Escolar Documentos
Profissional Documentos
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Anatomy
Roots
Location of Ganglia
Length of Fibers
Preganglionic
Postganglionic
Neurotransmitters
Preganglionic
Postganglionic
Receptor
Ganglia
Target Organ
SYMPATHETIC /
ADRENERGIC
(Fight, Flight,
Fright)
Thoracolumbar
(T1-T12, L1-L5)
PARASYMPATHETIC /
CHOLINERGIC
(Rest & Digest)
Craniosacral
(CN 3, 7, 9 & 10, S3-S4)
Short
Long
Long
Short
Acetylcholine
NE, Epinephrine,
Dopamine
Nicotinic
Alpha, Beta,
Dopamine
Acetylcholine
Acetylcholine
Nicotinic
Muscarinic, Nicotinic
SYMPATHETIC /
ADRENERGIC
(Fight, Flight,
Fright)
Dilation
(far vision)
Constriction
(near vision)
Bronchial smooth
muscle
Bronchodilation
Bronchoconstriction
Heart
(+) chronotropic
(+) inotropic
(-) chronotropic
(-) inotropic
Closed
motility
Opened
motility
Closed
Relaxation
Ejaculation
Opened
Contraction
Erection
Eye
Pupils
Ciliary muscle
GIT
Sphincters
Intestinal wall muscle
Secretions
Bladder
Sphincter
Wall muscles
Male genitalia
PARASYMPATHETIC /
CHOLINERGIC
(Rest & Digest)
Uterus
Salivary glands
Lacrimal glands
Vascular smooth
muscle
Skin / gut
Skeletal muscle
Skin
Pilomotor muscles
Sweat glands
Metabolic fxns
Liver
Fat cells
Kidney
CHOLINERGIC RESPONSE
Diarrhea
Urination
Miosis
Bradycardia
Bronchoconstriction
Emesis
Lacrimation
Salivation
Sweating
Contraction
SYMPATHETIC /
ADRENERGIC
(Fight, Flight, Fright)
Thick, viscid secretion
Relaxation
PARASYMPATHETIC /
CHOLINERGIC
(Rest & Digest)
Copious, water
secretion
Secretion
Constriction
Dilation
Contraction
sweating
Gluconeogenesis
Glycogenolysis
Lipolysis
Renin release
ALICE IN WONDERLAND
Hot as a hare: hyperthermia, fever
Red as a beet: tachycardia,
vasodilation/flushing
Blind as a bat: blurring of vision, cycloplegia,
mydriasis
Mad as a hatter: delirium, hallucinations
Dry as a bone: decreased gland secretions
Autonomic Transmission
- involves two neurons:
1. Presynaptic neurons extend from the brain to autonomic ganglia
where they transmit CNS signals to postsynaptic neurons by releasing
acetylcholine into the synaptic cleft
2. Postsynaptic neurons subsequently transmit impulses to end organs
by releasing norepinephrine or acetylcholine
CHOLINERGIC TRANSMISSION
Synthesis
Molecules
Enzyme
Reaction
Storage
Carrier
Release
Receptor
Removal
Enzyme
DRUGS
Hemicholinuminhibits transport
ADRENERGIC TRANSMISSION
1. Tyrosine Dopa (RLS)
2. Dopa Dopamine (dopaminergic neurons)
3. Dopamine Norepinephrine (sympathetic
postganglionic neurons)
4. Norepinephrine Epinephrine (adrenal medulla)
1 Tyrosine hydroxylase (TH)
2 Dopa decarboxylase (DD)
3 Dopamine--hydroxylase (DH)
4 Phenylethanolamine-N-methyltransferase (PNMT)
Vesicle-associated transporter
(VAT)
Voltage-sensitive Ca+2 -channels
in the terminal membrane are
opened influx of Ca+2
DRUGS
Metyrosine/methyltyrosine- inhibits TH
Carbidopa- inhibits DD
Vesamicol- inhibits
transport
DA NE
Vesicular monoamine transporter (VMAT)
Reserpine-depletes
transmitter stores
-latrotoxinpromotes Ca+2
release
botulinum toxininhibits release
Acetylcholine
receptor/Cholinoceptor
