes
Duration: 5-8 min
Ganglionic inhibition/release of histamine: No

Front 65

Specific contraindications for non-depolarizing NMJ blockers (e.g. tubocurarine) (4)

Back 65

1) Myasthenia gravis: lack of Ach receptors = exacerbate effects?
2) Impaired hepatic/renal function
3) Several antibiotics potentiate tubocurarine
4) Hypotension: curare can worsen hypotension through ganglionic blockade/histamine release

Front 66

Contraindications for succinylcholine

Back 66

1) O-P intoxication (deactivates cholinesterases)
2) Cardiac insufficiency (CHF, trauma, neuromuscular disease etc)- excess release of K+ into blood due to constant depolarization of skeletal muscle can lead to heart problems
3) Glaucoma- extraocular muscle contraction = increased IOP

Front 67

2 Drugs that are used to reverse NMJ blockade (ONLY competitive non-depolarizing. No reversal for succinylcholine) and their durations

Back 67

1) Edrophonium (short duration- 10 min)
2) Neostigmine (60 min)

Front 68

Why would you administer atropine with neostigmine/edrophonium when reversing NMJ blockade?

Back 68

Because those drugs inhibit AchE, they also stimulate muscarinic receptors. To reduce side effects, you administer atropine (M receptor blocker).