Dugga 3 - cardiovascular Flashcards
What are risk factors for cardiovascular disease?
Hypertension (high blood pressure), obesity, smoking, diabetes and lack of exercise
Which are important targets for antihypertensive agents?
Renin and angiotensin coverting enzyme (ACE) are key enzymes in the RAAS cascade
What is aliskiren?
An approved renin inhibitor for treating hypertension
How are most ACE inhibitors administered?
As prodrugs to lower their polarity and increase absorption
What do all ACE inhibitor drugs contain?
A functional group that binds to the zinc ion cofactor of ACE
What are important binding groups for sartans, and important for activity?
Two acidic groups and a hydrophobic substituent
What are sartans?
Antihypertensive agents that act on the AT1 receptor as either antagonists or inverse agonists
What are mineralocorticoid receptor antagnists?
They block the effects on aldosterine and have antihypertensive effects
What are endothelins?
Endogenous peptides with potent vasoconstrictive properties
Are endothelin antagonists hypertensive agents?
Yes
What are vasodilators?
They relieve hypertension by dilating blood vessels and reducing blood pressure
Which secondary messenger promotes dilation of blood vessels?
Cyclic GMP
How can levels of cyclic GMP be increased?
By enhancing the activity of soluble guanylate cyclase
How can levels of cyclic GMP be enhanced?
By inhibiting phosphodiester type 5 (PDE5) which catalyses the hydrolysis of cyclic GMP
What are calcium entry blockers?
Drugs that block voltage gated L type calcium ion channels used to treat hypertension and angina
What are the 3 structural classes of calcium entry blockers?
Dihydropyridines, phenylalkylamines and benzothiazepines
Where do calcium entry blockers bind?
To distinct binding sites in the alpha 1 subunit of calcium ion channel
What are dihydropyridines mainly used for?
To treat hypertension
What do dihydropyridines contain?
Five substituents including an aromatic ring and two ester groups. The nitrogen is unsubstituted.
What do the phenylalkylamines do?
Bind to calcium ion channel by approaching from the intracellular side of the ion channel. They must cross cell membrane to be effective
What is the name of the only benzothiazepine approved for the clinic?
Diltiazem
What inhibits the funny ion channel and is approved for treatment of angina?
Ivabradine
What are statins?
Cholesterol lowering agents that block the enzyme involved in the rate-limiting step of cholesterol biosynthesis
Do all statins contain the same polar head group?
Yes, and then have differing hydrophobic groups attached
What is the most important agent prescribed for lowering cholesterol?
Statins
What does the polar head group of statins contain?
Two OH groups and one COOH group
What do statins do?
Inhibit the enzyme important in biosynthesis of cholesterol
What does the polar head group of statins do?
Mimicks the natural substrate for the target enzyme
How do fibrates lower triglyceride levels?
By activating peroxisome proliferator activated alpha receptors in the liver
What is mipomersen?
An antisense drug that inhibits the translation of apolilpoprotein B, a key component of low density lipoprotein particles
How does lomitapide lower levels of cholesterol and triglycerides?
By inhibiting a triglyceride transfer protein
What are antithrombotic agents?
They help to prevent blood clots in the circulatory system to reduce the risk of heart attack and stroke
What can antithrombotic agents be classified as?
anticoagulent, antiplatelet agents and firbrinolytic agents
What do anticoagulents do?
Inhibit the formation of thrombi
What is thrombi?
a blood clot formed in situ within the vascular system of the body and impeding blood flow
What are heparins, hirudin and parins and what do they do to the enzyme thrombin?
They bind to the enzyme thrombin and inhibit its action
What are platelets?
Platelets, or thrombocytes, are small, colorless cell fragments in our blood that form clots and stop or prevent bleeding
What is warfarin?
An oral anticoagulent that inhibits vitamin K epoxide reductase (but low therapeutic window and drug-drug interaction)
What is dabigatran
A thrombin inhibitor
What is idarucizumab?
a monoclonal antibody that reverses the effect of dabigatran
What is a factor Xa inhibitor?
Anticoagulents that block the conversion of prothrombin to thrombin
How do antiplatelate agents work?
They block platelet aggregation by binding as antagonists to platelet receptors
What are fibrinolytic drugs?
Enzymes which convert plasminogen to plasmin. Plasmin catalyses the degradation of fibrin leading to the breakdown of thrombus
What is RAAS short for?
Renin Angiotensin Aldosterone System
Where is renin formed?
In kidneys
What does renin do?
catalyses formation of angiotensin 1 which indirectly affects vasoconstriction (vessels becoming narrow)
What does ACE do?
Converts angiotensin 1 to angiotensin 2
Drugs that act on this are called -prilat or -prill
What are sartans?
Selective AT1 antagonists bind the receptor AT1 which is responsible for vasoconstriction
Angiotensin 2 promotes the release of what?
Aldosterone which is a vasoconstrictor
What do mineralocorticoid receptor antagonists do?
Bind the receptor that aldosterone would have bound and promoted vasoconstriction. Now there will be no constriction
