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What do beta blockers do?
- Reduce cardiac output
- Reduce myocardial O2 demand
- Reduce heart rate
- Reduce blood pressure
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Beta blocker cautions and contrindications
- C/I
- - Asthma
- - Uncontrolled heart failure
- - 2nd or 3rd degree heart block
- Caution
- - Diabetics on insulin (masks hypoglycaemia)
- - COPD
-
Beta blocker side effects
- Bradycardia
- Fatigue
- Bronchospasm
- Peripheral vasoconstriction
- Impotence
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Calcium channel blocker effects
- Interfere with inward displacement of Ca2+ ions
- Coronary artery vasodilation increases myocardial O2 supply
- Also cause peripheral vasoconstriction and reduce BP
- May affect force and rate of contraction (diltiazem, verapamil)
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Diltiazem
- 1st choice is unable to use a beta blocker
- Negative ionotropic and chronotropic effects
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Verapamil
- Significant anti-arrhythmic and negative ionotropic properties
- Impairs AV conduction
- Verapamil/beta blocker combination contraindicated (can stop heart)
- Constipation common in elderly
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Amlodipine and nifedipine
- Ca2+ channel blockers
- Potent coronary artery vasodilators
- Dilation of peripheral arteries (swollen ankles, facial flushing, headache)
- No effect on conducting tissues
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Nitrates
- Relax vascular smooth muscle by releasing NO
- Coronary artery vasodilation increases myocardial O2 supply
- Reduce left ventricular workload by venous dilation and so reduce myocardial O2 demand as well
- Reduce blood pressure to a lesser extent
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Nitrate side effects
- Headache
- Dizziness
- Facial flushing
- Hypotension
- Tachycardia
- Tolerance to effects - need to have a nitrate free period
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Nicorandil
- Relaxes vascular smooth muscle
- Potassium channel activator (indirect calcium channel blocker
- Increase myocardial O2 supply - coronary artery dilation
- Reduces myocardial O2 demand - venous dilation
- Peripheral vasodilation still a problem
- No real effect of BP or HR at normal doses
- More expensive
- Good evidence base - generally used 3rd line
- Can be used in patients on b blockers +/or Ca channel blockers but still having chest pain (nitrate alternative)
- Can be used in patients unable to tolerate or with C/I to one of the other drug groups
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Nicorandil side effects
- Headache
- Dizziness
- Nausea
- Palpitations
- Fatigue
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Ivabradine
- Selective sinus node inhibitor
- Decreases resting heart rate
- Licensed for chronic stable angina in pts with normal sinus rhythm who have a contraindication or intolerance of b-blockers
- Interactions with verapamil and diltiazem due to heart block risk
- Visual luminous phenomena in 1st 2 months to 30% of pts
- Maybe useful in normo/hypotensive pts
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Ranolazine
- Newest agent
- Unknown mech
- Lots of interactins
- Causes; headaches, dizziness, weakness
- Add on therapy if other combinations C/I or ineffective
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Aspirin
- Inhibits platelet aggregation by blocking COX (reduces thromboxane A production)
- Reduction of risk of non fatal MI and CVA by 33% and mortality by 25%
- Side effects: GI irritation/ulceration, bruising, bronchospasm if atopic asthmatic
- No reduction of ulceration and bleeding with enteric coated tablets
- If GI intolerant add PPI
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Clopidogrel
- Prevents ADP binding (blocks platelet activation)
- Marginally better efficacy then aspirin
- Overall bleeding prfile similar to aspirin
- More expensive (only used with true aspirin allergy/significant GI intolerance)
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Who is at risk of developing an MI and should by targeted by primary prevention?
- Hypertension
- Hyperlipidaemia
- Obesity
- Diabetes
- Family hx of premature heart disease
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How is CVD risk estimated?
- Prediction charts based on
- Gender
- Age
- Smoker/non-smoker
- BP
- Cholesterol
Not validated for ethnic groups
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How to reduce CVD risk?
