cardio: CAD Flashcards
etiology of IHD
primarily caused by coronary atherosclerotic plaque formation -> imbalance between oxygen supply and demand -> myocardial ischaemia
types of IHD
- stable angina: significant fixed lesion, atheromatous obstruction
- unstable angina: unstable plaque that leads to rupture (recurrent platelet rich, non-occlusive thrombi) -> acute MI
- vasospastic angina: transient spasm of localised portions of vessels
factors that increase risk of death in IHD
- number of coronary vessels obstructed
- presence of heart failure
- smoking
- left main or left main equivalent coronary artery disease
- diabetes
- prior MI
during systole,
heart pumps blood throughout the body oxygen and nutrients
during diastole,
blood supply to the heart occurs via the arteries which arise from the aorta
oxygen supply
- coronary blood flow
- oxygen extraction (heart unable to extract oxygen from blood itself)
- oxygen availability: Hb concentration, o2 saturation
oxygen demand
- heart rate
- contractility
- intramyocardial wall tension
reduced coronary blood flow results from
- formation of atherosclerotic plaque in coronary (most common)
- coronary vasospasm (sudden tightening: triggers may include drug, smoking, cold weather, extreme stress or exertion) or dissection (when there is a cut in the inner diameter of the coronary blood vessel, a clot may form inside the wall that blocks blood flow, hence reduction of flow to heart)
diameter of coronary blood vessels: <50% obstruction
usually pain free even at exertion
diameter of coronary blood vessels: >= 70% obstruction
found in most coronary artery stenoses, linear decrease in coronary flow as plaque occupies more arterial lumen
diameter of coronary blood vessels: >= 80% obstruction
high-grade obstruction, loss of linear decrease between coronary flow and plaque size
diameter of coronary blood vessels: >= 95% obstruction
absence of blood flow
clinical presentation of angina
location: in the chest, may radiate to epigastrium, lower jaw, teeth, between the shoulder blades, or in either arm to the wrist and fingers
character: pressure, tightness, heaviness, sometimes strangling/constricting/burning
duration: brief =< 10 minutes
symptoms increase with exercise and other precipitating factors (eating, emotions, extreme temp), relieved quickly by sublingual nitrates
CTA
coronary computed tomography angiography - visualises coronary artery lumen and wall using an iv contrast agent
antianginal drugs
nitrates, bb, ccb, ranolazine, ivabradine
vasculoprotective drugs
aspirin/clopidogrel, statin, acei/arb
non-modifiable risk factors of IHD
age, gender (male), family history
modifiable risk factors of IHD
smoking, htn hld, dm, physical inactivity, obesity, stress
b1 receptor
heart -> hr
b2 receptors
lungs -> bronchodilation
systemic circulation -> vasodilation
incr HR -> incr arterial wall stress -> ?
-> release of endothelin, angiotensin, etc. resullting in incr atherosclerosis: chronic stable angina
-> incr risk of coronary plaque rupture: acute coronary syndromes
decr HR -> incr diastole
incr coronary perfusion time -> incr blood flow -> incr o2 supply -> decr o2 demand/supply mismatch -> decr angina
decr HR -> decr myocardial work
decr o2 demand -> decr o2 demand/supply mismatch -> decr angina
mortality benefits of bb are not demonstrated in which group of patients?
only patients with chronic stable angina
- decr morbidity and mortality in patients with HTN, acute MI and/or HF
which is the best tolerated: BB, nitrates, CCBs?
