1 Neurotransmission

what does the CNS consist of?

brain and spinal column

what does the PNS consist of?

motor (somatic and autonomic/visceral divisions) and sensory divisions

what does the somatic motor division provide?

innervation to skeletal muscle and controlled voluntary movements

what does the ANS do?

carries information to glands, cardiac and smooth muscles

what are the divisions of the ANS?

sympathetic and parasympathetic

where does the ANS carry nerve impulses?

away from the CNA to the effector organs

what is a preganglionic neuron?

the cell body of the first nerve cell located in the CNS emerging from the brain or spinal cord and synapse in ganglia in the PNS

what is a postganglionic neuron?

ganglia where the cell body of the second nerve cell is located that terminates on the effector organs

what are does the ANS provide innervation for?

heart, blood vessels, exocrine glands, visceral organs, smooth muscle

what does the ANS control?

controls digestion, cardiac output, blood flow and glandular secretions

where do sympathetic preganglionic neurons arise from?

thoracic and lumbar regions of the spinal cord

how many post ganglionic neurons can one preganglionic neuron interact with? why?

multiple so numerous effector organs can be activated at once

where do parasympathetic preganglionic neurons arise from?

brain and sacral region of the spinal cord

what is the arrangement between a parasympathetic preganglionic neuron and an organ? why?

one-to-one so activation is localized

what are effects of our fight or flight response?

trachea and bronchiole dilation

increased HR and contractility

relaxation of the detrusor muscle, contraction of bladder sphincter

decreased GI motility and tone

dilation of skeletal muscle vasculature

constriction of vasculature to the skin and mucus membranes

increased serum glucose

pupil dilation

what are the effects of rest and digest?

decreases HR and BP

increases GI movement and secretions

pupil constriction

bladder and bowel emptying

what is the physiology of neurotransmission?

electrical impulses are sent over the nerve fibers that end at effector cells which respond to the release of NTs

what are autonomic drugs?

those that affect the functioning of the ANS by either stimulating or blocking the action of the autonomic nerves

what does a neuron do?

generates and propagates an action potential along its axon, the transmits this signal across a synapse by releasing NTs

what are presynaptic neurons?

neurons that release NTs

what are postsynaptic neurons?

neurons that receive NT signals which may stimulate or inhibit the receiving cell, depending on the NT and receptor involved

what is conduction?

passage of an impulse along an axon

what is transmission?

passage of an impulse across a synaptic or neuroeffector junction

do most drugs modify transmission or conduction?

transmission

what drugs modify axonal conduction?

local anesthetics

what does the arrival of the action potential at the axonal terminal initiate?

a series of events triggering the transmission of either an excitatory or inhibitory impulse across the synapse or neuro-effector junction

what are the steps of junctional transmission?

storage and release of the NT into the synapse

NT interacts with post junctional receptors and produces and post junctional potential- either excitatory or inhibitory in its effect

initiation of another post-junctional activity

enzymatic destruction or dissipation of the NT

what are the NTs for parasympathetic preganglionic neuron?

acetylcholine

what are the NTs for sympathetic preganglionic neuron?

acetylcholine

what are the NTs for parasympathetic postganglionic neuron?

acetylcholine

what are the NTs for sympathetic postganglionic neuron?

norepinephrine

what are the receptors for parasympathetic preganglionic neuron?

nicotinic (cholinergic)

what are the receptors for sympathetic preganglionic neuron?

nicotinic (cholinergic)

what are the receptors for parasympathetic postganglionic neuron?

muscarinic (cholinergic)

what are the receptors for sympathetic postganglionic neuron?

alpha or beta (adrenergic)

what are the types of cholinergic receptors?

nicotinic and muscarinic

what enzyme is involved in the synthesis of Ach?

choline acetyltransferase

what enzyme is involved in the degradation of Ach?

acetylcholinesterase (AChE)

what are the sympathethic NTs?

catecholamines: norepinephrine (NE), dopamine (DA), epinephrine (epi)

what is the predominant transmitter of the extrapyramidal system of the brain?

dopamine

what is the major hormone of the adrenal medulla?

epinephrine

how are norepi and epi terminated by?

reuptake

what does metabolic transformation cause?

inactivation

what are two enzymes that perform metabolic transformation?

monoamine oxidase (MAO) and catechol-O-Methyltransferase

where are alpha 1 receptors primarily located?

blood vessels, pupils, urinary sphincter, stomach and prostate

where are alpha 2 receptors primarily located?

post-ganglionic presynaptic neuron

what do alpha 1 receptors do?

vasoconstriction at vascular smooth muscle

pupillary dilation

urinary sphincter contraction

what do alpha 2 receptors do?

pre-synaptic inhibition causing reduction of NE release

where are beta 1 receptors located?

heart

where are beta 2 receptors located?

lungs

what do beta 1 receptors do?

increase HR, cardiac contractility, release of renin

what do beta 2 receptors do?

bronchodilation, vasodilation of skeletal muscles

are cholinergic agonists parasympathetic or sympathetic?

parasympathetic

what are cholinergic agonists?

