Ganglionic level neurotransmitter for

Symp

&

Parasymp

post ganglionic pre synaptic neurotransmitters

Symp

&

Parasymp

Symp - Norepi

Parasymo - Ach

M1, M3 & A1

PLC

IP3 (increase in ca2+) - DAG (protein kinase C)

M2 & A2

Decrease in Adenylyl Cyclase

Decrease in cAMP - Decrease in protein Kinase A

B1, B2 & B3

Increase Adenylyl Cyclase

Increase cAMP

Increase Protein Kinase A

M2

coupled & response

Gi 

 Decrease in AC

Decrease in cAMP

Decrease in HR

M3

coupled & response

Gq

PLC & IP3-DAG

smooth muscle contraction and gland secretion ...

Urination, bronchospasm, lacrimation

Pupil constriction - Miosis thus increased flow of AH

B1

Coupled & response

Gs

Increase in AC & cAMP

Increases HR

B2

coupled & response

Gs

Increase in AC & cAMP

smooth sucle relaxation 

bronchodilation, urinary retention, uterus relaxation

B3

coupled & response

Gs

Increase in AC & cAMP

Fat lipolysis

A1

coupled & response

Gq

PLC & IP3 - DAG

VASOCONSTRICION

*** remember if you want to vasodilate you have to block this receptor!*

Pupil dilation (mydriasis)

A2

coupled & response

Gi 

Decrease in AC & cAMP

Reduces the release of Norepi leading to bradycardia

Decreased insulin release

1.Hemicholinium stops initial choline from being transformed into acetyl-CoA+Choline

2.Blocked from going in to mobile via vesamicol

3.Vesicle blocked from docking via botulimoum

1.Metyrosine blocks tyrosine from converting to DOPA

2.Stopped from entering the mobile poos via reserpine

3. Vesicle blocked from docking via bretylium & guanethidine (increases docking via amphetamine)

4. Block Re-uptake pump via amphetamine, cocaine and TCA's

binds to endothelium of the blood vessel releasing NO.. ONLY

if endothelium layer is intact

Bethancol 

1. class of drug

2. Uses

1. Direct acting cholinergic agonist

2. Paralitic ileius

2. Atony of the Bladder

Symptoms of Atony of the bladder

how is it treated?

non obstructive urinary retention, usually seen in patients with neurological problems and post opp. patients

Pilocarpine

1. class of drug

2. Uses

1. Directs acting cholinergic agonist

2. Glaucoma & Sjogrens syndrome

** lipid soluble and penetrates the cornea very well**

Sjogrens syndrome sympotoms

how is it treated?

How do indirect acting cholinergic agonists work?

what are the classes of indirect acting cholinergic agonists?

1. They block the AchE enzyme from breaking down Ach at the synaptic cleft, thus increasing the amount of Ach avaliable

2.There are reversible and irreversible types

Neostigmine

Physostigmine

Pyridostigmine

Edrophonium

Tacrine

Danopezil

Ecothiophate

Malathion

Parathion

Sarin

reversible indirect acting cholinergic agonists

Neostegmine

1.class of drug

2.use

1. reversible indirect acting cholinergic agonist

2. Acute cases of MG - given via IV

Phyridostegmine

1. Class of drug?

2. Use

1. Indirect acting reversible cholinergic agonist

2. longer duration that nenostegmine, thus given for long term/ maintenance - given orally

Edrophonium

1. Class of drug

2. Use

1. Reversible indirect acting cholinergic agonist

2. Shortest duration of action (5 mins) thus used in the Tensilon test to check for MG - differentiate cholinergic crisis (excessive drug therapy) from myashtenic crisis (insufficient medication)

MG is an autoimmune disease with autoantibodies directed against post synaptic Ach receptors - WEAKNESS WORSENS WITH REPEATED CONTRACTIONS - associated with thymic hyperplasia and thymomas

Eaton-Lambert syndrome - autoantibodies directed against the presynaptic calcium channels  leads to a decrease in ACh release - extra-occular muscles are spared - WEAKNESS IMPROVES WITH REPEATED CONTRACTION - commonly a paraneplastic syndrome of small cell lung cancer

in the case of Mg - patient will get better

in pt with cholinergic crisis the pt will get worse

Tacrine,

Rivastigmine

Donepezil

& NMDA antagonists - Memantine (blocks glutamate at the NMDA receptors)

They cross the bbb

symptoms of OP poisioning

what is responsible for these symptoms?

miosis, blurred vision, bradycardia ,salivation, sweating, urination (urinary incontinence), bronchial constriction, vomiting, and diarrhea.

Phosphorylation (irreversible inhibition ) ofthe enzyme resulting in excess acetylcholine 

what is the sign that enough atropine has been adminstered?

when is it administered?

dilated pupils

given immediately when OP poisoning has occured

What is given to treat OP poisoning after atropine is immediately given?

what is the condition of the use of the drug?

Parlidoxamine - which is an AchE activator that acts by hydrolysing the drug bound enzyme

it must be given before the enzyme has 'aged' - this is when the interaction between the drug and the enzyme is irreversible

Anticholinergics - refer to

NMJ blockers/ skeletal muscle relaxants- refer to

muscarenic blockers

nicotinic blockers

Atropine

1. class of drug

2.action

1. anticholinergic

2. crosses BBB

pupillary dilation & cycloplegia - loss of accommodation reflex thus blurred vision

dry mouth

tachycardia

bronchodilation

constipation

urinary retention

excitation/hallucinations

Elderly

BPH patients

Hyperthermic infants

Tropicamide

1. class of drug

2. Use

1. Anticholinergic

2. short acting (4 hours) produces mydraisis and cycloplegia - for refractive error testing fundoscopy

Benztropine

1. class of drug

2. use

1. anticholinergic

2. Used in drug induced Parkinsonism to treat EPS symptoms

1. anticholinergic

2. COPD /Bronchial asthma (not much systemic  absorption, so less side effects)

due to bronchodilation as it blocks M receptors

1. anticholinergic

2.to treat peptic ulcers - as it reduces the secretions in GI

Scopolamine 

1. Class of drug

2. Use

1. anticholinergic

2.to prevent Motion sickness 

Dicyclomine  

1. class of drug

2. use

1. anticholinergic

2. to treat GI spasm, spamodicabdominal pain Eg: Menstrual pain or renal colic

1. Anticholinergic

2. used in GA to reduce bronchial secretions (before intubation)

Oxybutynin

Class of drug?

Use?

Anticholinergic/antimuscurenic/ muscurenic antagonist

Reduce urgency in mild cystitis and reduce bladder spasms

Hexamethonium

Class of drug?

Use?

ADR?

Nicotinic antagonist - Ganglionic blocker

Used in experimental models to prevent vagal reflex responses to changes in blood pressure - eg prevents reflex bradycardia caused by NE

Orthostatic Hypotension

Blurred vision

Constipation

Sexual dysfunction

What is given in an atropine OD?

Class of drug?

Physiostegmine

Indirect acting cholinergic

also used in glucoma

Carbacol

Class of drug?

Use?

direct acting cholinergic

Glaucoma - Miosis and release of intraocular pressure

Methcholine

Class of drug?

Use?

Direct acting cholinergic

Challenge test for diagnosis of asthma