Exam2Lec1ANSPharmacology Flashcards
what are the 3 Natural catecholamines?
- Dopamine
- Epinephrine
- Norepi
Describe the general mechanism of action for natural catecholamines
They directly stimulate the adrenergic receptors
What are 2 indirect-acting sympathimimetics drugs?
Cocaine and Amphetamine
Describe the general mechanism of action for indirect-acting symphathomimetics
They DO NOT directly stimulate the adrenergic receptors
They elevate the levels of natural catecholamines
What are the 2 mixed-action sympathomimetics drugs?
- ephedrine
- Pseudoephedrine
Describe the general mechanism of action for mixed-action sympathomimetics
Have some effects like natural catecholamines and some effects like indirect-acting symphathomimetics (mainly amphetamine effects)
Autonomic Nervous system
target tissue?
distal synapse lxn?
Post synaptic nerves?
Networks?
Results of denervation?
- Target tissue: visceral organs, glands, smooth muscle
- distal synapse lxn: peripheral ganglia
- Post synaptic nerves: non-myelinated
- Networks: forms networks
- Results of denervation: spontaneous activity
Somatic Nervous system
target tissue?
distal synapse lxn?
Post synaptic nerves?
Networks?
Results of denervation?
- target tissue: skeletal muscle
- distal synapse lxn: cerebrospinal axis
- Post synaptic nerves: myelinated
- Networks: does not form networks
- Results of denervation: paralysis, atrophy
What are the preganglionic and postganglionic neurons for the SNS?
SHORT ACH/Cholinergic preganglionic neurons
LONG Norepi/Adrenergic postganglionic neurons
remeber there are exceptions
What are the preganglionic and postganglionic neurons for the PNS
LONG ACH/Cholinergic preganglionic neurons
SHORT ACH/Cholinergic postganglionic neurons
Does SNS or PNS mainly do broad regulation of the body?
SNS
can also do some orgna specific regulation such as regulating HR.
PNS does organ specific regulation
Neurons in the PNS are found in what region of the spinal cord?
a. cervical
b. thoracic
c. lumbar
d. sacral
cervical
If you are running from a bear, and your SNS is now stimulated, list what sympathetic action occurs to each tissue listed below.
SA node/contractility
Blood vessles in skeletal muscle and coronary
Bronchial smooth muscle
Uterus, bladder, GI tract
Sweat glands
Liver
PNS nerve endings
- SA node/contractility: HR and blood flow to muscle incr
- Blood vessles in skeletal muscle and coronary: dilates/relaxes
- Bronchial smooth muscle: dilates/relaxes to breathe
- Uterus, bladder, GI tract: relaxes (sphinter contracts)
- Sweat glands: you sweat
- Liver: incr gluconeogenesis to breakdown energy
- PNS nerve endings: decr ACh release
opposite for pns
During a symp response, do you want to incr or decr insulin secretion?
Incr insulin secretion lvls to get gluc into cells but not too much where lots of gluc gets stored
During sympathetic response, is the eye dilated or constricted and what muscle is involved?
Eyes are dilated by radial muscle to see better (mydriasis)
adregernic receptor
During parasympathetic response, is the eye dilated or constricted, what muscle(s) are involved?
Constricted by circular muscle and ciliary muscle and aq humor is released so it can repair the eye
Cillary muscle interacts with the trabecular network to relase aqueous humor that repairs the eye
How is homeostasis maintained in the ANS?
Combinations of neurons that send out a signal (efferent) and neurons that are sensing a variety of things from distension to chemicals (afferent)
What are afferent and efferent neurons?
Afferent: Signal going TO CNS
Efferent: Signal going AWAY from CNS
What does NOT have parasymp innervation?
BV, sweat glands, hair follicles, and adrenal medulla
What is the response that helps maintain homestasis in the cardiovascular system? Where can they be found and what triggers a response?
- Baroreceptors (chemo-and mechanoreceptor)
- Carotid sinus and body & Arch of aorta
- Respond to change in blood pressure
What is a common feedback loop in the ANS?