drugs that will stimulate a cholinergic/parasympathetic response when they stimulate the muscarinic reseptors

what is another name for cholinergic agonists?

parasympathomimetics

where are muscarinic receptors primarily found?

autonomic effector cells

what are the autonomic effector cells innervated by?

post-ganglionic parasympathetic nerves

what happens when muscarinic receptors are stimulated by Ach?

parasympathetic response- body does “regulatory housekeeping” activities

what are “regulatory housekeeping” activities?

vasodilation, decrease HR, decrease cardiac contractility

what happens in the GI system with muscarinic receptor agonists?

increase tone (cramping)

increase amplitude of contraction, peristaltic activity (belching and defecation)

enhanced secretory activity (nausea, emesis)

what happens in the urinary tract with muscarinic receptor agonists?

increase ureteral peristalsis

contraction of the bladder muscles

increase maximal voluntary voiding pressure

decrease bladder capacity

what happens to secretions with muscarinic receptor agonists?

increase lacrimal, tracheobronchial, salivary, digestive, sweat secretions

what happens in the eye with muscarinic receptor agonists?

miosis of the pupil (constriction)

what happens with direct stimulators of muscarinic receptors?

increased GI motility and tone

stimulates the detrusor muscle of the bladder promoting urination

rapid miosis, ciliary mm contraction when applied directly to eye

potent stimulator of secretions

what happens with indirect stimulators of muscarinic receptors?

work by inhibiting acetylcholinesterase, increasing amount of ach in the synaptic space

prolong parasympathetic activity

what is the treatment for mushroom poisoning?

atropine

what are cholinergic antagonists?

drugs that will inhibit a cholinergic/parasympathetic response when they bind to the cholinergic receptors, block the muscarinic receptors and prevent the effects of Ach (anticholinergics)

what is another name for cholinergic antagonists?

anticholinergics/antimuscarinics

what happens to the sympathetic innervation when the parasympathetic activity is blocked?

sympathetic innervation is left unopposed- gets more sympathetic

what happens to the cardiovascular system when the muscarinic receptors are blocked?

tachycardia and hypertension

what happens to the respiratory system when the muscarinic receptors are blocked?

bronchodilation and inhibition of secretions

what happens to the GI system when the muscarinic receptors are blocked?

decreased tone and secretions (saliva)

what happens to the urinary system when the muscarinic receptors are blocked?

increased bladder capacity, decreased detrusor contractions

what happens to the eye when the muscarinic receptors are blocked?

cycloplegia (loss of accommodation), mydriasis (pupil dilation)

what are the effects of atropine?

preoperatively to inhibit salivation and secretions; treatment of bradycardia, antidote for overdose of cholinergic, treatment of organophosphate poisoning and some types of mushroom poisoning

what are the effects of lomotil?

anti-diarrheal

what are the effects of opthalmic agents?

pupillary dilation

what are the effects of ditropan?

urinary anti-spasmodic

what are the effects of atrovent?

short acting bronchodilator for asthma

what are the effects of spiriva?

long acting bronchodilator for COPD

what are the effects of cogentin and artane?

for Parkinson’s disease and extrapyramidal effects of anti-psychotics

what are the effects of bentyl and levsin?

GI anti-spasmodic

what are the effects of many antihistamines and antidepressants?

anti-muscarinic activity

what are the major limitations of any anticholinergic drug?

ability to attain a desired therapeutic response without concomitant side effects

what is the saying for atropine poisoning sx?

hot as a hare (fever)

blind as a bat (extreme mydriasis)

dry as a bone (no secretions)

red as a beet (atropine flush)

mad as a hatter (mental status change)

what are anticholinergic effects?

dry mucous membranes- nose, mouth

difficulty swallowing and speaking

dry, hot flushed skin

mydriasis, cycloplegia, photophobia

constipation

tachycardia

fever

urinary retention

decreased muscle coordination

mental status changes- agitation, confusion, hallucinations

respiratory depression

paralysis and death

what are adrenergic agonists?

drugs that will stimulate a sympathetic response when they stimulate the adrenergic receptors by promoting the stimulation of sympathetic nerves

what is another name for adrenergic agonists?

sympathomimetics

what is the response to a sympathomimetic determined by?

density and proportion of alpha and beta adrenergic receptors in the effector organ

what occurs when we stimulate the adrenergic receptors?

fight or flight

what are catecholamines?

2 hydroxyl groups on the benzene ring

what are examples of naturally occurring catecholamines?

norepinephrine, epinephrine, dopamine

what are examples of synthetic catecholamines?

isoproterenol and dobutamine

what are non catecholamines?

does not have the 2 hydroxyl groups on the benzene ring

is oral usability effective in catecholamines or non catecholamines?

non catecholamines

is duration of action longer acting in catecholamines or non catecholamines?

non catecholamines

is CNS penetration better in catecholamines or non catecholamines?

non catecholamines

what do direct agonists bind to?

receptors

what are indirect agonists do?

cause release, inhibit reuptake or inhibit degradation of epinephrine or norepinephrine- but do not directly interact with post synaptic receptors

what do mixed agonists do?

things of both direct and indirect agonists