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CVS > Vasodilator pharmacology > Flashcards

Vasodilator pharmacology Flashcards

1
Q

How do vasodilators have an indirect action on heart function

A

they work on smooth muscle cells

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2
Q

How does smooth muscle contract

A

when a smooth muscle cell is stimulated hormones, local factors, nervous system effects
1. calcium enters teh cell
2. calcium binds to proteins inside the muscle cells
3. leading to the activation of an enzyme called myosin light-chain kinase (MLCK)
4. MLCK then phosphorylates (adds a phosphate group to) myosin,
5. causes more stuff to happen
6. myosin and actin bind together

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3
Q

How do drugs interfer to cause vasodilation

A

-they can affect the vasoconstrictor
-or affect what happens in the smooth muscle

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4
Q

How do indirect vasodilators work

A

these are drugs which block vasoconstriction
-they use natural circulating substances released by the autonomic nervous system

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5
Q

How do indirect vasodilators use cirlcuating factors

like what natrual stuff does our body release, that indirect vasodilator

s like to affect

A
  • ANS
  • causes a sympathetic blockade, by blocking alpha 1 receptors,
    • blocks noradrenaline, which decreases vasocontriction, which means guess what VASODILATION

RAAS
- Angiotensin 2 is a vasoconstrictor,
- if we block angiotensin 2 we can have a vasodilator action
- this mechnaims uses a angiotensin two antagonist

 Endothelins
- usually released by smooth muscle cells 
- drugs don't usually work here, but they can
- since endothelins does vasoconstriction
- they block natural vasoconstriction

just a note: there are significant differences between biological sexes between action of endothelial receptors, this can lead to differences in how we treat it

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6
Q

How do vasodilators act direlecty

A
  • can work on calcium inside cells

How can they interfre with this
– voltage-gated calcium channels can be affected by anything changing membrane potential
- can impact channels and calcium levels
- cyclic GMP determines smooth muscle action as it affects calcium channels(hwo long they are open for), and also intermediates affect myosin actin interaction

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7
Q

What clinical conditiosn do we use direct vasodilators for

A

-Hypertension
-Angina pectoris

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8
Q

What are the causes of angina pectoris

A
  • Atheromatous obstruction
  • Arterial spasm (smooth spasms)
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9
Q

So how do these drugs work for angina pectoris or hypertension

A
  • increase coronory flow
  • decrease increase cardiac work
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10
Q

Drugs treating angina

How do do we classify drugs that treat angina

A

Class A, B

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11
Q

Give an example of drug class A

A

Beta blockers
Ivabradine

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12
Q

What is the mechanism of beta blockers

A

they block the beta 1 receptor

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13
Q

How does Ivabradine woek

A

inhibits the I-F channel
which is responsible for pacemaker curve
by inhibiting reduce HR
reduces CW

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14
Q

True or False

Class A drugs are vasodilators

A

FALSE
some of them are not vasodilators

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15
Q

Give an example of class B drugs

A

Organic nitrates
Glyceryl trinitrate (GTN)
* they do not selectivley target coronary vasculature, they act systemitcally
Isosorbide mono/dinitrate
-these are more selective

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16
Q

How do class B drugs vasodilate

A
  • contain nitrogen, so when they are brokendown it makes NO
  • NO via actions on a the enzyme guanylate cyclase can increase cyclic GMP
  • by increasing cGMP can promote relaxation
  • Increasing cGMP can be done by two ways
    1. action of calcium channels
    2. or actions on Actin-Myosin interactions
17
Q

How does GTN treat angina

A

Works on systemic vessels
- has action on venous vessels compared to aterial vessels
- means we decrease venous return
- which decreases cardiac work (starling),
- so we reduce oxygen demand,
- so specific reduction in cW, -coronary blood supply has o2 for cardiac mycoutes

GTN can also effect on coronary vessels (minor effect)