- Excercise (30 min mod ex daily)
- Sensible diet (5 a day- reduce risk by 30%, 2 portions fish weekly- reduce risk by 30%)
- Lower cholesterol (diet, statins)
- Preventing/treating obesity (diet, exercise, orlistat)
- Treating hypertension (aim for <140/85mmHg, diabetic <140/80, neuropathy <130/80)
- Smoking cessation (stopping for 2-3
- Low dose aspirin
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Blood pressure treatment thresholds
BP < 130/85 - recheck every 5 yrs
BP <140/90 - reassess yearly
BP140-159/90-99 - treat if at risk
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Hypertension "at risk patients"
- Target organ damage (e.g. renal)
- Established CV disease
- 10 yr CV risk =/>20% (e.g. smoker with high cholesterol
- Diabetes
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Thiazide diuretics in hypertension
- First choice for many patients
- Good response in elderly and afro-carribean pts
- Inexpensive
- Once daily
- Low dose
- Mild diuretic action increases excretion of K, Na and water
- Reduced circulation vol = reduced preload, reduced cardiac output and BP
- Long term auto-reguation restores cardiac output but results in decreased peripheral vascular resistance
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Thiazide side effects and contraindications
- Side effects:
- Hypokalaemia
- Acute gout
- Impaired glucose tolerance
- C/I:
- Hypokalaemia
- Severe renal impairment
- Avoid in diabetics
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Calcium channel blocker side effects and C/I's
- Ankle oedema
- Headache
- Facial flushing
- Bradycardia (rate limiting CCB)
- C/I:
- Pregnancy
- Heart failure (rate limiting)
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Calcium channel blockers in hypertension
- Alternative or supplementary
- Alternative for patients with hypertension and angina
- Dihydropyridines act mainly by peripheral vasodilation, e.g., amlodipine, felodipine, nifedipine
- Other classes also slow heart rate and AV node conduction, e.g. verapamil, diltiazem
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ACE inhibitors in hypertension
- First line use in patients with diabetes, proteinurea, heart failure
- Other hypertensive patients recommended as alternative or supplementary
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ACE inhibitor side effects and C/I's
- Dry cough
- Hypotension
- Hyperkalaemia
- Reduce risk by carful initiation, montior BP and U&E's
- Avoid potassium sparing diuretics and potassium supplements
- C/I
- Pregnancy
- Bilateral renal artery stenosis
- Aortic stenosis
- Hypotension
- Hyperkalaemia
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Angiotensin II antagonists in hypertension
Reserve for patients unable to tolerate ACE inhibitor
Alternative method of blocking RAAS
-
Angiotensin II antagonist side effects
- Similar to ACE inhibitors
- Hyperkalaemia
- Hypotension
- Renal impairment
- Angioedema
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Beta blockers in hypertension
- Not preferred initial therapy
- Alternative to ACE inhibitors in patients >55yrs in whom ACE is not tolerated or C/I
- Less effective in afro-carribean and elderly
- Mostly inexpensive
- Mostly one daily
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Alpha blockers in hypertension
- Effective at lowering BP, no evidence that prevent clinically important end-points
- Not used first line
- May be useful in men with prostatism
- Block NA at peripheral post-synaptic alpha-1 receptors - fall in peripheral resistance
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Alpha blocker side effects
- Headache
- Fatigue
- Postural hypotension
- Urinary incontinence in women
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Centrally acting drugs in hypertension
- e.g. methyldopa, clonidine, monoxidine
- Stimulate alpha-2 adrenoceptors, reduce central sympathetic tone, leads to a fall in cardiac output and peripheral vascular resistance
- Side effects include; sedation, dry mouth, fluid retention
- Methyldopa safe to use in hypertensive pregnant women
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MI risk factors
- Sex
- Age
- Family history
- Diet
- Lipids
- Smoking
- Exercise
- Diabetes
- Hypertension
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MI initial therapy
- Aspirin 300mg - prevents 23 deaths for every 1000 patients treated
- Morphine - pain, detachment, reduces anxiety therefore reduces heart workload
- Antiemetic - (metoclopramide/clyclizine i.v.) - nausea
- Oxygen
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STEMI therapy
- Fibrinolytics (not first line now - angioplasty)
- Only used in STEMI as clot = fibrin rich
- Ideally given within 12 hrs (over 24h risks>benefits)
- Streptokinase
- Alteplase, reteplase, tenecteplase
- 18% relative risk reduction in mortality at 35 days post MI
- Saves 30 lives per 1000 (6h)
- Treatment every hour earlier means 10 more lives saved per 1000 pts treated
- Side effects:
- Major haemorrhage
- Stroke
- Allergic reaction
- Hypotension (starch fluid given to counteract)
- C/I's
- Surgery in last 2 weeks
- Stroke in last 4 weeks
- Active peptic ulcer
- Trauma from prolonged CPR
- Severe hypertension
- Shock
- Abnormal clotting
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Streptokinase in STEMI
- Bacterial protein
- 1 hr infusion 1.5 million units
