Cholinergic Drugs Flashcards
(70 cards)
1
Q
All choline esters and natural alkaloids activate ___, ___and ____receptors
A
All choline esters and natural alkaloids activate M1, M2 and M3 receptors
2
Q
- Activation of postsynaptic receptors alters the ____ of ____ organs.
- Activation of presynaptic receptors _____ the release of various ______
A
- Activation of postsynaptic receptors alters the function of effector organs.
- Activation of presynaptic receptors inhibits the release of various neurotransmitters
3
Q
Initial activation on N-receptors (nicotinic receptors) causes ______of the ____-_______ cell membrane which triggers the ____ ______ and therefore the response of the effector organ.
A
Initial activation on N-receptors (nicotinic receptors) causes depolarization of the post-junctional cell membrane which triggers the action potential and therefore the response of the effector organ.
4
Q
Prolonged activation of N-receptors causes a persistent _____of post-junctional cell membrane which prevents the _____to the _____ state, and the _____membrane is resistant to further _____ and the response of the effector organ is ______(known as depolarization blockade).
A
Prolonged activation of N-receptors causes a persistent depolarization of post-junctional cell membrane which prevents the return to the resting state, and the depolarized membrane is resistant to further depolarization and the response of the effector organ is blocked (known as depolarization blockade).
5
Q
muscarinic effects= _____ effects
A
parasympathetic
6
Q
cholinergic agonists have a _____ effect, activating the ______ nervous system responses.
A
muscarinic, parasympathetic
7
Q
Acetylcholine is highly susceptible to ____ while carbachol and bethanechol are not.
A
cholinesterases
8
Q
Do choline esters cause increased or decreased heart rate?
A
decreased
9
Q
Generalized vasodilation is caused by what receptor?
A
M3
10
Q
Increased tone, amplitude of contractions, peristaltic activity and secretions of GI tract is caused by what receptor?
A
M3
11
Q
Contraction of the lower esophageal sphincter is caused by what receptor?
A
M3
12
Q
Increased ureteral peristalsis is caused by what receptor?
A
M1
13
Q
Contraction of detrussor muscle in GU system is caused by what receptor?
A
M3
14
Q
Relaxation of trigone and internal sphincter of urethra is caused by what receptor?
A
M3
15
Q
Erection in male is caused by what receptor?
A
M3
16
Q
Bronchial smooth muscle contraction is caused by what receptor?
A
M3
17
Q
Increased tracheobronchial secretions is caused by what receptor?
A
M3
18
Q
Increased secretion of sweat glands is caused by what receptor?
A
M3
19
Q
Pupil constriction and lacrimal glands are activated by what receptor?
A
M3
20
Q
Choline ester absorption by oral route is _____; hydro____.
A
Choline ester absorption by oral route is poor; hydrophilic.
21
Q
Choline esters are distributed to _____ ____ only, quaternary state drugs do not enter the ______.
A
Choline esters are distributed to peripheral tissues only, quaternary state drugs do not enter the CNS.
22
Q
Carbachol and bethanechol are _____to hydrolysis by _____
A
Carbachol and bethanechol are resistant to hydrolysis by cholinesterases
23
Q
Is acetylcholine resistant to cholinesterases?
A
no
24
Q
Choline esters are excreted by the ____
A
kidney
25
Acetylcholine and carbachol are administered by _____ \_\_\_\_\_ on the \_\_\_\_\_\_\_.
Acetylcholine and carbachol are administered by topical instillation on the conjunctiva.
26
Bethanechol is administered by \_\_\_\_\_\_or**_\_\_\_\_\_\__**
Bethanechol is administered by **_mouth_** or **_subcutaneously_**.
27
Adverse effects of choline esters when given locally on the conjunctiva (Carbachol, Ach):
* Visual difficulty on _____ vision or in ___ \_\_\_\_\_.
* Reddening, stinging and burning of the conjunctiva.
* Postoperative _**\_\_\_\_**_.
