CHOLINESTERASE INHIBITORS AND ANTICHOINERGICS

Question 1

Cholinergic agonists moa

Answer 1

Bind to cholinergic receptors and mimic the actions of acetylcholine

also called parasympathomimetic drugs; copy parasympathetic nervous system

Question 2

Anticholinesterase moa

Answer 2

Inhibit acetylcholinesterase enzyme (the enzyme that destroys acetylcholine). This increases acetylcholine levels at the receptor sites and prolonging its effects.

Question 3

Examples of cholinergic agonists

Answer 3

Bethanechol
Carbachol
Cevimeline
Pilocarpine

Question 4

cholinergic Pharmacokinetics administration forms and how are they excreted?

Answer 4

Action and metabolism vary widely
Administered topically, orally, and subcutaneously
No I/V or I/M because rapid break down and rapid actions leads to crisis
Metabolized at the muscarinic and nicotinic receptor sites in the plasma and liver
Excreted by the kidneys

Question 5

Cholinergic drugs

Pharmacodynamics COMMIT to memory

Answer 5

Mimic (copy) the actions of acetylcholine
Combine with the receptors on the target organs’ cell membranes
Actions
Salivation, slow heart rate, dilation of blood vessels, constriction of bronchioles , increase gut activity, contraction of urinary bladder and constriction of pupil

Question 6

Cholinergic drugs Pharmacotherapeutics:

Cholinergic agonists are used in the following conditions

Answer 6

Urinary retention due to weak or atonic bladder
Lack of bowl movements especially post op period
Glaucoma to reduce intraocular pressure
Salivary gland hypofunction

Question 7

cholinergic drug

Drug interactions

Answer 7

Other cholinergic drugs leads to toxicity
Cholinergic blocking agents
Quinidine

Question 8

Cholinergic drugs:
Adverse reactions (wet as ocean)
7 things

Answer 8

Decrease heart rate* and lower BP
Nausea/vomiting
Increased activity of gut  cramping and diarrhea
Excessive sweating/salivation
Increase urination
Blurred vision due to pupillary constriction
Shortness of breath due to bronchoconstriction

Question 9

ACH

Answer 9

Acetylcholine applies breaks on heart but accelerates gut and bladder smooth muscles

Question 10

Anticholinesterase drugs MOA

Answer 10

Block action of enzyme acetylcholinesterase , preventing breakdown of acetylcholine
This increases levels of acetylcholine are receptor sites leads to more stimulation by acetylcholine
Anticholinesterase drugs can be divided into two groups
Reversible- short duration of action; examples- physostigmine
Irreversible- long-lasting effects; examples- insecticides, nerve gas for warfare

Question 11

Cholinergic drugs: Anticholinesterase drugs

pharmacokinetics

Answer 11

Absorbed from GI tract, subcutaneously, and mucous membranes
Can cross blood-brain barrier
Metabolized by enzymes in plasma
Excreted by the kidneys

Question 12

cholinergic drugs: anti cholinesterase pharmacodynamics

Answer 12

Produce a stimulant or depressant effect on cholinergic receptors based on site, dose, and duration of action

Question 13

Anticholinesterase drugs

Pharmacotherapeutics/ Indications

Answer 13

Glaucoma to reduce eye pressure
To increase bladder motility
To increase tone and motility of GI tract in patient with post op low gut motility ( paralytic ileus)
To improve muscle strength in myasthenia gravis
Antidote for cholinergic blocking agents
To treat dementia in Alzheimer’s’ disease (Alzheimer’s disease is due to deficiency of acetylcholine in brain)

Question 14

when do we put scopolamine on

Answer 14

dont touch it, wash your hands, put it on in PRE op. take it off after 3 days.

Question 15

..

Answer 15

..