The Baroreceptor Reflex
If there is an incr in MAP, explain how the baroreceptor reflex regulates it
- Incr in BP
- BR senses that and stretches
- Incr firing to vasomotor center
- Parasymp activated
- Decr HR (a little contractile force) to decr CO to then decr BP
REMEBER PNS doesnt inn ventricles so it has no effect on peripheral resistance or venous tone
PNS can only do HR AND LITTLE contrictility
If there is a decr in MAP, explain how the baroreceptor reflex regulates it
- Decr in BP
- BR senses that and decr signal firing to vasomotor center
- Sympathetic is activated
- This incr: HR, Peripheral vascular resistance (constriction), Contractile force, and venous tone
- BP now incr
What parts of the heart are not affected by the parasympethetic output of the baroreceptors?
NO effect on peripheral resistance and venous tone
What is the sympathetic output of the baroreceptor reflex involved in?
- Normal physiological responses
- Pathophysiological (disease or injury) responses (e.g Cardiac Heart Failure)
- Unwanted side effects (E.g vasodilator)
What does inhibition of the sympathetic output of the baroreceptor reflex cause? And explain
Orthostatic hypotension
BP drops when standing up b/c bv too constricted. Can cause appearance of floaties. Older pts tend to fall and substain hip damages
What does both parasympathetic and sympathetic GANGLIA have?
Both have Presynpatic Cholinergic Neurons
What are the synapses for all parasympathetic target organs?
Cholingeric synapses
A few Symphathetic target organs have choligernic synapses. What are they?
- Sweat Glands
- Vascular system (blood vessels)
Acetylcholine is the primary neurotransmitters in which organs/systems?
Adrenal gland (secrete systemically)
Skeletal muscle
All ganglia
What is the primary neurotransmitter in the somatic nervous system and where is it located?
Acetylcholine
Located in the Neuromusclar Junction
List the steps of the synthesis, storage, and release of Acetylcoline
- Choline transported into the cell, Acetyl CoA is made from pyruvate
- Acetyl CoA +Choline→becomes Acetylcholine (ACh) via Choline Acetly Transferase (outside of the vesicle)
- ACh transported and stored inside the vesicle
- IC Ca2+ increases and ACh is relased
- Binds to receptor (nicotonic or muscarinic) and depending on receptor/location causes effect
ach is produces outside of vesicle and then transportes into the vesicle
cholinoceptors: nicotine and muscurine
How is Acetylcholine terminated in the post synapse of the cell?
- The excess ACh is mainly broken down by Acetylcholine esterase
- Very little ACh diffuses out of the cell b/c ACh rarely leaves the synapse
- Choline is pumped back into the cell to make more ACh
drugs will target ach esterase or receptors.
What are the type of receptors located in the post-synaptic cell of the cholinergic juncture?
Cholinergic
Autoreceptors
Heteroreceptors
Other receptors
What are the main cholinergic receptors for Acetylcholine?
Muscarinic Receptors
Nicotinic Receptors
Muscarinic are what type of receptors and what is the normal speed?
G Coupled Protein Receptor (GPCR)
SLOW transmission
slower effects and longer lived
Nicotinic are what type of receptors and what is the speed of transmission?
Ligand gated ion channels
Fast transmission
see primarily where we need fast transmission (ex skeletal muscle and ganglia)
For the nicotnic receptor subtype Nm, what is the
location?
effector?
physiological response?
- location: NMJ
- effector: Na and Ca channels
- physiological response: skeletal muscle contraction
M for MUSCLE contraction
For the nicotnic receptor subtype Nn, what is the
location?
effector?
physiological response?
- location: autonomic ganglia, brain
- effector: Na and Ca channels
- physiological response: ganglionic transmission (to send signal downstream)
N for neuronal
If you were to injest amanita muscaria (fly agaric) plant, what would occur?
You would see more parasymp effects b/c it has muscarine as a primary agonist
ex: incr contractility of GI tract and bladder, lower HR, incr conractility of lungs
muscarine would bind onto muscaranic gpcr receptor
What are the 2 main classes to know for muscuraninc receptors and mention if they are inhib to excitatory
Odd: M1,3,5 EXCITATORY
Even: M2,4 INHIBITORY
For the odd muscarinic recptors, explain how it is excitatory?
