L11 - L17 Flashcards
Cholesterol & LDL’s
- LDL Pathways
- LDL removed by receptors goes to liver to be utilised or excreted
- when LDL exceed receptor availability it is taken away by “scavenger pathway” by monocytes and macrophages leading to a high blood cholesterol level
LDL Scavenger Pathway
- when LDL level exceeds receptor capacity
- LDL enters arteries promoting accumulation of monocytes and inflammatory cells causing plaque build up
- LDL cholesterol is oxidised as macrophages are newly bound to them. these become foam cells
- macrophages recruit smooth muscle cells to site which forms a fibrous cap over plaque
- lipids release from foam cells & further ulceration leads to proliferation of atheroma
Platelet Function
- why antiplatelets needed
endothelial blood vessel damage =
- loss of endothelium antithrombotic properties (adenosine triphosphate & NO)
- increased procoagulant functions like tissue factor and factor Xa
- platelets stick to breaks in the endothelium & change conformational to allow fibrinogen binding
Antiplatelets
- aspirin mechanism of action
- thromboxane A2 is platelet agonist produced by COX-1
- aspirin blocks production of thromboxane A2 by inhibiting COX-1, irreversibly binding
Antiplatelet
- Clopidogrel (irreversible)
- ADP platelet agonist produced by platelets
- clopidogrel irreversibly inhibits ADP P2Y12 receptor to prevent ADP activating platelets
Ticagrelor
- same receptor but reversibly binds
Ischemia
- definition & symtpoms
- lack of blood supply to heart
- coronary artery block causes less blood to heart
symptoms - angina, chest pains
ACS
- Angina
- Causes: HF, severe anaemia, HTN lv hypertrophy
Stable - angina on physical exertion, fixed plaques
Unstable - angina on minimal exertion or rest. can be confused for MI, check troponin
Prinzmetals - coronary artery spasm, causes temp ischemia
Angina Management
- treatment
Treatment
1 - BB 1st line (if intolerable then rate limiting CCB)
- add CCB if symptoms poorly controlled by BB
- sublingual GTN tablets or spray
- morning and afternoon
Cardiac Monitoring
- Holter Monitor
portable cardiac monitoring device to detect silent ischemia
- records ST segments to check for ST depression of 1-2mm or more
- this is the telltale sign of ischemia
Angina Severity Classifications
Class 1 - angina during prolonged activity
Class 2 - Angina during vigorous activity
Class 3 -symptoms with everyday activity
Class 4 - inability to perform any task without angina
Angina ECG & Treatment
- Not seen on ECG because it only causes temporary changes to reading
Treatment:
- lifestyle : no smoking, limit alcohol, diet and exercise
- antiplatelet
- beta blockers (1st Line)
- if intolerant , give rate limiting CCB
- GTN Nitrates (symptom relief)
Angina Treatment
- Beta Blockers (1st line)
- treatment
Bisoprolol 5–10 mg once a day
- acts on B2 receptor , preventing NA binding , stopping vasoconstriction and inc. BP
- decreases oxygen demand of heart by lowering rate (less NA) & force of contraction (less sodium entry means less Ca2+ entry)
- less demand = less ischemia
blocks NA/A binding to Beta-adrenoceptor stopping activation of adenyl cyclase which inc. cAMP to activate PKA. PKA would have increased contractility etc.
Treating Angina
- CCB
(Verapamil 80-160mg 3 times daily)
- if BB isn’t able to be given , give rate limiting CCB
- Blocks calcium entry into L-type calcium channels
- reducing heart contractions & lowering oxygen requirement of myocardium muscle
- ischemia increases Ca influx, inc. contraction from membrane depolarization. CCB prevent this
Angina Treatment
- Potassium Channel Activator (Nicorandil)
10-20mg twice daily titrated up to 40mg if required
- Nicorandil activates K+ ATP channels on SMC to hyperpolarise the membrane, decreasing Ca2+ entry
Nicorandil is a nitrate and a PCA
- at low conc. it dilates coronary arteries
- at high conc. it is PCA
Surgical Angina Treatment
- Stenting
- Angioplasty
- Bypass Surgery
Stenting - coronary intervention to widen the artery and allow better perfusion
Angioplasty - balloon inserted with tube running through to allow blood flow
Bypass Surgery
- bypass from veins bringing blood to heart, around the blockage, back into arteries
STEMI vs. NSTEMI
STEMI
- complete occlusion of minor coronary artery or partial occlusion of major coronary artery
- causes partial thickness damage of heart muscle
NSTEMI
- occurs by complete occlusion of major coronary artery previously affected by atherosclerosis
- causes full thickness damage to heart muscle
Damage During MI EVENT
- stages
1- irreversible damage can occur within 20-40min after blood flow interruption
2- large amounts of tissue can be saved if flow is restored within 6hrs of coronary occlusion
3- infarction of tissue will lead to cellular changes like disproportionate thinning
Diagnosing MI
- troponin test - released from damaged muscle
- myoglobin test - present in skeletal muscle not specific to MI
Troponin
- requires rise and gradual fall of troponin
- or rapid rise & fall of creatinine kinase MB
- chest pains, SoB and Q-wave plumet
Myoglobin
- released within 1-2hrs of MI , peaking at 13-15hrs
Electrical Conduction of Heart
- SA & AV nodes
