Lecture 10: Sympathetic Modulation

Question 1

Effects of B1 sympathetic modulation innervation on pacemaker in SA node?

Answer 1

B1 can increase cAMP and PKA
increase Ca2+
depolarization
reach threshold faster
steeper

Question 2

Role of protein kinase phosphorylation on 4 components

Answer 2

1. Voltage gated calcium channel
2. Sarcoplasmic reticulum
3. Myosin actin crossbridge
4. Ca/ATPase pump

Leads to increase heart contractility

Question 3

IPE

Answer 3

VASODILATOR
non-selective Beta agonist
low affinity at Alpha receptor
decrease peripheral vascular resistance
increase cardiac output via B1 positive inotropic and chronotropic effect

Question 4

EPI

Answer 4

Vasodilation and vasoconstriction

vasoconstriction of skin renal FI blood vessels via a1

low dose- dilation in skeletal muscle vasculature as B2 more sensitive than a1

high dose- epi used to treat shock, urticaria, hay fever and angioneurotic edema

Question 5

adrenergic modulation on insulin

Answer 5

B2 increase insulin release and uptake
A2 decrease insulin release
A1 decrease GLUT4 transporters

A1 and A2 can lead to hyperglycemia

Question 6

Phenylephrine (PE)

Answer 6

selective A1 agonist

no catecholamine transferase activation, longer half life
activate B receptor at very high doses
less potent than NE

Increase blood pressure
decongestant
mydriatic (dilation of eyes)

Question 7

Clonidine and Apraclonidine

Answer 7

Selective a2 agonist

treats hypertension
IV - decrease BP and heart rate (bradycardia)

rebound hypertension if sudden withdrawal

adverse effect: anticholinergic: dry mouth, constipation, bradycardia, sedation

Apraclonidine- more selective and used for adjunct glaucoma (increased pressure within eyeball)

Question 8

Dobutamine

Answer 8

selective B1 agonist
greater positive inotropic effect than chronotropic
increase contractility more than heart rate

long term increase mortality because increase O2 demand
short term treatment of heart failure

Question 9

Salbutamol and Salmeterol

Answer 9

selective B2 agonist
ASTHMA TREATMENT
bronchodilators
decrease TPR
can be used to delay premature labor

Salmeterol (longer action)
Terbutaline only used short term for premature labour

Question 10

Mirabegron

Answer 10

selective B3 agonist

treat overactive bladder

Question 11

Cocaine and Desimipramine

Answer 11

increase neurotransmitter by blocking DAT and NET (block reuptake of NE or EPI)

Question 12

Clorgyline

Answer 12

MAO-A inhibitor: anti-depressant by increasing Dopamine and Norepinephrine

Question 13

Amphetamine

Answer 13

increase NE and DA at synaptic cleft

block Na/Cl dependent reuptake

Question 14

Tyramine

Answer 14

no direct effect, VMAT substrate
naturally occur in fermented foods
degraded rapidly by MAO with poor oral absorption

CANT BE USED WITH MAO INHIBITORS: SUDDEN AND SEVERE INCREASE OF BLOOD PRESSURE

Question 15

Ephedrine and Pseudoephedrine

Answer 15

bind to a1, b1 and b2
vasopressor
increase HR, bronchodilation and skeletal muscle tone

pseudoephedrine: a1 and b2 agonist
OTC decongestant
METH can be created from this

Question 16

Phenoxybenzamine

Answer 16

non-selective A antagonist
irreversible
decrease BP, DP VR

baroreceptor can lead to tachycardia

Question 17

Phentolamine

Answer 17

reversible and competitive inhibitors for a1
similar to phenoxybenzamine

use for short term hypertension treatment

BARORECEPTOR reflex increase heart rate, tachycardia

Question 18

Prazosin

Answer 18

selective a1 antagonist

treat moderate hypertension

BARORECEPTOR reflex

first dose can lead to orthostatic hypotension

First Dose Phenomenon

Question 19

Tamsulosin

Answer 19

selective a1 antagonist

treat moderate HT and benign prostatic hyperplasia (BPH)

Question 20

Yohimbine

Answer 20

selective a2 antagonist at low dose
reversible competitive a2 antagonist at low dose

increase BP, HR, excitation, tremor, ADH release
blocks clonidine

HIGH doses: block a1 to decrease BP
binds to 5HT receptor

Question 21

Propranolol

Answer 21

non-selective B antagonist
equal affinity for B1 and B2

treat hypertension, arrhythmia and angina

Question 22

Nadolol, Pindolol and Timolol

Answer 22

non-selective B antagonist

Nadolol - longest acting, slow absorption

Timolol- used in glaucoma

Question 23

Labetalol

Answer 23

antagonist at a1/b1
partial agonist at b2

decrease BP without reflex tachycardia and increase cardiac output

Question 24

Carvediol

Answer 24

antagonist at a1 and B with higher affinity for B

reduce TPR improve LV ejection fraction

Question 25

Metoprolol and Atenolol

Answer 25

selective b1 antagonist
less activity at b2
angina, HT and Heart failure

Question 26

Reserpine

Answer 26

binds to VMAT
depletes NE, 5-HT and DA

chronic treatment leads to receptor upregulation (super sensitivity to catecholamines)

decrease HR CO and BP (bradycardia)
antihypertensive effect

increase parasympathetic tone

Question 27

Guanethidine

Answer 27

competition for NAT with NE
depletion of NE
super sensitivity to NE

used in patient with severe HT

Question 28

a-Methyldopa

Answer 28

substrate for dopa decarboxylase: FALSE TRANSMITTER
activates a2 receptors

decrease HR BP CO TPR

adverse effect: drowsiness depression parkinsons dry mouth nasal stuffness GI disturbance

hypersensitivity

Question 29

a-methyltyrosine

Answer 29

inhibits biosynthesis of catecholamines centrally
competitive inhibitor of tyrosine hydroxylase

decrease sympathetic tone

adverse effect: sedation, severe diarrhea
excreted in urine, can lead to urine crystals