The autonomic nervous system is responsible for
Pharmacology maintaining the internal environment of the body or
homeostasis Within the autonomic nervous system,
two neurons are required to reach a target organ, a
• An agonist is a compound that binds to a
preganglionic neuron and a postganglionic neuron. All
receptor and produces the biological preganglionic neurons release acetylcholine as their
response transmitter. The acetylcholine binds to nicotinic
•A partial agonist produces the biological
response but cannot produce 100% of the receptors on the postganglionic cell
biological response even at very high doses
• Efficacy is the maximal response a drug can AUTONOMIC NERVOUS SYSTEM
produce SYMPATHETIC
• Potency is a measure of the dose that is - Catabolic
required to produce a response - Thoracolumbar
• Antagonists block or reverse the effect of - Long postganglionic
agonists. They have no effect of their own PARASYMPATHETIC
FIRST-PASS EFFECT - Anabolic
• The liver is a metabolic machine and often - Craniosacral
inactivates drugs on their way from the GI tract - Short postganglionic
to the body. This is called the first-pass effect. All of the parasympathetic postganglionic fibers release
• Drugs cross membranes by passive diffusion or acetylcholine. at the target organ acetylcholine
• active transport interacts with muscarinic receptors. Acetylcholine is
A drug tends to pass through membranes if it synthesized from acetyl coenzyme A (acetyl CoA) and
• is uncharged choline. Its action is terminated by
Uncharged drugs or more lipid-soluble than acetylcholinesterase.
charged drugs. In addition, many drugs are
There are two major classes of receptors for
weak acids or weak bases.
acetylcholine, muscarinic and nicotinic
These muscarinic receptors are predominantly found in
Bioavailability is the amount of drug that is absorbed the viscera (GI tract)
after administration of route x compared with the
Nicotinic receptors are found at the motor end plate,
amount of drug that is absorbed after intravenous
in all autonomic ganglia, and in the adrenal medulla
administration. X is any route of drug administration
other than IV. Activation of muscarinic receptors results in the
bioavailability = AUC oral / AUC IV following responses:
Clearance is a term that indicates the rate at which a Eye miosis (constriction of pupil)
Cardiovascular (decrease in heart rate)
drug is cleared from the body. It is defined as the
volume of plasma from which all drug is removed in a Respiratory bronchial constriction and increased
given time. Thus, the units for clearance are given in secretions
volume per unit time Gastrointestinal (GI) increased motility, relaxation of
clearance = rate of removal of drug (mg/min) / plasma sphincters
concentration of drug (mg/min) Genitourinary (GU) relaxation of sphincters and
The total body clearance is the sum of the clearances
bladder wall contraction
from the various organs involved in drug metabolism
and elimination
DIRECT CHOLINERGIC AGONISTS
Esters Alkaloids
RENAL EXCRETION BETHANECHOL muscarine
renal elimination of drugs involves three physiological carbachol pilocarpine
processes:
a. glomerular filtration Bethanechol is used in the treatment of urinary
b. proximal tubular secretion retention Carbachol administered ocularly to induce
c. distal tubular reabsorption miosis to reduce intraocular pressure in the treatment
of
, glaucoma is also used to stimulate micturition by Muscarinic antagonists
contraction of detrusor muscle. Atropine
Muscarine is a nonselective agonist of the muscarinic Benztropine
acetylcholine receptors Ipratropium
Pilocarpine is a medication used to reduce pressure Scopolamine
inside the eye and treat dry mouth
Muscarinic antagonists are used preoperatively to
CHOLINESTERASE INHIBITORS
reduce secretions
REVERSIBLE INHIBITORS SCOPOLAMINE Is used to prevent a motion sickness
Edrophonium IPRATROPIUM Is used in the treatment of chronic
Neostagmine obstructive pulmonary disease to
produce
Pyridostagmine bronchodilation
ambenomium
demecarium The competitive neuromuscular blocking drugs are
physostigmine used to produce skeletal muscle relaxation
SUCCINYLCHOLINE Is a depolarizing neuromuscular
blocker.
