[03.17] Adrenergics & Anti-Adrenergics V2.1.pdf

PANS (Parasympathetic Autonomic Nervous System)

The division of the ANS referred to as "Rest and Digest" or "Housekeeping"

SANS (Sympathetic Autonomic Nervous System)

The division of the ANS referred to as "Fight or Flight" or "Emergency" response

Acetylcholine (ACh)

The neurotransmitter primarily associated with the PANS

Epinephrine, Norepinephrine, Dopamine

The neurotransmitters primarily associated with the SANS

Craniosacral

The origin of nerves for the PANS

Thoracolumbar

The origin of nerves for the SANS

Muscarinic

The main receptor type for autonomic target organs in the PANS

Alpha (ɑ) and Beta (β)

The main receptor types in the SANS

Blood pressure increases, Heart rate increases, Bronchodilation, Pupillary dilation, Decreased bowel movement

The primary effects of the sympathetic nervous system during emergencies

Antimuscarinic drugs

The type of drugs that block cholinergic effects and mimic sympathetic effects

Cholinergic fibers

The type of fibers found in the preganglionic neurons of both the parasympathetic and sympathetic systems

Nicotinic receptors

The receptors activated by ACh from preganglionic neurons in both PANS and SANS

Far from the target organ

The location of SANS ganglia relative to target organs

Near or even within the target organ

The location of PANS ganglia relative to target organs

ACh

The neurotransmitter secreted by PANS postganglionic neurons

Muscarinic receptors

The receptors activated by PANS postganglionic neurons

Catecholamines (Epinephrine, Norepinephrine)

The neurotransmitters secreted by SANS postganglionic neurons

Alpha (ɑ) or Beta (β) receptors

The receptors activated by SANS postganglionic neurons

Adrenal gland

What SANS also activates to produce catecholamines for systemic effects

Dilate/Mydriasis

The sympathetic effect on pupils

Constrict/Miosis

The parasympathetic effect on pupils

Accelerates

The sympathetic effect on heart rate

Decelerates

The parasympathetic effect on heart rate

Constricts (except skeletal muscle vessels)

The sympathetic effect on blood vessels

Dilation

The parasympathetic effect on blood vessels

Dilate

The sympathetic effect on bronchioles

Constrict

The parasympathetic effect on bronchioles

Decrease

The sympathetic effect on GI peristalsis

Increase

The parasympathetic effect on GI peristalsis

Contract

The sympathetic effect on sphincters

Relax

The parasympathetic effect on sphincters

Relaxes (Promotes urinary retention)

The sympathetic effect on the bladder

Contracts (Promotes micturition)

The parasympathetic effect on the bladder

Increase sweating (M), Pilomotor contraction

The sympathetic effects on skin

Prostate contraction, Ejaculation

The sympathetic effects on the male reproductive system

Penile erection

The parasympathetic effect on the male reproductive system

Relaxes

The sympathetic effect on the uterus

Contracts

The parasympathetic effect on the uterus

↑ Gluconeogenesis, ↑ Glycogenolysis, ↑ Lipolysis, ↑ Renin Release

The sympathetic effects on metabolism

Pupillary dilation, Increased heart rate, Constriction of blood vessels

The effects expected in an emergency situation (sympathetic response)

Blood vessels of skeletal muscles

The exception to sympathetic vasoconstriction, where blood supply is increased

Penile erection upon waking up

A "rest and digest" function explained by the parasympathetic response

Alpha 1 (α1) receptor

The receptor that promotes contraction of the radial muscles of the iris, causing pupillary dilation

M3 receptor

The receptor that promotes contraction of the circular muscles of the iris, causing pupillary constriction

β1 and β2 receptors

The receptors responsible for increased heart rate and contractility in SANS

Alpha (ɑ) receptors

The receptors important for vasoconstriction in SANS blood vessels

β2 receptors

The receptors that relax bronchiolar smooth muscles in SANS

Relax walls and contract sphincters

The sympathetic effects on the GI tract

Bladder wall relaxes, Sphincter contracts

The sympathetic effects on GU smooth muscles

Eccrine (Muscarinic (M) receptors), Apocrine (ɑ receptors)

The types of sweat glands activated by SANS

ACh (Acetylcholine)

The neurotransmitter secreted by sympathetic postganglionic neurons in sweat glands and certain blood vessels of the skin and skeletal muscles

Atropine

The prototype antimuscarinic drug that blocks parasympathetic activity, leading to sympathetic effects and dry skin

Extension of their physiologic or expected actions

What side effects of autonomic medications are considered

Tachycardia

A side effect of β2 receptor activation (e.g., asthma medication) also activating the heart