* \_\_\_\_ (rare, with long term use!!)
* \_\_\_\_\_\_detachment (with long term use!!)
Adverse effects of choline esters when given locally on the conjunctiva (Carbachol, Ach):
* Visual difficulty on **_far_** vision or in **_dim light_**.
* Reddening, stinging and burning of the conjunctiva.
* Postoperative **_iritis_**.
* **_Cataract_** (rare, with long term use!!)
* **_Retinal_** detachment (with long term use!!)
28
Adverse effects of choline esters when given systemically (Bethanechol):
* Nausea and vomiting, abdominal pain, diarrhea
* \_\_\_\_\_\_\_ cough
* Sweating, lacrimation, \_\_\_\_\_\_
* \_\_\_\_ and \_\_\_\_\_of the skin
* Urinary \_\_\_\_\_
* \_\_\_\_\_\_ (M3 via NO)
Adverse effects of choline esters when given systemically (Bethanechol):
* Nausea and vomiting, abdominal pain, diarrhea
* **_Bronchospasm_**, cough
* Sweating, lacrimation, **_salivation_**
* **_Flushing_** and **_warmth_** of the skin
* Urinary **_urgency_**
* **_Hypotension_** (M3 via NO)
29
Contraindications and precautions of choline esters given systemically:
## Footnote
* Asthma, ____ \_\_\_\_ \_\_\_disease.
* Cardiac \_\_\_\_\_, coronary artery disease, _____ disease, hypotension.
* Peptic ulcer disease, GI obstruction, irritable bowel disease, inflammatory bowel disease, peritonitis.
* Urinary tract \_\_\_\_\_.
* **\_\_\_\_**thyroidism.
Contraindications and precautions of choline esters given systemically:
* Asthma, **_chronic obstructive pulmonary_** disease.
* Cardiac **_arrhythmias_**, coronary artery disease, **_myocardial_** disease, hypotension.
* Peptic ulcer disease, GI obstruction, irritable bowel disease, inflammatory bowel disease, peritonitis.
* Urinary tract **_obstruction_**.
* **_Hyperthyroidism._**
30
* Pilocarpine is a ____ \_\_\_\_ contained in ____ of the genus Pilocarpus.
* Muscarine is a _____ \_\_\_\_\_\_compound contained mainly in ______ of the genus Inocybe and Clitocybe.
* Pilocarpine is a **_tertiary amine_** contained in **_plants_** of the genus Pilocarpus.
* Muscarine is a **_quaternary ammonium_** compound contained mainly in **_mushrooms_** of the genus Inocybe and Clitocybe.
31
* Peripheral effects of natural alkaloids are very similar to those of ____ \_\_\_\_\_. Stimulation of \_\_\_\_and ______ is particularly prominent.
* Central effects include \_\_\_\_\_, excitation, _____ and tremors
* Peripheral effects of natural alkaloids are very similar to those of **_choline esters_**. Stimulation of **_salivation_** and **_sweating_** is particularly prominent.
* Central effects include **_arousal_**, excitation, **_headache_** and tremors
32
Adverse effects of natural alkaloids:
* Most adverse effects are very similar to those of ___ \_\_\_\_\_
* Poisoning produced by mushrooms is called \_\_\_\_.
* Symptoms of mycetism from muscarine containing mushrooms develop within \_\_\_\_\_\_\_minutes of ingestion and include salivation, lacrimation, sweating, nausea and vomiting, visual disturbances, abdominal colic, bronchospasm, bradycardia, hypotension, headache, tremors, confusion, convulsions and coma.
* Contraindications and precautions: Very similar to those of ____ \_\_\_\_\_
Adverse effects of natural alkaloids:
* Most adverse effects are very similar to those of **_choline esters._**
* Poisoning produced by mushrooms is called **_mycetism_**.
* Symptoms of mycetism from muscarine containing mushrooms develop within **_30-60_** minutes of ingestion and include salivation, lacrimation, sweating, nausea and vomiting, visual disturbances, abdominal colic, bronchospasm, bradycardia, hypotension, headache, tremors, confusion, convulsions and coma.