- PQRST
P - Wave (initial spike)
- firing of SA node and depolarisation of atria (contraction)
PR interval
- electrical conduction through atria AND AV delay
PR segment
- 0.05 second delay of impulse at AV node
QRS (spike)
- ventricular depolarisation, contraction forcing blood out of heart to body
ST Segment (should be flat)
- the beginning of ventricular repolarization
T Wave
- ventricles repolarize back to base electrical state
Electrical Conduction During MI
- T-waves
- ST elevation
- Q depression
- T waves become tall & narrow at start of MI
- then become inverted further on - when ST segment raises = NSTEMI
- as a result, baseline voltage prior to QRS is depressed
- during STEMI, ST segment stays at 0 but seems elevated because baseline voltage is below 0
ACS Management
- MONA Therapy
- during/after MI
M - morphine 5-10mg IV slow injection for pain & metoclopramide to counteract sickness
O - oxygen 94-98%
N - nitrates as infusion to dilate blood vessels since sublingual GTN wont work in MI
A - aspirin 300mg stat (if already on antiplatelet therapy give 75mg)
Extras
- Fondaparinux 2.5mg SC to prevent +laque build up
- Ticagrelor 180mg stat
Secondary Prevention after MI
Dual Anti-Platelet
- Aspirin 75mg
- Ticagrelor 90mg BD
- Beta Blocker (1yr to lifelong)
- ACE-I ramapir;
- High dose statin (atorvastatin 40-80mg)
STEMI Immediate Management
- PCI within first 2hrs
- Ticagrelor 180mg loading
- aspirin 300mg
- thrombolyse with tenectaplase
- give BB bisoprolol
Heart Failure
- SoB ,Tiredness, odema
- reduced cardiac output and/or elevated intracardiac pressures. output cant meet metabolic needs
- Heart Disease : structure abnormality (valves/chambers/muscle)
Systolic HF: heart can’t eject blood properly
Diastolic HF: Heart cant fill with blood properly
HF Treatment
- ACE-I
- ARB
ACE-I
- 1st enalapril 20mg BD
- ramipril if they have MI before HF
- GIVE WITH BETA BLOCKER bisoprolol 2.5mg if patient is stable
ARB (valsartan)
- never use with ACE-I
- give if patient experiences s/e with ACE-I
HF Treatment
- Beta Blocker
- Aldosterone Antagonist
- Diuretic
Beta Blocker
- Only given to patients with Stable HF
- given with ACE-I
- GIVE FUROSEMIDE FIRST
Aldosterone Antagonist
- eplerenone if EJF is <40%
- for adv HF (NYHC class III - IV)
Pharmacokinetic Interactions
- ADME process affected
Adsorption
- doxy cant be given with iron/calcium/zinc
- iron can bind to drug reducing adsorption
Distribution
- weakest pharmacokinetic interactions
- phenytoin displaced from target site by aspirin
Metabolism
- any drug affecting CYP450
Excretion
- lithium is narrow ther. index. if given with diuretic it will inc. conc. causing lithium toxicity
Pharmacodynamic Drug Interactions
- adding second drug causes interaction
Synergistic
- drugs enhance each others effect
- good in HTN, bad in Heart Blockage (BB + rl CCB)
Antagonistic
- giving agonist and antagonist at the same time
Metabolic
- digoxin has narrow therapeutic index. with low K+ levels it will sensitise heart to digoxin causing s/e
Heart Failure Aetiology
chronic - long-term symptoms
acute - emergency situation rapid HF
- increased resistance causes HTN and heart muscle hypertrophy , increasing oxygen need
- ischemia prevents oxygen supply to heart preventing it from doing its job
- Left side failure most common. blood backed up from left atrium into pulmonary veins
- causes pulmonary oedema - RHS failure much more rare
Starlings Law
- higher preload = greater contraction force
- if fibres are overstretched then contraction is reduced
- high HR means higher CO. unless excessive HR because of inadequate filling time for heart. so stroke volume decreases
Bodies Response to Heart Failure
- Increase Cardiac Output
- Sympathetic innervation - NA release
- Myocardial Hypertrophy - inc. CO
- Hormonal Response - RAAS system
- inc. sympathetic innervation. NA increases contractility and HR.
- this causes peripheral vasoconstriction, inc. afterload - Myocardial Hypertrophy - thickening of heart walls, increasing muscle mass and contraction strength
- Hormonal Response from reduced Cardiac Output
- detected by baroreceptors in JG apparatus
- stimulates kidney renin release, stimulating Ang conversion to AngI
- causes aldosterone release
- increases fluid volume, peripheral constriction & BP
Diagnosing Heart Failure
- Chest X-ray
- ECG
Chest X-Ray
- shows heart structure to see if it is enlarged
ECG
- estimate ejection fraction from heart activity
Other Drugs in Heart Failure
- SGLT-2 Inhibitors (dapaglifozin)
- Exacerbating Drugs
SGLT-2 inhibitors
- causes urination, decreasing sodium & glucose in blood
- takes H2O with it to decrease blood pressure
- inc. risk of UTI bc inc. glucose attracts bacteria
Exacerbating Drugs
- NSAID’s, COX2 inhibitors, rate-limiting CCB, corticosteroids
Diuretics Use
Thiazide
- Bendroflumethiazide 2.5mg OD
- works on distal convoluted tubule, inhibiting Na/Cl channel to stop ion reabsorption
Loop Diuretic
- Furosemide IV, given during stroke/HF
- inhibits Na/K/2Cl channel to stop ion reabsorption. works on proximal convoluted tubule
S/E
- increased urination, don’t take in evening
- angioedema ankle swelling
- causes hypokalaemia
