Drug treatment for complex heart disease Flashcards
Define myocardial infarction
Irreversible necrosis of heart muscle secondary to prolonged ischaemia
4 particularly prevelant risk factors for MI
High blood pressure
High blood cholesterol
Diabetes
Family history of premature CAD
Function of thrombolytics
Clot buster
What is tissue plasminogen activator
Fibrinolytic agent found in endothelial cells
Exhibits significant fibrin specificity and affinity binding of tpa and plasminogen to fibrin induces conformational change
faciliates conversion of plasminogen to plasmin clot dissolves
What inhibits conversion of plasminogen to plasmin
Plasminogen activator inhibitor 1 (PAI 1)
What activates conversion of plasminogen to plasmin
tissue plasminogen activate t-PA
What inhibits conversion of plasmin to fibrin
Thrombin activatable fibrinolysis inhibitor (TAFI)
What inhibits conversion of fibrin to thrombin
FDPs
Simple mechanism of aspirin
Irreversible inhibitor of COX
Platelets cannot make new proteins as lack nucleus
Stops thromboxane production
What is thromboxane
Potent platelet stimulator
How are side effects minimised when a low dose of aspirin is gievn
Low dose inhibits platelets in portal blood so is rapidly destroyed in systemic circulation
When is aspirin contraindicated
Children <16 y old
Small risk of fulminant liver failure
When is aspirin cautioned
Bleeding diathesis
Severe hypertension
Why is aspirin given to pregnant women and what are potential side effects
To reduce risk of pre-eclampsia
Small risk of closure of DA which could lead to PPHN
Can you use aspirin when breast feeding
Small amounts get into breast milk- avoid due to risk of Reyes syndrome
Can you give aspirin to patients with liver disease?
Avoid due to bleeding risk
Often auto-anticoagulated due to reduced clotting factors
Can you given aspirin to patients with renal disease
Increased risk of bleeding
Salt and water retention
Why are beta blockers used for patients with AMI?
BBs reduces infarct size and early mortality when started early
Lowers risk of death when continued long term
Where are beta 1 receptors found
Heart and kidney
Where are beta 2 receptors found
Lungs, peripheral blood vessels, skeletal muscle
Action of beta blockers on the kidney?
Blocks beta 1 receptors
Inhibits renin release
Reduces RAAS
Action of beta blockers of the heart
Blocks beta 1 receptors on SAN reduces heart rate (negative chronotrophic effect(
blockage of beta 1 in myocardium reduces contractibility (negative inotropic effect(
Action of beta blockers on the central and peripheral nervous system
Blockage of beta-receptors in the brainsteam and of prejunctional beta receptors in the periphery inhibits release of neurotrasmitters and decreases sympathetic nervous system activity
Give three examples of cardioselective beta blockers
atenolol
bisoprolol
metoprolol
Name a beta blocker which acts as a local anaesthetic and anti-arrhythmic effect
sotalol
Name a beta blocker with partial agonist activity
Pindolol
What risks are associated with a mother using beta blockers during pregnancy?
Intra-uterine growth restriction
Neonatal hypoglycaemia
Bradycardia
Can you be on beta blockers as a breast feeding mother?
Infants should be monitored as small chance of toxicity. However, usually too small amount to affect infants
Can you use beta blockers if you have renal disease
Sometimes
Some beta blockers are renally excreted and accumulate in renal failure
What is the rate limiting step in cholesterol synthesis
HMG-coA
What are statins
Competitive natural or synthetic inhibitors of HMG-coA
What is propranolol and where does it act
Beta antagonist
Acts to prevent renin release
Where does aliskiren act?
Conversion of angiotensinogen to angiotensin 1
anti hypertensive
Where does captopril act?
Angiotensin 1 to angiotensin 2 (ACE inhibitor)
anti hypertensive
Where does losartan act?
Blocks AT1 receptors
anti hypertensive
How do ACE inhibitors work?
Competitive inhibitor of plasma ACE enzyme, preventing conversion of angiotensin 1 to active 2
leads to vasodilation by preventing ang 2 constriction
effects greatest when RAAS ssytem is up
True or false- most ACE inhibitors are pro drugs that require conversion to active form
TRUE
Describe the events that occur after an MI which can lead to ventricular remodelling and myocardial dysfunction
- Survivors of MI have significant risk of future cardiovascular events
- Infarct expansion due to thinning and stretching of infarct zone
- Significant left ventricular dilation can begin within 3 hours
- Remodelling process begins with myocyte necrosis and formation of fibrotic scar.
- Followed by elongation of infarcted segment and then dilation and hypertrophy of border zone ventricular myocardium
Basic mechanism of clopidogrel?
P2Y12a inhibitor
Further inhibits platelet aggregation
What is the role of thrombolytics?
Immediately stop ongoing infusion of thrombolytic drug
Stop all antiplatelet and anticoagulant therapies
7 side effects of ADRs
Bronchospasm Bradycardia Hypotension Memory Diabetogenis Erectile dysfunction Worsens psoriasis
What is the main affect of ACE inhibitors
Dry irritant cough