* Contraindications and precautions: Very similar to those of **_choline esters_**.
33
Symptoms of muscarine mushroom toxicity typically occur within 1 hour of ingestion, last for \_\_\_\_\_hours.
Symptoms resolve in most cases without drug therapy or with a dose of ____ when excessive bronchial secretions compromise\_\_\_\_\_\_\_or bradycardia
Symptoms of muscarine mushroom toxicity typically occur within 1 hour of ingestion, last for **_4-24_** hours.
Symptoms resolve in most cases without drug therapy or with a dose of **_atropine_** when excessive **_bronchial_** secretions compromise **_breathing_** or bradycardia
34
Pilocarpine
* Used locally in case of \_\_\_\_-\_\_\_\_\_ \_\_\_\_\_\_\_
* Sometimes used _____ in case of \_\_\_\_\_\_due to radiation therapy or associated with ______ syndrome
Pilocarpine
* Used locally in case of **_open-angle glaucoma_**
* Sometimes used **_orally_** in case of **_xerostomia_** due to radiation therapy or associated with **_Sjögren’s_** syndrome
35
Cholinesterase inhibitors can be:
* Reversible:\_\_\_\_\_ (physostigmine and neostigmine), _____ (edrophonium), others (donepezil)
* Irreversible: _______ (organophosphorus derivatives)
Cholinesterase inhibitors can be:
* Reversible: **_carbamates_** (physostigmine and neostigmine), **_alcohols_** (edrophonium), others (donepezil)
* Irreversible: **_organophosphates_** (organophosphorus derivatives)
36
Mechanism of action for cholinesterase inhibitors:
* Are ______ for both acetylcholinesterase and butyrylcholinesterase.
* The ____ of these enzymes for Anti-ChE is \_\_\_\_\_Xs higher than that for Ach. and the drugs are able to ____ both enzymes.
* Most effects of Anti-ChEs of are due to \_\_\_\_\_of \_\_\_\_\_\_\_\_
Mechanism of action for cholinesterase inhibitors:
* Are **_substrates_** for both acetylcholinesterase and butyrylcholinesterase.
* The **_affinity_** of these enzymes for Anti-ChE is **_1000Xs_** higher than that for Ach. and the drugs are able to **_inhibit_** both enzymes.
* Most effects of Anti-ChEs of are due to **_inhibition_** of **_acetylcholinesterase_**
37
Edrophonium reversibly binds to the ____ \_\_\_\_of the enzyme so preventing \_\_\_\_\_access. The bond is short-lived (\_\_\_\_\_minutes)
Edrophonium reversibly binds to the **_active site_** of the enzyme so preventing **_Ach_** access. The bond is short-lived (**_2-10_** minutes)
38
Carbamates undergo a \_\_\_-\_\_\_\_ \_\_\_\_\_similar to that of Ach. However the carbamoylated enzyme is more ______ to hydrolysis and the second step is more\_\_\_\_\_\_ (\_\_\_\_hours).
Carbamates undergo a **_two-step hydrolysis_** similar to that of Ach. However the carbamoylated enzyme is more **_resistant_** to hydrolysis and the second step is more **_prolonged_** (**_1-6_** hours).
39
Some quaternary carbamates (neostigmine) also can directly activate \_\_\_\_\_receptors at the ______ \_\_\_\_\_.
Some quaternary carbamates (neostigmine) also can directly activate **_nicotinic_** receptors at the **_neuromuscular junction_**.
40
Irreversible inhibitor mechanism of action:
## Footnote
* Organophosphates bind to the ______ site.
* The phosphorylated enzyme is extremely \_\_\_\_\_.
* The phosphorus-enzyme bond is further strengthened with time by the loss of one ____ \_\_\_\_, a process called \_\_\_\_.
Irreversible inhibitor mechanism of action:
* Organophosphates bind to the **_esteratic_** site.
