Vasodilator drugs

Question 1

How is vascular tone controlled?

Answer 1

ANS, hormones, local mediators

Question 2

Drugs that target smooth muscle cell function affect the vessels. Where does the secondary affect occur?

Answer 2

Affecting vessels influences the heart

Question 3

How can vasodilators act?

Answer 3

Directly to alter actin-myosin interactions by preventing Ca entry through VGCC or interfering with cGMP.
Indirectly to interfere with vasoconstrictors through sympathetic blockade of alpha1 receptors or using RAAS.

Question 4

What are direct vasodilators used to treat?

Answer 4

Hypertension and Angina Pectoris

Question 5

What is angina pectoris?

Answer 5

Pain due to inadequate coronary blood flow due to obstruction or arterial spasm.`

Question 6

What is the aim of drugs that treat angina?

Answer 6

To increase coronary flow and reduce cardiac work to reduce the O2 demand.

Question 7

What drugs can treat angina that are not vasodilators?

Answer 7

beta Blockers to limit work

Ivabradine affects pacemaker channels IH to limit work.

Question 8

What is the mechanism of action of organic nitrates?

Answer 8

e.g. GTN (glyceryl trinitrate), isosorbide mononitrate. Used to target arterial spasm.
Spontaneous decomposition of nitrates in the drug will increase NO to interfere and increase cGMP, inhibiting Ca and actin-myosin interaction for less contraction of the vessels.

Question 9

Which vessels do organic nitrates affect the most?

Answer 9

Venous>arterial affecting the preload and decreasing VR for less cardiac work.

Question 10

What are the s.e. of organic nitrates?

Answer 10

They affect all smooth muscle so cause excess dilation = hypotension —> syncope and reflex tachycardia, headaches, GIT motility, bronchi

Question 11

How is GTN administered?

Answer 11

Sublingually at thin mucosa to bypass liver metabolism for fast, short effect.
Transdermally for prophylaxis via diffusion

Question 12

What is the risk of wearing GTN patches?

Answer 12

It is explosive so should not be defibrillated

Question 13

What is the issue with using GTN long term?

Answer 13

Develop physical (upregulates mechanisms to resist dilation) and pharmacological (less effect from same does) tolerance.
Sublingual preferred as less tolerance development with it only being taken when required.

Question 14

Why are isosorbide mononitrates rarely used?

Answer 14

Severe s.e. but has a longer duration

Question 15

What is the effect of CCB?

Answer 15

e.g. DHPs act on vasculature, Verapamil acts in the heart, diltiazem on both.
DHPs affect A>V so influence afterload to reduce TPR and cardiac work. Secondary mechanism to increase coronary flow

Question 16

What are the s.e. of CCB?

Answer 16

Flushing, reduced GIT activity.

No affect on skeletal muscle

Question 17

What is Nifedipine used to treat?

Answer 17

CCB: Treats peripheral vascular disease such as Raynaud’s. Works to reduce the inappropriate vessel spasms due to stress but doesn’t work in all pt’s so treat conventionally by avoiding the cold.

Question 18

What is Sildenafil used to treat?

Answer 18

PDEi: Also known as Viagara to treat impotence. PDEi increases cGMP causing vasodilation.
Erections are controlled by the corpora cavernosa vessel and NO. Targets genital tissue directly via type 5 selectivity.

Question 19

What is minoxidil used to treat?

Answer 19

Also known as Regaine. Used to treat hair loss by inducing hypertrichosis (increased growth). When applied topically it causes local vasodilation around the follicles by opening K channels to hyperpolarise and reduce VGCC opening to limit constriction.

Question 20

Why are CCB used after a stroke?

Answer 20

Reduce post-haemorrhagic vasospasm, increase healing and improve cerebral function

Question 21

What causes vascular dementia?

Answer 21

An interruption to blood flow. By dilating it may improve dementia.