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Pharm II Unit I > 2 Cholingergic Agents > Flashcards

2 Cholingergic Agents Flashcards

1
Q

Transport of newly synthesized ACh into synaptic vesicles is blocked by a compound called…

A

Vesamicol

Get it, VES-amicol…

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2
Q

Release of ACh from the presynaptic terminal into the synaptic cleft is blocked by …

A

Botulinum toxin (onabotulinumtoxinA, or Botox)

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3
Q

AChE inhibitors are used clinically to …

A

Prolong the action of released ACh

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4
Q

Effects of muscarinic receptor agonists are most pronounced in..

A

The eye, GI tract, bladder, and salivary/sweat glands

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5
Q

Cholinergic agonists and inhibitors of ACh breakdown (cholinesterase inhibitors) are considered together to be …

A

Cholinergic stimulants

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6
Q

Non-selective cholinergic agonists, as well as cholinesterase inhibitors, will have very diverse actions due to…

A

Stimulation of BOTH muscarinic and nicotinic receptors

Drugs that are selective for either muscarinic or nicotinic receptors will have more discrete effects

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7
Q

Drugs that bind to and activate the receptor are _______ and most will ___________ between muscarinic and nicotinic receptors

A

Direct-acting, will discriminate

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8
Q

Cholinesterase inhibitors are considered _____________.

A

Indirect acting - they amplify the effects of ACh, and increase its effectiveness at BOTH nicotinic and muscarinic receptors

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9
Q

Effects of muscarinic stimulation on the eye

A

Constricts circular muscle of the iris sphincter, causing MIOSIS

Constracts the ciliary muscle, causing ACCOMMODATION for near vision

Constriction of the pupil opens the angle between the iris and the lens, increasing access to the trabecular meshwork, promoting drainage of aqueous humor and DECREASING intraocular pressure

Also causes the lens to become rounder, facilitating near vision but causing BLURRED VISION

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10
Q

Effects of muscarinic stimulation on the cardiovascular system

A

Vagal inputs releasing ACh normally SLOW the HR (M2 receptors decrease cAMP and open K+ channels, slowing SA node).

Conduction is also decreased through the AV node

Presynaptic M2 receptors inhibit NE release —> enhances reduction in HR by removing some NE stimulation

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11
Q

The effect of cholinergic stimulation in the heart is primarily on the

A

Atrium

Vagal inputs affect the SA node

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12
Q

Even though blood vessels are not innervated by parasympathetic neurons, stimulation of M3 receptors can cause coronary vasodilation. How does that shit work?

A

Stimulation of M2 cholinergic receptors on ENDOTHELIAL cells in the blood vessels release nitric oxide —> vasodilation.

This is most commonly seen when ACh is injected IV, but is rare at therapeutic doses of other cholinergic agonists

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13
Q

Although vagal stimulation can have profound effects on the heart, at therapeutic levels, muscarinic agonists ….

A

Have very few cardiovascular effects

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14
Q

Respiratory effect of muscarinic agonists

A

Bronchoconstriction

Can be quite striking in asthmatics exposed to cholinergic agonists

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15
Q

GI effect of muscarinic agonists

A

Secretory activity and peristalsis is INCREASED in the GI tract, and sphincters are relaxed

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16
Q

Muscarinic agonist with the most pronounced GI, bladder, and GU effects

A

Bethanechol

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17
Q

GU effect of muscarinic agonists

A

Muscarinic receptors stimulate the bladder destructor muscle and relax the trigone and sphincter muscles. This increases void pressure and decreases bladder capacity.

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18
Q

Salivary and gastric effect of muscarinic agonists

A

Gland secretion is increased greatly by muscarinic stimulation.

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19
Q

Muscarinic agonsists with particularly significant effects on salivary glands

A

Pilocarpine and cevimeline

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20
Q

Glandular effect of muscarinic agonists

A

Secretion of sweat, lacrimal, and nasopharyngeal glands is increased by cholinergic agonists, especially pilocarpine

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21
Q

Brain effect of muscarinic agonists

A

M1 muscarinic receptors in the brain are involved in MEMORY, but no selective drugs are available yet. Maybe one day.

