Vasodilators Flashcards
What effect does cGMP have in the process of myocyte contraction?
It has a negative inotropic effect.
What protein activates myosin light chain kinase?
What is the function of myosin light chain kinase?
- Calmodulin activates myosin light chain kinase.
- Myosin light chain kinase phosphorylates myosin so that it is able to bind to actin (once troponin has moved from the actin binding site by way of Ca2+).
What are the two types of vasodilators?
1 - Direct vasodilators.
2 - Indirect vasodilators.
How do indirect vasodilators cause vasodilation?
By blocking other substances that cause vasoconstriction.
How do direct vasodilators cause vasodilation?
1 - By interfering with the pathways that raise intracellular Ca2+.
2 - By interfering with cGMP.
What is the cause of angina pectoris?
Which drugs are used to treat it?
- Inadequate coronary blood flow for higher levels of activity, usually due to atheromatous obstruction.
- Both direct and indirect vasodilators are used to treat angina.
List 2 nonvasodilator drugs that can decrease cardiac work.
1 - Beta blockers.
2 - Ivabradine.
Briefly describe the mechanism of action for ivabradine.
It inhibits the mechanisms that underpin the pacemaker potential.
List 3 direct vasodilators.
Organic nitrates:
1 - Glyceryl trinitrate (GTN).
2 - Isosorbide mono/dinitrate.
Calcium channel blockers:
3 - Dihydropyridines (DHPs) such as amlodipine.
Describe the mechanism of organic nitrates.
Organic nitrates spontaneously break down to release nitric oxide, which increases cGMP.
What type of vessel is most strongly affected by glyceryl trinitrate (GTN)?
Why is this advantageous?
- Veins (more effect than on arteries).
- This decreases venous return (primary effect of GTN), so decreases cardiac work.
What is the secondary effect of glyceryl trinitrate (GTN)?
To cause vasodilation at coronary arteries, which increases coronary flow.
List 2 unwanted effects of glyceryl trinitrate (GTN).
1 - Excess vasodilation, causing hypotension and headaches.
2 - Decreases activity of other smooth muscle, such as the GIT and bronchi.
List 2 symptoms of hypotension in a patient that is being treated for heart failure.
1 - Syncope.
2 - Reflex tachycardia.
How is glyceryl trinitrate (GTN) administered?
Why?
- Sublingually or via transdermal patches (for patients that need GTN all the time).
- To avoid 1st pass metabolism that the drug would otherwise be subjected to if it was taken orally.
- To increase speed of action (faster than orally).
How do dihydropyridines differ from other calcium channel blockers such as verapamil?
Verapamil primarily targets cardiac myocytes whereas dihydropyridines primarily target the vasculature.
Give an example of a calcium channel blocker that affects both cardiac myocytes and the vasculature to an equal degree.
Diltiazem.
What type of vessel is most strongly affected by calcium channel blockers?
Why is this advantageous?
- Arteries.
- This decreases total peripheral resistance, so decreases cardiac work.
What is the secondary effect of calcium channel blockers?
To cause vasodilation at coronary arteries, which increases coronary flow.
List 2 unwanted effects of calcium channel blockers.
1 - Flushing.
2 - Decreased GIT activity.
Why don’t calcium channel blockers affect skeletal muscle activity?
- In the heart, Ca2+ release from the sarcoplasmic reticulum is Ca2+ induced, which is controlled by voltage gated Ca2+ channels.
- In the skeletal muscle, Ca2+ release from the sarcoplasmic reticulum is triggered by action potentials which penetrate the myocyte and act on the sarcoplasmic reticulum directly.
What is Raynaud’s syndrome?
A peripheral vascular disease which causes spasm in peripheral vessels induced by cold weather.
Give an example of a drug treatment for Raynaud’s syndrome.
To which drug class does this drug belong?
- Nifedipine.
- Dihydropyridines (calcium channel blockers).
Describe the mechanisms by which smooth muscle relaxation occurs in the corpora cavernosa of the penis to produce erections.
- Nitric oxide release increases cGMP production.
- cGMP inhibits the contraction of smooth muscle in the corpora cavernosa, producing an erection.
Which drug class is used to treat male impotence?
Give an example of a drug within this class.
- Phosphodiesterase inhibitors.
- Sildenafil (Viagra).
Describe the mechanism of action for phosphodiesterase inhibitors for treatment of male impotence.
- Phosphodiesterases degrade cGMP (type 5 phosphodiesterases are present in genital tissue).
- Inhibition of type 5 phosphodiesterase in genital tissue results in an increase in cGMP.
- Increased cGMP increases inhibition of smooth muscle contraction in the corpora cavernosa, producing an erection.
Why do drugs that are used to treat male impotence not have many side effects?
Because they are selective for type 5 phosphodiesterases which are only found in genital tissue.
What is minoxidil used for?
How is it administered?
- To decrease hair loss.
- It is applied topically.
Describe the mechanism of action for minoxidil.
- Minoxidil opens K+ channels on the myocytes in local vessels.
- This hyperpolarises the cells, decreasing Ca2+ influx and therefore calcium induced calcium release.
- This reduces contraction, resulting in local vasodilation, improving blood flow to hair follicles.
How can calcium channel blockers be used to treat poor cerebral function?
1 - Ca2+ channel blockers can be used to treat post-haemorrhagic vasospasm by causing vasodilation in the vessels supplying the brain.
2 - The same mechanism can be used to treat dementia.
