VF: Week 4 Parasympathetic Nervous System

What Neurotransmitter is released at the post-ganglionic parasympathetic nerve terminal?

Acetylcholine

What G-protein receptor stimulation leads to bradycardia?

Muscarinic

What is the origin of the preganglionic neurons?

Cranio-sacral region

Where in the spinal cord are the pregangiolic neurons?

Intermediolateral gray matter or the nuclei in the brainstem

Where are the ganglia of the parasympathetic system located?

Near or within the target effector

The ganglia of the parasympathetic are in the target effector this causes what in comparison to the sympathetic?

Little divergence

What is the ratio of preganglionic fibers to post ganglionic fibers?

3:1

With such a small ratio of pre gang fibers to post gang fibers what does this mean about the reach of the parasympathetic?

Its not widespread, discrete and localized with only specific tissues being stimunated

In the Ganglion all the preganglionic neurons sympathetic and parasympathetic are?

Cholinergic

What does cholinergic mean?

The synthesis and release of acetylcholine as their primary transmitter

What is always mediated by acytelcholine?

Autonomic ganglia

What are the receptors for cholinergic?

Nicotinic

What are the postganglionic receptors?

Muscarinic receptors

How does the parasympathetic nervous system effect the eyes

Constricts the pupils (muscarinic)

How does the parasympathetic nervous system effect the GI tract?

Stimulates gastrointestinal activity (muscarinic)

How does the parasympathetic nervous system effect the Lungs?

Bronchoconstriction (Muscarinic)

How does the parasympathetic nervous system effect the Heart?

Decreases heart rate (muscarinic)

Decreases BP

How does the parasympathetic nervous system effect the Glucose concentration?

Lowers BG concentration

How does the parasympathetic nervous system effect Insulin production?

Increases insulin realease

Blood vessels have what kind of nerve?

Nonparasympathetic nerve

Sympathetic nervous system causes what kind of change in the eye?

Mydriasis: Pupillary dilation constriction of the radial muscles to open pupil

Parasympathetic causes what kind of change in the eye?

Miosis: Pupillary constriction stimulation of the circular muscles to close the pupil.

What is the effect of the parasympathetic division stimulation on the pupil diameter?

Miosis

What are parasympathetic cholinergic agonists called?

parasympathomimetics

What do parasympathomimetics produce?

Acetylcholine-like effects on effector cell

What are the two types of Parasympathmimetics?

Direct-acting

Indirect-acting

What is the function of a Direct acting cholinergic agonist?

Activates cholinergic receptors on effector cells

What is the function of a Indirect-acting cholinergic agonist?

Acetylcholine accumulates in synaptic junction, increases cholinergic action

What is another name for an Indirect-acting cholinergic agonist?

Cholinesterase inhibitor

What are the two types of direct-acting parasympathomimetics?

Choline Esters

Natural Alkaloids

What are examples of Choline Esters

Carbachol

Bethanechol

What is an example of Natural Alkaloids?

Pilocarpine

What is the mechanism of action for direct-acting parasympathomimetics?

Acts on post synaptic cholinergic receptors of target cells innervated by cholinergic nerve

What is a type of Indirect acting parasympathomimetics?

Cholinesterase inhibitors

What are the two types of Cholinesterase inhibitors?

Reversible

Irreversible

What is an example of a reversible cholinesterase inhibitor?

Edrophonium

What is an example of an irreversible cholinesterase inhibitor?

Organophosphate

What is the mechanism of action for the Cholinesterase inhibitors?

Inactivates or inhibts ACHE causing an ACH accumulation with in turn increases the cholinergic activity

What does Edrophonium support?

Diagnostis of myastonia gravis

What does Organophosphate Treat?

Ticks

Flea

Pesticides poison

What are two effects of cholinergic agonist?

Miosis

Bradycardia

What are the characteristics of Bethanechol?

Selectively stimulate muscarinic receptors

Resistant to hydrolysis to ACHE

Very potent, long lasting

What indications of Bethanechol?

Urinary retention (Bladder muscle atony)

Gi paralytic ileus

What is GI paralytic ileus?

Lack of contractility on the GI

When do you only use Bethanechol?

When there is no mechanical obstruction in GIT

What type of parasympathmimetic is Bethanechol?

Direct acting

What type of parasympathomimetic is Pilocarpine?

Direct acting

What type of agonist is Pilocarpine?

Muscarinic receptor agonist

What are uses of Pilocarpine?

Contraction of the cillary muscle of the lens

Contraction of the pupil circular muscle, leading to the iris sphincter constriction

Increase outflow of aqueous through trabecular meshwork

What are the therapeutic uses of Pilocarpine?

Glaucoma

Keratoconjuncititis sicca

What is Keratoconjunctivitis sicca?

dry eye

What are the adverse effects of parasympathomimetics?