- Do not give again if pt has another MI (antibody risk)
- Indirect plasminogen binding
- Higher incidence of allergic reactions
- Higher incidence hypotension
- Similar instance major bleed
- Lower incidence stroke
- ~£80
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Alteplase in STEMI
- Recombinant DNA tech
- Identical to human tPA
- Theoretically more effective
- 2 i.v. dose regimens over 90 mins or 3 hrs
- Can be repeated
- Direct plasminogen binding
- Lower allergic reactions
- Lower instance hypotension
- Similar instance major bleed
- Greater incidence of haemorrhagic stroke - particularly in elderly
- ~£600
- Higher efficacy if thrombus in anterior coronary arteries
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Reteplase in STEMI
- Genetically modified rTPA
- Double bolus dose minutes apart
- Similar efficacy to alteplase
- Can be repeated
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Tenecteplase in STEMI
- Genetically modified rTPA
- Use within 6 hrs
- Single i.v. bolus (0.5 mg/kg up to max 50 mg) quickest "door to needle" time
- Can be repeated
- ~£600
- As effective as alteplase
- same price as alteplase
- ? use for all STEMI pts
- Increased cost vs quickest door to needle time
- NSF target door to needle time within 20-30 mins (60 min call to needle)
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Complications of MI
- Cardiac arrhythmias
- Acute heart failure
- Pericarditis
- Thrombus
- Cardiac arrest
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Short term adjunct therapy in MI
- Beta blockers
- Heparins
- Clopidogrel
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Beta blockers in short term MI treatment
- iv atenolol/metoprolol at time of MI if BP will allow
- reduced rate or reinfarction and cardiac arrest
- Saves 7 lives per 1000 pts treated
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Long term use of beta blocker in MI
- Oral beta blocker started within 7 days of MI
- Continued for at least 3 years
- Relative death and reinfarction risk reduced by ~20% to 30%
- Prevents 15 deaths and 5 further MI's for every 1000 pts treated
- Atenolol and bisoprolol used in practice
- Few absolute C/I's (inc heart failure) apart from asthma
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Heparins in MI
- Given with non-strep kinase thrombolytics only for 48h to prevent reocclusion and reinfarction
- Unfractionated heparin vs LMWH
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Clopidogrel in MI
- If going for coronary stent insertion
- given 300-600mg stat
- would then receive parenteral glycoprotein IIb IIIa inhibitors as well
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Secondary MI prevention non pharmacological interventions
- Diet
- Exercise
- Smoking cessation
- Weight reduction
- Cardiac rehabilitation programmes
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Secondary MI prevention pharmacological interventions
- Aspirin/clopidogrel
- beta blockers
- lipid lowering agents
- ace inhibitors
- angiotensin II antagonists
- nitrates
- calcium channel blockers
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Aspirin and clopidogrel in secondary prevention of MI
- Aspirin:
- Long term and short term benefits
- Reduce strokes and non-fatal MI by 33% and mortality by 25%
- 16 CV events prevented for every 1000 pts treated
- 75 mg - min effective dose
Aspirin and clopidogrel given for 1 month for STEMI or 12 months for NSTEMI or a stent
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Statins in secondary prevention of MI
- HMG CoA reductase inhibitors
- HMG CoA responsible for cholesterol production in liver
- Side effects: change in bowel habit, myositis and liver dysfunction
- 30% reduced death from any cause
- 42% reduced death from any cardiac cause
- 34% reduced MI
- Aim to get total cholesterol <4mmol/L; LDL cholesterol <2mmol/L; TC/HDL <4
- 1000 pts treated prevents; 6 deaths, 12 MI, 4 CHF, 11 revascularisations
- Rosuvastatin most potent
- Atorvastatin inc risk of muscle tox
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ACE inhibitors in secondary prevention
- Pts with heart failure benefit most
- if given within 24h of MI will prevent 5-8 deaths per 1000 pts
- prevents 20-30 deaths per 1000 pts in those with clincal heart failure
- but risk of hypotension
- Long term;
- mortality reduced by 10%
- low LV ejection fraction: mortality reduced by 20%
- clinical heart failure mortality recued by 30% or more
- LV dysfunction: 60 death prevented by 1000 pts
- No LV dysfunction: 18 deaths prevented by 1000 pts
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Angiotensin II antagonists in secondary prevention
- Evidence of benefit post MI for valsartan
- reserve for pts unable to tolerate ACE inh
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CCB in secondary prevention
- No real evidence of benefit
- symptomatic relief
- rate limiting ones used when B-blockers C/I
- Verapamil worsens heart failurew
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Eplerenone
- Selective aldosterone receptor antagonist licensed for use post MI in pts with CHF
- less affinity for androgen and progesterone receptors than spironolactone
- 25-50mg daily
- need to monitor serum K if on ACEI
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Who should get what in secondary prevention?
