Pharm Topic 8: Cholinergic Agonists And Antagonists

Front 1

Types of muscarinic agonists

Back 1

1) Choline esters:
-Acetylcholine, methacholine, bethanechol
2) Alkaloids:
-pilocarpine, muscarine

Front 2

General actions of Ach at muscarinic receptor sites

Back 2

1) Stim of exocrine glands
2) Stim of SM
3) Relaxation of sphincters
4) Vasodialation
5) Decreases HR, slows conduction, increases refractory period.
6) Causes miosis and accomodation

Front 3

When are muscarinic agonists contraindicated

Back 3

1) Asthma
2) Coronary insufficiency
3) peptic ulcer
4) Obstruction of GI and Urinary tract

Front 4

Name choline ester examples and what theyre used for

Back 4

1) Acetylcholine
2) Methancholine
3) Carbachol
4) Bethanechol

All can be used as miotics or to treat wide angle glaucoma.
Bethanechol is used to stim GI motility and contraction of bladder.

Front 5

Bethanechol (drug type, administration, soluability, receptors, function)

Back 5

Muscarinic agonist (choline ester).
-Administered orally or Sub Q
-Poor lipid soluability and does not Cx BBB
-Favors M3 receptors (SM and Glands)
-Decreases bladder capacity and increases tone of detrusor muscle helping patients void. Also stim GI, often used after surgery

Front 6

Is bethanechol hydrolyzed by Ach esterase?

Back 6

No, giving it longer half life.

Front 7

Muscarinic agonist side effects

Back 7

-salivation
-lacrimation
-nausea and vomiting
-headache and visual disturbanes
-bronchospams
-bradycardia
-hypotension
-diarrhea
-urination
-increased sweating
-pupil constriction
-cns activation

Front 8

Pilocarpine (drug type, administration, soluability, receptors, function)

Back 8

Muscarinic Agonist (Alkaloid)
-Administered via eyedrops, contacts, gels ect. or orally
-well absorbed, good lipid soluability
-muscarinic receptors (though has some effect on nicotnic)
-Used for narrow and wide angle glaucoma, stims sweat and saliva.

Front 9

Name the anti muscarinic drugs (belladonna alkaloids)

Back 9

1) Atropine
2) Scopolamine - For motion sickness
3) Ipratroprium - For asthma attack
4) Tolterodine - For bladder effects
5) Oxybutin - For bladder effects

Front 10

Atropine/scopolamine (identity, administration, absorbtion, excretion)

Back 10

Muscarinic Antagonist:
-Oraly, IM, IV, Sub Q, eye drops
-Well absorbed and distributed. Crosses BBB
-40% metabolism 60% excretion

Front 11

Effects of muscarinic antagonists (eye, heart, BP, SM, Glands, CNS)

Back 11

Eye - Dilation, no accommodation, ^ intraocular pressure.
Heart - Low dose cause brachy, high dose causes trachy
BP - no effect
Sm - Relax
Glands - Inhibits exocrine gland secretion. Lack of sweating increasses body temp, pancreas not effected.
CNS - Atropine is a stimulant while scopolamine is a depressant.

Front 12

Ipratropium (identity, administration, absorbtion)

Back 12

Muscarinic Antagonist:
-Administered via inhalation, Poorly absorbed, does not cross BBB
Used for asmtha attacks

Front 13

What are antimuscarinics therapeutically used for?

Back 13

CNS - Sleeping pills, motion sickness, parkinsons, sedation pre surgery, sedation for labor
Eye - Eye exams, mydriatics and cyclopegics (no accomodation)
Resp - Decrease secretions, asthma, COPD, cold
Heart - Brachycardia, SA arrest, SA block post MI
GI - IBS, Diarrhea
Bladder - Incontinence, Enuresis (bed wetting)
Also useful during a cholinergic crisis (wont effect nicotinic though) and prior to surgery anesthesia to reduce mucus and muscle spasm.

Front 14

Most at least sensitive effects of atropine

Back 14

Most - Salivation
Least - Accommodation

Front 15

What is the mech by which belladona alkaloid muscarinic antagonists work

Back 15

Competitive inhibition, therefore will only counteract stimulation if there is pre existing stim to block.

Front 16

Acetylcholineesterase vs Plasma choline esterase

Back 16

Ach esterase - Located in synapse, selective for Ach
Plasma choline esterase - Located in plasma (non-neuronal), Selective for Ach, Succinylcholine, and local anesthetics

Front 17

Main therepeutic targets of anti Ach esterase drugs (organ systems)

Back 17

Eye, intestine, and NMJ

Front 18

Which Ach esterase inhibitors do not cross the BBB

Back 18

Edrophonium and neostigmine

Front 19

Sarin and Soman

Back 19

Nerve gas, covalently irreversibly binds to Ach Esterase. Well absorbed through skin, lungs, gut, conjunctiva

Front 20

What type of receptors are present in ganglionic neurons

Back 20

Both nicotinic and muscarinic

Front 21

In ganglionic transmission, what receptor is responsible for the fast EPSP and what drugs block it.