Question 16

Cholinergic drugs: Anticholinesterase drugs

Adverse effects

Answer 16

Cardiac arrhythmias
Nausea/vomiting
Diarrhea
Shortness of breath, wheezing
Headache, seizures

Question 17

best drugs to dry up secretions

Answer 17

rybinol

Question 18

Cholinergic blocking agents/Anticholinergic Drugs
how do they act?

what are some examples?

are they competitive or noncompetitive antagonist

Answer 18

Interrupt parasympathetic nerve impulses in the central and autonomic nervous systems

Examples– atropine, belladonna, scopolamine
Atropine competes with acetylcholine for receptor sites – competitive antagonist

Question 19

hr 58

hr 30

Answer 19

58- glycol

30- atropine

Question 20

Cholinergic blocking agents pharmacokinetics

Answer 20

Pharmacokinetics
Absorbed through GI tract, eyes, mucous membranes, skin
Crosses blood-brain barrier
Metabolized in liver; excreted by kidneys

Question 21

cholinergic

Pharmacodynamics

Answer 21

Stimulating or depressing effects depending on target organ and disorder

Question 22

Cholinergic BLOCKING agents Pharmacotherapeutics / Indications. what do they do to the smooth muscles of the GI and Urinary bladder?

Answer 22

All cholinergic blocking agents relax smooth muscles of GI and urinary bladder. Therefore these are used in
Hyperactive bladder (e.g. Detrol ®)
Hyperactive gut (colic/ irritable bowel syndrome)
Biliary colic
Before endoscopy or sigmoidoscopy to relax GI smooth muscles

Question 23

reglan- in class discussion who do we not give it to?

Answer 23

bowel obstruction!

Question 24

when is Atropine give

Answer 24

is given before surgery to dry up secretions
To speed up heart rate during bradycardia *
To dilate pupil for eye exam
As an antidote for pesticide poisoning; blocks DUMBELSS i.e. Diarrhea, Urination, Miosis, Bronchospasm, Bradycardia, Excitation of skeletal muscles, Lacrimation, Salivation (and abdominal cramps)