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22
Q

ACh will cause effects similar to those of parasympathetic stimulation, with the exception that…

A

ACh will cause vasodilation due to direct stimulation of muscarinic receptors on blood vessels, and sweating, while parasympathetic stimulation will not cause either of these effect

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23
Q

Does ACh cross the BBB?

A

Nope

It’s an ester with a quaternary amine, so will not cross.

It’s also not absorbed orally

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24
Q

Why doesn’t ACh have any clinical use?

A

It’s too rapidly metabolized (5-20 sec)

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25
Q

A quaternary ester similar to ACh but not rapidly hydrolyzed and selective for muscarinic receptors.

A

Bethanechol (Urecholine)

It does NOT cross the BBB

Effects are primarily in the Urinary and GI tracts

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26
Q

Relatively specific drug for muscarinic receptors that is an alkaloid, and therefore well absorbed orally and easy to get into the brain.

A

Pilocarpine (Pilocarpine)

Sweat and salivary glands are very sensitive to pilocarpine

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27
Q

________ also stimulates M1/M3 receptors, but causes less sweating than pilocarpine

A

Cevimeline

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28
Q

_________ is selective for nicotinic receptors

A

Nicotine

Duh.

Nicotine patches and VARENICLINE are used clinically to help people quit smoking.

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29
Q

______________ rapidly decrease intraocular pressure and are used in narrow-angle glaucoma

A

Muscarinic agonists (generally pilocarpine)

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30
Q

Muscarinic agonists are rarely used for open-angle glaucoma. Why?

A

Due to side effects, in particular BLURRED VISION

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31
Q

Conditions that involve decreased GI activity without obstruction (ie post-op lieu’s and congenital megacolon) may be treated with ….

A

Muscarinic agonists

Bethanechol most common to stimulate peristalsis and increase voiding in patients with urinary retention

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32
Q

DOC for dry mouth

A

Cevimeline

Somewhat more selective for M1 receptors and does not cause as much sweating as pilocarpine.

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33
Q

Drugs used to increase salivation in treatment of Sjogren’s syndrome or dry mouth following radiation

A

Pilocarpine or cevimeline

Pilocarpine causes PROFOUND SWEATING but cevimeline less so (more selective for M1 over M3)

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34
Q

Side effects and toxicity of muscarinic agonists

A 
Nausea, vomiting, diarrhea
Abdominal cramps, belching
Salivation and sweating
Cutaneous vasodilation
Bronchoconstriction
Bladder tightness
Blurred vision
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35
Q

Contraindications for use of a muscarinic agonist

A

Peptic ulcer

Coronary insufficiency

Asthma

Bowel obstruction

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36
Q

Nicotinic receptors are located in…

A

The autonomic ganglia, the brain, and on skeletal muscle

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37
Q

Nicotinic receptors are _______ channels

A

Ligand-gated ion channels

Nicotinic agonists cause an immediate activation, followed by a rapid desensitization if the receptors continue to be stimulated. Receptor activation opens the channel and increases permeability to Na+ and Ca2+ ions

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38
Q

Central effects of nicotinic agonists

A

Low doses of nicotine can increase alertness and attention.

Higher doses cause tremor, vomiting, and increased respiration

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39
Q

Peripheral effects of nicotine

A

Similar to discharge of both parasympathetic and sympathetic neurons, due to stimulation of autonomic ganglia

CV effects mostly sympathetic - HTN and inc HR, which may alternate with vagal bradycardia

GI/GU - mostly parasympathetic - vomiting, diarrhea, and urination

NMJ - initially cause stimulation of the muscle depending on the size of the stimulus, depending on size of the stimulus; long lasting stimulation —> desensitization —> flaccid paralysis

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40
Q

Nicotine poisoning can occur in children who eat tobacco products (just two cigarettes can be fatal if eaten). What are the predicted side effects?

A

Vomiting, generally fairly rapidly

CNS stimulation may cause convulsions, coma, resp arrest

NMJ stimulation may cause muscle contractions, then desensitization —> paralysis

HTN and cardiac arrhythmias

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41
Q

Treatment for nicotine poisoning

A

Atropine to block muscarinic receptors

Anticonvulsants to decrease seizures

Mechanical respiration

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42
Q

How does varenicline (Chantix) work to stop someone from smoking?

