PANS

Exception: Blood vessels only have SANS innervation

SANS ganglia

-lie close to the spinal cord;

PANS ganglia

-are located near, or in, the organ innervated.

Norepinephrine (NE) is the predominant neurotransmitter released at SANS nerve endings and activates adrenergic receptors (also called adrenoreceptors) of two main  types: alpha receptors & beta receptors

Epinephrine (E) is released into the blood from the adrenal medulla and activates ALL adrenoceptors

Dopamine (DA) is a neurotransmitter at vascular smooth muscle in kidney and the enteric circulation

Alpha receptors: subtypes include alpha-1 and alpha-2

Beta receptors: subtypes include beta-1 and beta-2

Nicotinic receptors:

• subtypes include Neuronal receptors (N_N) and Neuromuscular receptors (N_M)

Neruronal Nicotinic

It is a type of nicotinic receptor under the class of cholinergic receptors which are part of the PANS

Neuromuscular Nicotinic receptor. 

This is a Nicotinic receptor, which is a type of cholinergic receptor which is part of the PANS

Which part of the nervous system uses adrenergic receptors?

Which types of neurotransmitters do adrenergic receptor utilize?

Adrenergic receptors are part of the SANS.

They utilize norepinephrine, epinephrine and dopamine

Nicotinic receptors. 

These are located in the preganglia receptors of the ganglia in the SANS and PANS

They are also located at the end of the motor neurons of the somatic nervous system, where they innervate skeletal muscles. 

The enteric nervous system (ENS) directly controls activities in the gastrointestinal system. It is capable of autonomous functions such as the coordination of GI reflexes (“the second brain”), although it does receive innervation from the ANS and is often considered a part of it.

Activities include control of gastrointestinal peristalsis & secretion of hormones and enzymes.   

The ENS uses the same neurotransmitters ACh and NE.

Cholecystokinin (CCK) – possible co-transmitter in ENS

Enkephalins – small peptides found in ENS neurons (& elsewhere) - inhibit peristalsis & increase GI secretions

Related peptides (endorphins) mediate pain responses in the spinal cord

Nitric oxide (NO) – ENS co-transmitter, vascular relaxation

Serotonin* (5HT) – transmitter in the ENS

Substance P – sensory neurotransmitter in ENS 

ENS neurons are collected into two types of ganglia known as myenteric (Auerbach’s) and submucosal (Meissner’s) plexuses. 

True or False

AChE inhibitors do NOT have actions at receptors that are not innervated!

2. Inhibitors of acetylcholinesterase, the enzyme that

    inactivates ACh – these agents increase ACh

    actions at both M & N receptors – non-selective!

3. Blockers (antagonists) of M receptors

4. Blockers (antagonists) of N receptors

When a drug can work on more than one receptor and tissue, how do you produce a highly selective action?

What are the effects of ADVERSE EFFECTS of CHOLINOCEPTOR ACTIVATING DRUGS?

DUMBBELSS

diarrhea, urination, miosis, bradycardia, bronchoconstriction, excitation (CNS), lacrimation, salivation, sweating

activation increases both SANS and PANS resposnes.

Nicotinic Neuronal (Nn) receptors are involved in these responses. 

What effect does losing your dopamine function have on your cholinergic function?

What medication could you take to correct this?

The patient's ANS tone and reflexes (barorecptor reflex changes in HR) will be blocked becuase the ganglion blocker acts on the PANS. 

Though both the PANS and SANS are stimulated, PANS always dominates unless the tissue is vascular or a thermoregulatory sweat gland. 

This is a theoretical patient, since ganglion blockers have no clinical use. 

Adreniergic Pharmacology

Because of more More complicated than Cholinergic Pharmacology because there are more

drugs & drug “targets”, more clinical uses & more adverse effects.

EDROPHONIUM (Tensilon)

• Type: Cholinesterase Inhibitor, non-selective

• Receptor: none

• Indications: Diagnostic for myasthenia gravis & for determining treatment adequacy, Gi Ileus, Reverse neuromuscular blockage, non-depolarizing

• Contraindications: Allergic to this drug

• Drug-Drug:

• Route: IV, IM

• Side FX:, bradyarrythmia, HTN, WET picutre [sweating, abnormal gastric secretions, ↑ salivation, N/V/D (nausea, vomiting, dizziness)], dysphagia

·         MOA: AChE inhibitor, so causes activation of both M & N receptors

PHYSOSTIGMINE (Eserine)

Type: Cholinesterase Inhibitor

• Receptor: NA

• Indications: Glaucoma, Anticholinergic agent toxicity (atropine toxicity)