IRREVERSIBLE INHIBTORS Nondepolarizing blockers
malathion d-TUBOCURRANE mivacurium cisatracurium
parathion pipecuronium vecuronium
sarin Atracurium pancuronium doxacurium rocuronium
soman The neuromuscular junction and other cholinergic
synapses can also be blocked by drugs that block the
release of acetylcholine
These drugs have all the same actions and side effects
Botulinum toxin blocks the release of acetylcholine at
as the direct acting drugs (muscarinic). In addition,
all cholinergic synapses
because they increase the concentration of
We usually think of botulinum toxin as a very potent
acetylcholine, they have effects at the neuromuscular
poison that causes botulism. However, it has found a
junction (nicotinic).
therapeutic use in the treatment of prolonged muscle
Edrophonium is used in the diagnosis of myasthenia
spasm and for excessive sweating. a small amount of
gravis.
the toxin is injected directly into a muscle fiber
Neostigmine, Pyridostagmine, and ambenonium paralyzing the muscle, or in the skin blocking
are used in the treatment of myasthenia gravis. stimulation of the sweat glands. botulinum toxin is
Other uses of reversible cholinesterase inhibitors: also being used to treat wrinkles.
treatment of open-angle glaucoma
Pralidoxime and atropine are used to treat Most of the sympathetic postganglionic fibers
poisoning with organophosphates. release norepinephrine. at the target organ
The prototypic muscarinic antagonist is ATROPINE. norepinephrine interacts with a variety of
All of the muscarinic antagonists are competitive receptors.
antagonists for the binding of acetylcholine to the
muscarinic receptor. The effect of NE is terminated predominantly by
the effects and side effects of these drugs are the reuptake into the neuron from which it was
opposite of the drugs considered in the previous released.
chapter (the cholinomimetics) Norepinephrine can also be inactivated by
Eye mydriasis, cycloplegia ( blurred vision) enzymes in the liver (mostly) and brain (some).
Skin reduced sweating, flushing The degradative enzymes are called COMT
Gastrointestinal reduced motility and secretion MAO
(catechol-omethyltransferase) and
Cardiovascular increased heart rate (high doses) (monoamine oxidase)
Respiratory bronchial dilation and decreased
secretion
Genitourinary urinary retention
Pharmacology maintaining the internal environment of the body or
homeostasis Within the autonomic nervous system,
two neurons are required to reach a target organ, a
• An agonist is a compound that binds to a
preganglionic neuron and a postganglionic neuron. All
receptor and produces the biological preganglionic neurons release acetylcholine as their
response transmitter. The acetylcholine binds to nicotinic
•A partial agonist produces the biological
response but cannot produce 100% of the receptors on the postganglionic cell
biological response even at very high doses
• Efficacy is the maximal response a drug can AUTONOMIC NERVOUS SYSTEM
produce SYMPATHETIC
• Potency is a measure of the dose that is - Catabolic
required to produce a response - Thoracolumbar
• Antagonists block or reverse the effect of - Long postganglionic
agonists. They have no effect of their own PARASYMPATHETIC
FIRST-PASS EFFECT - Anabolic
• The liver is a metabolic machine and often - Craniosacral
inactivates drugs on their way from the GI tract - Short postganglionic
to the body. This is called the first-pass effect. All of the parasympathetic postganglionic fibers release
• Drugs cross membranes by passive diffusion or acetylcholine. at the target organ acetylcholine
• active transport interacts with muscarinic receptors. Acetylcholine is
A drug tends to pass through membranes if it synthesized from acetyl coenzyme A (acetyl CoA) and
• is uncharged choline. Its action is terminated by
Uncharged drugs or more lipid-soluble than acetylcholinesterase.
charged drugs. In addition, many drugs are
There are two major classes of receptors for
weak acids or weak bases.