* The phosphorylated enzyme is extremely **_stable_**.
* The phosphorus-enzyme bond is further strengthened with time by the loss of one **_alkyl group_**, a process called **_aging_**.
41
Cholinesterase inhibitors that can enter the CNS may cause:
* After moderate doses: increased \_\_\_\_\_, stimulation of various \_\_\_\_\_activities.
* After high doses: confusion, \_\_\_\_\_, loss of r\_\_\_\_\_, generalized convulsions, coma and central respiratory \_\_\_\_\_.
Cholinesterase inhibitors that can enter the CNS may cause:
* After moderate doses: increased **_alertness_**, stimulation of various **_central_** activities.
* After high doses: confusion, **_ataxia_**, loss of **_reflexes_**, generalized convulsions, coma and central respiratory **_paralysis_**.
42
Cholinesterase inhibitor effects in eye, respiratory, GI, urinary systems:
•\_\_\_\_\_\_tone is the predominant tone in these systems and the effects of Anti-ChE are similar to those of ____ \_\_\_ \_\_\_\_\_\_.
Cholinesterase inhibitor effects in eye, respiratory, GI, urinary systems:
•**_Parasympathetic_** tone is the predominant tone in these systems and the effects of Anti-ChE are similar to those of **_direct acting cholinomimetics_**.
43
The net effects of cholinesterase inhibitors on cardiovascular system depend on the dose:
* After moderate doses: _______ and no change or a modest fall in ____ \_\_\_\_\_\_.
* After high doses: marked bradycardia and \_\_\_\_\_\_.
The net effects of cholinesterase inhibitors on cardiovascular system depend on the dose:
* After moderate doses: **_bradycardia_** and no change or a modest fall in **_blood pressure._**
* After high doses: **_marked_** bradycardia and **_hypotension_**.
44
Effects of cholinesterase inhibitors at the neuromusclar junction:
## Footnote
* After moderate doses: _____ strength of \_\_\_\_.
* After high doses: \_\_\_\_\_, neuromuscular \_\_\_\_\_.
Effects of cholinesterase inhibitors at the neuromusclar junction:
* After moderate doses: **_increased_** strength of **_contraction_**.
* After high doses: **_fasciculations_**, neuromuscular **_blockade_**.
45
Absorption of cholinesterase inhibitors:
## Footnote
Oral bioavailability:
* good for ____ \_\_\_\_\_
* low for ____ \_\_\_\_\_\_ compounds
* very good for \_\_\_\_\_\_\_
* Organophosphates are absorbed by ____ \_\_\_\_including the \_\_\_\_\_
Absorption of cholinesterase inhibitors:
## Footnote
Oral bioavailability:
* good for **_tertiary amines_**
* low for **_quaternary ammonium_** compounds
* very good for **_organophosphates_**
* Organophosphates are absorbed by **_all routes i_**ncluding the **_skin_**.
46
Distribution of cholinesterase inhibitors:
## Footnote
* \_\_\_\_ ____ enter the CNS.
* Quaternary compounds distribute only in ____ \_\_\_\_.
* Organophosphates distribute in ____ \_\_\_\_\_.
Distribution of cholinesterase inhibitors:
## Footnote
* **_Tertiary amines_** enter the CNS.
* Quaternary compounds distribute only in **_peripheral tissues_**.
* Organophosphates distribute in **_all tissues_**.
47
biotransformation of cholinesterase inhibitors:
## Footnote
* Carbamates are hydrolyzed by ____ \_\_\_\_\_.
* Organophosphates are hydrolyzed by enzymes found in _____ and ____ called \_\_\_\_\_.
biotransformation of cholinesterase inhibitors:
## Footnote
* Carbamates are hydrolyzed by **_plasma esterases_**.
* Organophosphates are hydrolyzed by enzymes found in **_plasma_** and **_liver,_** called **_paraoxonases_**.
