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Flashcards in topic 20 Deck (54):
1

What are 6 types of cholinergic drug agents?

Directly acting muscarinic agonists

Muscarinic Antagonists

Anticholinesterases

Ganglionic Stimulant

ganglionic Antagonist

Neuromuscular blockers

2

What are two types of directly acting ACh agonists? Name 4 examples of one and 2 examples of the other.

Choline Esters: ACh, Methacholine, Carbachol, Bethanechol

Alkaloids: Pilocarpine, Cevimeline

3

What is the susceptibility to cholinesterases of the 4 choline esters? What is each primarily used for? Do they stimulate nicotinic receptors?

ACh-Very susceptible to Ach. the others not as much.

Methacholine-Used to diagnose bronchial hyperreactivity (not used in much else, acts strongly on heart)

Carbachol-Used mainly in research. Acts strongly on nicotinic receptors and thus can be used for that.

Bethanechol-The main one used clinically. It is not hydrolyzed by AChE. It is used to stimulate the motility of GI tract and contract the urinary bladder, often post-operatively.

4

What are the 2 alkaloids used?

Pilocarpine and Cevimeline

5

How is Bethanechol taken? What is its absorption? Distribution? What receptor does it favor? What does it do?

SC or PO

Poor lipid solubility

Does not cross BBB

Favors M3

Enhances function of GI tract and urinary bladder, especially post-op

6

How is Pilocarpine taken? What is its absorption? Distribution? What does it do? What is it used to treat?

PO or eyedrops

Well absorbed

Good lipid solubility

Marked stimulation of saliva and sweat

Used in both narrow angle and wide angle glaucoma



7

What receptor does Cevimeline work on? What drug is it simliar to? What does it do? What is sjogrens syndrome? Treatment of it?

Synthetic M3 selective agonist

Similar to Pilocarpine

Used for treatment of dry mouth associated with Sjogrens Syndrome (autoimmune where moisture producing glands are destroyed) or radiation damage of salivary glands.

Pilocarpine also used to treat sjogrens syndrome.

8

What is glaucoma? What are the two types? How are each treated?

Ocular disease characterized by an elevation of intraocular pressure leading to possible retinal damage

Primary open angle Glaucoma: More common. Problem in trabecular network so aqueous humor cant get out into schlemms canal. But angle is intact. This is usually treated step-wise with drugs. Pilocarpine is part of the 3rd step.

Narrow angle glaucoma: Less common. Iris bows forward and makes contact with cornea so aqueous humor cant get to anterior chamber. Emergency increased pressure. Pilocarpine used immediately followed by surgery.

9

What are the side effects of muscarinic agonists

Salivation, Lacrimation, Nausea and vomiting, bradycardia, diarrhea, sweating, urination, hypotension, bronchospasm, CNS activation, Headache and visual disturbances, Pupils constricted

10

What are the contraindications of muscarinic agonists?

Asthma/COPD, Hyperthyroidism, Coronary insufficiency, Peptic Ulcer Disease, Obstruction of urinary bladder or Gi tract.

11

What are 5 muscarinic antagonists or belladonna alkaloids? What are the prototypes? How do they work? What happens w/o parasymp tone?

Atropine***, Scopolamine***, Ipratropium, Tolterodine/Oxybutynin

They are competetive antagonists at muscarinic receptors. The more parasymp tone at a receptor, the greater their effect.

12

What are the routes of admin. of atropine? How is it absorbed orally? What is it distribution? How is it metabolized?

PO, IM, IV, SC, opthalmic drops

Well absorbed orally

Well distributed, crosses BBB

40% hydrolyzed and conjugated

60% excreted

13

What are the routes of admin. of Scopolamine? What is it distribution? How is it metabolized?

PO, IM, IV, SC, eyedrops,patches

Crosses BBB

Metabolism similar to atropine

14

What are the routes of admin. of Ipatropium? Absorption? What is it distribution? ?

Only inhaled

Poorly absorbed, doesn't cross membranes well

Doesn't cross BBB

15

What is the effect of muscarinic antagonists on the CNS? What are some therapeutic uses? How do scopolamine and atropine differ in their effects?

Atropine stimulates CNS and causes hallucinations. Scopolamine depresses CNA (drowsiness, euphoria). Antitremor in parkinsons.