BB
b1 selective bb
Bisoprolol (2.5-10 OD)
Atenolol (25-100 OD)
Metoprolol (80-240 OD for LA, 50-150 BD)
Nebivolol
bb with b1, b2 and a1 blockades
Carvedilol (6.25-50 BD)
Labetalol (200-800 BD)
bb with b1 and b2 blockades
Propranolol (80-240 OD for LA, BD)
cardioselectivity results in
reduced adverse effects
lose cardioselectivity at
higher doses
avoid bb with ISA
eg. acebutolol
- partially simulate beta receptors
- not as effective due to minimal decr in HR, resulting in small decr in MVO2
- generally reserved for patients with low resting HR, who experience angina with exercise
lipophilicity is a/w
more cns side effects
adr of bb
fatigue, bronchospasm, bradycardia, weakness, dizziness, sleep disturbance, loss of libido
- may mask hypoglycemic sx, hence use with caution in insulin-dependent DM
DHP CCBs
selective vasodilators: only act on peripheral and coronary vessels (vasculature)
- potential reflex incr in HR, myocardial contractility, and o2 demand
- amlodipine, nifedipine
non-DHP CCBs
equipotent for cardiac tissue (HR moderating) and vasculature
- verapamil, diltiazem
CCB on o2 supply
vasodilation of coronary arteries:
- decr coronary vascular resistance
- incr coronary blood flow
CCB on o2 demand
vasodilation of systemic arteries:
- decr systemic vascular resistance and arterial BP
non-DHP also decr myocardial contractility and conduction thru AV node, thereby decr HR
short-acting DHP CCBs
nifedipine
- powerful peripheral vasodilator effect, precipitates exaggerated reflex tachycardia, incr o2 demand
potential ddi of ccb
- high first-pass metabolism by cyp3a4
- profound adr on hr and contractility when in combi with bb
amlodipine dosing
2.5-10mg OD
nifedipine ER dosing
30-180mg OD
verapamil IR dosing
30-120mg TDS-QDS
verapamil SR dosing
120-240mg BD
diltiazem SR dosing
60-180mg BD
nitric oxide activates
solute guanylate cyclase, to increase intracellular conc of cyclic guanosine monophosphate -> vasorelaxation
nitrates MOA on IHD
incr o2 supply: dilation of large epicardial coronary arteries and collateral vessels in area with or without stenosis
decr o2 demand: vasodilation by stimulating incr cGMP production
SA nitrates are used for
acute relief of anginal attacks
LAN used for
prophylaxis
ddi of nitrates
PDEi
- sildenafil and verdenafil: within 24 hours
- tadalafil: within 48 hours
nitrate tolerance
reduction or loss of antianginal effects with continuous use
strategies to minimise nitrate tolerance
- maintain a nitrate free interval (approx 10-12 hours per day)
- lower doses of nitrate
- use LA»>SA
S/L SAN tab
- duration of action
- onset of action
- usual dosage
- shelf life
- duration of action: 10-30min
- onset of action: 1-3min
- usual dosage: 0.5mg/tab
- shelf life: 3-6months upon opening of the bottle, depending on brand
S/L SAN spray
- duration of action
- onset of action
- usual dosage
- shelf life
- duration of action: 10-30min
- onset of action: 2-4min
- usual dosage: 0.4mg/spray
- shelf life: 3 years
ISDN
- duration of action
- onset of action
- usual dosage
- duration of action: 2-6hr
- onset of action: 15-40min
- usual dosage: 10-60mg Q4-6H
ISDN SR
- duration of action
- onset of action
- usual dosage
- duration of action: 4-8hr
- onset of action: 15-40min
- usual dosage: 40-80mg Q6-8H
ISMN
- duration of action
- onset of action
- usual dosage
- duration of action: 7-8hr
- onset of action: 30-60min
- usual dosage: 10-20mg BD (am and midday), titrate to 20-40mg BD
ISMN SR
- duration of action
- onset of action
- usual dosage
- duration of action: 8-12hr
- onset of action: 30-60min
- usual dosage: 60mg OD, titrate to 30-120mg OD
transdermal patch LAN
- duration of action
- onset of action
- usual dosage
- duration of action: 4-8hr
- onset of action: 30min
- usual dosage: 0.2-0.4mg/hr
ISDN usually dosed
TDS before meals
ISMN is a ___ of ISDN
major active metabolite
- 100% bioavailable, no first pass metabolism
Transdermal nitrate patch: Area should be clean, dry, and hairless. If hair
is likely to interfere with patch adhesion or
removal, it can be ____
clipped but not shaved
ACEi use in IHD
vasculoprotective
- reduce LV and vascular hypertrophy, atherosclerosis progression, plaque rupture, and thrombosi
antiplatelet use in IHD
vasculoprotective
- inhibit platelet activation and aggregation -> prevent coronary thrombosis
- balanced against risk of bleeding
_____________ should be used in all patients with acute and chronic IHD, with or without manifest sx in the absence of contraindications
aspirin 75-162mg OD
for secondary prevention of MI and death, which antiplatelet (aspirin or clopidogrel) was superior?