48
Excretion of cholinesterase inhibitors:
## Footnote
* \_\_\_\_\_are excreted by the \_\_\_\_\_\_.
* Half-lives: edrophonium, _____ physostigmine, neostigmine \_\_\_\_\_\_
Excretion of cholinesterase inhibitors:
## Footnote
* **_Metabolites_** are excreted by the **_kidney_**.
* Half-lives: edrophonium, **_1-10 minutes_** physostigmine, neostigmine **_1-2 hours_**
49
Acute poisoning from cholinesterase inhibitors:
## Footnote
Symptoms and signs appear within \_\_\_\_\_minutes after \_\_\_\_, or within \_\_\_\_\_minutes after _____ or \_\_\_\_\_\_absorption.
acute poisoning from cholinesterase inhibitors:
## Footnote
Symptoms and signs appear within **_5-10 minutes_** after **_inhalation_**, or within **_30-60 minutes_** after **_gastrointestinal_** or **_percutaneous_** absorption.
50
adverse effect of cholinesterase inhibitors:
## Footnote
When given locally for the treatment of glaucoma _____ is a frequent adverse effect (treated for more than \_\_\_\_\_months!!)
adverse effect of cholinesterase inhibitors
## Footnote
When given locally for the treatment of glaucoma **_cataract_** is a frequent adverse effect (treated for more than **_6 months_**!!)
51
Treatment of adverse effects of cholinesterase inhibitors:
## Footnote
* Alleviation of convulsion with \_\_\_\_\_\_
* Administration of \_\_\_\_\_
* Administration of a ______ \_\_\_\_\_\_
Treatment of adverse effects of cholinesterase inhibitors:
* Alleviation of convulsion with **_diazepam_**
* Administration of **_atropine_**
* Administration of a **_cholinesterase re-activator_**
52
Chemistry of cholinesterase reactivators:
## Footnote
* All compounds are _____ (R-CH=NOH).
* Pralidoxime is a \_\_\_\_\_\_\_oxime.
* Obidoxime is a _____ oxime.
Chemistry of cholinesterase reactivators:
* All compounds are **oximes** (R-CH=NOH).
* Pralidoxime is a **_monoquaternary_** oxime.
* Obidoxime is a **_biquaternary_** oxime.
53
Mechanism for Cholinesterase Reactivators:
## Footnote
* Spontaneous hydrolytic regeneration of \_\_\_\_\_\_\_AchE is exceedingly long.
* Oximes have high affinity for the _______ atom and can rapidly regenerate the enzyme if the complex did not undergo aging.
* Oximes themselves have weak _____ activity and are not able to regenerate _____ blocked by \_\_\_\_\_\_.
Mechanism for Cholinesterase Reactivators:
## Footnote
* Spontaneous hydrolytic regeneration of **_phosphorylated_** AchE is exceedingly long.
* Oximes have high affinity for the **_phosphorus_** atom and can rapidly regenerate the enzyme if the complex did not undergo aging.
* Oximes themselves have weak **_AchE_** activity and are not able to regenerate **_AchE_** blocked by **_carbamates_**.
54
Pharmacological effects of cholinesterase reactivators:
* The reactivating action of oxides is:
* most pronounced at the _____ \_\_\_\_\_
* less striking at ____ \_\_\_\_\_sites
* insignificant in the \_\_\_\_\_.
Pharmacological effects of cholinesterase reactivators:
* The reactivating action of oxides is:
* most pronounced at the **_neuromuscular junction_**;
* less striking at **_autonomic effector_** sites
* insignificant in the **_CNS._**
55
Pharmacokinetics of cholinesterase reactivators:
## Footnote
* Oral bioavailability: \< 1%. Vd: ~ 15 L.
* The drug does not enter the \_\_\_\_\_\_
* Half-life: _______ hours
Pharmacokinetics of cholinesterase reactivators:
* Oral bioavailability: \< 1%. Vd: ~ 15 L.
