PNS pharm

Question 1

PNS divisions

Answer 1

nerves outside of CNS, afferent (sensory) and efferent (motor pathways)

afferent sensory nerves: sense and communicate information back to the CNS
Efferent motor nerves: emanate from the CNS and innervate peripheral tissues and organs (autonomic and somatic)

Question 2

Autonomic NS

Answer 2

innervates organs, blood vessels, glands, maintains homeostasis and responds to stress, involuntary bc beyond conscious control

2 neuron system,

Question 3

Somatic NS

Answer 3

innervates skeletal muscle, under conscious control by higher centers in the brain, voluntary NS

single neuron system

Question 4

sympathetic vs parasympathetic nerves

Answer 4

Parasympathetics: long pre ganglionic, short post, Low divergence, highly localized effects, excitatory/inhibitory, regulates homeostasis

Sympathetics: short pre, long post, high divergence, wide spread effects, fight or flight

Question 5

function of sympathetic NS

Answer 5

normally continuously active, but he degree of activity varies from organ to organ

increased HR, blood pressure, shifts blood flow from skin to skeletal muscles, increases blood glucose levels and fatty acids, bronchilar + pupillarry dilation, sweating

Actions reinforced by epinephrine from adrenal glands

Question 6

function of the parasympathetic NS

Answer 6

discrete localized discharge

decrease HR and blood pressure, increase in GI movement and secretion, absorption of nutrients, empty bladder and rectum

Question 7

neurotransmission steps

Answer 7

1. axonal conduction (passage of an impulse along an axon)

2. junctional transmission (storage and releaase of NT, post junctional activity, destruction of transmitter)

Question 8

synthesis, storage and release of acetylcholine

Answer 8

choline is taken up by the vesicle Na-dependent carrier (CHT1), the rate limiting step in acetylcholine synthesis blocked by hemicholinum

choline acetyltransferase (ChAT) synthesizes Ach from acetyl CoA + choline

Acetylcholine is transported into vesicle by VAChT (vessicle associated ACh transporter) inhibited by vesamicol

Acetylcholine released into the synaptic cleft by expcytosis inhibited by botulinum toxin

Question 9

metabolism of ACh

Answer 9

Very rapidly hydrolyzed and inactivated by the enzyme AChE (acetylcholinesterase)

Question 10

nicotinic receptors

Answer 10

ligand-gated ion channels- activation always causes a rapid increase in cellular permeability for NA and Ca, depolarization and excitation

5 subunits around central pore

at neuromuscular junction, autonomic ganglia, adrenal medulla, the CNs, non-neuronal tissues

muscle type and neuronal type

Question 11

muscarinic receptors

Answer 11

all are G-PCRs
5 subtypes

most have a few different types of muscarinic receptor types but one usually dominates

M1, M3, M5: Gq family: depolarization, activate phospholipase C-> IP3 and Dag-> increase Ca + PKC

M2 and M4: Gi: hyperpolarization, inhibit adenylyl cyclase, (decrease cAMP, activate potassium channels inhibit Ca channels

Question 12

adrenergic synthesis

Answer 12

tyrosine->DOPA->dopamine-> NE-> epinephrine in adrenals

rate limiting step= tyrosine hydroxylase tyrosine -> DOPA
alpha methyltyrosine is a blocker of tyrosine hydroxylase

Question 13

storage and release of adrenergics

Answer 13

dopamine synthesized in nerve terminals transported into storage vesicles via vesicular monoamine transportere 2 (VMAT 2) where its converted to norepinephrine blocked by reserpine

upon depolarization granules fuse with nerve terminal and release NE into synaptic cleft

NE is removed by synaptic cleft by:

1. reuptake into nerve terminals norepinephrine transporter NEt blocked by cocaine (87%)
2. diffusion
3. uptake by extraneural transporter

Question 14

metabolism of catecholamines

Answer 14

monoamine oxidase and catechol-o-methyltransferase (COMT) -initial metabolism

MAO: oxidatively deaminates catecholamines, found on outer surface of mito, liver and kidney, MAO A and B

COMT: transfers methyl group cytosolic

intraneural norepinephrine not taken into storage granules is metabolized by MAO, metabolites diffuse away and are converted into VMA and secreted in urine

Question 15

adrenergic receptors

Answer 15

a1: Gaq family: contraction and secretion from glands, phospholipase C
a2: Gai family: decreased NE releasem decrease secretion/contraction, inhibit adenylyl cyclase family

B1: Gas: increased force and rate of contraction, increased secretion, activate ac (increased cAMP)

B2: Gs: relaxation, glycogenolysis, activate Ac

B3: Gs: lipolysis, activate AC