Question 25

Cholinergic blocking agents drug interactions

Answer 25

Tricyclic and tetracyclic antidepressants

Question 26

cholinergic blocking agents adverse reactions

Answer 26

``` Adverse reactions Dry mouth Decreased sweating Reduced bronchial secretions Blurred vision due to pupillary dilatation Confusion Tachycardia increase body temperature ```

Question 27

Treatment: antidote | for cholinergic blocking agents

Answer 27

physostigmine

Question 28

atropine greater than 10mg

Answer 28

hallucinations delirium and coma

Question 29

atropine greater than 5mg

Answer 29

rapid heart rate, palpitations, marked dryness of mouth dilation fo pupil some blurring of near vision

Question 30

atropine 0.5mg

Answer 30

slight cardiac slowing some dryness of the mouth inhibition of sweating

Question 31

Muscarinic receptors are located in:

Answer 31

Heart Salivary glands GI smooth muscle GU tract

Question 32

anticholinergic drugs moa

Answer 32

Competitively antagonize the neurotransmitter (NT) acetylcholine (Ach) at cholinergic postganglionic sites.

Question 33

Naturally occurring tertiary amine belladonna alkaloids are

Answer 33

Atropine and Scopolamine.

Question 34

glycopyrrolate naturally occurring or not?

Answer 34

, semisynthetic, and usually quaternary ammonium derivatives. These are usually more potent than their parent compound and NO CNS EFFECTS, secondary to poor penetration to the brain.

Question 35

Atropine & scopolomine:

Answer 35

Naturally occurring drugs are formed into esters. Resemble cocaine structurally. Atropine has a weak analgesic effect. Mixed of equal parts of dextrorotatory & levorotatory isomers. Anticholinergic effects are due to levorotatory form. Have a cationic portion that fits into muscarinic cholinergic receptor, like Ach

Question 36

Anticholinergic drugs MOA

Answer 36

Combine reversibly w/ muscarinic cholinergic receptors, preventing access of Ach to these sites. Anticholinergic drug w/ muscarinic receptors results in NO cell membrane change. DO NOT prevent release of Ach or react with it. They are competitive antagonists, the effects of anticholinergic drugs can be overcome by  concentration of Ach in the area of the muscarinic receptors.

Question 37

5 muscarinic cholinergic receptor subtypes:

Answer 37

M1…CNS & stomach M2…Lungs, heart & eyes M3…CNS, airway smooth muscle & glandular tissue M4 & M5…CNS which is not a CNS Subtype? Mu2

Question 38

glycopyrrolate and metabolic 02 consumption

Answer 38

Glycopyrrolate increases metabolic O2 consumption, atropine has no effect, & scopolamine has a decreased effect.

Question 39

scopolamine and antisialagogue effects

Answer 39

has greater antisialagogue (decrease production of saliva) & ocular effects than atropine.

Question 40

atropine and anticholinergic effects on the heart?

Answer 40

has greater anticholinergic effects on the heart, bronchial smooth muscle & GI tract than scopolamine.

Question 41

Atropine onset

Answer 41

~ 1 min. Duration of 30 – 60 min

Question 42

Glycopyrrolate onset

Answer 42

2 – 3 min (IM injection ~ 16 min), with same duration

Question 43

name the two anticholinergic drugs that can penetrate the BBB

Answer 43

atropine and scopolamine

Question 44

name drug that can't penetrate the bbb

Answer 44

glycopyrrolate

Question 45

hydrolysis of atropine

Answer 45

Atropine is hydrolyzed to tropine and tropic acid, little hydrolysis in plasma. T1/2=2.3h

Question 46

how much of scopolamine is broken down and excreted in the urine

Answer 46

Scopolamine is broken down almost entirely; ~1% excreted unchanged in the urine

Question 47

how is glycopyrrolate eliminated?

Answer 47

Glycopyrrolate elimination is more rapid than atropine T1/2= 1.25h, and is significantly prolonged in uremia

Question 48

Pts w/ glaucoma & pregnancy have special considerations:

Answer 48

Scopolamine > atropine > glycopyrrolate in causing mydriasis | Atropine and scopolamine can cross placenta, but fetal HR does not significantly change

Question 49

Scopolamine is the selected choice potency? | amnesia?

Answer 49

100X more potent than atropine in decreasing the activity of RAS Depresses the cerebral cortex, and also effects other areas of the brain causing amnesia

Question 50

scopolamine what effects do you see with opioids and benzos

Answer 50

Greatly enhances the sedative effects of concomitantly administer drugs, especially opioids & benzo’s

Question 51

Morphine + Scopolamine=

Answer 51

Morphine + Scopolamine = favored combo when a reliable sedative is needed in pre-op

Question 52

elderly considerations for scopolamine

Answer 52

Can have symptoms from restlessness to somnolence (drowsiness), which are more likely to occur in the elderly (which could explain the delayed awakening or agitation seen in post anesthesia care unit (PACU)

Question 53

atropine and memory deficit?

Answer 53

Atropine has been associated with an increased incidence of memory deficit after anesthesia (compared to glycopyrrolate)

Question 54