  • it increases cornory blood flow
  • BUT… if there’s an obstruction, causing vasodilation may not help

so main action is to reduce preload for systemic vessles

18
Q

What are the unwanted effects of GIT

A
  • too much vasodilation
  • can be hard to titrate drug
  • can cause hypotension (low bp) → can lead to syncope (fainting)
  • can also have headache due to excess vasodilation of blood vessles in brain
  • can affect GIT, smooth muscle relaxtion means reducing motlity, so you may need to chnage diet
19
Q

How do we adminster GTN

A
  • Sublingual
    • sprayed under tongue
    • under tongue highly vasocisled, since there;s thin mucosa,
    • means there’s rapid diffusion to enter circulatory system
    • short duration because metabolsied fast in liver
    • people with angina need it on a need basis, since it works fast

NOT TAKEN ORALLY:

because it is completely metabolsied through liver, so it doesn’t reach its target

20
Q

When can you take GTN transdermally

A
  • prophylaxis
    • use patches, where drug is constantly diffusing to prevent angina attack
21
Q

What tolerances can GTN cause

therapeutic issues of GTN

A
  • repeated use can cause a change in response (tolerance)
    • Physiological tolerance
      • if GTN works on one pathway, the other pathways can adapt an counteract the GTM effect
    • Pharmacological tolerance
      • can build tolerance
      • Can also cause Monday morning headache
22
Q

What are class C drugs

A

They are caclicum channel blockers: guess what they do?
-they block calcium, which causes vasodilation

23
Q

How do Class C drugs work

A

-calcium determines contractile state
-and some of the calcium entering through voltage-gated channels
-so reduce contraction if we block calcium channels
-causing vasodilation

24
Q

Give an example of class C drugs

A

Dihydropyridines (DHPs)
for example amlodipine (have ipine part of name)

25
Q

What is the diference between Verapamil and DHPs

A
  • Verapamil has relative selectivity for calcium channels
  • whereas DHPs has relative activity for vasculature
  • but diltiazem has characteristics of both
26
Q

What affects do Class C drugs have on vasculatoure

A
  • they affect the aterial system more than the venous
    • they decrease total pressure resistance
    • which decrease cardiac work
    • this can then increase coronary flow
27
Q

What are the unwanted effects of class c drugs

A
  • flushing
  • and decreases smooth muscle activity of GIT,
28
Q

What peripheral conditions can vasodilators affect

A

Raynaud’s syndrome
- Spasm induced by cold weather, so if they are warmer
- can be painful

29
Q

What drug can we use yo treat raynauds

A

Nifedipine works for some

30
Q

Vasodilators can also help erection
how?

A

During an erection, the orpora cavernosa needs to fill with blood

-this is controlled by NO, and how it works with cGMP
-PDEs can degrade cGMP
-so if there’s more cyclic GMP in the cell, and causes smooth muscle relaxation

31
Q

When targetting PDE how do we ensure that we don’t have systemic effects

A
  • there’s lots of types of PDE
    • so targeting a certain type can keep effects localised
32
Q

What drug can we use to cause erectioms

and how does it work

A

Sildenafil
- found primarily in genital tissue
- so this means it has a relatively localised action in these genetial tissue

33
Q

Can sildenafil interact with other drugs

A

if you are taking GTM and sildenafil can lead to serious effects

34
Q

Which vasodilator can we use to support hair growth

A

Minoxidil

35
Q

How do we use Minoxidil

A
  • hypertrichosis
  • topical application causes localised vasodilation → causes more blood flow to that area
  • can support hair growth
36
Q

How does minoxidil work

A
  • opens k+ channels
  • allows k+ to leave
  • causes membrane hyperpolarisation
  • these means calcium channels less likley to open,
  • so less intracellaur calcium
37
Q

How can using vasodilators help improve cerebral function

A
  • using drugs to change blood flow to brain
  • Stroke
    • Post-haemorrhagic vasospasm (blood vessels go into vasospasm)
      • this lasts for a long time
      • all things downstream of BV means its not supplied by blood,
      • so neurones are living in hypoxic conditions

  • calcium channel blockers are used

CVS (4 decks)

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