Acetylcholinesterase (AchE)
Hydrolysis Choline + Acetate
Reaction
Amphetamines,
methamphetamines,
tyramine, ephedrine
- promote release
INCREASED NE ACTIVITY
Cocaine, TCA- blocks
reuptake INCREASED NE
ACTIVITY
CHOLINOCEPTORS
Muscarinic Receptors
Exocrine glands
secretion
Secretion
Smooth muscles
contraction
Autonomic
ganglia
seizure activity
Eye
Miosis, ocular
accommodation
CNS
Blood vessels
(endothelium)
Vasodilation
Heart
Cardiac inhibition
CNS
CNS
Neural inhibition
M4
CNS
tremors; hypothermia;
analgesia
M5
CNS
Receptor
Location
M1
Exocrine glands
M2
Effect
M3
Enhanced locomotion
Salivary glands
Smooth muscle
contraction
Peripheral
nerves
Neural inhibition
ganglionic transmission
Nicotinic Receptors
Receptor
N1
Location
Effect
Ganglion
Stimulation
CNS
Neurotransmission
Skeletal muscle
Contraction
CHOLINERGIC DRUGS/CHOLINOMIMETICS
1. Cholinergic Agonists
-Direct-acting- bind, activate receptor
-Indirect-acting- inhibit AChE ACh
2. Cholinergic Antagonists
DIRECT-ACTING CHOLINERGIC AGONISTS
- choline bound to an acetyl derivative by an ester bond
- poorly absorbed & poorly distributed into the CNS
Properties
-ester of acetic acid & choline, a
quaternary amino alcohol
-both muscarinic and nicotinic
(M1M5)
- prototype cholinergic agonist
Indication
Miotic agent in cataract
surgery (10 min)
*CARBACHOL long
duration (1 hr)
Bethanecol*
-strongly muscarinic
(M1-M3)
Acute non-obstructive
urinary retention
Increase intestinal motility
after surgery
MUSCARINIC
CHOLINOMIMETICS
Carbachol
Methacholine/
Provocholine*
Pilocarpine
Muscarine
Administration
PO, SC
Duration: 1 hr
Advantages/Disadvantages
Limited therapeutic use
1. Rapid hydrolysis
2. Lack of selectivity
More hydrolysis-resistant
- strong nucleophile
- quaternary amine
- able to break the
phosphorous-enzyme bond
Atropine
Anticholinergic agent
IV
Muscarinic blocker
-contain a tertiary or quaternary amine group that can bind noncovalently to the anionic site of the enzyme
carbamylated enzyme
-carbamylated enzyme undergoes hydrolysis much more slowly (30 minutes to 6 hours)
CARBAMATES
Physostigmine/Eserine
Neostigmine/Prostigmin
-quaternary ammonium
carbamate
- more polar & therefore does
not enter the CNS
-direct agonist activity at NM
Pyridostigmine/Mestinon
-quaternary ammonium
carbamate
- has direct agonist activity at
NM
Carbamate Insecticides: Carbaryl, Propoxur (Baygon), Aldicarb
Cholinesterase regenerator
drug
* quaternary ammonium
group binds to the anionic
site of the enzyme & thereby
promotes dephosphorylation
IV
Should be given before
aging
-opthalmic, IV, IM
Duration: 0.5-2
hours
- PO, SC
- duration: 0.5-2
hours
- PO, IV, IM
- duration: 3-6
hours
QUATERNARY AMINE
Edrophonium/Tensilon
CHOLINERGIC ANTAGONISTS
-cholinergic blockers
-reversibly bind
electrostatically & by hydrogen
bonds to the active site, thus
preventing
access of acetylcholine
Short duration of
action (5-15
minutes)
- anticholinergic drugs
- block the actions of ACh at muscarinic or nicotinic cholinoceptors
I. Muscarinic Blockers
II. Neuromuscular Blockers/Skeletal Muscle
III.