arousal for atropine?

Answer 54

Arousal in 30 min after cessation of anesthesia is delayed after giving atropine-neostigmine (but not glycopyrrolate-neo mix) which is used to antagonize effects of NDNMB

Question 55

Inhaled anesthetics and anticholinergic drugs

Answer 55

Inhaled anesthetics can potentiate the effects of anticholinergic drugs on the CNS, which could lead to an increased in postop restlessness or somnolence

Question 56

Physiostigmine reversal??

Answer 56

is effective in the reversal of restlessness/somnolence secondary to CNS effects of tertiary amine anticholinergic drugs.

Question 57

scopolamine tell me about potency and antisialagogue effect

Answer 57

Scopolamine is 3X more potent as an antisialagogue than atropine Therefore, scopolamine is selected for the use when both antisialagogue and sedation are needed.

Question 58

why would you select glycopyrrolate

Answer 58

Gylcopyrrolate is selected for absence of sedative effects, and as an antisialagogue it is 2X more potent than atropine and the duration is longer Glyco is good for a juicy patient

Question 59

intraoperative bradycardia

Answer 59

Anticholinergics are the drug of choice treating intraoperative bradycardia, particularly that resulting from increased parasympathetic nervous system They work by increasing the HR by blocking effects of Ach on SA node (shortening the PR interval)

Question 60

Which anticholinergic is best for bradycardia is glycopyrrolate good for bradycardia?

Answer 60

Atropine (15-70µg/kg) has greater effect than scopolamine or gylcopyrrolate, indicating the degree of control normally exerted on the vagas nerve on the SA node. The same dosage of gylcopyrrolate given as atropine produces similar increases in HR, but with a slower onset

Question 61

Vagal tone:

Answer 61

Young adults w/ great vagal tone, the influence of atropine is enhanced… Versus infants/elderly, even large doses may fail to increase HR During anesthesia, where a volatile drug is used, the dose of atropine needed may increase perhaps due to depression of vagal centers

Question 62

Clinical uses: anticholinergics Combined with anticholinesterases

Answer 62

Given with anticholinesterase for antagonism of NDNMB to prevent parasympathetic effects that predictably go with IV administration of edrophonium, neo or pyridostigmine. The use of atropine (rapid) or glyco (slower), depends on the speed on onset Causes impairment of PSNS control of HR that persists early in the postop period, the use of glycopyrrolate has shorter duration of effect and may be preferred in patients at risk for CV complications, because impairment of PNS has been associated with increased incidence of dysrhythmias in response to myocardial ischemia and decreased survival after MI

Question 63

anticholinergics and bronchodilator

Answer 63

As bronchodilators, administered as aerosols, reflect antagonism of Ach effects on airway smooth muscle via muscarinic receptors (present predominantly in large and medium sized airways) in response to vagal nerve stimulation. As aerosols, the advantage is absence of adverse CV side effects. Atropine 1-2mg diluted in 3-5mL NS via nebulizer. This decreases airway resistance & increases dead space, especially in pts w/ asthma or chronic bronchitis

Question 64

atropine nebulizer

Answer 64

Atropine 1-2mg diluted in 3-5mL NS via nebulizer. | This decreases airway resistance & increases dead space, especially in pts w/ asthma or chronic bronchitis

Question 65

Glycopyrrolate as a bronchodilator,

Answer 65

Glycopyrrolate is equally effective as a bronchodilator, No CNS effects, HR effects are minimal

Question 66

scopolamine and bronchodilator

Answer 66

Scopolamine decreases airway resistance and increases dead space ~ 1/3, but the effects depend largely on degree of preexisting bronchomotor tone

Question 67

Ipratropium (Atrovent)

Answer 67

a N-isopropyl derivative of atropine, an anticholinergic aerosol selected for pts w/ COPD Prevents & treats bronchospasm due to β-adrenergic antagonists or psychogenic stimuli Has slower onset & less effective than β-agonists for bronchial asthma, because these drugs inhibit the release & the subsequent airway smooth muscle contraction caused by chemical mediators (histamine & leukotrienes) Is more effective than β-agonist for bronchodilation for chronic bronchitis or emphysema (blocks M3 receptors)

Question 68

Bronchoconstriction secondary to tracheal intubation treatment

Answer 68

Bronchoconstriction secondary to tracheal intubation (due to an irritant reflex response mediated by Ach from parasympathetic nerves acting on muscarinic receptors of airway smooth muscles) is responsive to inhaled ipratropium

Question 69

Effects of aerosol ipratropium on HR & intraocular pressure

Answer 69

Effects of aerosol ipratropium on HR & intraocular pressure do not occur (because of the <1% systemic absorption)… This also can relate to prolonged effect at the desired site of action. There is no tolerance to the bronchodilator effect.

