Ch 13 Flashcards
1
Q
cholinesterase inhibitors do what?
A
activate cholinergic receptors indirectly by preventing the breakdown of acetylcholine
2
Q
These 6 categories are what type of drugs? muscarinic agonists muscarinic antagonists cholinesterase inhibitors ganglionic stimulating agents ganglionic blocking agents neuromuscular blocking agents
A
cholinergic drugs
3
Q
muscarinic agonists selectively mimic the effects of _______ at the muscarinic receptors.
A
muscarinic agonists selectively mimic the effects of acetylcholine at the muscarinic receptors.
4
Q
The ________ ________ prevent the breakdown of acetylcholine by _______________. As a result, more ___________ remains available to activate cholinergic receptors.
A
The cholinesterase inhibitors prevent the breakdown of acetylcholine by acetylcholinesterase. As a result, more acetylcholine remains available to activate cholinergic receptors.
5
Q
______________selectively mimic the effects of acetylcholine at nicotinicN (neuronal) receptors of autonomic ganglia.
What is its common use
A
Ganglionic stimulating agents
Nicotine in smoking cessation programs
6
Q
______________, represented by mecamylamine, selectively block ganglionic nicotinicN receptors.
A
Ganglionic blocking agents
7
Q
_____________, represented by d-tubocurarine and succinylcholine, selectively block the effects of acetylcholine at nicotinicM (muscle) receptors at the neuromuscular junction.
A
Neuromuscular blocking agents
8
Q
muscarinic agonists are also known as
A
parasympathetic agents
9
Q
other names for Bethanechol
A
Urecholine
Duvoid
10
Q
MOA for Bethanechol
A
direct acting muscarinic agonist
Binds reversibly to muscarinic cholinergic receptors to cause activation
Acts selectively at muscarinic receptors, having little or no effect on nicotinic receptors, either in ganglia or in skeletal muscle
11
Q
pharm affects of Bethanechol
A
muscarinic receptor activation
heart - decreases heart rate
exocrine glands - increases sweating, salivation, bronchial secretions and secretion of gastric acid
smooth muscles - of lungs and GI tract - promotes contraction of bronchi and increased tone and motility of GI smooth muscle
bladder - contraction of the detrusor muscle and relaxation of the trigone and sphincter - results in bladder emptying
vascular - relaxation - hypotension
eyes - pupillary constriction (miosis) accommodation for near vision
12
Q
Bethanechol is given how?
A
oral administration
13
Q
Therapeutic uses Bethanechol
A
Approved only for urinary retention
muscarinic activation relaxes the trigone and sphincter muscles and increases voiding pressure by contracting the detrusor muscle which composes the bladder wall.
approved to treat urinary retention in postoperative and postpartum patients and to treat retention secondary to neurogenic atony of the bladder
do not use in obstruction
14
Q
muscarinic receptor locations
A
sweat glands
blood vessels
all organs regulated by the parasympathetic NS
15
Q
Muscarinic effects of receptor activation
A
many including
decreased HR
Increased gland secretion
smooth muscle contraction
16
Q
Muscarinic Receptor agonists
A
Bethanechol
17
Q
receptor location for NicotinicN
A
All ganglia of the autonomic NS
18
Q
effects of receptor activation for NicotinicN
A
Promotes ganglionic transmission
19
Q
Receptor agonists for NicotinicN
A
Nicotine
20
Q
Receptor location for NicotinicM
A
Neuromuscular junctions
21
Q
Effects of Receptor Activation for NicotinicM
A
Skeletal muscle contraction
22
Q
Receptor agonists for NicotinicM
A
Nicotine
23
Q
Pilocarpine (Isopto Carpine, Diocarpine, Pilopine HS, Salagen) metabolism
A
hepatic
24
Q
Pilocarpine (Isopto Carpine, Diocarpine, Pilopine HS, Salagen) half life
A
1-1.5 hrs
25
Pilocarpine (Isopto Carpine, Diocarpine, Pilopine HS, Salagen) elimination
urine
26
Cevimeline (Evoxac) metabolism
hepatic
27
Cevimeline (Evoxac) elimination
urine - 84%
| feces
28
Muscarinic agonists
| children
safety and effectiveness unknown for bethanechol and cevimeline
29
Muscarinic agonists
| pregnant women
Unknown
30
Muscarinic agonists
| Breastfeeding women
Unknown if excreted in breastmilk
| recommended nursing be discontinued while taking these drugs
31
Muscarinic agonists
| Older adults
because older patients may have decreased cardiac, hepatic or renal function, care must be taken to evaluate risks on an individual basis
32
adverse affects bethanechol
| cardiac
hypotension (secondary to vasodilation)
| Bradycardia
33
adverse affects bethanechol
| GI
excessive salivation
increased gastric acid
abd cramps
diarrhea
34
adverse affects bethanechol
| Urinary
increase pressure in the urinary tract - can be hazardous to someone with obstruction or weakness of the bladder wall
35
adverse affects bethanechol
| resp
exacerbation of asthma
| can cause bronchoconstriction
36
adverse affects bethanechol
| in patients with hypothyroidism
dysrhythmias - can increase heart rate to the point of a dysrhythmia for patients with hypothyroidism due to their heart being exquisitely sensitive to the effects of norepinephrine.