Bronchoconstriction

Bradycardia

Miosis

Salivation, sweating

Vomiting and diaherria

Urinary incontinence

Neuromusclular effects

CNS effects

Uterus contraction (abortions)

What is the pharmacological effect of Bethanechol?

Increases GI contractions

What type of parasympathomimetic is Organophosphate compounds?

Indirect Irreversible Cholinesterase inhibitors

What is the mechanism of action for Organophosphate compounds?

Interacts with AChE at esteratic site

Phosphorylation of esteratic site

Requires de novo synthesis of new enzyme

What kind of parasympathomimetic is Edrophonium?

Indirect reversible cholinesterase inhibitors

What is the Mechanisms of action for Edrophonium?

Combines with AChE and inhibits hydrolysis of ACh

Builds up the concentration of ACH in the synapsis and prolongs the action of ACH

Reactivated enzyme hydrolyse ACH

What are the uses of Edrophonium?

Glaucoma

Myasthenia gravis

Revert neuromuscular blockade

How does Edrophomium cause muscle weakness?

Blocks nicotinic receptors so not enough ACH can reach them.

What type of Parasympathomimetic is Organophosphorus compound?

Indirect Irreversible Cholinesterase Inhibitors

What are the parasympathomymetic effects of Organophosporus compounds?

Profuce salivation

Vomiting

Hypermotility of GIT

defacation

Urination

Bradycardia

Hypotension

Severe brochoconstriction

excess Bronchial secretions

miosis

What are the skeletal effects of Oganophosphorus compound?

Skeletal muscle fasciculations

Twitching

convulsions

muscle paralysis

Death

What is the antidote for for Organophosphorus compound?

Atropine

What is another name for Cholinergic antagonists?

Parasympatholytics

How do Cholinergic antagonists work?

They inhibit actions of acetylcholine by blocking cholinergic receptors

What are three types of Cholinergic antagonists?

Anti-muscarinic

Ganglionic blockers

Neuromuscular blockers

Ganglionic antagonize what kind of receptors?

Nicotinic receptors

How do Antimuscarinic agents work?

Inhibits muscarinic action of acetylcholine and related cholinergic agonists

Atropine and Scopolamine are extracted from what plants?

Atropa Belladona

Datura stramonium

What is the first step in the Mechanism of Action of Antimuscarinic agents?

Interacts with muscarinic receptor of effector cells

What is the second step in the Mechanism of Action of Antimuscarinic agents?

Prevents ACH binding to these receptors

What is the third step in the Mechanism of Action of Antimuscarinic agents?

Competitive antagonism

What is the fourth step in the Mechanism of Action of Antimuscarinic agents?

Blockage of cholinergic effect- sympathetic action is dominant

What is the fifth step in the Mechanism of Action of Antimuscarinic agents?

Salivary and sweat glands- susceptible to small doses of atropine

What is the sixth step in the Mechanism of Action of Antimuscarinic agents?

Vagolytic effect- requires large doses

What are the pharmacological effects of Atropine in the heart?

Tachycardia

Increased CO

Increased BP

What are the pharmacological effects of Atropine in the GIT?

Decreased GIT motility

Decreased Secretion of GIT mucosa

Relieves intestinal spasm and hypermotility

What is the pharmacological effects of Atropine in the Urinary system?

Relaxes smooth muscle of the urinary bladder

Spasmolytic effect of ureters (urinary retention)

What is the pharmacological effects of Atropine in the Bronchioles?

Decreased secreations

Bronchodilation

What is the pharmacological effects of Atropine in the eyes?

Mydriasis

Paralysis of the ciliary muscle

What does antimuscarinic drugs contraindicate?

Increased intraocular pressure

What are the pharmacological effects of Atropine in Sweat Glands?

One or more areas in which you can’t sweat

What is the pharmacological effect of Atropine in CNS?

Minimal effects

Excess dose can hallucinations followed by depression/coma

What is the pharmacological effect of scoplamine?

Slight sedation, antiemetic

What species is resistant to Atropine?

Rabbits

What are the characteristics of Glycopyrrolate?

Preanesthetic

Potent Antimuscarinic

Less lipophilic

How does Glycopyrrolate differ from Aptropine?

Less side effects then atropine

Duration of action is more than atropine

What is an example of a synthetic antimuscarinic agent?

Scopolamine Butylbroimide

What are the characteristics of Scopolamine Butylbromide?

Smooth Muscle relaxants

Charged quaternary ammonium compounds that don’t cross blood brain barrier

What is the therapeutic use of glycopyrrolate in horses?

Asthma

Sedation

Muscle relaxant

Preanesthetic

Induce Tachycardia

What is the antidote for cholinergic drug poisoning condition?

Atropine