clopidogrel, but the magnitude of difference was small
- acceptable alternative to aspirin
- combi with aspirin beneficial in high risk patients
MOA of ranolazine
inhibits late phase of inward Na channel in ischemic cardia myocytes
-> prevents Na+ overload -> prevents Ca2+ overload -> prevents electrical and mechanical dysfunction
ranolazine dose
375mg BD, titrate to 500mg BD after 2-4 weeks according to patient’s response, max 750mg BD
adr of ranolazine
dizziness, headache, constipation, nausea, qtc prolongation
c/i of ranolazine
- hepatic cirrhosis
- renal impairment, crcl<30
- concomitant adm with potent cyp3a4 inhibitors eg. ketoconazole and other azoles, clarithromycin, telithromycin. nefazodone, hiv protease inhibitors
- preexisiting qtc prolongation and concomitant qtc prolonging drugs ef. class 1a/3 antiarrhythmics
MOA of trimetazidine
inhibits 3-ketoacyl coA thiolase (3-KAT, fatty acid oxidation) -> improves myocardial glucose utilisation -> decrease o2 demand
trimetazidine dose
20mg TDS or 35mg BD (MR)
- dose adj for renal impairment
adr of trimetazidine
mainly GI (abdominal pain, nausea, vomiting, diarrhea), dizziness, headache
c/i of trimetazidine
- PD and motion disorders (tremor/shaking, muscle rigidity, walking disorders, RLS)
- renal impairment, crcl<30
ivabradine MOA
sinus node funny channel inhibitor -> prolongs diastole, decr HR -> decr o2 demand
ivabradine should only be used in chronic stable angina patients with
normal sinus rhythm and hr>= 70bpm
ivabradine dose
5mg BD, incr to 7.5mg BD after 3-4 weeks if resting sx persist and HR>60bpm
- elderly: initial dose of 2.5mg BD
avoid use of ivabradine if renal function <
15ml/min (lack of data)
when should we discontinue use of ivabradine?
if sx does not improve within 3 months after start of treatment
adr of ivabradine
bradycardia, blurred vision, luminous phenomena (transiently enhanced brightness in a limited area of the visual field)
warnings and precautions for ivabradine
- animal fetal toxicity - not reco in pregnancy, use contraception
- atrial fibrillation
- not reco in patients with 2nd deg AV block
ivabradine c/i
- acute decompensated HF
- BP <90/50mmHg
- sick sinus syndrome, sinoatrial block or 3rd deg AV block (unless a functioning demand pacemaker is present)
- resting HR <70bpm prior to treatment
- severe renal/hepatic impairment
- pacemaker dependence (HR maintained exclusively by the pacemaker)
- in combi w cyp3a4 inhibitors
standard therapy for CAD
BB or CCB -> BB + DHP-CCB -> add 2nd line drug
compelling indication: high HR > 80bpm
BB or non-DHP CCB -> BB + CCB -> BB + ivabradine
compelling indication: low HR < 50 bpm
DHP-CCB -> switch to LAN -> DHP-CCB + LAN -> add nicorandil, ranolazine, trimetazidine
compelling indication: LV dysfunction or HF
BB -> BB + LAN or BB + ivabradine -> add another 2nd line drug
compelling indication: low BP
low-dose BB or low-dose CCB -> switch to ivabradine, ranolazine or trimetazidine -> combine two 2nd line drugs
PCTA
percutaneous transluminal coronary angioplasty
- involves dilation of a coronary artery obstruction with balloon catheter
- balloon inflation are repeated until the plaque is compressed and blood flow resumes
- use of intraluminal stent to prevent restenosis
BB is not used in ____ angina
vasospastic
why are nitrates and ccbs used in vasospastic angina?
aside from decreasing myocardial o2 requirement, they redistribute coronary flow to ischaemic tissue and incr myocardial o2 deliver
nitrate-induced endothelial dysfuction
excess nitrates stimualte the oxidase system -> peroxynitrite produced, resulting in endothelial dysfunction
protection from nitrate-induced endothelial dysfunction by:
- carvedilol: BB with additional prevention of free radical generation
- nebivolol: BB with b3 agonism, incr nitric oxide synthase expression and NO (aka nitric-oxide potentiating vasodilatory effect - decr demand and incr supply)
- hydralazine: vasscular smooth muscle relaxant
- ACEi (captopril) and ARB (telmisartan)
- vit c (antioxidant)
- high doses of atorvastatin: reduces oxidative stress
adr of vastarel
nausea, vomiting, fatigue, dizziness, and myalgia
- increase parkinsonian symptoms: extrapyramidal rigidity, bradykinesia, and tremor
