Drugs and cardiovascular system

Question 1

Name some ACE inhibitors and Angiotensin receptor blockers (ARBs) that can be used to treat cardiovascular conditions. Give their MoA and side effects of ACE inhibitor.

Answer 1

ACEi - Ramipril (persistent cough) - block conversion of Angiotensin I -> II
ARBs - Losartan/Valsartan - directly block activation of the Angiotensin II Receptor on vascular smooth muscle

Question 2

How do ACEi and ARBs affect the body?

Answer 2

Reduced levels of Angiotensin II and Receptor activity decreases vasoconstriction in peripheral blood vessels

Leads to reduced peripheral resistance and reduced cardiac afterload, lowers blood pressure

Aldosterone secretion also reduced, leading to increased sodium and water loss - lowering plasma volume and decreasing cardiac preload

Question 3

Give examples of calcium channel blockers used for hypertension, what is their MoA?

Answer 3

Amlodipine and Nifedipine
Prevent opening of L-type voltage-gated calcium channels
Reduce Ca2+ influx into smooth muscle cells
Vasodilator effect in vessels reduces afterload and BP
Do not generally act on veins
Drive coronary artery dilation – improved blood flow to cardiac muscle

Question 4

What are key side effects of calcium channel blockers used for hypertension?

Answer 4

Ankle swelling and palpitations

Question 5

Give examples of nitrate vasodilators, their MoA and their side effects.

Answer 5

Glycerol trinitrate (GTN) and Isosorbide mononitrate (ISMN)
Release NO -> stimulates intracellular Guanylate Cyclase -> inc cGMP in vascular smooth muscle cells
Drives dephosphorylation of MLCs by activation of MLC phosphatase:
Inhibits influx of Ca2+ into smooth muscle cytoplasm
Drives vascular smooth muscle relaxation
Side effects: Headache

Question 6

What effects do nitrate vasodilator drugs have on the heart?

Answer 6

Nitrates can dilate arteries AND veins
Promote Venodilation – this reduces cardiac preload
Promote Coronary Artery Vasodilation – this increases blood and oxygen supply to the myocardium
Promote moderate arteriolar dilation – this helps to reduce cardiac afterload

Question 7

How is stimulation of β-Adrenoceptors lead to different results in smooth muscles compared to cardiomyocytes/cardiac muscle cells?

Answer 7

Cardiomyocytes - Activation of cAMP -> PKA -> inc Calcium -> Inc muscle contractility
Smooth muscle - activation of cAMP -> PKA -> dec calcium -> dec contractility/relaxation (e.g. lungs)

Question 8

Give examples of beta blockers for cardiac muscle and give their MoA. What are their side effects?

Answer 8

B1 antagonist - Atenolol, bisoprolol
B1 and 2 antagonist - Propranolol
Beta blockers are negative chronotropes & negative inotropes
Reduce Heart Rate and reduce cardiomyocyte contractility
Reduce workload of the heart – relieve oxygen demand
SEs: dizziness and constipation

Question 9

What do diuretics act on? How do they help patients with cardiovascular problems and give some examples.

Answer 9

Renal tubular epithelial cells
Furosemide, Hydrochlorothiazide, Spironolactone
Diuretics increase water and sodium output in urine
Reduce plasma volume and reduce cardiac preload
Reduce oedema

Question 10

What are neprilysin inhibitors and how do they help people with heart failure? give examples.

Answer 10

Sacubitril
Neprilysin is the major enzyme involved in the breakdown and inactivation of natriuretic peptides (NP).
Inhibition of neprilysin prolongs the presence & activity of NPs, which promote water & sodium excretion
Effective when used together with an ARB (for example, Valsartan)

Question 11

How would you treat a patient with acute heart failure? (Sympathomimetic)

Answer 11

Adrenaline (IV) (noradrenaline or dobutamine)
Powerful Sympathomimetic and +ve inotrope
Binds and stimulates cardiomyocyte β1-adrenergic receptors
Muscle contraction

Question 12

What is the treatment for sinus bradycardia? (dangerously slow HR)

Answer 12

Atropine (IV)
Blocks Muscarinic-type M2 Acetylcholine Receptors on cardiomyocytes
Inhibits the effects of parasympathetic, cholinergic vagus nerve transmission, which normally exerts negative chronotropy
Atropine accelerates the repolarisation rate in cardiac muscle.

Question 13

Name some antiplatelet drugs and what are they used for?

Answer 13

Clopidogrel (ADP receptor blocker on platelets)
Aspirin (COX inhibitor - inhibitor of thromboxane A2 production)
Platelet activation can drive thrombus formation leading to acute coronary syndromes

Question 14

How does Clopidogrel work?

Answer 14

Adenosine Diphosphate receptor inhibitor
Binds to and blocks the function of ADP receptors on platelet surfaces
Inhibits platelet activation and subsequent thrombus formation

Question 15

How does Aspirin work?

Answer 15

COX inhibitor
COX is required for synthesis of Thromboxane A2 (TXA2) production
Reduced TXA2 synthesis inhibits platelet activation and thrombus formation

Question 16

Can anti-platelet drugs and HMG-CoA reductase drugs affect blood pressure?

Answer 16

NO

can be used to treat/prevent cardiovascular disease WITHOUT affecting blood pressure

Question 17

What do HMG-CoA Reductase Inhibitors do? give examples. (hint - statins)

Answer 17

Atorvastatin and Simvastatin
Reduces cholesterol production in liver
Inhibition of mavelonate metabolism in cholesterol synthesis pathway

Question 18

Mary Wright has angina and uses Glyceryl Trinitrate (GTN). What is a key enzyme in vascular smooth muscle cells that is activated by the action of this nitrate drug?

Answer 18

Guanylate cyclase
Nitrate drugs release nitric oxide (NO) which selectively activates the guanylate cyclase enzyme in vascular smooth muscle cells. This subsequently promotes vascular smooth muscle relaxation

Question 19

A 77 year old man with cardiovascular disease is taking aspirin as part of his treatment programme. Which cell type is primarily targeted by aspirin in the context of treating cardiovascular disease?

Answer 19

Platelets
Aspirin inhibits the production of thromboxane A2 in platelets, which inhibits platelet activation and in turn reduces the risk of thrombus formation, thus protecting the cardiovascular system from blood vessel occlusion and ischaemia.

Question 20

Jim Scollen is taking Ramipril (but not as regularly as he should!). Pathways involving which intracellular signaling molecule in blood vessels would be affected when Jim takes this drug?

Answer 20

IP3
Normally, when Angiotensin II stimulates the Angiotensin Receptor on vascular smooth muscle cells, it stimulates the production of IP3, which in turn drives the contraction of muscle fibres. Thus when Ramipril is taken, this does NOT occur and IP3-dependent pathways would not be activated.

Question 21

An 82 year old man suffering from heart failure is taking the drug hydrochlorothiazide. This helps relieve oedema. How else can this drug directly help his condition?

Answer 21

Reduction in blood volume and cardiac preload
Hydrochlorothiazide is a thiazide diuretic drug that inhibits sodium reuptake into the blood and promotes urine production. This reduces circulating blood volume which in turn reduces cardiac preload, easing exertion by the heart and managing heart failure symptoms.