A

Partial agonist on a nicotinic receptor in the brain.

In smokers, nicotine increases dopamine release —> pleasure. A craving developers when levels of dopamine become low during nicotine abstinence

VARENICLINE substitutes for nicotine to cause just enough dopamine release to relieve the craving

But because it’s a partial agonist, it blocks the full effects of nicotine if a person smokes so smoking becomes less pleasurable

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43
Q

Common side effects of varenicline (Chantix)

A

Nausea, vomiting, fatigue, headache, constipation, and flatulence

Some serious CNS side effects: sleep disturbance, vivid nightmares, psychosis and mania, anxiety, and possible suicide

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44
Q

How do cholinesterase inhibitors work?

A

Inhibit the breakdown of ACh following its release into the synaptic cleft —> increased duration of action of ACh on receptors

Especially useful in diseases in which cholinergic inputs have been decreased, or where the responsiveness of receptors to ACh is reduced

Also used to reverse teh effects of neuromuscular blocking agents in surgery

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45
Q

The effects of each group of cholinesterase inhibitors difference based on…

A

their chemical structures

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46
Q

As a cholinesterase inhibitor group, ____________ form a covalent bond with an effect lasting 30 min to 6 hours

A

Carbamates

Ex:
Neostigmine and pyridostigmine - both quaternary amines (not well absorbed orally and DO NOT cross the BBB)
Physostigmine - tertiary amine so it IS absorbed orally and will get in to the brain

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47
Q

__________ must be injected, but will bind reversible to AChE with a very short duration of action (5-10 min)

A

Edrophonium

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48
Q

______ forms an irreversible bond with AChE. It is occasionally used in the eye to treat narrow angle glaucoma because it provides a long-lasting effect

A

Echothiophate

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49
Q

__________ are cholinesterase inhibitors used as pesticides and as nerve gases

A

Organophosphates

Note: they are highly lipid soluble, and phosphorylation the AChE to form a very long-lasting bond. This bond then undergoes “aging” - breaking one of the phosphorus-oxygen bonds increasing the strength of the bond until it’s irreversible.

So yeah. Bad.

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50
Q

__________ is a strong nucleophile which attracts the organophosphates and irreversibly binds to them. If added before aging occurs, it binds to the organophosphate and prevents attachment to AChE

A

Pralidoxime (2-PAM)

If not used to treat organophosphate exposure before aging, the poisoning may be fatal

Use with caution - can also produce HTN

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51
Q

Do we use 2-PAM for carbamate poisoning too?

A

It’s controversial.

Since the carbamates don’t undergo aging, 2-PAM itself binds to and inhibits AChE if it isn’t binding to organophosphate, so it could make things worse

But some EM protocols say use it anyway, esp if you don’t know what the pesticide was.

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52
Q

Why are the effects of cholinesterase inhibitors similar to stimulation of both muscarinic and nicotinic receptors?

A

Because the effect of ACh is enhanced at the tissues. The effect in a particular tissue will reflect the predominant tone in that tissue.

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53
Q

Effects of AChE inhibitors on the brain:

A

Increase alertness and improve memory via stimulation of M1 and Nn receptors in low doses

High concentrations act similarly to nicotine and may desensitize nicotinic receptors, cause convulsions, and produce respiratory arrest

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54
Q

Effects of AChE inhibitors on the eyes, respiratory tract, GI/GU tract:

A

Parasympathetic tone is dominant in these tissues, so the effect is similar to that of muscarinic agonists

55
Q

Effects of AChE inhibitors on the CV system:

A

In the heart, responses are mostly parasympathetic, including bradycardia, decreased force of atrial contraction and decreased CO

There is little effect on the vasculature since there is no direct cholinergic innervation.

Desensitization of ganglionic nicotinic receptors decreases sympathetic stimulation tho.

56
Q

Effects of AChE inhibitors on the NMJ

A

Low concentrations INCREASE the strength of contraction of skeletal muscle (useful in diseases such as myasthenia gravis or reversal of neuromuscular blockade following surgery)

Toxic concentrations —> initial contraction followed by neuromuscular blockade resulting from desensitization of nicotinic receptors

57
Q

An autoimmune disease in which antibodies to nicotinic receptors on the neuromuscular endplates develops.

