SIHD & Angina - Therapy Flashcards
Coronary artery disease happens as an interaction between both ______________________ risk factors.
modifiable and non-modifiable
How would you describe the interaction between risk factors leading to ACS/stable angina?
synergistic
Outline some modifiable risk factors.
smoking alcohol stress sleep diet/Na intake exercise
Outline some non-modifiable risk factors.
age
sex
Fx
What are the risk factors for SIHD/angina?
6
smoking hypertension hyperlipidaemia hyperglycaemic male post-menopausal female
Myocardial ischaemia can result from both supply ischaemia and demand ischaemia.
What are the determinants of demand ischaemia?
- HR
- contractility
- systolic BP
- myocardial wall stress
Myocardial ischaemia can result from both supply ischaemia and demand ischaemia.
What are the determinants of supply ischaemia?
- coronary artery diameter/tone
- collateral flow
- perfusion pressure
Most change in atherosclerosis are in which layer of the blood vessels?
Which cell types accumulate?
intima
macrophages (foamy macrophages), monocytes, lymphocytes, connective tissue
What are the aims of drug therapy in treating SIHN/angina?
What are some of the mechanisms behind drugs used? (3)
reduce O2 demand/increase O2 supply
reduce HR
reduce contractility
reduce afterload
What drug classes may be used in treating angina (give examples)?
(8)
- short acting nitrates (GTN)
- long acting nitrates (isosorbide mononitrate)
- beta blockers (bisoprolol)
- CCB (amlodipine)
- potassium channel openers (nicorandil)
- new drugs (ranolazine, ivabradine)
- antiplatelets (aspirin, clopidogrel)
- statins (atorvastatin)
Which drugs work by increasing blood/O2 supply?
How?
- nitrates (vasodilation)
- CCBs (vasodilation)
Which drugs work by reducing blood/O2 demand?
How?
- beta blockers (reduce HR)
- CCBs (reduce contractility)
Outline briefly how beta blocker work?
- antagonists of B1 and B2 receptors
- block the SNS
- reduce HR/contractility
- reduce CO/BP
- protect myocytes from O2 free radicals
What beta blockers may be used in treating angina?
bisoprolol
atenolol
What is the rebound phenomena?
- sudden cessation of beta blocker use may precipitate MI
What are the contraindications to beta blockers?
5
asthma peripheral vascular disease Raynaud's phenomena bradycardia/heart block HF
What are some adverse drug reactions that occur with beta blockers?
(3)
impotence
bradycardia (heart block)
bronchospasm (asthma)
What issues can arise from drug-drug interactions with beta blockers, and which drugs are the cause?
(2)
- hypotension (other antihypertensives/NSAIDs)
- bradycardia (CCBs e.g. verapamil/diltiazem)
Outline briefly how calcium channel blockers (CCBs) work?
- Prevent Ca2+ influx into myocytes and smooth muscle lining arteries and atrerioles by blocking the L-Type calcium channel.
- rate limiting (reduced HR/contractility)
- vasodilation (reflex tachycardia?)
What calcium channel blockers may be used in treating angina?
(4)
amlodipine/nifedipine
verapamil (rate limiting)
diltiazem (rate limiting)
CCBs reduce vascular ____ and produce __________ and reduce _______.
tone
vasodilatation
afterload
Rate limiting CCBs reduce the _______ and the force of myocardial ________.
heart rate
contractility
CCBS may also produce coronary __________ but of little importance.
vasodilatation
What are the contraindications to CCBs?
nifedipine:
- never use immediate release
- reflex tachycardia
- risk of acute MI/stroke
What are some adverse drug reactions that occur with CCBs?
4
- ankle oedema (no response to diuretics)
- headache
- flushing
- palpitations
How do nitrates work?
What are the different types?
(3)
- vasodilators
- short acting
- sustained release
Give examples of nitrates that may be used in treating angina.
State how they act.
(3)
- glyceryl trinitrate (GTN): short acting
- isosorbide mononitrate: long acting
- ivabradine (new drug)
Briefly outline how nitrovasodilators work.