Sleeping pills (scopolamine)

Motion sickness (scopolamine)

Parkinson's

Sedation prior to surgery (scop)

Sedation during labor (scop-truth serum)

16

What is the effect of muscarinic antagonists on the eye? What are some therapeutic uses?

Dilation and paralyzes accomodation (looking close) (cycloplegia).

Opthalmalgic use (eye exams)

mydriatics and cycloplegics

17

What is the effect of muscarinic antagonists on the respiratory system? SM in general? glands in general? What are some therapeutic uses?

SM in general is relaxed, so bronchioles are relaxed (opening airway). Gland secretions are inhibited, so resp tract gland secretion is inhibited.

Inhibition of secretions

Reduce or prevent vagal overactivity

Cold Remedies

Asthma

COPD

18

What is the effect of muscarinic antagonists on the Heart/BP? What are some therapeutic uses in CV system?

In heart, low doses--->slight bradycardia (due to vagal stimulation in CNS), but most tachycardia via blockage of SA node. No great effect on BP.

Atropine always in crash cart. After MI, it combats symptoms such as

Sinus Bradycardia

SA Arrest and SA Block

19

What is the effect of muscarinic antagonists on the GI Tract? Sphincters in general? What are some therapeutic uses?

Since SM is relaxed-->less motility and tone, less gall bladder secretion. Sphincters are blocked in general.

Inflammation (IBS and acute enterocolitis)

Travelers diarrhea

20

What is the effect of muscarinic antagonists on the bladder? What are some therapeutic uses?

Urinary incontinence in elderly using tolterodine and oxybutyin

Child enuresis

21

What are some side effects of Atropine and other muscarinic antagonists in order of when they appear with increasing doses

Less salivation (dry mouth), inhibition of sweating, Micturition speed lowered, acceleration of heart, dilation of pupil, blurring of vision, speech disturbed, headache, restlessness and fatigue, hot skin, difficulty swallowing, reduced peristalsis, ataxia, hallucinations, delirium, death.

22

What are atropine, scopolamine, ipratropium, tolterodine, and oxybutynin primarily used for? Why do some have less side effects?

Atropine-counteract muscarinic toxicity, mydriatic, reversal of bradycardia or cardiac arrest

Scopolamine-motion sickness

Ipratropium-Bronchodilator in asthma and copd

tolterodine/oxybutynin-reduce involuntary voiding.

The last 3 are used locally and have poor penetration across membranes and thus have fewer side effects.

23

What are the two types of cholinesterases? Where are they primarily located? What is their substrate selectivity? How are indirect ACh agonists different from direct?

AChE: Located in all cholinergic synapses (therefore it works in CNS and Neuromuscular synapses as well unlike the direct agonists). Specific for ACh.

Plasma Cholinesterase: Located in plasma (also intestines, etc.). Selective for ACh, succinylcholine, and local anesthetics

24

What are 7 Reversible AChE inhibitors?

Edrophonium, Physostigmine, Neostigmine, Pyridostigmine, Tacrine/Donepezil (alzheimers), demecarium (opthalmic)

25

What is edrophonium? How is it administered/distribution? How is it excreted? Which site does it bind to? How long does it stay on the enzyme/what type of interaction? How is it used?

IM or IV

No CNS Effects

Excreted in Urine

Non-covalent/very rapidly unattaches/binds to anionic site

Used to differentiate between myasthenia crisis and excess cholinergic excitation.

26

What are tacrine and donepezil used for? How are they administered? How are they metabolized? Distribution?

PO

Enter CNS

P450

Treatment of alzheimers

27

How is physostigmine administered? How is it hydrolyzed? How is it used clinically? How is it different from neostigmine?

IM, IV, Opthalmic

Hydrolyzed by ChE

Different in that it enters CNS

applied topically to treat wide angle glaucoma

Treatment of CNS toxicity due to anticholinergic poisoning

28

How is neostigmine administered? How is it hydrolyzed? How is it used clinically?

IM, IV, SC, PO

Hydrolyzed by ChE

Drug of choice for paralytic ileus and atony of bladder after surgery

Rx and diagnosis of myasthenia

Reversal of NM Blockade

29

How is Pyridostigmine administered? How is it hydrolyzed? How is it used clinically?

IM, IV, PO

Hydrolyzed by ChE

Pretreatment to reduce risk of mortality due to nerve gases

Rx of myasthenia

Reversal of NM Blockade

30

What are the 3 main drugs we use? Where do they bind to AChE? How long are they bound to AChE?