A

Myasthenia Gravis

The patient develops weakness and fatigue of muscles.

Cholinesterase inhibitors are used in MG to prolong the action of ACh in the synaptic cleft

58
Q

DOC for myasthenia gravis

A

Neostigmine (and pyridostigmine) for chronic therapy

Do not cross the BBB and though absorption is poor are given orally to increase the duration in MG patient

In addition to the inhibition of AChE in MG patients, neostigmine may also have some direct stimulators effect on the NMJ that has beneficial effect

59
Q

How is neostigmine/pyridostigmine administered for myasthenia gravis patients?

A

Orally, more than once a day b/c they are fairly short acting

Because the actions of ACh are everywhere, there are often muscarinic side effects (usually able to be tolerated. If not give a muscarinic agonist)

60
Q

How is edrophonium used for myasthenia gravis patients?

A

As a diagnostic, due to its short action

If the patient has MG, the edrophonium will cause an improvement in muscle strength that lasts about 5 min then fade

Can also be used to adjust the dosage of their chronic (long acting) meds.

61
Q

The effects of non-depolarizing neuromuscular blocking agents can be reversed by administration of …

A

Cholinesterase inhibitors such as NEOSTIGMINE OR EDROPHONIUM

62
Q

Acute close-angle glaucoma is treated with a combo of…

A

Pilocarpine and a cholinesterase inhibitor until the pressure is controlled and surgery can correct the problem.

63
Q

Muscarinic agonists are generally NOT used for open angle-glaucoma because…

A

Side effects (blurred vision and brow ache)

64
Q

An long action organophosphate AChE inhibitor applied in the eye when long-term control of intraocular pressure is required (ie - in narrow angle glaucoma emergencies).

A

Echothiophate

It is not lipid soluble so does not get absorbed systemically

65
Q

An overdose of muscarinic antagonists can produce…

A

CNS toxicity

Since there are no good agonists that penetrate the CNS to reverse this, physostigmine is used.

66
Q

The only systemic use for physostigmine

A

Treatment of muscarinic antagonist poisoning, because it can increase ACh to overcome the CNS effects of the antagonist.

It’s also applied directly in the eye to treat narrow angle glaucoma (rarely)

67
Q

Prototype for the organophosphate class

A 
Diisopropyl fluorophosphate (DFP)
Was developed as a pesticide

Malathion and dichlorvos are other commonly used pesticides

Woman and sarin are similar but are used as nerve agents with rapid action

68
Q

AChE inhibitors similar to physostigmine that are used to treat Alzheimer’s disease

A

Donepezil, rivastigmine, and galantamine. All well absorbed orally and get into the brain.

69
Q

How to remember the symptoms of toxicity to irreversible cholinesterase inhibitors

A 
SLUDGE
Salivation
Lacrimation
Urination
Defecation
Gastric distress
Emesis

Other possible Sx: miosis, sweating, bronchoconstriction, nausea, vomiting, diarrhea, bradycardia, hypotension

70
Q

The usual cause of death in AChE inhibitor poisoning?

A

Paralysis of respiratory muscles due to neuromuscular blockade

Think people choking on sarin gas. Not pretty.

Usually within 5 min to 24 hours, depending on amount and the specific agent.

71
Q

CNS effects of AChE inhibitor toxicity

A

Confusion, ataxia, slurred speech, convulsions and coma

All similar to nicotine overdose

72
Q

If exposure to an irreversible AChE inhibitor is by inhalation, what effects will be observed first?

A

Those on respiration and the eye (miosis, ocular pain, vision impairment)

73
Q

Oral administration of a toxic dose of AChE inhibitors is more likely to cause…

A

GI symptoms and decreased BP

74
Q

Treatment for toxic AChE exposure

A

Administer atropine until pupil become dilated to show you’ve successfully blocked the muscarinic receptors

Inject pralidoxime (PAM) to prevent enzyme aging (must be done RAPIDLY)

2-PAM is NOT used if you know the poisoning is from a carbamate, but should SHOULD be used if you have any suspicion of organophosphate exposure

Maintenance of respiration

75
Q

Cholinergic antagonists are subdivided into __________ blocking drugs and _________ antagonists

A

Muscarinic receptor blocking drugs and Nicotinic antagonists (used primarily as neuromuscular blocking agents in surgery)

76
Q

Muscarinic antagonists bind to muscarinic receptors and block the effects of _________.

