Steve Bull Flashcards
What is the major underlying cause of many cardiovascular diseases
Atherosclerosis
What is the genesis of a stroke
Pieces of plaque can travel to the bran and block blood vessels that supply blood to the brain
What are the controllable risk factors of hypertension
Alcohol use Excess sodium Lack of exercise Stress Smoking Obesity due to inactivity/overeating Medications
What are the uncontrollable risk factors of hypertension
Age Race Gender Family history Medical condition Obesity due to medical conditions Medications
What dietary therapies can be used to reduce risk of hypertension
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
What drug therapies can be used for hypertension
ACE (angiotensin-converting enzymes) inhibitors Angiotensin II receptor blockers Alpha blockers Alpha-2-agonists Beta blockers Calcium channel blockers Diuretic
What are the key features of the carboxypeptidase active site?
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
What are the key features of L-benzylsuccinic acid
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
Facts about Enalapril
Prodrug activated in vivo to enalaprilat
Eliminated by kidneys
60% bioavailability
Facts about enalaprilat
Active dicarboxylic acid
Not orally stable
IV administration only
Facts about Lisinopril
Active molecule
Lysine analogue of enalaprilat
Characterised by slow variable and incomplete absorption (30% not reduced by food)
Eliminated intact by kidneys
Facts about benazepril
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
How does the sympathetic nervous system work to constrict blood vessels and increases blood pressure
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
What is vasopressin
Cyclic peptide hormone released from pituitary that acts on smooth muscle in kidney to increase retention of water
What is angiotensin II
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
How does the symoathetic nervous system work to dilate the blood vessels and decrease blood pressure
Amount of norepinephrine released from adrenal medulla reduced
How does the parasympathetic nervous system work to reduce blood pressure and dilate blood vessels
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
Facts about prazosin (antagonist)
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
Facts about clonidine (agonist)
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
What do beta 1 selective receptor antagonists do
Bind to the target receptor
Do not induce biological response
Block the action of the neurotransmitter
Define angina pectoris
Chest pain due to is he is ( a lack of blood and hence oxygen supply) of the heart muscle
What is the biological role of cholesterol
Important component of cell membranes
Helps in digestion of lipids
Key component for biosynthesis of hormones
What is the mevalonic acid pathway
Used for the biosynthesis of cholesterol and isoprenoids (a group responsible for cell proliferation)
Three fundamentals of clotting process
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
What important role does the Renin-angiotensin system have?
Regulating blood volume, arterial pressure and cardiac and vascular function
Most important site for renin release is
Kidney
How does Angiotensin work?
- Contstricts vessels thereby increasing vascular resistance and arterial pressure
- Stimulates the adrenal cortex to release aldosterone
- Stimulates the release of vasopressin which acts upon kidney to increase fluid retention
- Facilitates norepinephrine release and inhibits reuptake from nerve endings
- Stimulates cardiac and vascular hypertrophy
What are the hypertensive effects of ACE?
Produces angiotensin II
Involved in the conversion of angiotensin II to angiotensin III
Catalyses hydrolysis of potent natural vasodilator bradykinin
What developments of Captopril increased binding affinity?
Methyl group to fill S1' Thiol added to interact with zinc 75% bioavailability Eliminated in urine Captopril, formed in vivo
What were two side effects of Captopril?
Rashes and loss of taste
Reversible when the drug was withdrawn
What two drugs are used in lotrel combination therapy?
Benazepril and Amlodipine
ACE inhibitor and Ca2+ channel blocker
Give three examples of beta 1 selective antagonists?
Atenolol
Acebutolol
Metoprolol
What do high density lipoproteins do?
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
What do low density lipoproteins do?
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
What are statins?
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.
Why don’t platelets stick to intact endothelium?
Prostacyclin and NO
Facts about Heparin
Naturally occurring mucopolysaccharide that is very acidic
A heterogenous group of substance
Inactivates thrombin and Xa
High affinity bonding with anti thrombin 3
