Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

PCL469 > Lecture 10: ANS: Sympathetic > Flashcards

Lecture 10: ANS: Sympathetic Flashcards

1
Q

Sympathomimetics: based on dopamine’s structure, substitution at the alpha carbon acts to…?

A

increase the half life, monoamine oxidase can’t degrade it anymore

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Sympathomimetics: based on dopamine’s structure, substitution at the beta carbon acts to…?

A

decrease CNS activity, less lipophilic can’t cross BBB
increased alpha and beta receptor activity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Sympathomimetics: based on dopamine’s structure, substitution of the amino group acts to…?

A

increase beta adr receptor activity, especially beta 2R (IPE)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Sympathomimetics: based on dopamine’s structure, substitution at C3/C5 acts to…?

A

increase beta 2 adrenergic receptor activity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Sympathomimetics: based on dopamine’s structure, loss of C3/C4 hydroxyl groups acts to…?

A

decrease potency at adrenergic receptors, increase oral absorption, increase half life (COMT and MAOs can’t break it down as well)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Short acting beta2 agonists (3)

often used as?

A
  • albuterol
  • salbutamol
  • terbutaline

rescue medication

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

long acting beta 2 agonists (2)

A
  • formeterol
  • salmeterol
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Once daily long acting beta2 agonists

A

Indacaterol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Overall CV effects of Adrenergics (5)

A
  • transient tachycardia via positive chronotropic effect of beta 1 receptors (makes APs quicker at SA node but then baroreceptor reflex kicks in and blocks this)
  • shortening of AV node refractory period
  • increased overall blood pressure (both SP and DP), which would trigger baroreceptor reflex
  • positive inotropic effect (increased SV, CO, and O2 use) which decreases cardiac efficiency
  • coronary vessels dilate via beta 2 and DP goes down
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

How do beta1 receptors make the heart beat
- faster
- stronger

A

faster - increases in cAMP increase PKA activity. PKA phosphorylates funny channels and t-type calcium channels to increase cation influx for faster depolarization

stronger - PKA phosphorylates L-type calcium channels (VGCaCh), induces calcium release from SR, phosphorylates myosin, puts more calcium back into SR so it replenishes stores for next release

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Adrenergic effects on the genitourinary tract

A
  • NE will increase frequency of contraction on pregnant uterus smooth muscle contraction
  • Epi will reduce uterine smooth muscle tone and contraction in last month of pregnancy and at parturition (Beta 2 agonists used to prevent premature labour)
  • there are alpha 1 adr receptors at the urethral sphincter and prostrate
  • beta 3 adr receptors on the detrusor muscle
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Adrenergic effects on the GI tract

A
  • alpha 2 presynpatic inhibition of cholinergic neurons which causes relaxation and reduced peristalsis
  • beta 2 inactivates MLCK (through increased cAMP) which decreases contraction
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Adrenergic effects on Respiratory system

A
  • beta 2 activation causes relaxation of bronchiole smooth muscle which decreases airway resistance - epi given during asthma attack
  • alpha1 R mediated vasoconstriction of upper mucosa (dilation of this causes congestion so alpha 1 agonists fix this)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Adrenergic effects on the eye

A
  • alpha1 adr R mediate dilation of the pupil (on the radial muscles or spokes of the eye) but this does not increase intraocular pressure
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Adrenergic effects on skeletal muscle

A
  • epi and beta1 agonists increase ACh release at NMJ
  • inhibition of alpha 2 increases ACh release at NMJ
  • beta 2 induced muscle tremor
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

why is ephedrine/amphetamine used to treat myasthenia gravis?

A

Myasthenia gravis is autoimmune condition that affects the NMJ
- ephedrine and amphetamine are sympathomimetics thus increase catecholamines and indirectly increase ACh release

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Adrenergic effects on metabolic function

A

think about it, all to help you get away in a stitch so more breakdown of fat and glycogen stores, creating glucose
- increased lipolysis and thermogenesis via beta3
- increased glycogenolysis via beta 2 to increase serum glucose
- increased gluconeogenesis
- increased oxygen consumption via beta 2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Adrenergic effects on endocrine function

A
  • beta 2 increases insulin release to mobilize glucose and increase uptake to cells
  • alpha 2 decreases insulin release to increase serum glucose conc and alpha 1 decreases GLUT4 transporters to increase serum glucose conc

beta effects increase glucose utilization and cause hypoglycemia but then alpha effects cause hyperglycemia and they counteract each other.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Adrenal medulla releases what ratio of epi to NE

