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Therapeutics > W24 Hypertension 2 > Flashcards

W24 Hypertension 2 Flashcards

1
Q

what two mechanisms can occur in the structure of resistance arteries

A

endothelium releases vasodilators

innervated by sympathetic nerves: noradrenaline acts on a1 receptors as the VSM contracts

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2
Q

Describe how the contraction of a smooth muscle cell works

A

smooth muscle cell made up of thick filaments of myosin and thin actin filaments

dense bodies are cytoplasmic anchorage points.

thick and thin filaments slide over each other during contraction. leading to cross bridge cycling and leads to the shortening of the fibres

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3
Q

describe the mechanism how contraction of vascular smooth muscle work

A

agonist e.g. noradrenaline binds to a g coupled protein receptor gaq on the vascular smooth muscle cell releasing IP3

this then binds to the IP3 receptor releasing calcium from the sarcoplasmic reticulum

released calcium binds to calmodium

leads to an increase in polarization opening voltage gated calcium channel which leads to calcium moving down the concentration gradient into the vascular smooth muscle cell binding to calmodulin also

calmodulin activates myosin light chain kinase (enzymes)

that then phosphorlyates the myosin light chain

the phosphorylation then initiates constriction

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4
Q

how does endothelial dependant relaxation work

A

agonist binds to endothelium

leading to increase in calcium which produces nitric oxide and relaxing factor

release of nitric oxide + relaxing factor

decrease calcium in vascular cell as they are absorbed

leading to smooth muscle relaxing

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5
Q

what do increases in EC [Ca2+] activate

A

nitric oxide synthase COX and EDHF

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6
Q

what happens to nitric oxide after produced in response to calcium increase

A

diffuses to SMC and activates soluble guanylate cyclase generating cGMP

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7
Q

what does cGMP evoke

A

relaxation by activating protein kinase G which prevents Ca2+ release and Ca 2+ entry while also regulating Myosin light chain kinase to evoke relaxation

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8
Q

what is PGI2 come from

A

COX

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9
Q

where does PGI2 diffuse to

A

SMC activates IP receptor

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10
Q

what does IP receptor do

A

coupled to AC - cAMP generated activates PKA

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11
Q

what does PKA do

A

regulates MLCK and activates some SMC K+ channels

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12
Q

what drugs can be used for antihypertension

A

ACE inhibitors

AT - 1 receptor antagonists

Calcium channel blockers

Potassium channel openers

a 1 adrenoceptor blockers

d1 dopamine agonists

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13
Q

how do calcium channel blockers stop constriction

A

they block the calcium channel that would be opened as a result of the release of Ca2+ from the sarcoplasmic reticulum

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14
Q

what is the role of calcium channel blockers

A

block L type VGCC

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15
Q

what are the 3 types of Calcium Channel Blockers

A

Dihydropyridines - Vascular

Phenethylalkylamines - Cardiac

Benzothiazepines - Mixed

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16
Q

what are 3 examples of dihydropyridines

A 
amlodopine
felopine
lacidipine
verapamil
diltiazem
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17
Q

what is an example of phenethylaklylamines

A

verapamil

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18
Q

what is an example of benzothiazepines

A

diltiazem

19
Q

what are the side effects of calcium channel blocker

A 
ankle swelling
flushing
palpitations
tremor
constipation
hypotension
cardiac effects
av block
weaken heart beat
nifedipine increase
20
Q

what do potassium openers do

A

hyperpolarization as K+ moves out lessening the concentration gradient meaning less calcium moves in so calmodulin cascade cant occur

21
Q

what do adrenoceptor antagonist do

A

prevent the release of IP3 so no release of Ca2+

22
Q

what system has a profound effect on blood pressure

A

total peripheral resistance has a profound effect on blood pressure

most antihypertensives agents act directly on the resistance vasculature

23
Q

what does hypertension tend to cause

A

tachycardia

24
Q

what is tachycardia

A

Heart rate over 100 beats a minute

25
Q

what system is useful in regulating blood pressure

A

renal

26
Q

what two systems regulate each other

A

sympathetic nervous system + renal system can regulate each other

27
Q

What do diuretics do

A

increase volume of urin and water loss

28
Q

what antihypertensive drugs act on the renal system

A 
Diuretics
Ace inhibs
AT - 1 receptor inhibitors
Beta adrenoreceptor antagonists
D1 Dopamine agonists 
Rennin inhibitors
29
Q

where is renin released from

A

juxtaglomerular cells of kidney

30
Q

what is renin release stimmed by

A

renin release is stimulated by many drugs including vasodilators, diuretics

31
Q

what does renin stimulate

A

conversion of angiotensinogen into angiotensin1

32
Q

what does angiotensin converting enzyme convert

A

angiotensin I to angiotensin II

33
Q

what does angiotensin II activates AT 1 receptor resulting in

A

vascular smooth muscle cell constriction and increasing blood pressure

increases release of aldosterone

34
Q

describe how the renin angiotensin + aldesterone works

A

low sodium in distal tubule,
macula densa
Juxtaglomerular cells

releases renin leading to a lower blood pressure and blood volume. As well as an increase in sympathetic NS beta adrenoceptor.

Renin converts angiotensinogen to angiotensin 1, Ace converts angiotensin 1 to angiotensin 2.

This leads to constriction by the AT1 receptor.

It also leads to an increased secretion of aldosterone which leads to an increased sodium reabsorption by distal tubule.

35
Q

Give some Ace inhbitors

A 
Ramipril
enalapril
lisinopril
imadapril
fosinopril
perindopril
quinapril
trandopril
36
Q

what do ACE inhibtors do

A

prevent conversion of angiotensin 1 to angiotensin 2

37
Q

what are the main side effects of ace inhibitor

A

cough rash hypotension

38
Q

what is ace inhibitors contra indicated with

A

in pregnancy and with NSAID treatment

39
Q

what is the mechanism of action for ramipril

A

inhibition of ace

40
Q

what are three examples of angiotensin 2 receptor antagonists

A

candesartan olmesartan valsartan

41
Q

what to angiotensin 2 receptor antagonists

A

block action of angiotensin 2 on AT1 receptor

42
Q

what do thiazide like diuretics do

A

effective antihypertensive weak diuretics

act on the Na/Cl symporter of covuluted distal tubule

43
Q

give 3 example of thiazide like diuretics

A 
bendroflumethiazide
hydrochlorothiazide
indapamide
chlortalidone
metolazone
44
Q

what are the side effects of thiazide like diuretics

A

hypokalaemia and metabolic alkalosis

Therapeutics (50 decks)

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