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Physiology of PNS, intro to cholinergic drugs, intro to adrenergic drugs

To understand any particular PNS drug you need 3 types of info?

(1) The type (or types) of receptor thru which the drug acts, (2) The normal response to activation of those receptors , (3) What the drug in question does to receptor function (ie, does it Inc/Dec receptor activation?)

Activating Beta1

Inc's cardiac output (by inc'g heart rate & force of contraction)

Activating Beta2

dilation of the bronchi & elevation of blood glucose

The Peripheral Nervous System employs 3 neurotransmitters

(1) acetylcholine, (2) norepinephrine, (3) epinephrine

Acetylcholine is the transmitter released by - 5

(1) ALL preganglionic neurons of the PNS, (2) ALL preganglionic neurons of the SNS, (3) ALL postganglionic neurons of the PNS, (4) ALL motor neurons to skeletal muscles, and (5) most postganglionic neurons of the SNS that go to sweat glands

Norepinephrine is the transmitter released by ?

Practically ALL postganglionic neurons of the SNS. The only exceptions are the postganglionic sympathetic neurons that go to sweat glands, which employ Ach as their transmitter.

Epinephrine is the major neurotransmitter released by?

Adrenal Medulla (the adrenal medulla also releases some NE)

List the 3 Cholinergic receptor subtypes

(1) NicotinicN, (2) NicotinicM, (3) Muscarinic

ACh can activate ?

All 3 Cholinergic receptor subtypes

NicotinicN receptors are located?

(1) Cell bodies of ALL Postganglionic Neurons of the PNS & SNS. (2) and the cells of the Adrenal Medulla

Response to NicotinicN receptor activation

Stimulation of Parasympathetic & sympathetic postganglionic nerves & release of Epinephrine from the Adrenal Medulla

Receptor Agonists for NicotinicN


Receptor Antagonists for NicotinicN


NicotinicM receptors are located?

Skeletal muscle

Response to NicotinicM receptor activation

Contraction of skeletal muscle

Receptor Agonists for NicotinicM

Nicotine( The doses needed to activate nicotinicM receptors of the NMJs are much higher than the doses needed to activate nicotinicN)

Receptor Antagonists for NicotinicM

d-Tubocurarine, succinylcholine

Muscarinic receptors are located?

(1) All Organs regulated by the PNS (2) sweat glands (of the SNS) Muscarinic cholinergic receptors on blood vessels rqr addtl comment. These receptors are not assoc'd w/ the nervous system in any way. That is, no autonomic nerves terminate at vascular muscarinic receptors. However, regardless of their physiologic relevance, the cholinergic receptors on blood vessels do have pharmacologic significance. Why? Because drugs that are able to activate these receptors cause vasodilation, which in turn causes blood pressure to fall.

Response to Muscarinic Receptor Activation

(1) Eye: contraction of the ciliary muscle focus the lens for near vision (2) contraction of the Iris sphincter muscle causes miosis (dec'd pupil diam) (3) Heart : dec'd rate (4) Lung : constriction of bronchi (5) Bladder: promotion of secretions, contraction of detrusor inc's bladder pressure, relaxation of trigone & sphincter allows urine to leave (6) GI tract: Salivation, Inc'd gastric secretions, Inc'd intestinal tone, & mobility, Defecation (7) Sweat Glands: generalized sweating (8) Sex organs: Erection (9) Blood Vessels: Vasodilation

Receptor Agonists for Muscarinic


Receptor Antagonists for Muscarinic


List Adrenergic Receptor Subtypes

(1) Alpha1 (2) Alpha2 (3) Beta1 (4) Beta2 (5) Dopamine

Adrenergic receptors - alpha, beta, or both are located?

(1) ALL Organs (except sweat glands) regulated by the SNS (2) & Organs regulated by Epinephrine released from the Adrenal Medulla

Response of Alpha1 Peripheral Adrenergic Subtype

(1) Eye: Contraction of radial muscle of iris (like spokes of wheel) causes mydriasis (Inc'd pupil sz) (2) Arterioles: Constriction (skin, viscera, mucous membranes (3) sex organs, male: Ejaculation (4) Prostate Capsule: Contraction (5) Bladder: Contraction of trigone & sphincter

Response of Alpha2 Peripheral Adrenergic Subtype

(1) Presynaptic nerve terminals: Inhibition of transmitter release (located on the nerve terminals and not on the organs innervated by the ANS)

Response of Beta1 Peripheral Adrenergic Subtype

(1) Heart: Inc'd rate, Inc'd force of contraction, Inc'd AV conduction velocity (2) Kidney: Release of renin (promotes synthesis of angiotensin, a powerful vasoconstrictor, helps elevated BP.