37
baseline data for bethanechol
```
vital signs
urinary trends (times and amounts)
```
38
Monitoring for bethanechol
intake and output
observe for signs of excessive muscarinic response - abnormal salivation, sweating, urinary urgency, bradycardia, hypotension
39
Bethanechol is contraindicated for patients with
```
peptic ulcer disease
urinary tract obstruction
intestinal obstruction
coronary insufficiency
hypotension
asthma
hyperthyroidism
```
40
How to minimize adverse effects for bethanechol
take on an empty stomach to reduce n/v
| treat excessive muscarinic stimulation with atropine and supportive measures
41
Xerostomia
dry mouth resulting from reduced or absent saliva flow
if untreated, it can lead to peridontal disease, dental caries, altered taste, oral ulcers, candidiasis, difficulty eating and speaking
42
Cevimeline also known as
Evoxac
43
what type of agonist is Cevimeline (Evoxac)
Muscarinic
44
what is Cevimeline (Evoxac) used for?
relief of xerostomia in patients with Sjogren syndrome (autoimmune disorder)
45
How does Cevimeline (Evoxac) work?
activates muscarinic receptors on residual healthy tissue in salivary glands - promoting salivation
46
What other things is Cevimeline used for but not approved for
keratoconjunctivitis sicca (inflammation of the cornea and conjunctiva) and dry eye
47
most common adverse effects of Cevimeline (Evoxac)
excessive sweating, nausea, rhinitis, diarrhea
| increased risk of UTI
48
Education for Cevimeline (Evoxac)
increased water intake
this medicine promotes miosis (constriction of pupil)
and may cause blurred vision - can make driving at night dangerous
49
Cevimeline (Evoxac) is contraindicated in what patient populations and why?
use with caution with heart disease
-can reduce heart rate and slow cardiac conduction
contraindicated in uncontrolled asthma patients
increases airway resistance
use in caution for controlled asthma patients, chronic bronchitis or chronic COPD
50
drug interactions for Cevimeline (Evoxac)
Can intensify cardiac depression caused by beta blockers bc both drugs decrease heart rate and cardiac conduction.
beneficial effects of cevimeline can be antagonized by drugs that block muscarinic receptors such as atropine, tricyclic antidepressants, antihistamines and phenothiazine antipsychotics
51
What type of agonist is Pilocarpine (Salagen)
Muscarinic
52
What is Pilocarpine (Salagen) mainly used for
topical therapy of glaucoma (ophthalmic disorder characterized by elevated intraocular pressure (IOP) with subsequent injury to the ophthalmic nerve
Treatment for dry mouth from Sjogren syndrome or for salivary gland damage from radiation therapy of the head and neck cancer. (oral version is under Salagen)
53
At lower doses the principal adverse effect for Pilocarpine (Salagen) is
sweating. If dosage is excessive, it can produce the full spectrum of muscarinic effects
54
Muscarinic poisoning can result from overdose with 2 kinds of medicine and ingestion of what?
1) Direct acting muscarinic agonists (bethanechol, pilocarpine)
2) indirect-acting cholinomimetics (cholinesterase inhibitors)
3) ingestion of certain mushrooms (Inocybe, Clitocybe spp. )
55
Muscarinic Toxicity symptoms
```
DUMBELS
Diaphoresis/Diarrhea
Urination
Miosis
Bradycardia/Bronchospasm/Bronchorrhea
Emesis
Lacrimation
Salivation
```
56
Treatment for muscarinic toxicity
Administer atropine (a selective muscarinic blocking agent) and provide supportive therapy
57
pt education for muscarinic agonists and cholinesterase inhibitors
Take drug 1 hour before meals or 2 hrs after meals to decrease risk of n/v
Inform patients about muscarinic toxicity and when to seek help
58
Cholinesterase inhibitors are drugs that prevent ____________________________
the degradation of acetylcholine by acetylcholinesterase (cholinesterase) - by doing this they increase the amount of ACh available to activate receptors, thus enhancing cholinergic action.
