Autonomic Nervous System(adrenergic) Flashcards
adrenergic system
fight or flight nervous system
physiological changes due to adrenegicsyetem
increased heart rate, increased sweating and pupil dilation
two key hormones in sympathetic nervour system
noradrenaline(noreponephrine) and adrelanine(epiinephrine)
noradrenaline released first
adrenaline erleasde when circumstances presist
locations where the hormones for sympathetic nervous system are produced
noradrenaline : adrenegic neurons adn adrenal medulla
adrenaline: adrenal medulla
location of the adrenagenic receptors
effectors organs only
what class do noradrelaine and adrenaline belong to
catecholamines
largely derived from the amino acid tyrosine
synthetic deravitive of noradrenaline
issoprenaline
catecholamine synthesis steps
l tyrosin to l dopa to dopamine to noradrelaine to adrenaline
tyrosine hyroxylase
l aromatic amino acid decarboxylase
dapamine B hydroxylase
phenylmethanomaine -n- methyltransferase
catecholamine sythesis negaative feedback
noradreanline to regualre noradrelaine sythesis
inhibit the tyrosine hydroxylase
what breaks down noradrenaline
monoamine oxidase (MAO)
MAO present in the cytoplasm
post synaptic receptors for adrenergenic
a and b
at synaptic cleft of adrenergic
75 % of nor adrenlaine recaptured and transported via noradrenaline transporter
bind ot a and b post snymaptic clift and mediast reaction
what are contorls of non adrelaine release
autoinhibitory feedback medicated by a2 receptor on pre snmaptic
when a lot bind to it, prevent further release
where are NA made
inside vesicles with dopamine beta hydroxylase
vascular monoamine trasnported allow for NA to enter the vescicel again
a receptors of adrenergic receptors
a1: contraction of smooth muscles
a2: feedback inhibition
b receptors of adrenergic receptor
b1: heart : increase the rate and force of contraction
b2: lungs : relaxation of smooth muscles
a1 receptor function
contraction of smooth muscles
vasoconstriction of smooth muscles of blood vessels
increase in peripheral vascular resistance
increase in blood pressure
– reactivates the baroreceptor and result in reflex(bradycardia)
at smooth muscle causes
- blood vessel constriction
-bronhco construction
gastrointestinal relax
sphincter contract
uterus contract
iris contract
at liver causes : glycogenolysis
at prostate : induced contraction
at heart: increased interaction
a2 receptor function
inhibit release of NA (autoinhibitory feedback,, so less A , less adrenergic activity
blood vessel constrict
relax gastrointestinal tract
decrease insulin sectrion from pancreatic islets
agonist potency order for a1
NA
A
ISO
agonist potency order for a2
A
NA
ISO
agonist potency order for b1
ISO
NA
A
agonist potency order for B2
ISO
A
NA
B1 receptor function
increase rate and force of heart contraction
increase release of renin from juxtaglomerular cells of kidney which raises blood pressurestep
stpes involved when b1 is activated
activation of b1 in juxtaglomerular cells
increase renin release
renin catalysed the conversion of angiotensinogen to angiotensin I
ACE converted AGTI into AGTII
AGTII increase aldosterone release at adrenal glands
sodium and water retentions
increased blood pressure
increase heart rate and heart contraction
b2 receptor
relax smooth muscles
- vasodilation
-bronchodilation
-relax uterine muscles
relax gastrointestinal tract
promotes relaxation
increase heart rate and heart contraction
@ liver, gylcogenolysis
agonist for which receptor causes bronchoconstriction
M3
asthma drug
Adregenic B2 agonist
seconadry messengers and effectors(a1)
increase inositol triphosphate
inscrease DAG
increase CA2+
seconadry messengers and effectors(a2)
decrease CAMP
seconadry messengers and effectors(b1)
increase CAMP
seconadry messengers and effectors(b2)
increase CAMP
norepinrpherine drug
a/b agonist
not clinically used
trasnmitter at postganglionic sympathetic neurons
epinephrine
a/b agonist
asthma and anaphylactic shock, cardiac attack
salbutamol
B2 agonist
asthma
premature labor
phenylphrine
a1 agnoist
nasal decongestion thr vaso constriction; reduce amt of fluid
clonidine
a2 partial agonist
hypertension
migraine
derease amt of sympathetic activity
propranolol
b antagnoist (non selctive)
angina
hypertenison
cardia dysrthmias
anxiety
tremor
A methyl-p-tyrosine
drug that affect NA biosynthesis
tyrosine hyroxylase inhibitor
reduce amt of noradrenaline and adrenaline
clinical use of A methyl-p- tyrosine
alternative treatmenr option phaenchromocytoma
(NA/ADR secreting tumour of adrenal medulla)
- high heart rate
symptoms representative of over active adrenaline system
Reserpine
drug that affect NA storage
- inhibitor of VMAT
inhibit uptake of vesicular uptake of NA
- NA remain in cytoplasm and get metabolised by MAO
-depletion of NA : interrupt sympathetic transmission
clinical use of resperpine
hypertension and mood disorders(schizophrenia)
adverse effect; dizziness, droziness, irregular heart beat , depression
name the drugs that affect the relase and uptake of noradrenaline
Amphetamine
cocaine
clonidine
yohimbine
drugs that are indirect sympathomimetics
Amphetamine that increases the relase of NA
cocaine that inhibits the reuptake of NA
drusg that are A2 agonist for release and reuptake of noradreanlaine
a2 receptor agonist, clonidine that decreases NA release