Response of Beta2 Peripheral Adrenergic Subtype

(1) Arterioles (heart, lung, & skeletal muscle) causes vasodilation (2) Bronchi: dilation (3) Uterus: Relaxation (4) Liver Glycogenolysis (5) Skeletal Muscle: Enhanced contraction, glycogenolysis

Response of Dopamine Peripheral Adrenergic Subtype

Kidney: dilation of kidney vasculature (In the CNS the dopamine receptors are of great therapeutic importance)

List the 3 Adrenergic transmitters

(1) Epinephrine (2) NE (3) dopamine

Receptor specificity of adrenergic transmitters

(1) Epinephrine can activate ALL Alpha & Beta receptors, but NOT dopamine receptors (2) NE can activate Alpha1, Alpha2, & Beta1 receptors, but NOT Beta2 or dopamine (3) Dopamine can activate Alpha1, Beta1, & Dopamine, but NOT Alpha2 or Beta2

Adrenergic agonists produce their effects by activating adrenergic receptors. Since the SNS acts thru these same receptors, responses to adrenergic agonists & responses to stimulation of the SNS are very similar. Thus, adrenergic agonists are often called?


Adrenergic agonists fall into 2 major chemical classes:

catecholamines & noncatecholamines

Catecholamines & noncatecholamines differ in 3 important respects:

(1) oral usability, (2) duration of action, (3) the ability to act in the CNS

Catecholamines have 3 properties in common:

(1) CANNOT be use orally, (2) brief duration of action, (3) CANNOT cross the blood-brain barrier (The actions of 2 enzymes monoamine oxidase (MAO) & catechol-O-methyltransferase (COMT) - explain why the catecholamines have short ½-lives and cannot be used orally. MAO & COMT are located in the liver & intestinal wall.

List the 5 catecholamines:

NE, Epinephrine, Isoproterenol, Dopamine, & Dobutamine

3 catecholamines are only effective if admin'd by cont infusion?

NE, dopamine, & dobutamine

Catecholamines are polar molecules, and hence CANNOT ____?

Cross the blood-brain barrier and thus have minimal effect on the CNS. The polar nature of the catecholamines are d/t the hydroxyl groups on the catechol portion of the molecule.

Noncatecholamines have ethylamine in their structure, but do NOT contain?

the catechol moiety that characterizes catecholamines.

3 Noncatecholamines:

(1) ephedrine, (2) albuterol, (3) phenylephrine

Noncatecholamines differ from catecholamines in 3 important respects?

(1)lack a catechol group so their ½ -lives are much LONGER, (2) Because they do NOT undergo rapid degradation by MAO & COMT they can be given ORALLY, (3) considerably less polar than catecholamines, and hence are more able to cross the blood-brain barrier.

Receptor specificity is relative, not absolute. The ability of a drug to selectively activate certain receptors to the exclusion of others depends on the dosage:?

(1) Low doses - selectivity is maximal, (2) As dosage Inc's - selectivity declines

Receptor Specificity of Representative Adrenergic Agonists Catecholamines: Epinephrine?

Alpha1, Alpha2, Beta1, Beta2

Receptor Specificity of Representative Adrenergic Agonists Catecholamines: NE?

Alpha1, Alpha2, Beta1

Receptor Specificity of Representative Adrenergic Agonists Catecholamines: Isoproterenol?

Beta1 & Beta2

Receptor Specificity of Representative Adrenergic Agonists Catecholamines: Dobutamine?


Receptor Specificity of Representative Adrenergic Agonists Catecholamines: Dopamine?

Alpha1, Beta1 & Dopamine

Receptor Specificity of Representative Adrenergic Agonists Noncatecholamines: Ephedrine?

Alpha1, Alpha2, Beta1, Beta2

Receptor Specificity of Representative Adrenergic Agonists Noncatecholamines: Phenylephrine?


Receptor Specificity of Representative Adrenergic Agonists Noncatecholamines: Albuterol?


To understand the effects of any specific adrenergic agonist, all you need is 2 types of info:

(1) identity of the receptors at which the drug acts (2) effects produced by activating those receptors. This will reveal a profile of drug action

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