59
cholinesterase inhibitors are aka
anticholinesterase drugs
60
Because of their lack of sensitivity, cholinesterase inhibitors are limited to only a few therapeutic applications such as
```
treatment of:
Myasthenia gravis
glaucoma
Alzheimer disease
Parkinson disease dementia
Poisoning by muscarinic antagonists
```
61
2 categories of cholinesterase inhibitors
reversible inhibitors - moderate duration
| irreversible inhibitors - long duration
62
trade name for pyridostigmine
Mestinon
| Regonol
63
What type of inhibitor is Pyridostigmine (Mestinon, Regonol)
reversible cholinesterase inhibitors
64
what is the drug of choice for management of MG (myathenia gravis) and also approved for what
Pyridostigmine (Mestinon, Regonol)
approved for reversal of nondepolarizing muscle relaxants
65
Pyridostigmine (Mestinon, Regonol) and crossing membranes/absorption
cannot readily cross membranes including those of the GI tract, blood brain barrier, and placenta
poorly absorbed after oral administration and has minimal effects on the brain and fetus
66
pharm effects of pyridostigmine
by decreasing the breakdown of aceytlcholine, pyridostigmine and other cholinesterase inhibitors make more ACh available which can intensify transmission at virtually all junctions where ACh is the transmitter.
(Pyridostigmine is the busy bone for cholinesterase)
67
muscarinic responses for pyridostigmine
identical to those of the direct-acting muscarinic agonists
by preventing breakdown of ACh, - indirectly cause bradycardia, bronchial constriction, urinary urgency, increased glandular secretions, increased tone and motility of GI muscle, miosis, focusing of the lens for near vision
68
neuromuscular effects of cholinesterase inhibitors
effects on skeletal muscle are dose dependent
at therapeutic doses they increase force of contraction
toxic doses reduce force of contraction
69
CNS effects of cholinesterase inhibitors
therapeutic levels can produce mild stimulation
| toxic levels depress the CNS - including respirations
70
Physostigmine metabolism
hydrolysis by cholinesterases
71
Physostigmine elimination
urine
72
Contraindications for cholinesterase inhibitors
```
Obstruction of gi tract
Obstruction in urinary tract
Poetic ulcer disease
Asthma
Coronary insufficiency
Hyperthyroidism
```
73
What is important to know about Neostigmine (Bloxiverz, prostigmin)
Oral absorption is poor, oral has been discontinued in US but still available in some countries
74
Physostigmine use
Can cross blood brain barrier
| Drug of choice for poisoning by atropine and other drugs that cause muscarinic blockade
75
Pyridostigmine treats
MG
76
Pyridostigmine baseline data
HR
BP
ECG
Assess muscle strength, fatigue, ptosis, ability to swallow to determine the extent of neuromuscular dysfunction
77
Pyridostigmine monitoring
```
HR
BP
Recheck ECG if pt has Bradycardia, palpitations, chest pain, shortness of breath
Titrate dose based on
1) times of drug administration
2) time fatigue occurs
3) state of muscle strength
4) signs of excessive muscarinic stimulation
```
Monitor for signs of myasthenic crisis
78
Signs of myasthenic crisis
Extreme muscle weakness
Paralysis of resp muscles
Manage Wirh resp support and increase dose)
Make sure it is not cholinergic crisis
79
Difference in myasthenic crisis and cholinergic crisis
Signs of excessive muscarinic stimulation - this will accompany cholinergic crisis but not myasthenic crisis
80
Pyridostigmine evaluating therapeutic effects
Assess for increased strength and muscle control
81
What are the 3 cholinesterase inhibitors that are approved for management of Alzheimer disease
Donepezil (Aricept)
Galantamine (Razadyne)
Rivastigmine (Exelon)
82
The irreversible cholinesterase inhibitors have only one indication
Glaucoma
83
What is the drug name of the one irreversible cholinesterase approved for glaucoma
Echothiophate
84
What is the concern with irreversible cholinesterase inhibitors
That these agent might be employed as weapons of terrorism
Highly lipid soluble
Readily absorbed from all routes of administration even through skin
85
Irreversible cholinesterase inhibitors are aka
Organophosphate cholinesterase inhibitors
86
Pharm effects or reversible cholinesterase inhibitors
Essentially the same as the reversible but the irreversible last a long time. Responsive to reversible inhibitors are brief
87
Organophosphate cholinesterase inhibitors are employed primarily as
Insecticides
88
Toxic doses of irreversible cholinesterase inhibitors produce excessive what
What type of crisis is this?
Excessive muscarinic, nicotine and CNS effects.
