Pharm. Test two material
The ANS is consists of efferent neurons in the peripheral nervous system. They control three different type of cells
-Smooth muscle, cardiac muscle, and gland cells, and gland cells.
Parasympathetic pathway:
ACh is released from the preganglionic neuron over the synapse and stimulates cholinergic (nicotine) receptors. Then ACh is released from the postganglionic neuron, which activates the cholinergic (muscarinic) receptors on the target tissue.
Sympathetic pathway:
Acetylcholine (ACh) is released from the preganglionic neuron and stimulates cholinergic (nicotine) receptors on the postganglionic neuron. Then, norepinephrine (NE) is released from the end of the postganglionic neuron, which is then transmitted to the target tissue, where it activates receptors on the surface. These adrenergic (sympathetic) receptors are either alpha (a) or beta (b).
The primary chemical neurotransmitter for both PANS and SANS /b/ the preganglionic and postganglionic fibers is __________________
Acetylcholine (ACh).
Mechanism of action
Acetylcholine- synthesis and inactivation (termination by the enzyme acetylcholinesterase ACHe) Choline acetyltransferase
Nicotinic
Areas affected - 1. Postganglionic neurons 2. Skeletal muscle end-plates neurotransmitter - ACh Location- autonomic ganglia and neuromuscular junction Stimulated by nicotine Blocked by hexamethonium (autonomic) and d-tubocurarine (neuromuscular junction)
Peripheral nervous system (PNS) divided into
Autonomic (Involuntary) nervous system (ANS) Somatic (Voluntary) nervous system (SNS)
Smooth muscle stimulation
Bronchoconstriction GI effects
preganglionic neurons that secrete ACh are also called _______________ neurons
Cholinergic
Cardiovascular effects
Cholinergic agents effects on the cardiovascular system. (Bradycardia, ¯ BP and ¯ cardiac output)
Adrenergic Receptors
Different effector tissues (smooth muscle, cardiac muscle, and glands) contain different types of receptors with which the sympathetic neurotransmitters, NE, and EPI, may interact.
Indirect-acting agents
Inhibit the enzyme cholinesterase (which breaks down ACh).
Cholinergic Agents
Mimics the effects of the Parasympathetic nervous system. o (miosis, salivation, GI tract motility, Bradycardia)
_______ organs of the body are innervated by neurons of both the sympathetic and parasympathetic divisions of the ANS.
Most
General rule: ______ is released from most postganglionic neurons (aka Adrenergic neurons), which then crosses the synapse and has an effect on the tissue/organs.
NE
___________________________ is the primary chemical neurotransmitter for the SANS /b/ the postganglionic fiber and the effector organ.
NOREPINEPHRINE (NE)
ACh causes excitation of the adrenergic postganglionic nerve and initiates the synthesis and release of __________________________ from most postganglionic nerve terminals into the neuroeffector junction.
Norepinephrine (NE)
SLUD
Salivation Lacrimation Urination Defecation
exceptions to the general rule regarding NE
Sweat glands Adrenal medulla
· Autonomic nervous system (ANS)
Sympathetic nervous system Parasympathetic nervous system
Pilocarpine (Isopto Carpine)
Treatment of glaucoma
Neurotransmitters
Two neurons do not actually contact each other; a nerve impulse from the brain cannot cross from one neuron to the next. Instead, in the synapse region the electrical signal that has been transmitted the length of the preganglionic neuron located in the brain is transformed into a chemical signal through the release of a substance called a neurotransmitter.
• Synapses of the autonomic system are classified as either
_cholinergic_, meaning that acetylcholine (ACh) is released, or _adrenergic_, meaning that norepinephrine is released.
Direct-acting agents
acetylcholine derivatives that mimic PANS simulation but for a longer duration and with greater selectivity. (example: Pilocarpine, acts like pan helps you salivate)
Neurotransmitters are released in response to the nerve ____________ _________ so as to interact with the receptor.
action potential
Norepinephrine is released by _________________ fibers
adrenergic
SANS: Norepinephrine (NE) is the transmitter substance released by the postganglionic nerves. It is called _____________
adrenergic
Postganglionic
after the synaptic cleft
Conventional neurotransmitters
amino acids Biogenic amines Purinergic neurotransmitters Acetylcholine Neuropeptides
Muscarinic
areas affected- smooth muscle, cardiac muscle, gland cells neurotransmitter -ACh location- synapse /b/ postganglionic and effector organ the PANS stimulated by muscarine blocked by atropine
Drugs that stimulate or inhibit different components of the ANS are the ____________ _________________
autonomic drugs
Preganglionic
before synaptic cleft
Cholinergic agents excite smooth muscle of the GI tract-producing and increase in GI motility, and an increase in activity, and secretion. Used to treat postoperative ileus (GI/GU) - [a painful obstruction of the ileum or other part of the intestine.] with drugs like...
bethanechol (Urecholine)
· Central nervous system (CNS)-
brain and spinal cord-receives sensory from the peripheral nervous system.
