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Drugs: from molecules to man > Stable Angina > Flashcards

Stable Angina Flashcards

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Organic Chemistry 101 flashcards
1
Q

what do angina and acute coronary syndrome both involve?

A

Chest pain caused by cardiac ischaemia

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2
Q

What are the features of Stable angina?

A

resolves with rest in a few minutes

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3
Q

What are the features and types of Acute Coronary syndrome?

A

• ACS: does not resolve quickly or with rest – likely to get worse:

  • Unstable angina
  • Non ST elevated myocardial infarction (NSTEMI) (heart attack)
  • ST elevated myocardial infarction (STEMI) (heart attack)
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4
Q

What is angina pectoris?

A
  • Crushing pain in chest that may radiate to arm, neck or jaw ‘strangling of the chest’
  • The pain results from cardiac ischaemia (referred pain)
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5
Q

What are the types of angina associated with an atherosclerotic plaque?

A
  • stable angina

- unstable angina

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6
Q

What are the types of angina associated with vessels constricting/spasming?

A
  • Prinzmetal’s angina (variant angina)

- Microvascular angina

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7
Q

What is the incidence, cause, triggers and relief of stable angina?

A
  • Incidence: The most common form
  • Cause of ischaemia Atherosclerosis of coronary arteries
  • Plaque is quite stable, prevented from rupture
  • Triggers: exercise, excitement, cold weather
  • Relief: rest
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8
Q

What is the incidence, cause, triggers and relief of unstable angina?

A
  • Incidence: rarer but more serious
  • Cause of ischaemia: atherosclerosis + blood clot
  • Triggers: unpredictable
  • Relief: not relieved by rest
  • May progress to MI
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9
Q

What are the two ways we can treat angina?

A
  • Too little O2 getting to cardiac muscle. We can:
  • Reduce O2 demand (reduce workload)
  • Increase O2 supply (improve blood flow)
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10
Q

What is the NICE care pathway with stable angina?

A
  • Offer short acting nitrate (relieves attack)
     Optimise angina drugs
     Beta blockers or calcium channel blockers
     Then adding more drugs
  • Secondary prevention drugs (preventing progression of atherosclerosis)
  • If drug treatment not satisfactory then you may consider surgical approaches such as stenting or through coronary artery bypass graph
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11
Q

What are drug treatment options with stable angina?

A
  • Aspirin – to prevent platelet aggregation

- Statins: lipid lowering, prevent plaque worsening, e.g. Atorvastatin

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12
Q

What is first pass metabolism?

A
  • Drug is absorbed by gut and taken to liver by hepatic portal vein
  • Liver detoxifies foreign substances
  • Amount of drug that reaches systemic circulation is called bioavailability
  • For organic nitrates bioavailability is extremely low if taken by oral administration
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13
Q

What are the routes of drug delivery?

A
  • Topic transdermal – applied to skin
  • Parenteral – injection
  • Mucous membrane
     Buccal: mouth sprays
     Sublingual: tablets that dissolve under the tongue
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14
Q

What are the routes of drug delivery important for organic nitrates?

A

Transdermal, buccal and sublingual most important for organic nitrates

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15
Q

What are the organic nitrates that are used to treat stable angina?

A
  • Glyceryl trinitrate (GTN/nitroglycerine)
  • (Amylnitrite)
  • Isosorbide dinitrate
  • (Nicorandil)
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16
Q

How is GTN given and what is it’s duration?

A
  • Given sublingually, buccally and as a patch
  • Avoid first pass metabolism
  • Duration of action 20-30 minutes (sufficient in helping relieving acute angina attack)
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17
Q

What does it mean that organic nitrates are prodrugs?

A

They need to be metabolised before they are effective

18
Q

How does GTN being metabolised in the site of action work?

A 
 Metabolised to NO (active principle) 
 Acts on SH groups of guanylyl cyclase, turns it into an active form 
 These leads to GTP:
 cGMP:
 PKG inactive -> PKG active: 
 Protein -> protein -PO4:
 Reduced [Ca2+]i
 Vasodilation
19
Q

How do the nitrates relieve an angina attack?

A
  • Not really by dilating coronary arteries – coronary arteries already maximally dilated by metabolites from ischaemic myocardium
  • Nitrates reduce cardiac work by reducing preload and afterload
20
Q

What does dilating peripheral blood vessels do?

A 
 Heart does not have to push so hard 
 Less blood returned to heart: lower force of contraction (lower stroke volume) 
 Decreases venous pressure 
 Decreases venous return 
 Decreased EDV (preload) and EDP 
 Decreased myocardial stretch 
 Decreased contractile force and systolic volume 
 Decreased cardiac work 
 Decreased angina
21
Q

Large doses of nitrates cause arteriolar dilation. What does this mean?

A

 Fall in peripheral resistance
 Reduction in cardiac afterload
 Reduces cardiac work

22
Q

How do organic nitrates improve coronary blood supply?

A
  • Angina + GTN dilates collateral vessel

- Collateral vessel runs around heart blockage

23
Q

What are two long acting organic nitrates?

A
  • isosorbide mononitrate
  • isosorbide dinitrate
  • dinitrate is initially metabolised to mononitrate
24
Q

What is released at the site of action with long acting organic nitrates?

A

NO

25
Q

How are Isosorbide mononitrate and dinitrate administered?

A
  • Dinitrate: tablets, sustained release tablets, sublingual tablets and buccal sprays, transdermal patches and i.v. injection
  • Mononitrate: tablets and sustained release tablets
26
Q

What is the duration of action of sustained release tablets?

A

Up to 12 hours

27
Q

Where on the NICE care pathway are the long acting organic nitrates?

A

Quite far down

28
Q

What are the unwanted effects of nitrates?