Physostigmine, Pyridostigmine, Neostigmine,

Bind to both anionic and esteric sites

2-8 hours



31

What are two types of Organophosphate AChE inhibitors that are irreversible that are used clinically (not totally irreversible)? What are they used to treat? What other organophosphate AChE inhibitors are there and what are there purposes? Where do they bind AChE? How are the organophosphates absorbed

Isoflourophate and Echothiophate-treats glaucoma

Nerve Gases-Serin and Soman

Insectisides-parathion

They bind to esteric site

They are absorbed well through skin, lung, gut and conjuctiva





32

What side effects are common to all AChE inhibitors including the clinically used ones? What side effects are caused by organophosphates (mainly Nicotinic and CNS effects)?

Muscarinic Effects: ciliary spasm, Miosis, bronchoconstriction, bradycardia, increased bronchial secretion, sweating, salivation, hypotension, involutary defecation and urination

Nicotinic effects: weakness, muscle fasciculation (twitching), muscular paralysis (too much ACh)

CNS: Confusion, ataxia, convulsions, Coma, respiratory depression, CV

33

What are general clinical uses of AChE inhibitors? What is myasthenia gravis? What can be given to combat the muscarinic side effects of these drugs?

Used to reverse NM blockade after surgery

Used to get bladder and GI going

Used to treat glaucoma (ectothiopate and Demecarium)

Used to treat Myasthenia gravis (PO Neostygmine and Pyridostigmine). Pyridostigmine lasts a little longer than neostigmine. The muscarinic side effects wear off with time, but atropine can be given. The cholinergic effects can become excessive leading to paralysis. To test between excessive cholinergic effects or myasthenia crisis, physostigmine is used. If it gets better=crisis, worse=excessive cholinergic.

Myasthenia gravis is autoimmune in which lymphocytes destroy nicotinic cholinergic receptors.

34

What can be used to treat poisining by organophosphates (nerve gasses or insectisides)? How is it made most effective? How does it work?

Atropine can help with the muscarinic effects.

To help with the nicotinic effects, Pralidoxime is used. It binds to anionic site and then binds to the organophosphate stronger than the enzyme does and thus releases it.

It should be used within a few hours b/c the bound enzymes can age.

35

What does demecarium used to treat? How is it administered

Glaucoma

Opthalmic

36

What happens at a ganglionic synapse?

ACh is released.

ACh mainly binds to a nicotinic receptor causing a F-EPSP (fast)

It can also bind to a muscarinic receptor on the postsynap. cell causing an S-EPSP (slow)

It can also bind to a muscarinic receptor on an interneuron causing it to releasing dopamine which binds to a dopamine receptor on the postsyn. cell causing an S-IPSP (inhibitory)...sometimes the interneuron isn't used and the ACh binds directly to a muscar. receptor on the post synap cell causing an S-IPSP.

Lastly, Autacoids from the blood stream (angiotension, etc.) can bind to an autacoid receptor on the post synap cell causing a late S-EPSP (very slow).

37

What is the main ganglionic stimulant? What are the sites of action of it and what does it do there?

Nicotine

CV System-Increases BP and heart rate due to release of NE and E from adrenal medulla and nerves

GI Tract-increase tone and motor activity

Exocrine glands- increased salivation and bronchial secretion

respiratory system-stimulates respiration

skeletal muscle-increase muscle fasiculations

CNS-stimulation, release of vasopressin, ADH, Emesis...increase in psychomotor, memory consolidation, attention, sensorimotor, and cognitive

Autonomic ganglia-increased depolarization

38

What are the withdrawal symptoms of nicotine?

craving, irritability, anxiety, anger, restlessness, difficulty concentrating, impatience, increased appetite, insomnia

39

What is the absorption, distributino, and excretion of nicotine?

Well absorbed from all tissues (especially oral, lungs, GI). Quickly is absorbed and distributes to brain. Metabolized P450 in liver, but also in kidney and lung and excreted in kidney

40

What are some possible ways to help people stop smoking?

Withdrawal symptoms, diagnose other conditions, treat other conditions, reduce drug craving, prevent relapse

Nicotine gum, inhalers, patches, nasal sprays, verinicline, antidepressants

Psychotherapy

41

What does verinicline do? How does it work? What are its side effects

partial agonist of nicotinic receptor.

Blocks nicotine from binding but activates the receptor much less than nicotine

Sx=GI related, altered dreams, but generally well tolerated.