All incr Ca2+ via Gq (incr Ip3, dag and Ca2+)
any type of contraction everywhere and incr secretions
Gq activiates PLC-> incr IP3 and DAG-> incr Ca2+
For the even muscuranic receptors, explain how it is inhibitory?
Incr K+, hyperpolarize (No AP)
Decr cAMP, decr SA node firing (If) and slow HR
Gi, inhibitory, decr cAMP how?
ACh binds to M2 wich has G-protein Gi, this inhibits adenyl cyclase (decr cAMP), K+ is activated, and this decr Ca2+-> decr SA node and contraction
Where do adregernic synapse at?
with what nervous system and neurotransmitter?
target organs with SNS as NE as the neurotransmitter
Explain the dopaminergic pathway of the noradrnergic juncture synthesis
- Tyrosine is transported into cells
- Tyrosine combines with DOPA to create dopamine outside cell
- Dopamine gets taken up into the vesicle
neuron just takes dopamine into vesicle
Explain the adrenergic pathway of the noradrnergic juncture synthesis
- Dopamine coverts to norepi INSIDE vesicle
- IC Ca2+ incr and NE is released from vesicle
adrenergic=neurons take up domapine into vesicle and convert it to NE
What are the two ways that NE can be terminated?
- NE is actively pumped back into pre-synaptic neurons by NET. MOST IMPT STEP
-some is recycles into vesicle
-some is metabolized by MAO - If NE is transported to POST junctional, it will be metaboliszed by COMT-1
reuptake is primary termination method
Alpha 1 adrenoceptor subtype
Gprotein?
location?
Physiological response?
Gq
vascular smooth muscle
Incr vasocontriction
primary receptor in bv for constric
excitatory, incr Ca2+
Alpha 2 adrenoceptor subtype
Gprotein?
location?
Physiological response?
Gi
pancreas and nerve terminals
Decr NT release and decr SNS tone
inhubutory, decr Ca2+, incr K+, decr symp activity, has more PS activity
Beta 1 adrenoceptor subtype
Gprotein?
location?
Physiological response?
Gs
Heart and Juxtaglomerular cells
Physiological response:
1. Heart: incr force and rate
2. jux cells: incr renin release (fluid retention, meaning more fluid in blood to incr BP)
HEART AND JUX CELLS
incr ca incr force of contraction, incr HR by Incr If
Beta 2 adrenoceptor subtype
Gprotein?
location?
Physiological response?
Gs
Lungs and Liver, skeletal muslce bv
Physiological response:
* Skeletal muscle v: relaxation/vasodilation (to incr blood flow to skel muscle)
* Lungs: bronchodilation of bronchial smooth muscle
* Liver: glucneogenesis and -lysis
symp for BV and lungs
Beta 3 adrenoceptor subtype
Gprotein?
location?
Physiological response?
Gs
fat cells and endothelial cells
Physiological response:
* fat cells: incr lipolysis
* enodthelial cells: NO production
fat breakdown
Explain the reuptake and repackaging of NE
- NET brings NE into the cell
- VMAT is a transporter for NE that repackages NE into vesicle
Cocaine is an indirect-acting sympathomimetic. Explain how it enhances noradrenergic transmission and what effects cocaine has
Cocaine blocks NET so NE is building up in the synapse.
Cocaine:
1. incr Hr
2. incr contractility
3. incrt activity of pacemakers
4. vasoconcristion
cocaine does indirecr effect b/c it isnt binding to receptor, its incr NE in system by blocking reuptake causing symp responses
Amphetamine and Tyramine are indirect-acting sympathomimetics. Explain how it enhances noradregernic transmission
Non - Vesicular release:
1. These drugs get taken up into cell by NET and VMAT imports them into the vesicle, and the vesicle gets filled up
2. Vesicle then dumps everything into pre-synap terminal causing NE buildup in pre-synap terminal
DOES NOT bind to receptor
Ephedrine and Pseudoephedrine are mixed-acting sympathomimetics. Explain how it enhances noradregernic transmission
Mixed action: Causes non-vesicular release and acts on adrenergic receptors
Binds to alpa and beta adrenergic recp and effects them, and ends up doing same effects and amph and tyramine
Epinephrine
A. what type of hormone?
B. Activates what type of receptors?
C. Effects? (cardiac, vascualr, smooth muscle, metabolic)
A. fight or flight hormone (made by adrenal gland)
B. activates all adrenergic recptors
C.