Cholinergic crisis
89
Overstimulation of muscarinic causes
```
Profuse secretions from salivary
Bronchiole
Involuntary urination and defication
Laryngospasm
Bronchoconstriction
```
90
Prominent nicotinic effects cause
Muscle weakness
Cramps
Twitching
91
Neuromuscular blockade can result in
Paralysis of resp muscles
| Death from apnea
92
What Meds to treat cholinesterase inhibitor poisoning
Atropine for muscarinic stinkin
Pralidoxime for reverse inhibition of cholinesterase
Benzodiazepines to suppress convulsions
Resp depression from cholinesterase inhibitors cannot be managed with drugs
Treatment consists of mechanical ventilation with oxygen
93
what is MG
neuromuscular disorder characterized by fluctuating muscle weakness and a predisposition to rapid fatigue
symptoms result from an autoimmune process where their immune system attacks nicotinicM receptors on skeletal muscle
94
common symptoms of MG
ptosis (drooping eyelids)
difficulty swallowing
weakness of skeletal muscles
95
In MG what are the signs of undermedication?
ptosis
| difficulty swallowing
96
In MG what are the signs of overmedication?
excessive salivation and other muscarinic response
97
When might a MG patient need to anticipate increased dosage needs?
30 - 60 minutes before activities such as eating or shopping
98
_______ can be used to overcome excessive muscarinic blockade by atropine
Cholinesterase inhibitors
99
______ can be used to reduce excessive muscarinic stimulation caused by cholinesterase inhibitors
Atropine - but cant be used routinely bc it can mask early signs (excessive salivation) of overdose with anticholinesterase agents
100
drug of choice for treating poisoning by atropine and other drugs that cause muscarinic blockade including antihistamines and phenothiazine antipsychotics but not tricyclic antidepressants owing to a risk for causing seizures.
Physostigmine
101
what medication is used for diagnosis for MG, not treatment
Edrophonium (Enlon)
102
drugs approved for Alzheimer disease
Donepezil (Aricept)
Galantamine (Razadyne)
Rivastigmine (Exelon)
103
what cholinesterase inhibitor is approved for Alzheimer and dementia of Parkinson Disease
Rivastigmine (Exelon)
104
irreversible cholinesterase inhibitors have only one indication
treatment of glaucoma
105
which med category were produced for possible use as nerve agents but never deployed
irreversible cholinesterase inhibitors
106
to break the bond and reverse the inhibition of cholinesterase for organophosphate cholinesterase inhibitors, we must administer
pralidoxime -cholinesterase reactivator
107
cholinesterase inhibitors are commonly employed primarily as
insecticides
can be absorbed through skin
108
toxic doses of irreversible cholinesterase inhibitors produce
organophosphate cholinesterase poisoning
excessive muscarinic stimulation and depolarizing neuromuscular blockade
```
overstim of muscarinic
profuse secretions from salivary and bronchial gland
involuntary urination and defecation
laryngospasm
bronchoconstriction
```
```
prominent nicotinic effects
muscle weakness
fasciculations - muscle twitch
cramps
twitching
```
neuromuscular blockade effects
paralysis
death from apnea
CNS effects
anxiety
confusion to delirium
convulsions
109
treatment of organophosphate cholinesterase poisoning
atropine to reduce muscarinic stim
pralidoxime to reverse inhibition of cholinesterase
benzodiazepine (diazepam) to suppress convulsions
resp depression from cholinesterase inhibitors cannot be managed with drugs ->mechanical ventilation
110
MG pt who are inadequately medicated may experience _____ which is a state characterized by extreme muscle weakness caused by ______
myasthenic crisis
| insufficient ACh at the NMJ
111
left untreated myasthenic crisis can lead to
death from paralysis of muscles of resp
112
what med is given in myasthenic crisis
cholinesterase inhibitor (ie: neostigmine)
113
overdose with a cholinesterase inhibitor can produce
cholinergic crisis
114
symptoms of cholinergic crisis
extreme muscle weakness or
paryalysis
excessive muscarinic stimulation
Dumbels
```
Diaphoresis/Diarrhea
Urination
Miosis
Bradycardia/Bronchospasm/Bronchorrhea
Emesis
Lacrimation
Salivation
```
115
treatment of cholinergic crisis
resp support
atropine
hold the offending cholinesterase inhibitor until muscle strength returned
116
how to distinguish myasthenic crisis from cholinergic crisis
1) look at history of med use and look for signs of excessive muscarinic stim
2) if this info is inadequate for your diff, use edrophonium
alleviates symptoms -> myasthenic
worsens symptoms -> cholinergic
117
MG pt in crisis edrophonium alleviates symptoms
Myasthenic crisis
118
MG pt in crisis edrophonium worsens symptoms
Cholinergic Crisis
