Steve Bull

Question 1

What is the major underlying cause of many cardiovascular diseases

Answer 1

Atherosclerosis

Question 2

What is the genesis of a stroke

Answer 2

Pieces of plaque can travel to the bran and block blood vessels that supply blood to the brain

Question 3

What are the controllable risk factors of hypertension

Answer 3

Alcohol use
Excess sodium
Lack of exercise
Stress
Smoking
Obesity due to inactivity/overeating
Medications

Question 4

What are the uncontrollable risk factors of hypertension

Answer 4

Age
Race 
Gender
Family history
Medical condition
Obesity due to medical conditions
Medications

Question 5

What dietary therapies can be used to reduce risk of hypertension

Answer 5

Lose weight
Stop smoking
Exercise
Reduce alcohol consumption
Reduc cholesterol intake
Reduce saturated fat intake
Increase amount of alpha omega 3 fatty acids
Increase consumption of fruits, vegetables and pulses

Question 6

What drug therapies can be used for hypertension

Answer 6

ACE (angiotensin-converting enzymes) inhibitors
Angiotensin II receptor blockers
Alpha blockers
Alpha-2-agonists
Beta blockers
Calcium channel blockers
Diuretic

Question 7

What are the key features of the carboxypeptidase active site?

Answer 7

Charged arginine - forms an ionic bond with terminal carboxylate acid
Zinc ion - binds to carbonyl terminal peptide bond
S1’ pocket - allows for the side chain of the terminal amino acid

Question 8

What are the key features of L-benzylsuccinic acid

Answer 8

Benzyl group fills the S1’ pocket
Carboxylate anion for ionic interactions with arginine
Second carboxylate to act as a ligand for the zinc ion
Isosteres of peptide bond prevents it from being hydrolysed and removed from the active site

Question 9

Facts about Enalapril

Answer 9

Prodrug activated in vivo to enalaprilat
Eliminated by kidneys
60% bioavailability

Question 10

Facts about enalaprilat

Answer 10

Active dicarboxylic acid
Not orally stable
IV administration only

Question 11

Facts about Lisinopril

Answer 11

Active molecule
Lysine analogue of enalaprilat
Characterised by slow variable and incomplete absorption (30% not reduced by food)
Eliminated intact by kidneys

Question 12

Facts about benazepril

Answer 12

Prodrug activated to benazeprilat
Eliminated by kidney and liver via urine and bile
High potency in vitro with low uptake 37% can be reduced when food is present

Question 13

How does the sympathetic nervous system work to constrict blood vessels and increases blood pressure

Answer 13

Stimulation of baroreceptors result in norepinephrine being released from the adrenal medulla into blood stream which binds to alpha and beta 1 receptors to stimulate contraction of arteries and increase the heart rate respectively

Question 14

What is vasopressin

Answer 14

Cyclic peptide hormone released from pituitary that acts on smooth muscle in kidney to increase retention of water

Question 15

What is angiotensin II

Answer 15

A peptide hormone that binds to blood vessels causing constriction
Also stimulates release of another hormone aldosterone that tells kidney to increase absorption of NA+ and as a consequence retain more water

Question 16

How does the symoathetic nervous system work to dilate the blood vessels and decrease blood pressure

Answer 16

Amount of norepinephrine released from adrenal medulla reduced

Question 17

How does the parasympathetic nervous system work to reduce blood pressure and dilate blood vessels

Answer 17

Acetylcholine dependant receptors stimulated that result in dilation of smooth muscle in artery and decreases heart rate
Nitric oxide released by endothelium that causes dilation of artery
Histamine released by mast cells of immune system

Question 18

Facts about prazosin (antagonist)

Answer 18

Alpha-adrenergic blocker specific for alpha 1 receptors that are found on vascular smooth muscle where they are responsible for the vasoconstricitve action of norepinephrine

Question 19

Facts about clonidine (agonist)

Answer 19

Stimulates presynaptic alpha 2 receptors in the brain stem decreasing cardiac output and lowering vascular resistance
Increasing evidence that it may also exhibit its antihypertensive effect via agonism if the imidazoline I1 receptor

Question 20

What do beta 1 selective receptor antagonists do

Answer 20

Bind to the target receptor
Do not induce biological response
Block the action of the neurotransmitter

Question 21

Define angina pectoris

Answer 21

Chest pain due to is he is ( a lack of blood and hence oxygen supply) of the heart muscle

Question 22

What is the biological role of cholesterol

Answer 22

Important component of cell membranes
Helps in digestion of lipids
Key component for biosynthesis of hormones

Question 23

What is the mevalonic acid pathway

Answer 23

Used for the biosynthesis of cholesterol and isoprenoids (a group responsible for cell proliferation)

Question 24

Three fundamentals of clotting process

Answer 24

When injury to a blood vessel occurs three major events happen to rapidly stop the loss of blood
Vasoconstriction occurs to reduce blood flow through the area
Clumping of the blood platelets at the site of injury to create a physical plug
Aggregation of fibrin into an insoluble clot that covers the rupture and stops loss of blood
The clot is then dissolved after repair of the blood vessel

Question 25

What important role does the Renin-angiotensin system have?

Answer 25

Regulating blood volume, arterial pressure and cardiac and vascular function

Question 26

Most important site for renin release is

Answer 26

Kidney

Question 27

How does Angiotensin work?

Answer 27

1. Contstricts vessels thereby increasing vascular resistance and arterial pressure
2. Stimulates the adrenal cortex to release aldosterone
3. Stimulates the release of vasopressin which acts upon kidney to increase fluid retention
4. Facilitates norepinephrine release and inhibits reuptake from nerve endings
5. Stimulates cardiac and vascular hypertrophy

Question 28

What are the hypertensive effects of ACE?

Answer 28

Produces angiotensin II
Involved in the conversion of angiotensin II to angiotensin III
Catalyses hydrolysis of potent natural vasodilator bradykinin

Question 29

What developments of Captopril increased binding affinity?

Answer 29

Methyl group to fill S1'
Thiol added to interact with zinc
75% bioavailability 
Eliminated in urine
Captopril, formed in vivo

Question 30

What were two side effects of Captopril?

Answer 30

Rashes and loss of taste

Reversible when the drug was withdrawn

Question 31

What two drugs are used in lotrel combination therapy?

Answer 31

Benazepril and Amlodipine

ACE inhibitor and Ca2+ channel blocker

Question 32

Give three examples of beta 1 selective antagonists?

Answer 32

Atenolol
Acebutolol
Metoprolol

Question 33

What do high density lipoproteins do?

Answer 33

Collect cholesterol particles as they travel through blood vessels and deposits them in the liver where they are transferred to bile acids and disposed off

Question 34

What do low density lipoproteins do?

Answer 34

Deposits on the walls of blood vessels and overtime builds up into cholesterol plaque and blocks blood vessels especially arteries that feed blood to the heart

Question 35

What are statins?

Answer 35

Related class of drugs that are competitive inhibitors of HMG-CoA reductive. They are structurally related and occupy the active site of the reductive preventing the enzyme from binding to its natural substrate.

Question 36

Why don’t platelets stick to intact endothelium?

Answer 36

Prostacyclin and NO

Question 37

Facts about Heparin

Answer 37

Naturally occurring mucopolysaccharide that is very acidic
A heterogenous group of substance
Inactivates thrombin and Xa
High affinity bonding with anti thrombin 3