-cardiac-postive inotropic (force) and chronotropic (time/speed/hr) efftc
-vascular: vasoconstriction (splanchninc) B1 and vasodilation (skel muscle) B2
-smooth muscle: relaxation of GI, uterine, and bronchial B2
-metabolic: elevates serum gluc and free fatty acids (B2)
Do we we see an alpha or beta response with low dose of epi? and explain
Beta resposne
incr Hr
incr Blood pressure
lower resisrance (b/c B2 effect)
Do we we see an alpha or beta response with high dose of epi?
Alpha 1 response
incr hr
incr in BP
Incr in resistance (b/c alpha 1 response)
What is the cardiovascular effects of epi systemically?
pulse rate?
blood pressure?
resistnance?
Pulse rate: incr HR (B1)
Blood pressure: slight incr bc heart is pumping stronger (incr contractlity.inotropic)
Resistance: decr
Why is there a decr in resistance when given epi?
Incr vasoconstriction (alpha 1)
decr peripheral resis to skeletal (beta 2)
net effect of activating A1 and B2=decr in resistance
What are 3 clinical uses for epinephrine and be specific as to which receptors are activates?
- Anaphylaxis: ( activate B2 for bronchodilation to dilate lungs to breath)
- Septic shock: (need to incr CO so A1 ia activated to incr vasoconcr to incr BP)
- Cardiac arrest (B1 activates to incr pumping force of heart)
Is epi administred orally?
NO, only by IV, topical, or inhaled. This is b/c they break down fast bc neurotransmitters (all catecholamines) have high 1st past effect.
they are natural substances in the body, your body is designed to get rid of them quicly, so they dont last long
Whate are some adverse effects of epi?
take what drugs do and take it too far
- Angina
- anxiety/fear
- cardiac arrhytmias (B1)
- Hypertension (A1)
- Tissue necrosis (end arteries)
you get angina which is chest pain b/c not enough O2 and gluc going to heart ( epi incr HR, incr force of contraction, O2 demand is high)
tissue necrosis ex: poke finger w/ epi pen, massive vasoconstriction, no bf to finger, it dies
Does this graph represent epinephrine or norepi?
epi
Norepinephrine
A. Activates what type of receptors?
B. Effects?
A. activates all receptors EXCEPT B2
C. effects similar to epi EXCEPT NO RELAXATION OF SMOOTH MUSCLE, so incr in BP are more exaggerated.
What is the cardiovascular effects of norepi systemically?
pulse rate?
blood pressure?
resistance?
Pulse rate: decr HR
Blood pressure: incr (b/c A1 vases vasoconstric)
Resistance: incr bc no B2 just A1
Why is there a decr in HR when given norepi?
This is bc BP/resistance incr. Parasymp gets activates and slows HR (no B2)
B/c there is an incr in BP, body responds by activating PNS to decr HR
What are 3 clinical uses of Norepi?
- Septic shock= septic =vasodilation-> need to vasoconstrict to incr BP (1st choice)
- hypotension
- vasopressor support in other types of shock
Why would you not use norepi to treat anaphylaxis?
Because no B2, can’t vasodilate
Norepi has similar adverse effects like epi except what?
Hypertension is more pronounced b/c alpha 1 stimulation, withought B2 balance
When dopamine binds to D1 receptors what occurs?
vasodilation
dop at low lvls affects dop receptors
When dopamine binds to D2, what occurs?
Inhibits further norepi
neg feedback
dop at low lvls affects dop receptors
At high levels of dopamine, it binds to B1, what occurs?
positve inotropic (CONTRACTION) and chronotropic (HR) effect
At even higher levels of dopamine, it binds to A1, what occurs?
vasoconstriction
What are some clinical uses for dopamine?
- Cardiogenic shock
- septic shock
- hypotension
for cardiogenic shock, heart is not beating strong enough, want to incr force of contraction, incr CO w/o incr afterload
Dopamine at high doses stimulates ____ just like ____
A1 and B1, norepi
What does this graph represent?
norepi