Ganglionic Blockers
Relaxants
CHOLINERGIC RESPONSE
Diarrhea
ALICE IN
Urination
WONDERLAND
Miosis
Hot as a hare:
Bradycardia
hyperthermia, fever
Bronchoconstriction
Red as a beet:
Emesis
tachycardia,
Lacrimation
vasodilation/flushing
Salivation
Blind as a bat: blurring
Sweating
of vision, cycloplegia,
mydriasis
Mad as a hatter:
delirium, hallucinations
Dry as a bone:
decreased gland
secretions
- Ng antagonists
- block nicotinic receptors in both sympathetic &
parasympathetic ganglia
*ACh: neurotransmitter in all sympathetic &
parasympathetic ganglia
- reduce the effects of whichever system is
predominant
- seldom used clinically
Sympathetic blocking effects
Arterioles
Dilate, high flow,
hypotension
Veins
Dilate, pool blood, low
return, low cardiac
output
Parasympathetic blocking effects
Heart
Tachycardia
Iris
Mydriasis
Ciliary muscle
Cycloplegia
GI tract
Low tone, low
motility, constipation
Bladder
Urine retention
Salivary glands
Xerostomia
Sympathetic (cholinergic)
Sweat glands
anhidrosis
MUSCARINIC BLOCKERS
Drug
Atropine/Hyoscyamine
Scopolamine/Hyoscine
Properties
-prototype
alkaloid from deadly
nightshade (Atropa
belladonna) & Jimson weed
(Datur stramonium)
- central & peripheral
muscarinic blocker
( M1-M5)
Indication
-irritable bowel syndrome
-mild diarrhea
-GIT & bladder spasms
-enuresis
-bradycardia
-bronchospasm
-reduces glandular & bronchiolar
secretions before anesthesia
-treats intoxication by cholinergic
agonists or
by acute mushroom poisoning
-produces mydriasis & cycloplegia
(ophthalmoscopic examination)
Contraindication
CI:
-glaucoma
-prostatic
hypertrophy
-heart disease
-obstructive bowel
disease
CNS
- longer duration of action
than atropine
Homatropine
Cyclopentolate
Tropicamide
Ipratropium bromide
Pirenzepine
Benztropine,
Trihexyphenidyl,
Oxybutynin
Dicyclomine
Ophthalmoscopic examination
(produce mydriasis & cycloplegia)
-M1, M2, M3, M4 blocker
- more peripheral effects,
less CNS effects
-M1 blocker
-selective for muscarinic
receptor in the stomach
- poorly absorbed, thus high
concentration in gut
-- secretion of acid &
pepsin
M1, M2, M3 blockers
Adverse effects:
few, relatively specific for
gastric secretions
*Adjunct- supporting
*Adjuvant-additional
Properties
Indication
Adjunct to anesthesia:
-muscle relaxant
-eases intubation & ventilation
-eases orthopedic manipulation
-controls respiration during chest
surgery
Administration
-IV
Short duration of action (25-40
min.)
-suitable for short surgical
procedures
Atracurium
useful in mechanical
ventilation of critically
ill
patients
Pancuronium
vagolytic actions
(increases HR)
Tubocurarine
-from Curare
(Strychnos sp.) used as
arrow poison in South
America
-hydrolyzed by plasma
cholinesterase
IV
Rocuronium
Pipecuronium,
Doxacurium
Mivacurium
heart rate
no histamine release
DRUG INTERACTIONS
I. Cholinesterase Inhibitors
- Neostigmine, Physostigmine, Edrophonium
- can overcome the action of nondepolarizing blockers
hypotension (histamine)
bronchospasm (ganglionic
blockade)
rapid hydrolysis by
acetylcholinesterase &
plasma
pseudocholinesterase
-IV, IM
rapid onset (30-60
sec.)
short duration (3-5
min.)
Reversal:
- cholinesterase inhibitors
- increased ACh concentration competes with
neuromuscular blockers
GANGLIONIC BLOCKERS
Drug
Nicotine
Properties
active ingredient in tobacco
Indication
smoking cessation therapy
Administration
transdermal patch,
chewing gum
Hexamethonium
Trimethaphan
Mecamylamine
treatment of hypertensive
emergencies caused by
pulmonary edema or dissecting
aortic aneurysm
treatment of moderately
severe to severe hypertension
short-acting