Back 21

Nicotinic receptor causes fast EPSP. Blocked by:
-hexamethonium
-mecamylamine
-trimethapan

Front 22

In ganglionic transmission, what receptor is responsible for the slow EPSP and what drugs block it.

Back 22

Muscarinic receptor causes slow EPSP. Blocked by atropine.

Front 23

In ganglionic transmission, what receptor is responsible for the slow IPSP and what drugs block it.

Back 23

Muscarnic receptor stim found on an intermediate cell (SIF cell) causes dopamine which causes the slow IPSP. This can be blocked by:
-atropine
-adrenoceptor antagonists
-dopamine antagonists

Front 24

SIF cells

Back 24

Small intensely flourescent cells. Cells which flouresce positivley for catecholamines near autonomic ganglia. Can either be a true interneuron or in close proximity to blood vessels. Stim via muscarninic receptors causes dopamine and the slow IPSP on autonomic ganglion neurons.

Front 25

Effects of nicotine (auto gang, adrenergic nerve terminals, NMJ, CNS, cardiovasc, GI, Exocrine)

Back 25

Auto gang - Stim of all auto gangs followed by blockade of transmission.
Adrengergic nerve terminals - causes release of nori
NMJ - Similar to gang but not as sensitive
CNS - increase respiration reflex, vomiting, ADH release and tremors in large doeses. Causes release of dopamine and increased cognitive function.
Cardiovasc - Increase BP and HR b/c sympa stim.
GI - Increased tone and motility due to para stim.
Exocrine - increase salivation and bronchial secretion.
All effects can be tolerized except cardivasc.

Front 26

Nicotine absorbtion, distribution, and excretion

Back 26

Absorption - Well absorbed from all tissues. 66-77% if dont inhale, 90-98 if you do.
Distribution - Distributes well everywhere and crosses BBB
Excretion - 80-90 % is metabolized by liver, kidney, lung and excreted by kidney.

Front 27

Nicotine Polarcrilex

Back 27

Nicotine gum.

Front 28

Transdermal nicotine

Back 28

Nicotine patch. Better than gum b/c more sustained concentration and fewer side effects.

Front 29

Clonidine

Back 29

A2 agonist to reduce withdrawal effects of nicotine, opioids, and cocaine.

Front 30

Mecamylamine

Back 30

Nicotine antagonist. Lots of side effects, not used often.

Front 31

Ganglionic antagonist receptors and examples

Back 31

Compete against Ach at nicotinic receptors on autonomic ganglia:
-Hexamethonium
-Mecamylamine
-Pentolinium
-Trimethaphan

Front 32

Effects of ganglionic antagonists in general and at organ level.

Back 32

Reduce whatever is the dominant tone of the organ system. Drug will cause...
Para:
Atrium/SA node - Tachycardia
Eye - Mydriasis and cycloplegia
GI - Constipation
Bladder - Uirinary retention
Sweat and salivary glands - decreased secretion
Sympa:
Ventricles - Decrease contractile force
Aterioles - Vasodialation, hypotension, and increased flow
Veins - Vasodialation, pooling of blood, decrease in venus return and cardiac output.

Front 33

Therapeutic uses of ganglionic antagonists

Back 33

1) Hypertension
2) Controlled Hypotension
3) Autonomic hyperreflexia

Front 34

Echothiophate

Back 34

Irreversibly binds to Ach esterase. Used to treat glaucoma

Front 35

Clinical use of Botox

Back 35

Eyes:
-strabismus (cross eyes)
-Blepharmospasm (spaz winking)
-Megi's synrome (dystonia of facial/oromandibular muscles
Muscles:
-Adductor spasmodic dysphonia
-Cervical dystonia
-Spasm of lower esophageal sphincter (ccs) Achalasia
Derm:
-Wrinkles
-Hyperhidrosis of palms and axilla

Front 36

Nondepolarizing antagonists of Ach at NMJ (examples and reversal drugs)

Back 36

1) Curare (Tubocurarine)
2) anything ending in -ium.
Works via competitive inhibition and can therefore be overcome by more agonist.
Treated with Neostigmine, edrophonium, and pyridostigmine to block Ach esterase.

Front 37

Depolarizing Ach blocker examples and mech

Back 37

Only drug is succinylcholine.
Succinylcholine binds the nicotinic receptors at the NMJ like Ach but is not metabolized by Ach esterase (only psuedo Ach esterase which is not found in high [] at NMJ), Leading to prolonged depolarization making it unresponsive to further stimuli (phase 1). In phase 2, membrane repolarizes but is unresponsive. While Ach esterase inhibitors make phase 1 worse, they can overcome phase 2.

