Pharmacological treatment of angina

complete - apart from mechanism of short acting nitrates diagram

what is coronary blood flow?

the blood flow that supplies the heart

when is coronary blood flow favoured?

when aortic pressure is greater than ventricular pressure

what is angina?

Angina pectoris is a form of chronic coronary syndrome but can destabilise to become an acute coronary soundrome (inadequate myocardial oxygen supply

what is the inadequate myocardial oxygen supply caused by?

• fixed vessel narrowing

• endothelial dysfunction

what are subtypes of angina?

• stable angina

• unstable angina

• variant angina

what is stable angina?

• episodic - brought on by exertion and relieved by rest

• fixed vessel narrowing and endothelial dysfunction

what is fixed vessel narrowing?

permanent narrowing of blood vessels

what is unstable angina?

• symptomatic at rest

• ruptured atherosclerotic plaque, platelet aggregation and thrombus formation, endothelial dysfunction

is variant angina a chronic coronary syndrome or acute coronary syndrome?

chronic coronary syndrome

what occurs in variant angina?

no obvious fixed vessel narrowing but intense vasospasm

what are the aims for the management of stable and variant angina?

• improve quality of life

• improve life expectancy

What are three categories of medication for the management of angina (improving quality of life)?

• immediate relief

• first line

• second line

what medication provides immediate relief for angina (improving quality of life)?

short acting nitrates

what is an example of a short acting nitrate?

glyceryl trinitrate (GTN)

what does it mean to say that glyceryl trinitrate is biologically inactive?

The drug itself does not provide relief, but its product after being reduced twice by proteins (nitric oxide) does

why does nitric oxide help symptoms of angina?

It activates the enzyme Guanylate cyclase which relaxes vascular smooth muscle to reduce venous return to the heart

what side effects can short acting nitrates cause?

• flushing

• light headedness

• headache

what is a downside to GTN being given orally?

It causes low bioavailability (only small proportion reaches bloodstream in active form)

what is the primary action of short acting nitrates?

on veins to reduce preload and reduce oxygen demand in the myocardium

what is preload?

the amount of blood that fills the ventricles before they contract/the amount the of stretch in heart muscle wall at the end of diastole

what is the secondary action of short acting nitrates?

dilate coronary collaterals to improve oxygen delivery to the ischaemic myocardium

is the mechanism of action for short acting and long acting nitrates the same or different?

the same

what are the first line treatments for management of angina (improving quality of life)?

• beta blockers

• calcium channel blockers

what are examples of cardio selective beta blockers?

Bisoprol, metoprolol and atenolol

what receptor do cardio selective beta blockers target?

Beta₁ adrenoreceptor

what is inotropy?

force of muscular contractions of the heart

what is negative chronotropy?

effect → reducing heart rate

what are the effects of beta blockers?

negative inotropy, negative chronotropy and improved relaxation → reduced myocardial oxygen demand

what are examples of non-cardio selective beta blockers?

carvedilol and propranolol

what receptors do non-cardioselective beta blockers target?

B₁ and B₂ receptors

what unwanted side effect can non-cardioselective beta blockers cause?

bronchospasm - which can be a problem in patients with asthma

what are examples of dihydropyradine calcium channel blockers?

• nifedipine

• amlodipine

• felodipine

what are the second line treatment for management of angina (improving quality of life)?

• long acting nitrates

• potassium channel openers

• ranolozine

• ivabradine

what are examples of long acting nitrates?

• isosorbide dinitrate

• isosorbide mononitrate

what is example of a potassium channel opener?

nicroandil

what do potassium channel openers act on?

ATP sensitive K+ channels

what is the mechanism of action of potassium channel openers?

•Hyperpolarises vascular smooth muscle cells, reducing afterload

•Reduces myocardial oxygen demand leading to symptom relief

what is ranolazine?

late inward sodium current blocker and delayed rectifier potassium channel current blocker

what is the mechanism of action of ranolazine?

•Delays repolarisation of the myocardium and reduces intracellular calcium concentrations, reducing myocardial oxygen demand

what are the side effects of ranolazine?

• headaches

• dizziness

• QT interval prolongation

what is Ivabradine?

A funny current channel blocker

what is the mechanism of action of ivabradine?

•Reduces rate of depolarisation in sinoatrial nodal cells and therefore reduces heart rate

•Reduces myocardial oxygen demand leading to symptom relief

what are the side effects of ivabradine?

• arrhythmias

• headaches

what are the medications used to manage angina (improving life expectancy)?

• aspirin

• angiotensin converting enzyme inhibitors

• angiotensin receptor blockers

• statins

what does aspirin inhibit?

Cyclo-oxygenase (COX)

what is the mechanism of action of aspirin?

• irreversibly acetylates COX-1

• COX-1 is needed to catalyse manufacture of thromboxane A₂ (TxA₂) which normally stimulates platelet aggregation

what does aspirin reduce?

mortality and non-fatal MI

what are the side effects of aspirin?

risk of bleeding

what is an example of angiotensin converting enzyme inhibitor?

ramipril

what is the mechanism of ramipril?

•Inhibits angiotensin-converting enzyme

what are the effects of ramipril?

•Reduces plasma volume and blood pressure

•Reduces myocardial oxygen demand leading to symptom relief

what are the side effects of ramipril?

•Can potentiate effects of bradykinin and therefore cause dry cough

which medication is not indicated for secondary management of angina but recommended for management of patients with angina and hypertension?

angiotensin receptor blockers

what do statins inhibit?

HMG CoA reductase

what is the mechanism of statins?

•Inhibits first step in sterol synthesis

•Reduces low-density lipoprotein receptor expression increases clearance of lipoprotein particles