A

Acetylcholine

Their effect will be to antagonize the actions of the parasympathetic stimulation

77
Q

The prototype drug for muscarinic antagonists?

A

Atropine

Atropine and scopolamine are naturally occurring alkaloids of the belladonna plant. Atropine also found in Jimson weed

78
Q

_________ does not penetrate the CNS well until high doses are reached so the majority of its actions in non-toxic doses are peripheral

A

Atropine

79
Q

________ enters the CNS very easily and causes sedation and amnesia, even euphoria if abused. It is well absorbed by the skin though and is applied in a patch form for prevention of motion sickness

A

Scopolamine

80
Q

The effect of blocking muscarinic receptors will depend to a great deal on …

A

The amount of prevailing parasympathetic tone in different tissues

Because of this, there is a dose-related sequence of effects of cholinergic blockage, demonstrated by increasing doses of atropine

81
Q

_________, ________, and _______ are affected at low doses of atropine.

A

Salivary glands, sweat glands, and bronchial tissues.

The initial side effects are dry mouth and decreased sweating

82
Q

Order of side effects noted as dose of atropine increases

A

0.5 mg - dry mouth and decreased sweating
1 mg - increased HR, very dry mouth and thirst
2 mg - blurred vision, tachycardia, and palpitations
5 mg - urinary retention, hot and dry skin, restlessness, and fatigue
10 mg - rapid and weak pulse, ataxia, hallucinations, delirium, and coma

83
Q

_______ has little effect on the CNS at normal doses but will cause hallucinations, delirium, and coma at toxic doses

A

Atropine

84
Q

__________, which crosses the BBB more readily, causes drowsiness and amnesia at low doses. At toxic doses, it may cause excitement, agitation, hallucinations, and coma

A

Scopolamine

85
Q

__________ is often used as a part of a pre-anesthetic regimen, both to cause sedation and amnesia, and to dry secretions

A

Scopolamine

86
Q

______________ is very effective at preventing motion sickness when administered as a transdermal patch

A

Scopolamine

The patch decreases side effects by the way. How cool.

87
Q

Anti muscarinic drugs are used to restore the balance between ____________ and __________ in the corpus striatum in conditions where dopamine receptors are blocked or dopamine is reduced

A

Acetylcholine and Dopamine

Examples:
Use of some antipsychotic drugs
Parkinson’s disease

Benztropine, trihexyphenidyl and diphenhydramine (Benadryl) are commonly used for this purpose

88
Q

Atropine and other cholinergic antagonists block activation of the ____________ by parasympathetic stimulation, causes eyes to dilate

A

Circular muscle, or iris sphincter

Term for this is mydriasis

Useful for dilated eye exams

89
Q

Muscarinic agonists also decrease cholinergic stimulation of the ciliary muscle, causing…

A

Cycloplegia (loss of accommodation for near vision)

The reflex to light is also blocked, producing photophobia

90
Q

Short-acting drugs administered directly into the eye for producing short-acting mydriasis

A

Tropicamide and homatropine

91
Q

Because anticholingeric drugs inhibit the ciliary muscle and close the trabecular system, they may

A

increase intraocular pressure, especially in narrow angle (closed) glaucoma

92
Q

_______________ is a contraindication to the use of anticholinergics

A

Narrow angle glaucoma

But can be used in patients with OPEN angle glaucoma that is being successfully treated

93
Q

Due to blockade of parasympathetic inputs that increase secretions, anticholinergic drugs cause…

A

Dry eyes

94
Q

With muscarinic antagonists, the blockade of postsynaptic M2 receptors in the SA node removes vagal effects, resulting in ….

A

Tachycardia

Most noticeable in a healthy young adult with high vagal tone (increase of 25-35 bpm).