A
  • Flushing of skin
  • Throbbing headache (dilation of cranial vessels)
  • Postural hypotension (fainting) caused by drop in blood pressure
  • Reflex tachycardia
29
Q

What may beta blockers do to normal tissue at rest?

A

Beta blockers may decrease blood flow in normal tissue at rest due to unmasking of alpha adrenoceptor mediated vasoconstriction

30
Q

What does Nicorandil do and what are it’s unwanted effects?

A
  • Activator of KATP potassium channels and NO donor (produces nitric oxide)
  • Dilates both arteries and veins
  • Effects vs angina similar to nitrates
  • Unwanted effects: headache, flushing, hypotension, nausea and vomiting
31
Q

What do beta blockers do with angina?

A
  • Block sympathetic nervous system receptor that increases heart rate
  • Blocks B-receptors in atrial and ventricular myocardium:
  • Heart slows
  • Atria beats less forcibly
  • Ventricles beat less forcibly
  • Cardiac work rate and O2 demand are reduced
  • Coronary blood flow only through diastole
  • Beta blockers prolong diastole due to slowing effect on heart – greater coronary blood flow
32
Q

What are the primary and secondary effects of beta blockers on angina?

A
  • Principle effect: reduction in cardiac work and hence reduction in O2 demand
  • Secondary effect: Coronary flow improved as a consequence of the prolongation of diastole
33
Q

What are Verapamil and Amlodopine?

A
  • Calcium channel blockers
  • Binding sites on the a-subunit of the L-type Ca2+ channel
  • Verapamil binds towards interior of cell
     Use-dependent block
     Cardiac selective
  • Amlodopine binds towards extracellular face
     Block voltage, not use-dependent
     Vascular selective
34
Q

What does Verapamil do in stable angina?

A
  • Blockade of Ca2+ channels is use-dependent
  • More potent on heart than vascular smooth muscle
  • Ca2+ channel blockade in myocardium reduces heart rate and cardiac output
  • Dilation of arterioles reduces cardiac afterload
  • Cardiac work and O2 demand are reduced
35
Q

What does Amlodipine do in stable angina?

A
  • Blockage of Ca2+ channels is NOT use-dependent (it is voltage dependent)
  • More potent on vascular smooth muscle than heart
  • Dilation of arterioles reduces cardiac afterload
  • Dilation of capacitance veins reduces cardiac preload
  • Cardiac work and O2 demand are reduced
36
Q

What are the two surgical approaches for treating angina?

A
  • Coronary artery angioplasty (percutaneous coronary intervention/PCI)
  • Coronary artery bypass graft (CABG)
37
Q

What happens in Coronary artery angioplasty?

A
  • A catheter is introduced into a large vessel in the groin or arm and is threaded into the heart and guided to the place where the coronary artery is blocked. The journey of the catheter to the blocked artery can be visualised by injecting a radio-opaque dye out of the catheter into the blood vessel and following it using an X-ray machine
  • When the catheter reaches the blockage, a balloon at its tip is inflated, which opens the artery, and also pushes open a metal mesh tube, called a stent
  • The stent will keep the artery open once the balloon is deflated and the catheter is removed
  • Stents can either be bare stainless steel or impregnated with drugs designed to reduce inflammation (drug eluting stents)
38
Q

What is coronary artery angioplasty used for and what does it do?

A
  • It is used to treat angina that has not been controlled by drugs. It is also used as an emergency treatment in patients who have had a heart attack,
  • In angina it can reduce the frequency of angina attacks and gives better control than drug treatment, but it does not reduce the risk of death or the chance of having a future heart attack
  • In heart attacks it can substantially improve outcomes if it is done quickly
39
Q

What are the adverse effects of angioplasty?

A
  • Stroke and myocardial infarction due to the angioplasty either triggering the formation of a blood clot or dislodging one that has already formed, which then travels through the blood to a smaller vessel and blocks it (embolism)
  • It was also suggested that angioplasty can lead to cognitive decline, due to blockage of very small blood vessels in the brain. However, recent studies have suggested that this is not the case
  • Restenosis (re-closing) of the artery can also happen. It is thought to occur in about 30% of patients who have bare metal stents, but only about 10% of those who have drug eluting stents
40
Q

What happens in a coronary artery bypass graft?

A
  • CABG is a much more invasive procedure than angioplasty – it is open heart surgery. It involved removing a non-essential blood vessel from another part of the body and using it to restore blood flow to the part of the heart in which the blood supply is compromised.
  • The most common blood vessels that are used are the internal mammary artery and the great saphenous vein (from the leg)
  • Depending on the number of new connections that are made, a CABG procedure may be referred to as a double bypass, triple bypass etc.
41
Q

When is a coronary artery bypass graft (CABG) used and what does it do?

A
  • It is used to treat angina that is resistant to drug treatment and where the location of the blockage means that stents can’t be used. It improves survival in patients who are at high risk, though the difference from drug treatment alone diminishes with time and does not reduce the risk of heart attacks
  • Like angioplasty, CABG seems to be more effective at controlling the symptoms of angina than drugs alone. Further, in terms of mortality and risk of heart attack, CABG is superior to angioplasty in patients with severe coronary artery disease
42
Q

What are the adverse effects of CABG?

A
  • Those that arise from surgery: poor wound healing, blood loss and dysrhythmias induced by the use of a general anaesthetic and those from the graft
  • Others include: myocardial infarction and stroke due to embolisms and debris from the surgery entering the circulation
  • It has also been suggested that CABG might cause cognitive decline, but like with angioplasty this has been questioned recently
  • Grafts last up to 15 years but will then need to be replaced

Drugs: from molecules to man (22 decks)

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