L3- Muscarinic Receptors

Question 1

M1 and M3 Receptor Locations, G proteins and Mechanisms

Answer 1

M1 - Nerves

M3- Glands, SM, Endothelium

Gq protein linked

IP3 and DAG cascade

Question 2

M2 Receptor Location, G protein and Mechanisms

Answer 2

Located in Heart, Nerves, and SM

Gi Potein Linked

Inhibition of cAMP production and activation of K+ Channels

Question 3

Action of M2 and M3 receptors in the gut Smooth Muscle cells

Answer 3

M3 receptors in gut >> #M2 receptors

M3 activation gets Gq to activate Phospholipase C and cleave IP3 and DAG and IP3 opens Calcium channels in SR for direct muscle contraction

M2 activation inhibits relaxation by blocking Adenylate Cyclase and therefore decreasing cAMP levels (cAMP inhibits contraction) therefore blocks relaxation

Question 4

Activation of Muscarinic Receptors in Endothelium of BV

Answer 4

No parasympathetic nerve stimulation there, but circulating agonists can activate M3 receptors in blood vessels and cause release of NO which causes vascular Dilation

Question 5

Activation of Sphinctors!

Answer 5

Predominant tone in sphinctors is adrenergic but pre-ganglionic parasympathetic neurons synapse on cholinergic neurons in the spinctor that activate inhibitory interneurons and lead to relaxation

Activation of M1 through intermediate neuron causes relaxation

Question 6

What are the names of the Muscarinic Agonists?

Answer 6

Carbamylcholine (Carbachol … more Nicotinic than Muscarinic)

Acetyl-Beta-Methylcholine (Methacholine)

Bethanechol

Question 7

Describe general characteristics of the synthetic muscarinic agonists?

Answer 7

ALL are CHARGED and so do NOT cross BBB or membranes

Non-descriminatory and non-selective

Question 8

What is the only non-charged Muscarinic Agonist?

Answer 8

Pilocarpine!!! Natural Alkaloid made by plants that is non-charged and can penetrate BBB

Question 9

What are the symptoms of Parasympathetic Overstimulation?

Answer 9

SLUDGE Salivation, Lacrimation, Urination, Deffecation, Increased GI motility, Emesis DUMBELS - better bc includes B which is Bradycardia and Broncorrhea (most pts die from Broncorrhea)

Also Miosis and constricted pupils, ataxia, slurred speech and restlessness

Question 10

What are clinical uses for Cholinomimetic Agonists?

Answer 10

Eyes - use Pilocarpine or Carbachol to constrict sphinctor muscles in narrow angle glaucoma

GI - Bethanechol used for post-operative ileus, congenital megacolon, Esophageal reflux disease

GU - used to increase urinary retention and tone of Detrussor

Salivary gland - use pilocarpine topically to treat xerostomia

Question 11

What are the contraindications for Muscarinic Agonists?

Answer 11

Ashtma and COPD

Hyperthyroidism (dont want to compromise rhythmicity of heart)

Coronary Insufficiency (M2 receptors leads to Bradycardia)

Peptic Ulcer (M1 for gastric secretions)

Mechanical Obstruction of GI or GU

Peritonitis

Question 12

What are the muscarinic Antagonists?

Answer 12

ATROPINE!! - naturally occurring alkaloid Cyclopentolate and Tropicamide

Glycopyrrolate Scopolamine Pirenzepine

Urinary - tolterodine and Darifenacin

Question 13

Which Muscarinic Antagonists are un-charged?

Answer 13

Scopolamine - crosses BBB!!! Atropine is also uncharged but crosses BBB slowly

Question 14

Which Muscarinic Antagonists have Receptor Specificity - what is it and how is it used?

Answer 14

Pirenzepine - M1 affinity and used to treat peptic ulcers

Tiotropium is M1/M3 specific used as an aerosolized spray in the lung

Tolterodine and Darifenacin are M3 specific and used for detrussor muscle in bladder

Question 15

What are the symptoms of Muscarinic Receptor Blockade?

Answer 15

Opposite of SLUDGE Tachycardia, Atropine Flush and vasodilation, improved respiration bc bronchiole dilation and decreased secretions reduced GI motility and glandular secretions dilation and cycloplegia

Question 16

Effects of Scopolamine?

Answer 16

Uncharged and Lipophillic so can cause Amnesia, Euphoria and dreamless sleep at low doses

Prevents motion sickness

Question 17

What are Muscarinic Antagonists used for in the pulmonary system?

Answer 17

Ipratropium Bromide can be used in cold to open bronchi

Rhinitis can be relieved (but really just use anti-histamines)

***Tiotropium Bromide aerosolized and M1/3 selective to dilate bronchioles and reduce secretions WITHOUT THICKENING THEM - used for chronic bronchitis and emphysema!!!

Question 18

What / how are muscarinic antagonists clinically used in GU and GI systems?

Answer 18

Used to stop intestinal hypermotility and non-infectious diarrhea = Glycopyrrolate

M3 selective Darifenacin (Enablex) or Tolterodine (Detrol) used for Overactive Bladder

Question 19

How are Muscarinic Antagonists used in Anesthesia?

Answer 19

Pre-anesthesia give Glycopyrrolate (charged) or Atropine (uncharged) to stop salivation/resp tract secretions for intubation

Recover from Anasthesia used to recover paralyzed muscle function (ex. Pancuronium non-depolarizing Nicotinic block reversed with Neostigmine anti-cholinesterase but need to balance parasympathetic with an antimuscarinic!) so give glycopyrrolate)

Scopolamine gives amnesia

Question 20

What antimuscarinics are used in the eye?

Answer 20

Tropicamide! Shortest acting anti-muscarinic to cause dilation

Next is cyclopentolate

Question 21

Motion sickness?

Answer 21

Prophylactically give Transdermal patch of Scopolamine!!!

Question 22

Contraindications for use of Muscarinic Antagonists?

Answer 22

Narrow-Angle Glaucoma Cardiac Arrhythmias Chronic Lung Disease

Question 23

Mushroom Poisoning and Cholinergic OD?

Answer 23

Treat with Atropine!! Treat SLUDGE with Atropine!