L3- Muscarinic Receptors Flashcards Preview

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Flashcards in L3- Muscarinic Receptors Deck (23):
1

M1 and M3 Receptor Locations, G proteins and Mechanisms

M1 - Nerves

M3- Glands, SM, Endothelium

Gq protein linked

IP3 and DAG cascade

2

M2 Receptor Location, G protein and Mechanisms

Located in Heart, Nerves, and SM

Gi Potein Linked

Inhibition of cAMP production and activation of K+ Channels

3

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

#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

4

Activation of Muscarinic Receptors in Endothelium of BV

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

5

Activation of Sphinctors!

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

6

What are the names of the Muscarinic Agonists?

Carbamylcholine (Carbachol ... more Nicotinic than Muscarinic)

Acetyl-Beta-Methylcholine (Methacholine)

Bethanechol

7

Describe general characteristics of the synthetic muscarinic agonists?

ALL are CHARGED and so do NOT cross BBB or membranes

Non-descriminatory and non-selective

8

What is the only non-charged Muscarinic Agonist?

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

9

What are the symptoms of Parasympathetic Overstimulation?

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

10

What are clinical uses for Cholinomimetic Agonists?

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

11

What are the contraindications for Muscarinic Agonists?

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

12

What are the muscarinic Antagonists?

ATROPINE!! - naturally occurring alkaloid Cyclopentolate and Tropicamide

Glycopyrrolate Scopolamine Pirenzepine

Urinary - tolterodine and Darifenacin

13

Which Muscarinic Antagonists are un-charged?

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

14

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

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

15

What are the symptoms of Muscarinic Receptor Blockade?

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

16

Effects of Scopolamine?

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

 

Prevents motion sickness 

17

What are Muscarinic Antagonists used for in the pulmonary system?

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!!!

18

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

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

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

19

How are Muscarinic Antagonists used in Anesthesia?

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

20

What antimuscarinics are used in the eye?

Tropicamide! Shortest acting anti-muscarinic to cause dilation

Next is cyclopentolate

21

Motion sickness?

Prophylactically give Transdermal patch of Scopolamine!!!

22

Contraindications for use of Muscarinic Antagonists?

Narrow-Angle Glaucoma Cardiac Arrhythmias Chronic Lung Disease

23

Mushroom Poisoning and Cholinergic OD?

Treat with Atropine!! Treat SLUDGE with Atropine!