• Contraindications: asthma, CVD (cardiovascular disease), DM (diabetes mellitus), gangrene, mech obs. Of GI & Urogen tract, vagotonic state (excessive vaginal tone)

• Drug-Drug: succinylcholine

• Route: IV, IM, eye drops

• Side FX: diaphoresis (perspiring profusely), N/V/D, excessive salivation, brady arr. seizures, hypersensitivity rxns

·         MOA: AChE inhibitor, so causes activation of both M & N receptors

DONEPEZIL (Aricept)

TACRINE (Cognex)

• Type: Cholinesterase Inhibitor

• Receptor: NA

• Indications: Alzheimer's, Multi-infarct dementia (Multi-infarct dementia (MID) is a form of dementia caused by a series of small strokes,

• Contraindications: Allergic to this drug

• Drug-Drug: succinylcholine, oxybutynin

• Route: Oral

• Side FX:, HTN, syncope (fainting/passing out), ↓ weight, N/V/D, bruising , cramping, ↑ creatine kinase, headache, insomnia, somnolence (drowsiness), uri. Incontinence (leakage), fatigue, AV block, GI hemorrhage

·         MOA: AChE inhibitor, so causes activation of both M & N receptors high lipid solubility increases CNS access to increase ACh

ATROPINE

Type: Muscarinic-1 blocker, Antagonist, non-selective

• Receptor: Muscarine-1, PANS, Cholinergic

• Indications: antispasmodic, antisecretory, antidiarrheal, antidote for organophosphates

• Contraindications: narrow angle glaucoma, reflux, esophagitis, obs. GI disease, ulcerative colitis, obs. Uropathy, unstable cardiovascular status in acute hemorrhage or thyrotoxicosis, paralytic ileus, intestinal atony, MG

• Drug-Drug:

• Route: PO, parenteral, ophthalmic

• Side FX: toxicity: dry mouth & decreased sweating – tachycardia, mydriasis(dilation of pupil) & cycloplegia (paralysis of the ciliary muscle of the eye) – hyperthermia (+ vasodilation) – urinary retention/constipation – weak pulse, hallucinations, delerium, coma.

TROPICAMIDE (Mydriacyl)

Cyclopentolate (Cyclogyl)

• Type: Muscarinic-1 Antagonist

• Receptor: Muscarinic-1, PANS, Cholinergic

• Indications: Ophthalmic examinations

• Contraindications: Glaucoma, allergy

• Drug-Drug: umeclidinium

• Route: ophthalmic

• Side FX: blurred vision, burning sensation, CNS complication, photophobia, ↑ intraocular pressure

IPRATROPIUM (Atrovert)

Tiotropium (Spiriva) 

• Type: Muscarinic-1 Antagonist/blocker

• Receptor: Muscarinic-1, PANS, Cholinergic

• Indications: COPD, nasal discharge, asthma management

• Contraindications: Allergies to atropine, allergy to this drug

• Drug-Drug:

• Route: inhalation, nasal spray

• Side FX: Increase ocular pressure, blurred vision, bronchodilation, increase HR, Decrease HCl acid, Decrease GI motility

BETHANECHOL (Urecholine)

·         Type: Muscarinic Agonist (direct activator)

·         Receptor: Activates all M receptors, PANS, Cholinergic

·         Indications: Commonly used to increase GI or bladder motility, Post-op/Postpart to ↑ bladder muscle tone w/ nonobstructive neurogenic urinary retention. After childbirth or surgery. After anesthetics.

·         Contraindications: Asthma, HTN (hypertension/high BP), compromised GI/Bladder wall, CAD (coronary artery disease), epilepsy, Hyperthyroidism, Parkinson's, peptic ulcers

·         Drug-Drug:

·         Route: PO, SC

·         Side FX: DUMBBELSS (diarrhea, urination, miosis (pupil constriction), bradycardia, bronchoconstriction, excitation (CNS), lacrimation, salivation, sweating).

ACETYLCHOLINE

·         Type: Cholinergic Agonist, PANS

·         Receptor: ALL cholinergic sites (muscarinic and nicotinic)

·         Indications: * Used for Miosis (pupil constriction) during ophthalmic surgery, coronary angiography, Know Ach ANS effects

·         Skeletal muscle-Contraction,

·         Ganglion-Stimulation,

·         CNS-Neurotransmissio

·         Contraindications: Allergy

·         Route: Eye drops

·         Side FX: DUMBBELSS (diarrhea, urination, miosis (pupil constriction), bradycardia, bronchoconstriction, excitation (CNS), lacrimation, salivation, sweating).

