W5: Cardiovascular Disease Drugs

Ramipril

D - ACEI (Angiotensin converting enzyme inhibitor)

D - Mild to moderate hypertension

MOA - Blocks the affects of the renin-angiotensin system through inhibiting ACE

AE - Dry cough, headache, fatigue

G - Taken in combination with diuretics, calcium blocking drugs, and beta blockers

Irbesartan

D - Angiotensin II receptor inhibitor

D - Mild to moderate hypertension

MOA - Similar effects to ACE inhibitors, given to patients that cannot tolerate ACEI, does not produce cough

AE - ?

Propranolol

D - Beta blocker 1 + 2

D - Mild to moderate hypertension

MOA - Blocks beta receptors in heart and bronchioles to reduce sympathetic activity, decreases cardiac output and blood pressure, also reduces renin release from kidneys

AE - Decreases exercise tolerance, bronchoconstriction (problems with asthma/OLD - CONTRAINDICATED), GIT disturbance, chills, increased LDL/HDL ratio, hypoglycaemia

G - Used alongside diuretics, calcium channel blockers (not verapamil), ACE inhibitors

Metoprolol

D - Beta blocker 1

D - Mild to moderate hypertension

MOA - Blocks beta receptors in heart to reduce sympathetic activity, decreases cardiac output and blood pressure, also reduces renin release from kidney

AE - Decreases exercise tolerance, GIT disturbance, chills, increased LDL/HDL ratio, hypoglycaemia

G - Used alongside diuretics, calcium channel blockers (not verapamil), ACE inhibitors

Nifedipine

D - Calcium channel blockers

D - Hypertension

MOA - Prevents rise in intracellular calcium, prevents contraction of vascular smooth muscle, relaxation/vasodilation occurs

AE - Oedema, flushing, dizziness

G - Used in combination of beta blocker (not verapamil - CONTRAINDICATED)

Verapamil

D - Calcium channel blockers

D - Hypertension

MOA - Prevents rise in intracellular calcium, reduces contraction of heart muscle, decreases cardiac output via decreased contractility of the heart

AE - Oedema, flushing, dizziness

G - Cannot be used in combination of beta blockers due to bradycardia - CONTRAINDICATED

Organic nitrates

D - Nitrovasodilators

D - Angina (chest pains)

MOA - Liberate nitric acid (NO), which stimulates guanylate cyclase (sGC) to produce cAMP and relax smooth muscle, vasodilator

AE - ?

G - Sublingual administration

Hydrochlorothiazide

D - Antihypertensive therapy

D - Mild to moderate hypertension, heart failure

MOA - Inhibits Na and Cl absorption in distal convoluted tubule through blocking co-transporter, increases urine output, decreases blood volume and cardiac output

AE - loss of K, hyperglycaemia, increased uric acid (gout)

G - Given in combination with beta blockers, ACEI, calcium channel blockers (25mg/day, works well in elderly)

Coagulation - extrinsic pathway

- Initiated by damaged tissues

- Exposer of underlying tissues

- Proteins cause coagulation and lead to activation of factor X

- Factor X leads to the formation of thrombin

Coagulation - intrinsic pathway

- Cascade of events that occur

- All factors are present in blood, no damage

- Factor XII activates factor XI

- Factor XI activates factor IX

- Factor IX activates Factor X (common link)

Platelet formation

1. Playlets adhere to and are activated by exposed collagen at the site of injury

2. Activated playlets release ADP and thromboxane A2

3. These chemical messengers work together to activate other playlets passing by

4. Newly activated playlets aggregate onto growing playlet plug and release even more platelet-attracting chemicals

5. Normal (uninjured) endothelium releases prostacyclin and nitric oxide, which inhibit platelet aggregation, so platelet plug is confined to site of injury

Aspirin

D - Anti-platelet drug

D - Clotting

MOA - Irreversibly inhibits cyclooxygenase (COX) from synthesising thromboxane A2 Meaning it is unable to activate platelets

AE - Bleeding, GIT bleeding

Clopidogrel

D - P2Y12 purinergic receptor antagonist

D - Clotting

MOA - Blocks the P2Y12 receptor from ADP and prevents platelet activation, stops increased intracellular calcium

AE - ?

G - Prodrug, metabolised in liver

Prasugrel

D - P2Y12 purinergic receptor antagonist

D - Clotting

MOA - Blocks the P2Y12 receptor from ADP and prevents platelet activation, stops increased intracellular calcium

AE - ?

G - Prodrug, metabolised in liver

Warfarin

D - Anti-coagulant

D - Venous thromboembolism

MOA - Vitamin K antagonist, blocks VKORC1 (enzyme responsible for activating vitamin k)

AE - Bleeding, GIT bleeding

G - Does not breakdown clots, genetic difference changes its effective (polymorphic)

Heparin

D - Anti-coagulant

D - Blood clots

MOA - inhibits coagulation by inactivating thrombin and factor X

AE - Bleeding

Enoxaparin

D - Anti-coagulant

D - ?

MOA - inhibits coagulation by inactivating thrombin and factor X

AE - Bleeding

Hirudins

D - Anti-coagulant

D - ?

MOA - Inhibit thrombin directly, leeches

AE - Bleeding

Dabigatran

D - Anti-coagulation

D - ?

MOA - Directly inhibits thrombin, synthetically produced

AE - ?

Rivaroxaban

D - Anti-coagulant

D - ?

MOA - Selectively inhibits factor Xa to prevent thrombin generation

AE - Bleeding

Apixaban

D - Anti-coagulant

D -

MOA - Selectively inhibits factor Xa to prevent thrombin generation

AE - Bleeding

Protamine sulphate

D - Anti-coagulation reversal

D - Heparin reversal

MOA - Binds to heparin, forming an inactive complex

AE - ?

Vitamin K

D - Anti-coagulation reversal

D - Warfarin reversal

MOA - Competitively binds to VKORC1 and stops warfarin

AE - ?

Idarucizumab

D - Anti-coagulant reversal

D - NOACs reversal

MOA - Neutralises dabigatran

AE - ?

alteplase

D - Fibrinolytic drug

D - Acute MI

MOA - Recombinant plasminogen activator, increase clot selectivity

AE - Bleeding

Renin-Angiotensin-Aldosterone System (RAAS) Overview

* Low sodium (Na⁺) levels in the distal tubule of the loop of Henle are detected by macula densa cells, which signal granular (juxtaglomerular) cells in the afferent arteriole to release renin.

* Renin, an enzyme, acts on circulating angiotensinogen (produced by the liver) to form angiotensin I.

* Angiotensin I is then converted to angiotensin II by the enzyme Angiotensin-Converting Enzyme (ACE), primarily in the lungs.

* Angiotensin II has several effects:

* Water retention (via stimulation of ADH)

* Salt (Na⁺) retention (via stimulation of aldosterone release)

* Vasoconstriction (increasing blood pressure)

* Vascular growth and remodeling