Babies and elderly people have little vagal tone, so cardiac effects of muscarinic blockage are smaller

95
Q

Atropine is sometimes used to reverse the effects of reflex vagal discharge (e.g. due to pain, stimulation of the carotid sinus, pressure on the eyes, irritation of the larynx following intubation), which may cause …

A

Enough depression of the SA and AV node to cause significant bradycardia and decrease CO

96
Q

___________ is used in surgery to prevent vagal bradycardia when visceral organs are to be handled

A

Glycopyrrolate

97
Q

_______ reverses bradycardia produced by muscarinic agonists or cholinesterase inhibitors

A

Atropine

98
Q

Atropine is used in myocardial infarction s to …

A

Decrease bradycardia or AV block by blocking vagal inputs to the heart —> facilitation of AV conduction

99
Q

Muscarinic antagonists have little effect on peripheral resistance or BP because…

A

Blood vessels do not receive parasympathetic inputs

BUT, vasodilation may result from release of NO from endothelial cells in response

100
Q

Atropine in toxic doses may cause vasodilation in the …

A

Face

It’s a reflex action to get rid of excess heat

101
Q

Why don’t we give muscarinic agonists to asthmatics?

A

Because they cause bronchoconstriction

102
Q

Blockade of muscarinic receptors can reverse bronchoconstrictions, so its helpful in patients with …

A

COPD or acute asthma

Muscarinic blockade may also decrease responsiveness to inflammatory meds in the lungs

Jimsom weed and belladonna cigarettes, which contain atropine, have been used for asthma treatment for centuries

103
Q

Two of the many muscarinic antagonists used for bronchodilation?

A

Ipratropium (Atrovent) and tiotropium (Spiriva)

All of the compounds used in the lung are quaternary ammonium compounds, which are inhaled and not well absorbed systemically, so really just effects the lungs

104
Q

How do muscarinic antagonists generally effect the GI and GU tract?

A

Inhibit motility and secretions

Have been used as antispasmodics ie Dicyclomine(Bentyl)

105
Q

Atropine combined with an opioid (diphenoxylate or Lomotil) is used to treat…

A

Diarrhea

The powerful effect of the opioid to decrease GI motility is potentiated by addition of atropine

The unpleasant effect of atropine at high doses lowers the abuse potential of the opioid

106
Q

Smooth muscle of the ureters and bladder wall are relaxed by __________ and voiding is reduced

A

Anticholinergics

A number of drugs have been recently approved for treatment of overactive bladder and urinary frequency

107
Q

___________ is a selective M3 receptor antagonist being marketed to decrease bladder overactivity

A

Tolterodine (Detrol)

It has few CNS side effects and is the preferred treatment in the elderly, in whom CNS muscarinic blockade can lead to delirium

108
Q

__________ is often used to prevent bladder spasm after prostate surgery

A

Oxybutynin (Ditropan)

109
Q

Why does body temp rise in atropine poisoning?

A

Because sweating is blocked

Especially common in children

110
Q

________ is a common side effect of even low doses of anti muscarinic drugs

A

Dry mouth

Because salivation is very sensitive to atropine

111
Q

Summary of the main side effects of anticholinergic drugs

A 
Dry mouth 
Decreased bronchial secretions
Tachycardia
Mydriasis and cycloplegia —> blurred vision
Decreased GI motility and constipation
Urinary retention
Hot, dry skin
Decreased sweating

All predictable if you think of the mechanism and dose

112
Q

The two main contraindications for use of anti muscarinic agents

A

Narrow angle glaucoma

Benign prostatic hyperplasia (BPH)

113
Q

Funny little line to describe atropine poisoning

A

Dry as a bone, blind as a bat, mad as a hatter, red as a beet

Dry mouth and mucous membranes
Mydriasis
Tachycardia
Decreased bowel sounds
Hot flushed skin 
Agitation and delirium

Scopolamine main cause toxic psychosis too

114
Q

Other drugs that have anticholinergic effects and may have toxic effects similar to atropine…

A

Tricyclic antidepressents, antihistamines, and phenothiazine antipsychotics

115
Q

Treatment for atropine poisoning?

A

Supportive and symptomatic (e.g. physostigmine, diazepam (Valium) to prevent seizures, ice bags and ethanol to reduce body temp, assist respiration)

Physostigmine is used because it gets into the brain, whereas the other therapeutic AChE inhibitors do not

116
Q

When using atropine to treat organophosphate poisoning, you inject large doses until…

A

Dry mouth and mydriasis appear, indicating that muscarinic receptors are being effectively blocked.