a2 antagonist yohimbine that increases NA release
how does amphetamine work on noradrenaline release
since they represent the NA structureally, they are taken up by NET and VMAT in exchange for reduced NA uptake
NA left in the cytosol is metabolized by MAO or escpated via NET back into synaptic cleft
– this causes increase in NA in cleft
- amphetamine have some inhibitory effect on MAO and can also increase dopamine release in a similar manner
– thus nre amt of NA increase
tyramine from chocolate and ephereine have similar action as amphetamine
amphetamine effect on NA
promote release of NA without depolarising nerve membranes
– bc everything in the pre snymaptinc leaks out
cocaine effect on Noradrenaline
inhibit reuptake of Noradrenaline into presynaptic by inhbiting respective trasnporters
— thus build up of noradrenaline in synaptic cleft leading to increased sympathetic activity
effect of sympathimimimetics
increased rate and force of contractility of heart(dose responsive tachycardia)
– construction of blood vessels leading to hypertension
– inhibition of gut motility(die to relaxation of GI tract)
–CNS stimulant
– euphoria(dopamine effect), increased energy and libido, reduced fatigue and appetite, and behavioral responses, such as increased self confidence and alertness
dangers of tyramine
can be dangerous if given with MAo blocker, which is required for catabolsim of tyramine
clinical use of tyramine
NA release
no clinica use but present in various foodi
clincial use of amphetamine
NA release, MAO inhibitor, NET inhibitor, CNS stimulant
CNA stimuant in narcolepsy, also in hyperactive children, appetite suppressant , drug of abuse
clinical use of ephedrine
NA release, B agonist, weak CNA stimulant action
nasal decongestion
a2 receptor agonist and antagonist regarding Noradrenaline
clonidine agonist
yohimbine(antagonist)
effect of a2 receptor agonist at noradrenaline
clonidine
inhibit NA release
clinical use: antihypertension
adverse effect : headache, dizziness, drowsiness, constipation, brandycardia
effect of “a” receptor antagonist regarding yohimbine
inhibit post snymaptinc a receptor as well,
so no used clinically
indirect sympathomimetic drugs- MAO and COMT inhibitors
moclabemide, anti depresant
how does moclobemide work
endogenous and exogenous catecholamine are metabolised mainly by two enzymes :
- monoamine oxidase and catechol-o-methyl -transferase
(CoMT metabolism substranets such as L dopa and are absent in the NA neurons)
inhibiting them will increase availability of neurotransmitters such as NA nd dopamine
what is the difference between the catecholamine and NA released from the sympathetic nerves
duration of activity of the catechoaimines released from the adrenal medulla is longer – so longer activity
NA immeidaytl removed from the neuroeffectory synapse by way of reuptake into the postganglinos neurons however circualtin is inactivate by COMT in liver, as such would have longer period of effect
capable of stimulating tiessies that are not directly innervated by the nerve
NA has limited affinity for B2 receptors, thus circulating A is capable of stimulating these receptors in airway smooth muscles
vascular smooth muscles in skeletal muscles contain a1 and b receptor,
NA which stimular only excitatory a1 receptor causes strong vasoconstriction
however, a which stimulates both type of receptor would cause weaker vasoconstrictions
receptors that are linked to blood pressure
a1 - vasoconstrictinos
b1- increased cardia output
b1 at juxtaglomerular cells - increase renin - renin causes angiotensinogen into at1-AEC– CONVERT AT1 TO AT2 - at2 increase aldostrong release at adrenal glands, - sodicum and water retention - increase in blood pressure
b2 - vasodilation
ISO
isoprenaline
noradrenaline effect
predominantly a agonist
expect vaso constrictions
peripheral resistance will increase
blood pressure increase
heart rate go down bc when blood pressure increase, baroreceptors can sense it and the refex is to lower heart rate
isoprenaline effect
potent b agnoist
vaso constrictions
peripeherial reisitance decrease
blood pressure decrease
also act on b1 receptor
heaty rate become higher
adrenaline effect
combines both action od noradrenaline and isoprenaline
activate all receptors – balance
what is anaphylactic shock
severem life threatening allergic reaction, can occure within seconds of exposure to the allergen ,, bc immune system will release floods fo checmincal that make the person going into a shock , blood pressure plummet airway narros, breathing becoming difficult
adrenaline mechanism of action during anaphylaxis
decreae the release of medators from mast cell, alleviate obstruction to airflow in the respirator tracts and improves cardiovascular response
- a1 adrenegic agonist effect : increased vasoconstriction, increased peripheral vascular resistance and decreased mucosal edema
- b1 adrenergic agonist effect : increased rate and force of contraction
-b2 adrenergic agonist effect: increased bronchodilator and decreased release of mediatiors of inflammation from mast cell and basophils
machanism of a1 receptor
plc activated, increased ip3, and dag, increased intracellular ca2+
mechanism of a2
ac inhibited, decreased cAMP
mechanism of b1
ac activated - increased camp
mechanism of b2
ac activated - increased camp