42

What mechanism of action do the clinically useful ganglionic antagonists use? What is the prototype drug? What are two other drugs? What can these drugs be used for? Why aren't they used much today? What are they used for sparingly today?

They are competitive inhibitors of Acetylcholine, preventing it from binding.

Prototype is Hexamethonium

Trimethaphan and mecamylamine can be used for vasodilation, lower bp.

They are only used in emergencies to lower BP today because of severe sx.

43

What are the side effects of ganglionic antagonists due to ganglionic blockade of organs and tissues under parasymp tone and symp tone?

parasympathetic: Tachycardia, mydriasis, cycloplegia, decrease in tone and motility of GI tract (constipation), urinary retention, dry mouth, decrease in secretion of sweat glands

symp: decrease in contractile force of heart, vasodilation, increase in peripheral blood flow, hypotension, pooling of blood in veins, decrease in venous return, decrease in cardiac output

44

How does BoTOX work? What are some clinical uses?

Blocks the SNARE system from releasing ACh.

Used to treat ocular conditions( spasms, cross eyes) and other muscle spasms (spasm of lower esophogeal sphincter, achalasia). Used dermatologocialy (hyperhidrosis, or excessive sweating, on palms and armpits AND facial wrinkles)

45

What are 3 types of NM blocking agents? What is the prototype of each?

BoTox-itself

NOndepolarizing agents (competitive agents)-curare

Depolarizing agents-succinylcholine, the only one

46

How do nondepolarizing agents work? How can they be combated? How do the different drugs differ?

They are basically competitive antagonists of ACh at the receptor. They block them from binding. Therefore, they can be overcome by adding more ACh through the use of AChE inhibitors (Edrophonium, Neostigmine, Pyridostigmine).

They differ basically in how long the effect lasts.

47

Which non depolarizing NM blockers have a short to intermediate duration b/c they are either metabolized by plasma ChE or spontaneously in order from shortest to longest?

Mivacurium, Atracurium, Cisatracurium

48

Which non depolarizing NM blockers has an intermediate duration due to largely hepatic elimination?

Vecuronium

49

Which non depol. NM blockers have a long duration due to primarily having renal elimination?

Pipercurium and Tubocurarine

50

What is the only depolarizing agent? How does it work? What is its duration? Its speed of onset? Can it be counteracted with more Ach

Succinylcholine.

Its duration is very short and so is speed of onset and thus is used for short procedures

It is basically a partial agonist of ACh. it causes the initial depolarization and thus some fasiculations but then it doesn't repolarize b/c it isn't broken down in the NM junction by AChE and the enzyme that breaks it down isn't there. B/c it doesn't repolarize, nothing else can stimulate the motor end plate during that period.

Can't be counteractedw ith more ACh.

51

What do the competitive NM blockade agents do to the respiratory system? What is their onset and duration? What do they do to the CNS? What are the side effects of Tubocurarine, gallamine, pancuronium? What are the drug interactions of them?

Competitive:

Resp. system: depression

Onset: 1-2 minutes

duration: 30-60 minutes

No CNS Effect

SX Tubocurarine: Hypotension, ganglionic blockade, bronchospasm, histamine release

SX Gallamine: Tachycardia, atropine like effect

SX Pancuronium: Very little side effects, some high BP

Other SX: block autonomic ganglia at high doses,

Drug interactions: Antagonized by AChE inhibitor, enhanced by some general anesthetics and certain antibiotics (NM Blockade)

52

What does succinylcholine do to the respiratory system? What is their onset and duration? What do they do to the CNS? What are the side effects of Tubocurarine, gallamine, pancuronium? What are the drug interactions of them?


Resp. system: depression

Onset: 20-40 sec.

duration: 2-5 minutes

No CNS Effect

SX: Intraocular pressure, muscle soreness, liberates potassium from cell-->cardiac arrythmias, prolonged apnea, Malignant hyperthermia

Drug interactions: Not antagonized by AChE inhibitors

53

What causes malignant hyperthermia? What drug is used to treat it? How does it work?

Hereditary impairment of ability of SR to sequester Ca2+--->massive muscle contracction, lactic acid, potass. in plasma, increase in body temp.

Treated with datrolene to decrease release of calcium.

54

What are NM Blockers used for clinically?

endotracheal intubation

muscle relaxation in surgery

maintain controlled ventillation