• Adrenergic neurotransmitter NE is also known as a ...
catecholamine.
Acetylcholine is released by ______________ fibers
cholinergic
• The terms cholinergic and adrenergic refer not only to the signaling molecule that is released but also to the __________ ___ _________ that each binds.
class of receptors
PANS is concerned with ...
conservation of body processes (Rest and Digest)
Sympathetic responses are more ____________ because a single SANS preganglionic fiber often synapse with numerous postganglionic neurons. The longer post-ganglionic fibers terminating at the effector organ or tissues.
diffuse
cholinergic agents are classified as ...
direct acting indirect acting
Biogenic amines
dopamine, norepinephrine, epinephrine, serotonin, and histamine, which are made from amino acid precursors. The biogenic amines are related to specific amino acids: o Dopamine, norepinephrine, and epinephrine, are synthesized from (and closely related to) the amino acid tyrosine.
The postganglionic neuron originates in the ganglia and innervates or passes out to the ____________ _____________
effector organ.
SANS is designed for ...
emergencies (Fight-or-Flight)
Cholinergic drugs affect the GI tract
excitation of smooth muscle, which causes increased activity and secretions. These secretions include salivation, lacrimation sweating, and increased stomach acid production.
Acetylcholine (ACh) is the neurotransmitter released
from the parasympathetic preganglionic and postganglionic nerves. In each instance, the released ACh binds to and acts on cholinergic receptors contained in the postsynaptic nerve and the effector tissue.
Glands
increased secretion of saliva; used to treat xerostomia
· Somatic nervous system
innervates the skeletal muscles, causing contractions.
PANS: The neurotransmitter released from the postganglionic nerve is acetylcholine. It is also termedcholinergic. Because the postsynaptic tissue responds to muscarine, it is called ___________
muscarinic
They are synthesized in the neuron and stored in vesicles located in the axon terminal of one neuron. In response to a nerve action potential (nerve impulse), the neurotransmitter is released from the vesicles into the synaptic space and bind to receptors on the post synaptic or postganglionic neuron.
neurotransmitters
• One response may be between the preganglionic and postganglionic nerves. In this response, acetylcholine is the neurotransmitter. Nerves that release acetylcholine are cholinergic. Because this synapse is stimulated by nicotine, it is termed ____________ in response.
nicotinic
Generally, stimulation of the sympathetic (adrenergic) and parasympathetic (cholinergic) nerves cause ___________ ____________. If one division increases the activity of an organ, the other generally decreases it.
opposite responses
Because post-ganglionic fibers are short and close to the effector organ, there is usually a low ratio of synaptic connections between pre and postganglionic neurons, thus ___________________ responses are discrete
parasympathetic
Acetylcholine (Ach) is also the chemical transmitter at the synapse between the __________________ __________________ ________________ and the effector organ.
parasympathetic postganglionic fiber
Alpha1 & Alpha2 receptors are located on _________ganglionic neurons.
post
The pre-ganglionic fiber leaves the CNS and extends to the ganglia, at the synapse with the ____________ ____________ _____________
post-ganglionic neuron.
ACh is released from ALL ____-ganglionic neurons (SANS & PANS).
pre
Acetylcholine (ACh)
primary neurotransmitter for both PANS and SANS /b/ the preganglionic and postganglionic fibers. is also the chemical transmitter at the synapse between the parasympathetic post-ganglionic fiber and the effector organ. Cholinergic fibers release acetylcholine.
The ________ of the neurotransmitter is to carry nerve impulses (action potentials) across the synapse.
purpose
The preganglionic fibers of the PANS are ...
relatively long and extend near or into the innervated organ
The only organs not innervated by both sympathetic and parasympathetic are the ...
sweat glands, smooth muscles of the hair follicles, the adrenal medulla, and blood vessels of the skin.
Communication between nerves or between nerves and effector tissue takes place by the release of neurotransmitters across the _________ ____________
synaptic cleft
Norepinephrine (NE)
the primary neurotransmitter for the sympathetic post-ganglionic fiber and the effector organ. Adrenergic fibers release norepinephrine.
• Neurotransmitters are released in response to the nerve action potential so as to interact with the receptor. The specificity of the neurotransmitter and receptors dictates the _____________ ______________
tissue response.