* The drug does not enter the **_brain_**
* Half-life: **_1-1.5 hours_**
56
Cholinesterase reactivators can be therapeutically used for poisoning by \_\_\_\_\_\_\_insecticides
Cholinesterase reactivators can be therapeutically used for poisoning by **_organophosphate_** insecticides
57
Contraindications of cholinesterase inhibitors:
## Footnote
* GI and urinary tract obstruction, inflammatory bowel disease, peritonitis.
* Cholinergic crisis in the ______ patient.
* Asthma, chronic obstructive pulmonary disease.
* \_\_\_\_\_tension, cardiac arrhythmias, coronary artery disease, myocardial disease.
* Peptic ulcer disease.
* \_\_\_\_\_\_thyroidism.
* Seizure disorder.
* \_\_\_\_\_\_\_disease.
Contraindications of cholinesterase inhibitors:
* GI and urinary tract obstruction, inflammatory bowel disease, peritonitis.
* Cholinergic crisis in the **_myasthenic_** patient.
* Asthma, chronic obstructive pulmonary disease.
* **_Hypotension_**, cardiac arrhythmias, coronary artery disease, myocardial disease.
* Peptic ulcer disease.
* **_Hyperthyroidism._**
* Seizure disorder.
* **_Parkinson disease._**
58
Therapeutic uses of cholinesterase inhibitors in neuromuscular system:
Myasthenia gravis diagnosis
* \_\_\_\_\_\_\_\_ is used:
* to confirm the clinical diagnosis: the test is positive when a brief ______ in muscular ______ is observed;
* to distinguish between cholinergic crisis and myasthenic crisis
Myasthenia gravis treatment
* Neostigmine, pyridostigmine, ambenonium (PO).
* \_\_\_\_\_\_ is generally co-administered to control \_\_\_\_\_effects.
Therapeutic uses of cholinesterase inhibitors in neuromuscular system:
Myasthenia gravis diagnosis
* **_Edrophonium IV_** is used:
* to confirm the clinical diagnosis: the test is positive when a brief **_improvement_** in muscular **_strength_** is observed;
* to distinguish between cholinergic crisis and myasthenic crisis
Myasthenia gravis treatment
* Neostigmine, pyridostigmine, ambenonium (PO).
* **_Atropine_** is generally co-administered to control **_muscarinic_** effects.
59
Therapeutic uses of cholinergic drugs:
-\_\_\_\_\_ angle glaucoma
* \_\_\_\_\_\_\_\_ (pilocarpine, bethanechol)
* Postoperative nonobstructive _____ (bethanechol, neostigmine)
* Postoperative and postpartum urinary _____ (bethanechol, neostigmine)
* Neurogenic \_\_\_\_\_\_(bethanechol, neostigmine
Therapeutic uses of cholinergic drugs:
-**_open_** angle glaucoma
* **_Xerostomia_** (pilocarpine, bethanechol)
* Postoperative nonobstructive **_ileus_** (bethanechol, neostigmine)
* Postoperative and postpartum urinary **_retention_** (bethanechol, neostigmine)
* Neurogenic **_bladder_** (bethanechol, neostigmine
60
Pralidoxime is a \_\_\_\_\_\_
cholinesterase reactivator
61
Parathion is a \_\_\_\_\_
cholinesterase irreversible inhibitor
62
Edrophonium is a \_\_\_\_\_
cholinesterase reversible inhibitor
63
Physostigmine is a \_\_\_\_\_
cholinesterase reversible inhibitor
64
Neostigmine is a \_\_\_\_
cholinesterase reversible inhibitor
65
Donepezil is a \_\_\_\_\_\_\_
cholinesterase reversible inhibitor
66
Pilocarpine is a \_\_\_\_-
natural alkaloid
67
Muscarine is a \_\_\_\_\_
natural alkaloid
68
Acetylcholine is a \_\_\_\_\_
choline ester
69
Carbachol is a \_\_\_\_\_
choline ester
70
Bethanechol is a \_\_\_\_\_
choline ester