Alpha (ɑ) receptors

Receptors found in vessels and pupils, causing vasoconstriction and pupillary dilation

Beta-1 (β1) receptor

Receptor found in the heart, causing accelerated heart rate

Beta-2 (β2) receptor

Receptor found in the lungs, causing bronchodilation

Catecholamines and Sympathomimetics

The two major groups of Adrenergics

Epinephrine (adrenaline) and Norepinephrine (noradrenaline)

The naturally occurring catecholamines

Adrenal medulla

The gland that secretes catecholamines during short-term/acute/emergency stress

Adrenal cortex

The gland that secretes corticosteroids during prolonged/chronic stress

Glucocorticoids

Corticosteroids that increase blood sugar

Mineralocorticoids

Corticosteroids that promote sodium retention

Sympathomimetics

Drugs that mimic the action of natural catecholamines

Direct

Mode of action where adrenergics bind directly to α and β receptors

Indirect

Mode of action where sympathomimetics enhance endogenous catecholamine action without direct binding

Trigger release of catecholamines, Inhibit reuptake of catecholamines, Inhibit metabolizing enzymes

Three mechanisms of indirect-acting sympathomimetics

Amphetamines

Sympathomimetics that trigger release of catecholamines from nerve endings

Cocaine and Tricyclic antidepressants

Sympathomimetics that inhibit reuptake of released catecholamines

Monoamine oxidase (MAO) and Catechol-O-methyltransferase (COMT) inhibitors

Examples of drugs that inhibit enzymes metabolizing catecholamines

G-protein-coupled receptors (GPCRs)

The type of receptors that mediate the effects of catecholamines

Gq

The G-protein linked to the α1 receptor

↑ Phospholipase C → ↑ IP3, ↑ DAG, ↑ Cytoplasmic Ca2+

The effector/signaling pathway for the α1 receptor

Gi (inhibitory)

The G-protein linked to the α2 receptor

↓ Adenylyl cyclase → ↓ cAMP

The effector/signaling pathway for the α2 receptor

Gs (stimulatory)

The G-protein linked to β receptors

↑ Adenylyl cyclase → ↑ cAMP

The effector/signaling pathway for β receptors

Dopaminergic receptors

Subtype under adrenergic receptors, including D1-D5

Phenylephrine

A drug with high affinity for α1, but can activate α2 and β at higher concentrations, demonstrating receptor selectivity is not absolute

Tolerance

Requirement of a higher dose to produce a given response, gradual over days or weeks

Tachyphylaxis

Acute, rapid tolerance, observable even at the initial dose

Refractoriness

Loss of therapeutic efficiency, a form of tolerance

Adrenoceptor polymorphisms

Common genetic variations in humans that can lead to changes in amino acid sequences with pharmacological importance

Haplotypes

Sets of distinct polymorphisms inherited together

Norepinephrine Transporters (NET)

Transporters found in the presynaptic neuron that remove neurotransmitters from the synaptic cleft

90%

The percentage of released norepinephrine taken back into the presynaptic neuron in the heart

60%

The percentage of released norepinephrine taken back into the presynaptic neuron in the vasculature

Reenter vesicles or Undergo metabolism through MAO

The fate of norepinephrine once inside the presynaptic neuron

Enter the bloodstream or Be taken up into extraneuronal cells and metabolized by COMT

The fate of norepinephrine in the extracellular space (synaptic cleft)

Reuptake blockers (e.g., Amphetamine, Cocaine)

Drugs that increase norepinephrine levels in the synaptic cleft by blocking NET

Epinephrine (Adrenaline)

A mixed alpha and beta agonist with equal affinity for all adrenergic receptors (ɑ1=ɑ2; β1=β2)

Vasoconstriction

Effect of α receptor activation by Epinephrine

Cardiac stimulation (+ inotropic, + chronotropic effect)

Effect of β1 receptor activation by Epinephrine

Bronchodilation

Effect of β2 receptor activation by Epinephrine

Hypovolemic shock, Asthma, Epistaxis, Combined with local anesthetics, Anaphylactic shock

Uses of Epinephrine

Anaphylactic shock

A type of distributive shock that Epinephrine is the most important treatment for

0.3-0.5 mL of 1:1000 solution of epinephrine

The dose for anaphylactic shock

Norepinephrine (Noradrenaline/Levarterenol)

A mixed alpha and beta agonist with ɑ1=ɑ2; β1 >> β2 affinity

Septic shock

The primary use of Norepinephrine

Vasoconstriction

How Norepinephrine increases blood pressure in septic shock