Continue administration unti the effects of the AChE inhibitor wears off.

117
Q

What are the two types of NMJ blocking agents?

A

1) Non-depolarizing competitive antagonists - bind to the receptor and cause blockade, holding channel closed. B/c they are competitive, their effect can be overcome by increasing ACh
2) Succinylcholine is the only depolarizing blocker - it initially depolarizes the NMJ but the action is prolonged and the receptors desensitize, so that the subsequent release of ACh does not have any effect and the muscle is paralyzed

118
Q

The prototype non-depolarizing competitive NMJ antagonist

A

D-Tubocurarine

119
Q

NMJ blocking agents are especially useful in surgery because…

A

They provide paralysis of skeletal muscle

But they DON’T produce unconsciousness or anesthesia because they don’t enter brain

So the patient will be paralyzed but awake 😲

120
Q

NMJ blockers must be injected because…

A

They will not be absorbed orally due to their high degree of ionization

121
Q

Because no depolarizing NMJ blockers are competitive antagonists, their action can be reversed by…

A

Increasing the amount of ACh in the synaptic cleft with cholinesterase inhibitors such as neostigmine

122
Q

Order of effect with the use of NMJ blockers

A

Small muscles (eye, jaw, larynx) generally affected first, followed by larger muscles (limbs, trunk). Intercostal muscles and diaphragm last and the first to recover

Recovery occurs in the reverse order of paralysis

123
Q

____________ is the only depolarizing NMJ blocker in use

A

Succinylcholine

Results in the initial stimulation and contraction of the muscle. The action of succinylcholine lasts longer than that of ACh, so receptor desensitization and blockage occur.

Both onset of action and recovery are very rapid

124
Q

How is succinylcholine deactivated?

A

Hydrolyzed by plasma pseudocholinesterase

125
Q

There are genetic differences in ability to metabolize succinylcholine, expressed in terms of dibucaine number. Dibucaine is a local anesthetic that causes inhibition of cholinesterase. When might you test with dibucaine?

A

If a family member has had problems with succinylcholine (ie taken hours to get over its effects instead of minutes)

126
Q

Because succinylcholine is hydrolyzed by cholinesterase, addition of a ____________ will delay recovery

A

cholinesterase inhibitor

127
Q

__________ may occur with repeated doses of succinylcholine and inhaled anesthetic, esp halothane, resulting from an uncontrolled release of Ca2+ from the SR —> muscle rigidity and high temp.

A

Malignant hyperthermia

Treated with dantrolene

128
Q

Patients who should not receive succinylcholine

A

Patients with extensive soft tissue damage or burns
Patients with non traumatic Rhabdomyolysis
Spinal cord injuries with paraplegia or quadriplegia
Muscular dystrophy

Children under 8

129
Q

Why can patients with burns or nerve degeneration, head traumas, etc receive succinylcholine?

A

May cause a pronounced release of potassium into the blood —> cardia arrest (life threatening, especially in patients with CHF)

130
Q

Uses of NMJ blockers

A 
Surgery: to relax muscles for surgery
Ventilation: to paralyze diaphragm 
Ortho: to allow manipulation of bones
Intubation, bronchoscopy etc
Convulsions: used in ECT to decrease muscle spasms
131
Q

Ganglion blockers are considered a subset of …

A

No depolarizing competitive antagonists

Hexamethonium and mecamylamine are not used clinically

132
Q

Because they block all autonomic ganglia, effects of ganglion blockers are similar to …

A

Inhibition of sympathetic and parasympathetic inputs - effects depend on the predominant tone of an organ

133
Q

Primary effects of ganglion blockers based on predominant ANS tone…

A

Eye: ciliary muscle primary affected —> cycloplegia; also, mydriasis
Blood vessels: primarily sympathetic —> orthostatic hypotension
Heart: contractility of heart reduced —> tachycardia due to decreased vagal tone
GU: urinary retention
Skin: sweating blocked but temp maintained due to vasodilation

Pharm II Unit I (4 decks)

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