Question 70

atropine & biliary tract & ureter effect.

Answer 70

Atropine decreases the tone of the smooth muscles of the biliary tract & ureter.

Question 71

sphincter of Oddi

Answer 71

May not be able to reverse opioid-induced spasm of the sphincter of Oddi, but Atropine may prevent spasm of the ureter produced by morphine (atropine + morphine to treat renal colic)

Question 72

anticholinergics- bladder effects

Answer 72

Diminishes the tone of fundus of bladder, & increases tone of sphincter, due to urinary retention (tx urinary incontinence)

Question 73

IM scopolamine

Answer 73

is a more potent mydriatic than atropine or glycopyrrolate-caution in pts w/ glaucoma

Question 74

atropine preop and iop

Answer 74

Atropine doses used for pre-op are unlikely to cause increased IOP, especially is an anticholinesterase or cholinergic topical is continued

Question 75

how many days to recover from atropine?

Answer 75

Complete recovery from atropine takes 7-14 days.

Question 76

resulting in mydriasis & cycloplegia

Answer 76

Topical anticholinergic block the action of Ach at both sites. Circular muscle of the iris that constricts the pupil, & is innervated by cholinergic fibers from III cranial nerve, also causes contraction of ciliary muscle, which makes the lens more convex In pts w/ glaucoma the mydriasis obstructs passage of intraocular fluid in the venous circulation, causing a hazardous increase IOP.

Question 77

Clinical uses: antagonism of gastric hydrogen ion secretion

Answer 77

Original use of glycopyrrolate to control gastric acidity, for the control of peptic ulcer disease (PUD) None of the anticholinergics are selective for this effect, the high doses required for PUD results in unacceptable secretory, ocular, & CV side effects Therefore, H2 antagonists have replaced their use Anticholinergic drugs have predictable effects on the tone and motility of the GI tract because the PSNS provides almost exclusive motor innervation High doses of anticholinergic drugs do prevent excess peristalsis of the GI tract that would be associated with anticholinesterases for the antagonism of NDNMB*

Question 78

Clinical uses: Prevention of motion-induced nausea

Answer 78

Transdermal absorption of scopolamine provides sustained therapeutic plasma concentrations that protect against motion-induced nausea without side effects such as sedation, cycloplegia, or drying or secretions Patch delivers 5µg/h for 72 hours Protection against nausea is best if applied 4 hours before noxious stimulus, but less effective after symptoms of nausea have presented Motion sickness is caused by stimulation of vestibular apparatus and scopolamine blocks transmission to the medulla of impulses from overstimulation.

Question 79

Clinical uses: management of parkinson disease

Answer 79

Benzotropine & trihexphendyl are used for tremor, rigidity and dysonia Also used to treat extrapyramidal side effects of antidopaminergic effects of metoclopramide Disadvantages of using anticholinergics in pts w/ Parkinson include memory impairment, hallucinations, visual blurring, and aggravation of glaucoma (especially in elderly)

Question 80

Central anticholinergic syndrome

Answer 80

Scopolamine & atropine (some) enter the CNS and cause symptoms of central anticholinergic syndrome Symptoms: restlessness and hallucinations, to somnolence and unconsciousness (often mistaken for delayed recovery from anesthesia) These responses reflect blockade of muscarinic cholinergic receptors and competitive inhibition of Ach in the CNS. Not likely w/ glycopyrrolate, since it doesn’t cross BBB Physiosigmine, is the treatment for central anticholinergic syndrome

Question 81

Overdose of anticholinergics

Answer 81

Rapid onset of symptoms characteristic of muscarinic cholinergic receptor blockade (dry mouth, swallowing & talking difficult, vision blurred, photophobia, prominent tachycardia, dry skin, flushed, rash in “blush area”) Even therapeutic doses of anticholinergic drugs sometimes may selectively dilate cutaneous vessels in the blush area Body temperature can be increased by anticholinergic drugs, especially when the room temperature is increased. This increase in body temperature reflects inhibition of sweating by anticholinergic drugs, reflecting innervation of sweat glands is by SNS that release Ach as the NT.

Question 82

Overdose of anticholinergics minute ventilation fatal effects

Answer 82

Causes increase in minute ventilation due to CNS stimulation & impact of physiological dead space secondary to bronchodilation Nicotinic blockade is reflected by skeletal muscle weakness, orthostatic hypotension Fatal events result in seizures, coma & medullary ventilatory center paralysis Treatment: Physiostigmine 15-60µg/kg IV, repeat doses may be necessary

Question 83

Decreased barrier pressure

Answer 83

Barrier pressure is the difference between gastric pressure and LES pressure. Administration of atropine or glycopyrrolate decrease LES pressure and barrier pressure and the resistance to acid reflux