8 Cardiovascular (Ischaemic Heart Disease) Therapeutics Flashcards
Define and describe Ischaemic Heart Disease
Vascular supply of Heart to the heart is impeded by atheroma, thrombosis or spasm of the coronary arteries
The resultant myocardial infarction occurs when oxygen demand exceeds myocardial oxygen supply
- Pain can be induced, but sometimes the ischaemia is ‘silent’
(e. g. in people with diabetes mellitus)
List some risk factors of Ischaemic Heart Disease
- Smoking
- Raised Serum Cholesterol
- Hypertension
- Diabetes
- Stress
- Obesity
- Male
Describe the prevalence of Ischaemic Heart Disease
- CHD levels lower in groups with higher incomes
- CHD deaths have fallen in this group since the 1970s (linked to a reduction in fat consumption/smoking)
- 3 million people in the Uk have had a myocardial infarction
- and 2 million have Ischaemic Heart Disease
Describe atherosclerosis, and the relation with CVD
IHD occurs when atherosclerosis occurs in the coronary arteries (starts to occur before adulthood)
- Atherosclerosis occurs in coronary arteries
- Fatty streaks contain LDL cholesterol, macrophages, T cells
The proliferation of smooth muscle cells into the inner coating of artery and build-up of collagen, glycoproteins leads to the formation of a fibrous cap surrounding cells leading to plaque formation
Describe plaque attack, and how this plaque can lead to ACS
Plaques reduce blood flow
- Coronary arteries get stiffer and have less dilation - less blood flow (ischaemia)
- The plaque can rupture, leading to a loss of endothelium
- This leads to a formation of a thrombus
Formation of ACS
(acute coronary syndrome)
Describe chest pain, and how it can present, and be caused
Chest pain can present in similar ways, and maybe caused by different things:
- Angina pectoris
- Variant angina (prinzmetals)
- GORD/oesophageal spasm
- Hypertrophic cardiomyopathy
- Pulmonary embolus
- Costochondritis
- Myocardial infarction
- Mitral valve prolapse
- Pneumonia/Lung cancer
Give the relation between chest pain and angina
and how it can be a concern for angina, ACS, and MIs
NICE guidelines:
- NICE considers those patients who present with acute, new-onset chest pain and those who present with intermittent, stable chest pain (develops chest pain after exercise)
There is a major concern that the pain may be due to Acute Coronary Syndrome (ACS), which includes conditions such as:
- Unstable Angina
- ST-segment-elevation MI (STEMI)
- Non-STEMI (NSTEMI)
Describe some symptoms of Acute Coronary Syndrome
- New-onset chest pain
- OR abrupt deterioration in previously stable angina, with recurrent chest pain occurring with little or no exertion. Episodes last > 15mins
- Pain in chest and other areas such as arms, back and jaw lasting longer than 15 mins
- Chest pain is associated with nausea and vomiting, breathlessness, marked sweating
Describe when/how to refer to the hospital if suspected of ACS
Send to hospital for suspected ACS
- currently have chest pain
- currently pain-free, but had chest pain in the last 12 hours, and a resting 12-lead ECG is abnormal
A normal ECG DOES NOT EXCLUDE ACS if other clinical features are present
Describe what to be aware of when taking a clinical history of a patient suspected of ACS/IHD
PMH - e.g. history of angina, MI, CVD and PCI (percutaneous coronary intervention)
- Risk factors for cardiac disease
- Pain history e.g. longer than 15mins
- Chest pain may not be the main presenting symptom (e.g. may present with mainly breathlessness)
> Diabetes can have damaged cardiac nerve endings
> Do not use response to GTN (glycerol Trinitrate) to diagnose whether pain is cardiac or not
Describe what to do if ACS is suspected (emergency)
ACS ASAP!
- Emergency admission
- Relieve pain with GTN (glycerol trinitrate) and/or opioid
- Aspirin 300mg unless allergic (then give clopidogrel)
- Carry out an ECG, and send to the hospital
- Measure O2 sats (give O2 if Sats <94%)
Describe a stable angina
and what is done to manage it
Some having a current angina
- they can undergo a PCI, where a stent is inserted
If it is an ongoing/chronic angina (MI)
- CABG (coronary artery bypass graft)
Describe factors affecting stable angina
(what can relieve it)
(imaging that can be used)
- Stable angina can be provoked by numerous factors including cold weather, exertion, eating a heavy meal, or stress
Angina attack can be relieved by Glyceryl Trinitrate (GTN)
Coronary Angiography is a procedure that uses contrast dye and X-ray pictures to detect blockages in the coronary arteries that are caused by plaque build-up
Describe Prinzmetal’s (Variant) Angina
- Achy, dull, tight, pressy pain
- Can occur at rest or at night
- Mainly in younger women
- Spasm of coronary artery
- Relieved by GTN
- ECG during attack must be done
- CCB’s first line (calcium channel blockers)
Describe the treatment for an angina attack
GTN - glycerol trinitrate - treatment for angina
- Relieves load on the heart
It is sprayed on the tongue
- as GTN has high 1st pass metabolism, so this way it can bypass the liver and enters the bloodstream directly
Describe the use of short-acting nitrates
Offer a short-acting nitrate, for use immediately before planned exertion or when the pain occurs
- Warn patients about SIDE EFFECTS:
> flushing, headache, and light-headedness
- If the patient is having to use it regularly, then it indicates poor control of symptoms
Describe what advice is given to GTN spray
British Heart Foundation advice:
- Carry GTN at all times
- IF you get pain, stop what you are doing, sit down + rest. Take a puff of GTN
- If the pain doesn’t ease within 5 mins, take the 2nd puff of GN
- If the pain doesn’t ease within 5 mins, take the 3rd puff of GTN and DIAL 999
Whilst waiting for the ambulance, take 300mg of aspirin
(if allergic, then just sit and wait for the ambulance)
Describe the management of stable angina
If a patient’s symptoms:
- are not satisfactorily controlled on a B-blocker or CCB, consider switching to the other option, or combination of the two
(BUT, do not give B-blocker + rate-limiting agents)
Do not routinely offer anti-angina drugs other than B-blockers as 1st line for stable angina
If a patient cannot tolerate B-blockers and CCBs, consider monotherapy with a:
- Long-acting nitrate
- Ivabradine
- Nicorandil
- Ranolazine
Describe the use of B-blockers in the treatment of ischaemic heart disease
AND give MOA
Beta-blockers (1st line) e.g. Bisoprolol
- Negative inotropic (slows heart rate)
> allows more efficient work - Negative chronotropic
> (reduce heart contraction - reduce load)
These effects reduce cardiac work + prevent symptoms
- Anti-arrhythmic effects and reduce the risk of Myocardial Infarction
- Provides symptomatic relief
Aim for a heart rate of 60bpm
Use more cardio-selective B1-blockers like:
- Bisoprolol, atenolol, and metoprolol
Describe some contraindications fo B-beta-blockers
- Asthmatic patients
- Patients who have bradycardia (can’t reduce heart rate anymore - not good!)
Describe the use of Calcium Channel Blockers in the treatment of IHD
give MOA
and SE, contraindications etc.
Calcium channel blocks (CCGs)
- These work by inhibiting Ca2+ channels, leading to depolarisation
CCGs can be used where B blockers are contra-indicated (another 1st line)
e. g. Asthmatics, bradycardia
- Useful in patients with underlying blood pressure issues
- Consider in patients who are diabetics, peripheral vascular disease
2 types:
Dihydropyridine type (long-acting)
- e.g. Amlodipine, felodipine, nifedipine
- work by relaxing smooth muscles
- they decrease afterload and improve coronary perfusion
- NO EFFECT ON RATE
Rate-limiting agents
- e.g. verapamil, diltiazem
- also have myocardial and bradycardic actions - Reducing cardiac work
- AVOID with B-blockers + patients with heart failure
Describe the use of Nitrates in the treatment of IHD
give MOA
Nitrates
e.g. GTN (glycerol trinitrate)
They work by causing vasodilation of veins - reducing preload
- They relax the smooth muscle by causing endothelium to produce Nitric Oxide (NO), which relaxes vascular smooth muscle
SO, it improves coronary blood flow
Nitrates are rapidly broken down by a liver enzyme
- SO, can be given orally,
- transdermally (RARE) and
- sublingually (under tongue - GTN)
Give some important prescribing points to keep in mind when giving Nitrates as a treatment
(SE, contraindications, uses etc.)
SE of nitrates:
- Dizziness, flushing, headache, postural hypertension, tachycardia, GI disturbances
Tolerance is a major issue
- need to have a nitrate-free period 6-10 hours a day
- Modified release tablets tend to be given in the morning
- They release nitrates during the daytime, but evening washout period when the patient is less active
Describe the MOA of Potassium Channel Activators in the treatment of IHD
K+ channel activators
- e.g. Nicorandil
MOA:
Nicorandil is a combined NO donor and activator of ATP-sensitive K+ channels:
- Once these ATP-sensitive K+ channels are activated
- It causes hyperpolarisation
- and relaxation of cardiac muscle cells
Describe the use of Potassium Channel Activators in the treatment of IHD
Potassium Channel Activators
- e.g. Nicorandil
Nicorandil is now a second-line treatment for Angina
- use Nicorandil for treatment of stable angina only in patients:
> whose angina is inadequately controlled by 1st line anti-anginal therapies
> or who have a contraindication/intolerance to 1st line anti-anginal therapies
i.e. B-blockers or CCB
Give some side effects/contraindications of Potassium Channel Activators like Nicorandil
SE:
- Can cause serious skin, mucosal, and eye ulceration:
> including GI ulcers, which may progress to perforation, haemorrhage, fistula or abscess
STOP NICORANDIL TREATMENT
- if ulceration occurs
- consider the need for alternative treatment, or specialist advice if angina symptoms worsen
Describe the use of Ivabradine in the treatment of IHD
And any SE’s/contraindications
Ivabradine inhibits If channels
- pacemaker Na+/K+ currents in the SAN
Ivabradine:
- reduces heart rate
- BUT NOT the force of contraction (heart failure use)
> those with symptomatic angina had increased CV death
STOP Ivabradine treatment if:
- the resting heart rate remains below 50bpm
- or symptoms of bradycardia persist
AVOID in:
- patients on Diltiazem/Verpamil (rate-limiting CCB’s)
Describe the use of Antiplatelet drugs in the treatment of IHD
Antiplatelet treatment is drug treatment that:
- decreases platelet aggregation + inhibits thrombus formation in the arterial circulation
e. g. Aspirin
- irreversibly inhibits COX + blocks the production of thromboxane
In angina, use
- Aspirin 75mg
- Clopidogrel 75mg daily
(should be considered for px who are unable to take aspirin)
Describe the principle behind how statins work
HMG-CoA reductase inhibitors
HMG-CoA reductase inhibitors
- in the pathway for cholesterol synthesis
- 3-hydroxy-3-methylglutaryl coenzyme A reductase catalyses the first step of cholesterol synthesis
Describe the use of statins in the treatment of IHD
give the MOA
SE, interactions etc.
Statins reduce plasma cholesterol
e. g. Atorvastatin and simvastatin
- The receptors in hepatic cholesterol synthesis leads to an upregulation of hepatic LDL receptors, promoting LDL uptake
Side effects:
- Muscle damage
(simvastatin must be taken at night)
Drug-Drug interactions:
- with macrolides (e.g. clarithromycin)
- with CCB’s (simvastatin and amlodipine)
Drug-food interactions:
- with grapefruit juice
Describe why patients with IHD need to be on a statin
Primary prevention - treat patients with >10% risk of CV or over in the 10 years (balancing risks vs benefits vs cost) - assess this via QRIS3 [20mg atorvastatin) - low intensity]
Secondary Prevention
- or patients with CVD
- 80mg atorvastatin [high intensity]
Describe the Quad treatment policy post-ACS
Dual antiplatelet therapy
- e.g. aspirin + clopidogrel required after PCI (stents)
ACE inhibitor
- ramipril
Beta-blocker
- e.g. Bisoprolol
- OR CCB like amlodipine (reduced load)
- or verapamil (reduced load + reduced heart rate as well)
Statins
- atorvastatin