A

80% epi and 20% NE
also a little bit of DA (negligible)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Vasculature in response to NE

A

overall vasoconstriction via alpha1 activation
- increase in TPR and BP both SP and DP

at low doses it is positive inotropic and chronotropic but the BaroR reflex blows chronotropy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Vasculature in response to IPE

A

overall vasodilation
- IPE is a non-selective beta agonist and poorly activates alpha receptors
- vasodilation of vascular smooth muscle via beta 2 and therefore decreased TPR and lower DP
- increases CO via beta 1 mediated positive inotropic and chronotropic effect

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Vasculature in response to Epi

A

both vasodilation and vasoconstriction
- alpha1 receptors will respond and constrict VSM in skin, renal, and GI blood vessels
- beta 2 receptors will also respond and vasodilate skeletal muscle vasculature
- a very high dose of Epi will look similar to NE

23
Q

Why do cold meds contain alpha1 adr R agonists?

A

Vasoconstriction of upper mucosal blood vessels
- reduces congestion

24
Q

phenylephrine

A

selective alpha 1 agonist
- not COMT inactivation so increased half life
- used clinically for hypotensive states, as decongestant, and for pupil dilation

25
Q

clonidine

A

selective alpha 2 agonist
- trials as decongestant but caused hypotension, sedation, and bradycardia

  • blockage of NE release at nerve terminals so we see a decrease in CO, BP, and HR.
  • tricyclic antidepressants will interfere with this (they increase NE in the synapse)

adverse effects
- dry mouth and constipation (reduced release from cholinergic fibres). low heart rate and sedation
- will get decreased TPR with chronic use and sudden withdrawal can cause rebound hypertension

26
Q

apraclonidine

A

more selective clonidine (alpha 2 agonist) used to treat open angle glaucoma (reduces cAMP and thus reduces production of aqueous humour, therefore decreasing IOP)

27
Q

isopreterenol

A

most potent beta 1 and beta 2 agonist
- causes peripheral vasodilation and tachycardia
- severe cardiac side FX and O2 insufficiency

(beta 2 activation increases o2 consumption and vasodilation, beta 1 activation increases heart rate)

28
Q

dobutamine

A

selective beta1 R agonist
- use for short term heart failure, low dose increases CO
- greater positive inotropic than chronotropic effects

29
Q

salbutamol

A

selective beta2 agonist
- causes bronchodilation (for asthma)
- used to delay premature labour

30
Q

salmeterol

A

selective beta 2 agonist
- longer acting

31
Q

Drugs used to delay premature labour

A

salbutamol and terbutaline both short acting beta 2 adr agonists

32
Q

Indirect sympathomimetics include agents that:

A
  • increase synthesis
  • stimulate release
  • inhibit re-uptake
  • inhibit degradation

of catecholamines - so basically cocaine, antidepressants like MAOA-inhibs, amphetamine, tyramine

33
Q

how can tyramine and MAOIs cause a hypertensive crisis? give one MAOI

A

tyramine displaces NE from vesicles as it is a substrate of VMAT2. Tyramine is also broken down by MAOIs so prevention of tyramine breakdown means it displaces NE. more NE ends up released in the synapse.
think about all the effects of NE - vasoconstriction, increased TPR and BP.

clorgyline

34
Q

What adrenergic drugs are mixed action i.e. bind multiple adrenergic Rs?

A

ephedrine - binds alpha 1, beta1, beta2

pseudoephedrine - isomer of ^. is decongestant. binds alpa1 and beta 2 Rs.

35
Q

phenoxybenzamine

A

non-selective alpha adrenergic antagonist
- irreversible
- decreasing but persistent block for 3 days post exposure
- dirty drug (binds other things) but mainly enhances NE release by blocking action of alpha2 autoreceptors

CV effects: increased heart rate because more NE being released in heart and no baroreceptorR because decreased TPR, decreased venous return.
Metabolic: also causes insulin secretion and lipolysis (alpha receptors cause insulin decrease so blocking them means increase)

treats pheochromocytoma (tumour in adrenal glands)

36
Q

phentolamine

A

reversible and compet inhibitors of alpha adrenergic receptors
- similar effects, similar indications

37
Q

prazosin

A

selective alpha 1 antagonist
- decreased TPR, DP, VR, pulmonary congestion
- increased CO
- clinically used for mild to moderate HT, CHF.
- tachycardia via BaroR may occur (decreased TPR results in increased sympathetic flow to the heart). this is NOT a result of lack of autoinhibition by alpha 2 R