The postganglionic fibers, originating in the ganglia, are ...
usually short and terminate on the innervated tissue.
How does one neuron communicate with the next neuron and with the organ they innervate?
via neurotransmitters o Chemical substances made in the neurons that are released when an action potential comes down the neuron
Each systems consists of a chain of two neurons connecting the CNS to the target cell. The difference is
where they start and whether there is a short first axon and long second axon (SANS) or long first axon and short second axon (PANS).
what are cholinergic drugs used for ...
· primarily used in the treatment of xerostomia (cevimeline, pilocarpine) and Alzheimer's disease (donepezil, tacrine, rivastigmine).
Sympathetic Division: Neurotransmitters aka Catecholamines
• Catecholamines derived from the amino acid tyrosine are water-soluble and are 50% bound to plasma proteins in circulation. • Others: epinephrine (adrenaline), norepinephrine (noradrenaline), and dopamine. • Release of the hormones epinephrine and norepinephrine from the adrenal medulla of the adrenal glands is part of the fight-or-flight response.
• Receptors are located on the
• Dendrites of postganglionic neurons and • On/in smooth muscle, cardiac muscle, and glands
Alpha1 (α1)
• Found in smooth muscle cells of blood vessels. • The principal effect of activation of these receptors is vasoconstriction and smooth muscle of most organs (skin, eye bladder, intestine, salivary glands) when NE is released. • Blood vessels with α1-adrenergic receptors are present in the skeletal muscles, skin, the sphincters of gastrointestinal system, kidney (renal artery), coronary vessels, brain, and eyes (mydriasis). • Activation of α1 -receptors (fight-or-flight response) leads to vasoconstriction resulting in decreased blood flow to these organs. (vasoconstriction, decreased GI motility, urinary retention, and mydriasis)
Alpha2 (α2)
• Found on postganglionic neurons • Activation of α2-receptors (autoreceptors) causes inhibition of NE release, decreases secretion of insulin, decreases blood pressure, and decreases eye secretion. (Functions like a feedback inhibition loop)
• Β2
• Found on smooth muscle of the __bronchioles__ (bronchodilation), uterine, and vascular beds (arteries, veins) • Blood vessels to skeletal muscles (vasodilation) • Blood vessels supplying the heart and kidneys. • Activation causes relaxation of these smooth muscles thus vasodilation lowering peripheral resistance. (Cancels effect of β1 regarding mean blood pressure)
• β3
• Found on/in fat tissue
• β1
• Found on/in heart tissue • Activation(stimulation) leads to • _increase__ heart rate (positive chronotropic effect) tachycardia • _increase__ heart contractility or strength (positive inotropic effect) • Found in Kidneys • Activation reduces secretion of renin (involved in the formation in the blood stream of angiotensin II that causes hypertension.
adrenal medulla
• Innervated by a sympathetic preganglionic nerve that releases ACh. • The ACh then causes the release of two hormones, EPI (85%) and NE (15%). • No postganglionic fibers
Muscarinic (cholinergic)Receptors
• Mainly found ins smooth muscle, heart, and glands • Chief neurotransmitter is Acetylcholine (ACh) • Located in tissue innervated by parasympathetic postganglionic nerves (and by sympathetic cholinergic nerves), which innervate sweat glands and skeletal muscles, also in parasympathetic postganglionic nerves of eyes, gut, penis, lung. • Activation of muscarinic receptors resembles those produced when a person eats poison mushroom Amantia muscaria (thus the name).
Parasympathetic Nervous System
• Parasympathetic innervation predominates over sympathetic innervation of salivary glands and lacrimal glands.
drugs for glands
• Pilocarpine (Salagen)- Tx for xerostomia (p.o.) (affinity for muscarinic receptor) • Cevimeline (Evoxac) - Tx for xerostomia (p.o.) (muscarinic receptor stimulation)
• Bronchoconstriction—stimulates bronchial smooth muscle
• [methacholine (Provocholine) -diagnosis of Asthma]
These adrenergic receptors are referred to as
• alpha (α) • beta (β)-receptors.
sweat glands
• innervated only by sympathetic cholinergic pathway, which releases ACh to cause sweating. • Thus, these postganglionic fibers are cholinergic, not adrenergic.
Nicotinic Receptors
• skeletal muscle (neuromuscular junction) • central nervous system • Stimulation causes contraction of skeletal muscle and neurotransmission in the CNS. • Chief neurotransmitter is Acetylcholine (ACh) • Activation of nicotinic receptors on skeletal muscle causes muscle contraction. Not many pharmacologic applications of stimulating nicotinic receptors.
what are the three subtypes of beta receptors
• β1 • Β2 • β3