5
- relax smooth muscle
- releases NO
- stimulates release of cGMP
- reduced preload/afterload
- reduced O2 consumption
How do vasonitrates relieve angina, in terms of reducing afterload?
(3)
- arterial dilation
- reduced afterload
- reduced myocardial O2 consumption
- reduced O2 demand
How do vasonitrates relieve angina, in terms of reducing preload?
(3)
- peripheral venodilation
- reducing venous return
- reduced preload
- reduced myocardial workload
Why is GTN spray often administered sublingually?
to avoid first pass metabolism
Which nitrates tend to be given orally?
2
- sustained release, long acting nitrates
- used for prophylaxis
When might nitrates be administered intravenously?
- unstable angina
- in combination LMWH (e.g. enoxaparin)
What is a problem associated with overuse of nitrates?
How is this overcome?
- tolerance built up
- giving asymmetric dose, sustained release formulation
What are some adverse drug reactions that occur with nitrates?
(2)
- headache
- hypotension (GTN syncope)
Which CCB tends to increase vasodilation?
amlodipine
Which CCBs tends to reduce contractility and heart rate?
verapamil
diltiazem
Advances in understanding of myocardial ischaemia have prompted evaluation of a number of new antianginal strategies, including:
Ischaemic preconditioning with _________.
nicorandil
Advances in understanding of myocardial ischaemia have prompted evaluation of a number of new antianginal strategies, including:
Sinus node inhibition with _______.
ivabradine
Advances in understanding of myocardial ischaemia have prompted evaluation of a number of new antianginal strategies, including:
Late Na+ current inhibition with __________.
ranolazine
- Activate “ATP sensitive potassium channels.
- K+ entry into cardiac myocytes inhibits Ca2+ influx and so has a negative inotropic action.
Which drug is this describing?
nicorandil
- Nicorandil acts as a pharmacological ___________ agent.
- It has a ___________ effect.
preconditioning
cardioprotective
- a selective sinus node channel inhibitor.
- slows the diastolic depolarisation slope of the SA-node.
- results in a reduction in heart rate.
What drug is this describing?
Ivabradine
- inhibits persistent or late inward sodium current (INa) in heart musclein a variety of voltage gated sodium channels.
- inhibiting that current leads to reductions in intracellular calcium levels.
Which drug is this describing?
Ranolazine
________ is a potent inhibitor of platelet thromboxane production.
Aspirin
Thromboxane stimulates ______________ and ____________.
platelet aggregation
vasoconstriction
Aspirin
Use for the symptomatic treatment of chronic stable angina in adults with normal sinus rhythm and heart rate _____ bpm.
≥ 70
- inhibits ADP receptor activated platelet aggregation.
- prevention of atherosclerotic events in PVD.
- same incidence of bleeding as _______ but possibly lower GI bleeding.
Which drug is this prescribing?
What is the blank?
clopidogrel
aspirin
What type of drugs are cholesterol lowering agents?
Give examples. (3)
statins
atorvastatin
simvastatin
pravastatin
What is the treatment regime for stable angina? Give examples of drugs.
(10)
- short acting nitrate (GTN)
- beta-blocker (bisoprolol)
- rate limiting CCB (verapamil, diltiazem)
- dihydropiridine CCB (amlodipine)
- long acting nitrate (isosorbide mononitrate)
- new drugs (Ivabradine/ Ranolazine)
- K channel activator (nicorandil)
Secondary preventors:
- statin (atorvastatin)
- antiplatelet (aspirin, clopidogrel)
- ACE inhibitor
What are the NICE guidlines, in terms of the order in which drugs should be prescribed for anginal patients?
- beta-blocker (+GTN)
- CCB
- combination, or other therapy
What drugs should be taken as secondary preventors pf further ACS/MI? Give dosage.
(4)
- aspirin (75mg/day)
- atorvastatin (80mg/day)
- ACE inhibitor
- antihypertensives/beta-blocker