Front 38

Succinylcholines effect on Autonomic ganglia, cardiac muscarinic receptors, and histimine release.

Back 38

Stims auto gang and cardiac muscarinic receptors. Causes slight histamine release.

Front 39

clinical uses of depolarizing and non depolarizing Ach blockers

Back 39

1) General anesthesis in endotrach tubes and during surgery
2) During electroshock therapy to prevent muscle contraction
3) To prevent muscle spasms in convulsive disorders
4) Diagnose MG (only competitive blockers)

Front 40

Competitive Ach blocker side effects and drug interactions

Back 40

SE - hypotension, ganglionic blockade, bronchospasm, histamine release.
DI - Antagonized by Ach esterase agents. Enhanced by general anesthetics and some antibiotics (streptomycin, neomycin, and polymyxin)

Front 41

Depolarization Ach blockers side effects and drug interactions

Back 41

SE - Increased intraoccular pressure, muscle soreness, liberates potassium from cells which can lead to cardiac arrhythmias, prolonged apnea
DI - Not antagonized by Ach esterase bockers via Phase 1

Front 42

Malignant hyperthermia and its treatment

Back 42

Occurs after use of general anesthesia and succinylcholine on people with the genetic predisposition for the disease. Cant get calcium back into sarco reticulum causing sustained muscle contraction, lactic acid buildup, acidosis and increased body temp.
Treat by cooling patient, correcting acidosis and IV injection of Dantrolene (dantrium) to reduce calcium release.

Front 43

Clinical problems associated with Neuromuscular blockers

Back 43

1) Potentiated by inhaled anesthetics (Isoflurane)
2) " " aminoglycosides and calcium channel blockers
3) Can block auto gang at higher doses
4) Respiratory paralysis

Front 44

Dantrium (mech, clinical uses, side effects)

Back 44

Reduces Ca+ release from sarco reticulum and blocks contraction.
Used in cerebral palsy, MS, and malignant hypothermia.

Front 45

Effect of a muscarinic agonist on blood vessels.

Back 45

Cause Vasodilation (even though there is no para innervation, there are receptors). Does this 2 ways:
1) Activation of muscarinic receptors on sympathetic nerves decreases nori release.
2) Muscarinic antagonists cause secretion of relaxants from endothelial cells such as NO.

Front 46

Effect of Pilocarpine on the cardiovascular system

Back 46

May cause hypertension and tachycardia from its nicotinic actions in the sympathetic ganglia and adrenal medulla.

Front 47

Spectrum of sensitivity to muscarinic antagonists

Back 47

1) Salivary and bronchial, and sweat secretions
2) Pupil, Cilliary muscle, and heart
3) Bladder and GI
4) Gastric secretions

Front 48

Adverse effects of Muscarinic antagonists

Back 48

-Dry mouth
-blurred vision
-tachycardia
-constipation
-urinary hesitancy

Front 49

What are the clinical features and diagnosis for atropine poisoning?

Back 49

Present with dialated pupils, tachycardia, hot skin, and fever.
Diagnose by giving methacholine. If you dont get brachycardia, sweating, GI distress, it was atropine.

Front 50

Edrophonium

Back 50

Reversible, non-covalent Ach esterase inhibitor.
Rapid onset, short duration.
No CNS effects. Acts at NMJ and actually stimulates the end plate.

Front 51

Physostigmine

Back 51

Reversible, covalent Ach esterase inhibitor.
Medium onset and duration.
Used for acute angle glaucoma. Effects CNS

Front 52

Neostigimmine

Back 52

Reversible, covalent Ach esterase inhibitor.
Medium onset and duration.
Activates GI and bladder post surgery. Diagnoses MG, reversal of NM block.

Front 53

Pyridostigmine

Back 53

Reversible, covalent Ach esterase inhibitor.
Medium onset and duration.
Treats MG, pre-treatment to nerve gas, reverses NM block

Front 54

Echothiophate

Back 54

Irreversible covalent Ach esterase inhibitor.
Long duration, highly toxic.
Used to treat Glaucoma

Front 55

Isophlorphate

Back 55

(DFP). Irreversible covalent Ach esterase inhibitor.
Long duration, highly toxic.
Used to treat Glaucoma

Front 56

Parathion

Back 56

Ireversible Ach esterase inhibitor.
Well absorbed through skin and gut.
Is an insecticide.

Front 57

How do you treat anti-ach esterase poisoning?

Back 57

With atropine for the muscarinic effects and pralidoxime for the nicotinic.

Front 58

Botulinium mech

Back 58

Prevents vessel fusion and Ach secretion at NMJ.