SAAB
Statin (fibrates alternative if C/I)
ACE inh (AIIA alternative if C/I, strict glucose control if diabetic)
Aspirin (if no C/I +clopidogrel short ter depending on STEMI or NSTEMI)
B-blocker (CCB alternative if C/I)
- Omacor if dont eat oily fish
- eplerenone is LV dysfunction or heart failure post MI
- amiodarone/antiarrhythmics if necessary
- Warfarin only if LV thrombus
Hope hospital uses COBRAA
- Clopidogrel
- Omacor
- Bisoprolol
- Ramipril
- Aspirin
- Atorvastatin
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Symptoms of heart failure
- Dysnopoea
- Nocturnal cough
- Paroxysmal nocturnal dysnopoea
- Confusion
- Renal failure
- Oedema
- Reduced exercise tolerance, lethargy, fatigue
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Heart failure management
- Improvement in symptoms;
- diuretics
- digoxin
- ACEI
- Improvement in survival;
- ACEI
- B-blockers
- spironolactone
- oral nitrates plus hydralazine
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Diuretics in heart failure
- Combat oedema
- Remove pulmonary congestion
- Improves symptoms and exercise tolerance
- Side effects: dehydration, hypotension, electrolyte imbalance (K esp)
- Monitoring: renal failure and electrolyte imbalance (esp if also taking ACEI)
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ACEI in heart failure
- All pts with LVD without C/I
- Block arterial/venous constriction
- Inc cardiac output and renal function
- slow LV tissue damage
- Reduced mortality 30-40%
- Delay disease progression
- Reduce hospital admissions and need for diuretics
- Improvement in NYHA class
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AII antagonists in heart failure
Pts unable to tolerate ACEI
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B-blockers in heart failure
- Consider in pts with chronic stable heart failure resulting from LVD
- Carvediol, bisoprolol, nebivolol (licensed for heart failure)
- Used in addition to diuretics and ACEI
- Low dose titrated up every 1-2 weeks
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Digoxin in heart failure
- Consider for pts with heart failure due to AF
- Positive ionotropic agent
- Improved symptom control
- Reduce hospital admissions
- No change in mortality
- More controversial in AF absence
- CI;
- severe heart block
- Wolff-Parkinson-White syndrome
- Side effects:
- arrythmias, anorexia, nausea, vomiting, confusion
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Spironolactone in heart failure
- Pts with moderate to severe who are symptomatic despite taking ACEI, diuretics and /or digoxin
- Low dose 25mg daily
- Improves symptom control
- Reduce hospital admissions
- Reduce mortality
- C/I:
- pregnancy
- severe renal failure
- Side effects;
- hyperkalaemia
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Nitrates plus hydralazine in heart failure
- Not really used in practice
- Used if ACEI and AII C/I (e.g. severe renal impairment)
- ACEI side effects
- pt has other conditions (e.g. angina)
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Drugs to avoid in CHF
- Class I antiarrythmic drugs e.g. lidocaine, flecanide
- NSAIDs
- Negative ionotropic calcium channel blockers e.g. diltiazem, verapamil
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Drugs exacerbating angina
- short acting nifedipine
- sumatriptan
- sildenafil
- excess thyroxine
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Important interactions
- Warfarin and simvastatin
- ACEI and NSAIDs
- Amiodarone and antipsychotics
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Monitoring for ACEI
Renal function and electrolytes
-
Montoring for statins
- LFT's before, 1-3 months q6m for a year
- if muscle pain occurs - creatinine kinase
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Monitoring for amiodarone
- TFT's before and q6m
- LFT's before and q6m
- CXR before
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Monitoring for warfarin
INR daily or alternate days; longer intervals (up to 12 weeks depending on response)
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Counselling for amiodarone
- phototoxic reactions;
- shield skin from light
- use a wide spec sunscreen
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Digoxin in AF
- Controls heart rate
- cannot cardiovert
- inc toxicity in elderly, renal impairment, hypokalaemia, drug interactions
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Amiodarone in AF
- Anti-arrythmic
- Can cardiovert
- long t1/2
- "dirty" drug
- - corneal microdeposits
- - thyroid disease
- - pulmonary fibrosis
- - hepatotoxicity
- - photosensitivity/skin discoloration
- - serious interaction with warfarin and digoxin
-
Sotalol in AF
- B clocker with class III activity
- used for long term control rather than amiodarone unless asthmatic
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Treatment of DVT
- Once suspected start high dose i.v. unfractionated heparin (continuous infusion adjusted by lab monitoring)/LMWH (once daily dose based on weight, no need for monitoring)
- Tests to confirm diagnosis
- Oral anticoagulants started after diagnosis confirmed
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Target INR's
2.5 for AF and treatment of DVT/PE or tissue prosthetic heart valves
3.5 for recurrent DVT/PE or a mechanical prosthetic heart valve
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Warfarin antidotes
- Phytomenadione (vit K) injection - dose depends on INR and is haemorrhage is life threatening
- Clotting factor concentrates/fresh frozen plasma - immediate reversal
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Alarm symptoms for peptic symptoms
- Recurrent vomiting
- Dysphagia
- Bleeding
- Weight loss
- Unexplained dyspepsia >55yr
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