acetylcholine, muscarinic and nicotinic
These muscarinic receptors are predominantly found in
Bioavailability is the amount of drug that is absorbed the viscera (GI tract)
after administration of route x compared with the
Nicotinic receptors are found at the motor end plate,
amount of drug that is absorbed after intravenous
in all autonomic ganglia, and in the adrenal medulla
administration. X is any route of drug administration
other than IV. Activation of muscarinic receptors results in the
bioavailability = AUC oral / AUC IV following responses:
Clearance is a term that indicates the rate at which a Eye miosis (constriction of pupil)
Cardiovascular (decrease in heart rate)
drug is cleared from the body. It is defined as the
volume of plasma from which all drug is removed in a Respiratory bronchial constriction and increased
given time. Thus, the units for clearance are given in secretions
volume per unit time Gastrointestinal (GI) increased motility, relaxation of
clearance = rate of removal of drug (mg/min) / plasma sphincters
concentration of drug (mg/min) Genitourinary (GU) relaxation of sphincters and
The total body clearance is the sum of the clearances
bladder wall contraction
from the various organs involved in drug metabolism
and elimination
DIRECT CHOLINERGIC AGONISTS
Esters Alkaloids
RENAL EXCRETION BETHANECHOL muscarine
renal elimination of drugs involves three physiological carbachol pilocarpine
processes:
a. glomerular filtration Bethanechol is used in the treatment of urinary
b. proximal tubular secretion retention Carbachol administered ocularly to induce
c. distal tubular reabsorption miosis to reduce intraocular pressure in the treatment
of
, glaucoma is also used to stimulate micturition by Muscarinic antagonists
contraction of detrusor muscle. Atropine
Muscarine is a nonselective agonist of the muscarinic Benztropine
acetylcholine receptors Ipratropium
Pilocarpine is a medication used to reduce pressure Scopolamine
inside the eye and treat dry mouth
Muscarinic antagonists are used preoperatively to
CHOLINESTERASE INHIBITORS
reduce secretions
REVERSIBLE INHIBITORS SCOPOLAMINE Is used to prevent a motion sickness
Edrophonium IPRATROPIUM Is used in the treatment of chronic
Neostagmine obstructive pulmonary disease to
produce
Pyridostagmine bronchodilation
ambenomium
demecarium The competitive neuromuscular blocking drugs are
physostigmine used to produce skeletal muscle relaxation
SUCCINYLCHOLINE Is a depolarizing neuromuscular
blocker.
IRREVERSIBLE INHIBTORS Nondepolarizing blockers
malathion d-TUBOCURRANE mivacurium cisatracurium
parathion pipecuronium vecuronium
sarin Atracurium pancuronium doxacurium rocuronium
soman The neuromuscular junction and other cholinergic
synapses can also be blocked by drugs that block the
release of acetylcholine
These drugs have all the same actions and side effects
Botulinum toxin blocks the release of acetylcholine at
as the direct acting drugs (muscarinic). In addition,
all cholinergic synapses
because they increase the concentration of
We usually think of botulinum toxin as a very potent
acetylcholine, they have effects at the neuromuscular
poison that causes botulism. However, it has found a
junction (nicotinic).
therapeutic use in the treatment of prolonged muscle
Edrophonium is used in the diagnosis of myasthenia
spasm and for excessive sweating. a small amount of
gravis.
the toxin is injected directly into a muscle fiber
Neostigmine, Pyridostagmine, and ambenonium paralyzing the muscle, or in the skin blocking
are used in the treatment of myasthenia gravis. stimulation of the sweat glands. botulinum toxin is
Other uses of reversible cholinesterase inhibitors: also being used to treat wrinkles.
treatment of open-angle glaucoma
Pralidoxime and atropine are used to treat Most of the sympathetic postganglionic fibers
poisoning with organophosphates. release norepinephrine. at the target organ
The prototypic muscarinic antagonist is ATROPINE. norepinephrine interacts with a variety of
All of the muscarinic antagonists are competitive receptors.
antagonists for the binding of acetylcholine to the
muscarinic receptor. The effect of NE is terminated predominantly by
the effects and side effects of these drugs are the reuptake into the neuron from which it was
opposite of the drugs considered in the previous released.
chapter (the cholinomimetics) Norepinephrine can also be inactivated by
Eye mydriasis, cycloplegia ( blurred vision) enzymes in the liver (mostly) and brain (some).
Skin reduced sweating, flushing The degradative enzymes are called COMT
Gastrointestinal reduced motility and secretion MAO
(catechol-omethyltransferase) and
Cardiovascular increased heart rate (high doses) (monoamine oxidase)
Respiratory bronchial dilation and decreased
secretion
Genitourinary urinary retention
