ANS Receptors: parasympathetic

neurotransmitter:  ACh for pre- and post-ganglionic neurons

target organs have muscarinic cholinergic receptors

ACh is degraded by scetylcholinesterase

neurotransmitters:  ACh for pre-ganglionic, norepinephrine for post-ganglionic

targets have adrenergic receptors (alpha and beta)

also, nicotinic receptors on chromaffin cells cause release of epinephrine, which stimulates adrenergic receptors in target organs

reuptake into adrenergic neuron is the major form of inactivation

ionotropic ligand-gated cation channel

ACh binding opens the channel pore

sodium influx=depolarization

heart:  bradycardia, decreased conduction

vessels:  vasodilation

lungs:  bronchoconstriction, increased secretions

GI:  increased motility, increased secretion

UT:  contraction (promotes urination)

Eye:  lacrimation, miosis

SLUDGE and DUMBELS

Salivation

Lacrimation

Urination

Defecation

GI symptoms

Emesis

Diarrhea/diaphoresis

Urination

Miosis

Bronchorrhea, bronchospasms, bradycardia

Emesis

Lacrimtion

Salivation

endogenous cholinergic

rarely used clinically

rapid degradation by AChE and plasma butyrylcholinesterase

mechanism: direct acting cholinergic agonist

effects:  muscarinic stimulation, some GI/urinary bladder sensitivity

promotes voiding by contraction of the setrusor and relaxation of the trigone sphincter

used to treat urinary retention when obstruction is absent

not as much cardiac activity?

mechanism:  direct acting cholinergic agonist

effects:  stimulates muscarinic receptors

not used clinically

found in certain mushrooms (along with other toxins)

mechanism:  direct acting cholinergic agonist

effects:  muscarinic stimulation

topical ophthalmic use to induce pupil constriction and decrease intraocular pressure during glaucoma

mechanism:  buildup of ACh at sites of release

effects:  stimulation of autonomic effector organs (muscarinic receptors)

stimulation, then depression of autonomic ganglia and skeletal muscle (nicotinic receptors)

stimulation, then possible depression, of cholinergic receptors in the CNS

physostigmine, neostigmine, pyridostigmine

covalent inhibitors

effects:

smooth muscle atony (GI tract and urinary bladder)

glaucoma (topical)

reversal of non-depolarizing neuromuscular blocking agents

myasthenia gravis (ACh receptor deficiency)

counter CNS symptoms of anticholinergic intoxication (physostigmine)

reversible covalent acterylcholinesterase inhibitor

effects:  stimulate visceral smooth muscle

reversible covalent acetylcholinesterase inhibitor

can cross the BBB

used to counter anticholinergic activity

organophosphates, insecticides, nerve gases

excess muscarinic stimulation (SLUDGE and DUMBELS)

treat with cholinesterase "reactivators" (pralidoxime; 2-PAM)

treat symptomatically with anti-cholinergics

mechanism:  cholinergic antagonist (competitively inhibits binding and stimulation of muscarinic receptros by ACh and other muscarinic agonists)

enters the CNS

effects:

heart:  increased cardiac output (tahcycardia, increased conduction)

lungs:  bronchodilation, decreased secretions

decreased GI motility, secretions

urine retention

mechanism:  cholinergic antagonist

enters the CNS

effects

increased cardiac output, bronchodilation, similar to atropine

low dose:  slight sedation

high dose:  excitement

antiemetic (generally not the drug of choice)

mechanism:  cholinergic antagonist

quarternary (does not cross BBB)

effects:

decrease salivary and airway secretions

prevent vagally-mediated bradycardia

little CNS effects

used as adjunct to general anesthesia

mechanism:  cholinergic antagonist

effect:  used topically in eye to produce mydriasis and cycloplegia (shorter duration than atropine)

mechanism:  cholinergic antagonist

effect:  promote bronchodilation and decrease airway secretions

quaternary:  restricted distribution (administer via inhalation)

mechanism:  cholinergic antagonist

effects:  decreases detrusion contraction

increases trigone and sphincter contraction

promotes urine retention

mechamism:  decreased autonomic regulation of target organs

effect depends on relative tone of sympathetic and parasympathetic

cause inhibition without prior stimulation

effects wide-spread, difficult to predict, not used clinically

mechanism:  NMJ blocker (competitive ACh antagonist at nicotinic receptors in NMJ)

used to make arrow poison in south america

mechanism:  non-depolarizing competitive MNJ blocker

effects:  initial muscle weakness followed by flaccid paralysis (especially in diaphragm)

long duration of action

renal elimination 

mechanism:  competitive NMJ blocker

effect:  initial muscle weakness followed by flaccid paralysis

intermediate duration

half-life not increased with renal disease

rate of degradation reduced with hypothermia and acidosis

promotes histamine release

mechanism:  competitive NMJ blocker

effect:  initial muscle weakness followed by flaccid paralysis

short duration of action

half-life not increased with renal disease

promotes histamine release

mechanism:  depolarizing non-competitive NMJ blocker

effect:  initial muscle fasciculations followed by relaxation

not pharmacologically reversible (with anti-acetylcholinesterase)

rapid onset

some histamine release

hyperkalemia

mechanism:  direct acting adrenergic agonist

effects:

cardiac:  increased cardiac output (beta1), decreased cutaneous, visceral, renal blood flow (alpha1), increased skeletal muscle blood flow (beta2)

respiratory:  powerful bronchodilator (beta2)

used for rapid relief of hypersensitivity, topical hemostatic agent, adjunct with local anesthetics

mechanism:  endogenous catecholamine (major NT release by post-ganglionic nerves)

similar to epi

beta1:  EPI=NE

beta2:  EPI>>>>>NE

alpha1:  EPI>NE

intense vasoconstriction and increase in blood pressure

limited use

mechanism:  endogenous catecholamine (precursor to NE and EPI)

effects:

low dose:  stimulates vascular D1 dopamine receptors, increases renal blood flow and sodium excretion, positive inotropic effect

high dose:  vasoconstriction, decreased renal blood flow, etc.

used as IV infusion for congestive heart failure with compromised renal function (short term only)

mechanism:  non-selective beta adrenergic agonist

effects:bronchodilator, increase heart rate

rarely used clinically

mechanism:  non-selective beta adrenergic agonist

effects:  mostly B1 agonist, some B2 and A1 activity

increased cardiac contractility with minimal changes in heart rate

minimal change in blood pressure

used as positive inotrope during heart failure

mechanism:  selective B2 adrenergic agonist

effect:  for bronchospasm in dogs, cats, horses

mechanism:  selective B2 adrenergic agonist

effect:  used for allergic bronchitis, recurrent airway obstruction, and bronchoconstriction in horses

mechanism:  selective alpha1 adrenergic agonist

effect:  decongestant, vasopressor