PILOCARPINE (Salagen)

·         Type: Cholinergic Agonist, PANS

·         Receptor: Muscarinic (ALL)

·         Indications: Increases salivary excretions; ophthalmic use for glaucoma, radiation induced xerostomia (dry mouth), ↓ intraocular pressure, Sjögren's syndrome (Sjogren syndrome is an autoimmune disorder in which the glands that produce tears and saliva are destroyed)

·         Contraindications: When miosis is undesirable, pupillary block glaucoma, uncontrolled asthma

·         Drug-Drug: NA

·         Route: eye drops, tablets

·         Side FX: DUMBBELSS (diarrhea, urination, miosis (pupil constriction), bradycardia, bronchoconstriction, excitation (CNS), lacrimation, salivation, sweating).

VARENICLINE (Chantix)

·         Type: Cholinergic Agonist, direct activator, PANS

·         Receptor: Neuronal nicotinic (Nn). Some selectivity for CNS nicotinic receptors

·         Indications: Smoking cessation

·         Contraindications: Allergies

·         Drug-Drug:

·         Route: PO

·         Side FX: DUMBBELSS (diarrhea, urination, miosis (pupil constriction), bradycardia, bronchoconstriction, excitation (CNS), lacrimation, salivation, sweating).

·         Type: Cholinergic Agonist

·         Receptor: Muscarinic all (1,2,3)

·         Indications: no clinical use. However, toxicity of this mushroom product is due to ibotenic acid.

·         Contraindications: Allergies

·         Drug-Drug:

·         Route: PO

·         Side FX: DUMBBELSS (diarrhea, urination, miosis (pupil constriction), bradycardia, bronchoconstriction, excitation (CNS), lacrimation, salivation, sweating).

NICOTINE

·         Type: Cholinergic Agonist, direct activator, PANS

·         Receptor: Nicotinic (ALL), some selectivity for CNS nicotinic receptors

·         Indications: Smoking cessation

·         Contraindications: Allergies

·         Drug-Drug:

·         Route: PO, Gum, transdermal patch

·         Side FX: DUMBBELSS (diarrhea, urination, miosis (pupil constriction), bradycardia, bronchoconstriction, excitation (CNS), lacrimation, salivation, sweating).

NEOSTIGMINE (Prostigmine)

·         Type: AChE inhibitor, indirect activator, cholinergic, PANS

·         Receptor: Muscarinic, indirect activator, indirectly causes activation of both M & N receptors

·         Indications:MG (Myasthenia gravis), Use to ↑ GI & bladder motility

·         Contraindications: mechanical intestinal tract obstruction, peritenitis, mech. urinary tract obstruction

·         Drug-Drug: Succinylcholine

·         Route: PO, parenteral

·         Side FX: bradycardia, excessive salivation, muscle fasciculation (a brief, spontaneous contraction), AV block, Bradyarrhythmia, cardiac arrest, dysrhythmia, anaphylaxis, LOC, seizures

SCOPOLAMINE

• Type: cholinergic blocker, muscarinic Antagonist, PANS

• Receptor: Muscarinic-2

• Indications: Motion sickness

• Contraindications:

• Drug-Drug:

• Route: PO, parenteral, opthalmic, patch

• Side FX: drowsiness, xerostomia

OXYBUTININ (Ditropan)             

Tolterodine (Detrol) 

·         Type: Muscarinic Antagonist, cholinergic, PANS

·         Receptor: Muscarinic-3, selective M3 blocker

·         Indications: For urinary urgency, cysitis, slow GI hypermotility

·         Contraindications: Urinary retention

·         Drug-Drug: Donepezil

·         Route: PO

·         Side FX: Angioedema

BENZTROPINE (Cogentin)

• Type: Muscarinic Antagonist, Cholinergic blocker, PANS

• Receptor: Muscarinic-2

• Indications: Parkinson's, Tx for OD of antipsychotic drugs (e.g. haloperidol)

• Contraindications:

• Drug-Drug:

• Route: PO, parenteral

• Side FX: 

SUCCINYLCHOLINE

• Type: Nicotinic Antagonist (Depolarizing neuromuscular blocking agent). Cholinergic, PANS

• Receptor: Nicotinic

• Indications: Produce muscle relaxation before and during surgery, and to facilitate intubation of the airway.

• Contraindications: If bloodwork indicates high [K+], risk of hyperkalemia→cardiac arrest, not for 3° burn victims, children

• Drug-Drug: Do not use with Physostigmine (eserine); donepezil (aricept); Neostigmine (prostigmine)

• Route: IV, IM

·         MOA: causes persistent depolarization of end motor plate > fasisculation > fatigue  relaxation

Type: Adrenergic, SANS, Direct-acting Beta Agonist, non-selective

• Receptor: β1 & β2

• Indications: Rx bronchospasm/constriction, atrioventricular block/heart block, bradycardia

• Contraindications:

• Drug-Drug:

• Route: Inhalant, parenteral

• Side FX: flushing, angina, arrhyth, ↓ tone & motility of gut

·         MOA: B1 cardiac stimulation; B2 bronchodilator

DOBUTAMINE (Dobutrex)

Type: Direct-acting Beta Agonist, more-selective beta agonist

• Receptor:  β1>β2 & Alpha

• Indications: acute heart failure, cardiogenic shock, used for heart stimulation during heart surgery

• Contraindications:

• Drug-Drug:

• Route: parenteral

• Side FX:

·         MOA: primarily stimulates B1 receptors with smaller effect on B2 and alpha receptors

EPINEPHRINE (Adrenalin)

 Type: Direct-acting Beta agonist, Adrenergic, SANS

• Receptor: ALL (alpha and beta). Low dose = b1/b2. High dose = a1, b1, b2

• Indications: Rx or hemostatis (stop bleeding), adjunct to local anesthetics, Rx for acute asthma, DOC (drug of choice) for anaphylaxis, cardiac arrest, hypotension

• Contraindications:

• Drug-Drug:

• Route: aerosol, parenteral, ophthalmic

• Side FX: vasoconstriction (a1), ↑BP (a1), bronchodilation (b2)

·         MOA: Released from the adrenal medulla into the bloodstream. Vasocontriction at alpha2, increased BP at alpha 1, cardiac stimulation at B1, and bronchodilation at B2

ALBUTEROL (Ventolin)

Type: Direct-acting beta agonist, adrenergic, SANS

• Receptor: β2 selective

• Indications: Acute asthma

• Contraindications:

• Drug-Drug:

• Route: inhalant

• Side FX: Possible tremors

·         MOA: bronchodilation of B2

PHENYLEPHRINE (Neo-Synephrine)

Type: Direct-acting Adrenoreceptor Agonist, SANS

• Receptor: α1 selective, agonist

• Indications: Rx for nasal congestion, Used to elicit mydriasis/dilation of eye (without cycloplegia =ciliary muscle paralysis which leads to loss of accomodation), Tx of shock, hypotension, maintenance of BP

• Contraindications:

• Drug-Drug:

• Route: PO, parenteral, nasal, ophthalmic

• Side FX: Angioedema, Vasoconstriction, Increased BP, Mydriasis (VIAM)

·         MOA: activates A1 adrenoreceptors; smooth muscle contraction

AMPHETAMINE (Ritalin)

Type: Indirect Agonist, NE-releaser, adrenergic

• Receptor: SANS-innervated tissues that have receptors but are not innervated (includes some skeletal muscle blood vessels), CNS

• Indications: Rx for ADHD, narcolepsy

• Contraindications:

• Drug-Drug:

• Route: PO

• Side FX: vasoconstriction, ↑ CNS stimulation, cardiac stimulation, increase in BP (VIIC)

·         MOA: high lipid solubility and increases sympathetic concentrations of NE in the CNS and PNS. 

COCAINE

• Type: Indirect adrenergic agonist

• Receptor: NA, NE reuptake blocker

• Indications: Used for topical vasoconstriction, local anesthetic

• Contraindications:

• Drug-Drug:

• Route: Inhalation

• Side FX: vasoconstriction, cardiac stimulation, ↑BP, ischemia & necrosis of nasal mucosa (VIICN)

EPHEDRINE

• Type: Indirect Adrenergic Agonist, NE-releaser

• Receptor: SANS-innervated tissues that have receptors but are not innervated (includes some skeletal muscle blood vessels), CNS

• Indications: decongestant, cold remedy, vasoconstriction, bronchodilation

• Contraindications: do NOT use on children <6yo

• Drug-Drug:

• Route: PO, Parenteral

• Side FX: tachycardia, ↑ BP, urinary retention, insomnia (UTII)

PSEUDOEPHEDRINE(Sudafed)

• Type: Indirect Adrenergic Agonist, NE-releaser

• Receptor: NE releaser, binds to agonist alpha 1 receptors

• Indications: Tx for nasal congestion, cold, and allergies

• Contraindications:  do NOT use on children <6yo

• Drug-Drug:

• Route: PO

• Side FX: tachycardia, ↑ BP, urinary retention, insomnia (UTII)