38
Q

Which drug is associated with first dose phenomenon

A

Prazosin - may see extreme orthostatic hypertension

related: clonidine may cause rebound hypertension is removed quickly

39
Q

Tamsulosin

A

treats mild HT and also symptoms of BPH
- over 70% of alpha1A adrenergic Rs are in prostate and sphincter of bladder

40
Q

Yohimbine

A

reversible competitive alpha 2 antagonist
- not used - inhibits autoreceptors so stimulates NE release
- increased HR, BP, excitation, tremor

at high doses blocks alpha 1 adr receptors for transient decrease in BP

41
Q

propranolol:
- some points about the drug
- therapeutic
- unwanted effects
- adverse effects and toxicity

A

non-selective beta adr R ant
- equal affinity for beta1and beta2
- efficacy of the block depends on the sympathetic tone
- extensive first pass metabolism , F <30%
- half life of around 4 hours

therapeutic effects
- bradycardia
- negative inotropic effect, decreased CO and O2 use
- unbalanced vagal tone results in decreased AV conduction
- initial elevation in TPR via unopposed alpha adr Rs but then hypotension with chronic use

unwanted effects
- potentiates bronchospasm (no Beta 2 bronchodilation)
- inhibits lipolysis
- inhibits insulin secretion by beta 2 activation
- blocks hyperglycemic response to epi

adverse effects and toxicity
- severe bradycardia, CHF, bronchoconstriction, hypoglycemia (nogluconeogenesis), aggravation of peripheral artery disease (unopposed alpha adr activity)
- CV effects with abrupt withdrawal (weaned over 1-2 weeks)

42
Q

Will a beta blocker affect a nomotensive person?

A

A normal person wont really experience effects on a beta blocker. circulating NE is higher in hypertensive individuals

43
Q

How do beta blockers block hyperglycemic response to epi

A
  • alpha adrenergic activity will be unopposed - insulin levels will drop and blood glucose will increase
  • may induce hypoglycemia following exercise or insulin admin because no release from glycogen stores
  • can mask hypoglycemic symptoms
44
Q

nadolol

A

long acting non selective beta antagonist
- half life of 14-24 hours

45
Q

pindolol

A

non-selective partial beta receptor agonist in absence

46
Q

timolol

A

non-selective beta adr R antagonist
- similar half life as propranolol (4 hours ish) but it’s less potent
- clinically used for glaucoma to decrease IOP

47
Q

non-selective beta adr R antagonists

A

propranolol
nadolol
timolol

pindolol (partial agonist so could block with excess catecholeamine signalling)

48
Q

Selective beta 1 antagonists

A

metoprolol and atenolol
(for angina HT and heart failure)

esmolol - short acting

betaxolol - for glaucoma

49
Q

third generation beta blockers

A

labetalol
- antagonist at alpha1 and beta 1, partial agonist at beta2
- decreased BP without causing reflex tachycardia and decreased cardiac output (seen with alpha adr R blockers)

carvedilol
- antagonist at alpha 1 and beta with 10x higher affinity for beta. will reduce TPR

50
Q

Cimetidine and first pass metabolism of some beta blockers

A

Cimetidine inhibits CYP associated with first pass metabolism of propranolol, metoprolol, and labetalol so will increase bioavailability and therefore plasma conc.

(one from each category: nonselective, beta 1 selective, and third gen)

51
Q

reserpine and antihypertensive agents are

A

additive
- reserpine depletes catecholamines
- antihypertensives act against catecholamine action

52
Q

reserpine

A

it depletes catecholamines
PS tone will be more pronounced

clinical CV effects - decreased HR, CO, and BP

adverse effects
- bradycardia, flushed skin, hypotension, Na+ and fluid retention, nasal congestion, increased GI tone and secretions.
- super-sensitized adrenergic receptors

CNS issues
- Parkinsonism, lethargy, depression

abolishes response to any indirect acting sympathomimetics like cocaine, TCAs, clorygline (bc there are no catecholamines for them to act on)

53
Q

guanethidine

A

competes with NE for NET - NET takes it into the cell instead of NE, thus there is a gradual depletion of NE
- effects of indirect sympathomimetics are reduced

54
Q

alpha-methyldopa and alpha-methyltyrosine

A

both reduce heart rate and BP
- affect the enzymes producing catecholamines
- methyldopa inhibits AADC (enzyme turning LDOPA to DA)
- methyltyrosine inhibits TH

PCL469 (18 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions