cardiovascular therapeutics Flashcards
ischaemic heart disease
Vascular supply of heart to the heart is impeded by atheroma, thrombosis or spasm of the coronary arteries.
Resultant myocardial ischaemia occurs when oxygen demand exceeds myocardial oxygen supply.
Pain can be induced but sometimes the ischaemia is “silent”.
risk factors
Smoking Raised serum cholesterol Hypertension Diabetes Stress Obesity Male
prevalence
CHD levels tend to be lower in groups with higher incomes. CHD death rates have fallen in this group since the 1970s (linked to reduction in fat comsumption/smoking).
About 100,000 deaths a year due to CHD/IHD
1.3 million in the UK have had a myocardial infarction and 2 million have IHD
aetiology
IHD occurs when atherosclerosis occurs in the coronary arteries and starts to occur before adulthood.
The formation of fatty streaks containing lipids (LDL cholesterol), macrophages and T-cells.
Proliferation of smooth smooths cells into inner coating of artery and build-up of collagen, glycoproteins to form a fibrous cap surrounding cells leading to plaque formation
plaque
The presence of these plaques leads to a reduction in blood flow.
The coronary arteries become stiffer and less able to dilate leading to reduce blood flow and ischaemia.
The plaque can rupture lead to loss of the endothelium leading to the formation of a thrombus causing ACS
Statins role?
chest pain
Angina pectoris Variant (Prinzmetal’s) angina GORD/oesophageal spasm Hypertrophic cardiomyopathy Pulmonary embolus Costochondritis Myocardial infarction (ACS) Mitral valve prolapse Pneumonia/lung cancer
chest pain and angina
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).
Major concern that pain may be acute coronary syndrome (ACS) which includes conditions such as unstable angina, ST-segment-elevation myocardial infarction (STEMI) and non-ST-segment-elevation (NSTEMI)
symptoms of ACS
New onset chest pain or abrupt deterioration in previously stable angina, with recurrent chest pain occurring frequently with little or no exertion. Episodes often lasting longer than 15 minutes
Pain in chest and other areas such as arms, back and jaw lasting longer than 15 minutes
Chest pain is associated with nausea and vomiting, breathlessness, marked sweating
hospital referral
Send to hospital as an emergency 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.
history
Past medical hx. eg. history of angina, MI, CVD disease and PCI
Risk factors for cardiac disease
Pain history eg. longer than 15 minutes
Chest pain may not be the main presenting symptom (eg. may present with mainly breathlessness).Diabetes can have damaged cardiac nerve endings.
Do not use response to GTN to diagnose whether pain cardiac or not
ACS ASAP
Emergency admission Relieve pain with GTN and/or opioid Aspirin 300mg unless allergic ECG and send to hospital Measure oxygen saturations and give oxygen if sats. less than 94%
factors- stable angina
Stable angina can be provoked by numerous factors including cold weather, exertion, eating a heavy meal, stress.
Angina attacks can be relieved by glyceryl trinitrate.
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.
printzmetal’s (Variant) Angina
Achy, dull, tight, pressing pain Can occur at rest or at night Mainly in younger women Spasm of coronary artery Relieved by GTN ECG during attack CCBs first-line
Short-Acting nitrates
Offer a short-acting nitrate, for use immediately before planned exertion or when pain occurs
Warn patients about side-effects such as flushing, headache and lightheadedness
If patient having to use frequently then indicates poor symptom control
GTN spray advice
British Heart Foundation Advice:
Carry GTN at all times
If you get pain, stop what you are doing, sit down and rest. Take a puff of GTN
If the pain doesn’t ease within five minutes, take a second puff of GTN
If the pain doesn’t go within 5 minutes take a third puf of GTN and dial 999
Whilst waiting for the ambulance, take 300mg of aspirin. If allergic, then just sit and wait for the ambulance
beta-blockers
Negative inotropic and chronotropic effects reducing cardiac work and preventing symptoms.
Coronary flow only occurs during diastole, then by slowing the heart the diastolic period will be increased, as will the time for coronary blood flow.
Anti-arrhythmic effects and reduce the risk of myocardial infarction.
Provide symptomatic relief. Aim for heart rate of 60 bpm.
Use more cardioselective β-blockers such as bisoprolol, atenolol and metoprolol.
calcium channel blockers
Can be used where β-blockers are contra-indicated eg. asthmatic patients
Useful in patient with underlying blood pressure issues.
Consider in patients who are diabetics, peripheral vascular disease.
Dihydropyridine type are long-acting (eg. amlodipine,felodipine and nifedipine) and work by relaxing smooth muscles. Decrease afterload and improve coronary perfusion. No effect on rate
Rate limiting agents(e.g. verapamil, diltiazem) also havemyocardial depressant and bradycardic actions,so reducing cardiac work.Avoid withβ-blockers and patients with heart failure
Verapamil also exerts Class IV anti-arrhythmicactivity.
stable angina: management
If a patient’s symptoms are not satisfactorily controlled on a β-blocker or CCB consider switching to the other option or using a combination of the two.
Do not routinely offer anti-angina drugs other than β-blockers as first-line for stable angina.
If patient cannot tolerate β-blockers and CCBs consider monotherapy with a long-acting nitrate, ivabradine, nicorandil or ranolazine
nitrates
Work by causing vasodilation of veins reducing preload. Relax smooth muscle by causing the endothelium to produce nitric oxide which relaxes vascular smooth muscle.
Improves coronary blood flow
Rapidly broken down by liver enzymes. Can be given orally, transdermal (hardly used) and sublingually.
prescribing points
Dizziness, flushing, headache, postural hypotension, tachycardia, GI disturbances.
Tolerance is a major issue. Need to have a nitrate-free period 6-10 hours out of every day.
Modified-release tablets tend to be given in the morning. They release nitrates during the daytime but washout period during the evening when the patient is less active.
free period
Avoid giving modified-release tablets twice daily but if patient needs 120mg a day give as a single dose in the morning. Branded prescribing can be much cheaper (Drug Tariff alert)
Standard shorter-acting nitrates such as isosorbide mononitrate 20mg are given at 8am and 2pm to ensure there is an evening washout period.
potassium channel activators
Nicorandil: combined NO donor and activator of ATP-sensitive K-channels.
The target is the ATP-sensitive K+-channel (KATP):
nicorandil as second-line treatment for angina
Use nicorandil for treatment of stable angina only in patients whose angina is inadequately controlled by first line anti-anginal therapies, or who have a contraindication or intolerance to first line anti-anginal therapies such as beta-blockers or calcium antagonists
Nicorandil can cause serious skin, mucosal, and eye ulceration, including gastrointestinal 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
ivabradine
InhibitsIfchannels(pacemaker Na/K currents inthe Sinoatrial (SA) node)
Reduces heart rate but not force of contraction (HF usage)
In the SIGNIFY studythose with symptomatic angina had increase CV deathN Engl J Med 2014; 371:1091-1099
Stop ivabradine treatment if the resting heart rate remains below 50 bpm or symptoms of bradycardia persist. MHRA Drug Safety Update11 December 2014.
Avoid in patients on diltiazem/verapamil
antiplatelet drugs
Antiplatelet treatment is drug treatment thatdecreases platelet aggregation and inhibit thrombus formation in the arterial circulation.
Aspirin— this irreversibly inhibits cyclo-oxygenase and blocks the production of thromboxane.
In angina use aspirin 75 mg.Clopidogrel 75 mg daily should be considered for people unable to take aspirin.
statins
Reduce plasma cholesterol. Examples include atorvastatin and simvastatin
The reduction in hepatic cholesterol synthesis leads toan upregulation of hepatic LDL receptors, promotingLDL uptake
Muscle damage can be side effect
Simvastatin taken at night
Drug-drug interactions withmacrolides (eg. clarithromycin) andcalcium channel blockers (simvastatin and amlodipine)
Drug-food Interactions with grapefruit juice
Patients with IHD need to be on a statin!
