Week 6: Cardiovascular 2 - Arrhythmia, Antiplatelets, Anticoagulants, Dislipidaemia Flashcards
What is an arrhythmia?
An arrhythmia is a problem with the electrical impulses in the heart - abnormal impulse formation or conduction
Leads to ineffective and inefficient filling and ejection of blood from heart
Normal Heart rhythm - physiology
Sinus rhythm is the normal heart rhythm
- Atria contract and pump blood into ventricles
- Right ventricle pumps blood into lungs
- Left ventricle pumps blood to body
A heartbeat is initiated by electrical signals that follow conduction pathways within the heart
Signs and Symptoms of arrhythmia
- Palpitations due to cardiac rhythm imbalance
- Breathlessness/Fatigue as tachycardia can cause LV systolic impairments
- Falls/Blackouts
- Chest pain
- Resuscitation sudden death - arrhythmia’s can be fatal
- No cardiac symptoms at all
Classification of arrhythmia’s
Tachyarrhythmia - rapid heart beat - Sinus tachycardia - Atrial flutter - Atrial fibrillation - Ventricular tachycardia Bradyarrhythmia - slow heart beat - Sick sinus syndrome - AV block
Atrial fibrillation
- First line therapy
Most common sustained arrhythmia associated with high incidence of stroke and heart failure
- Can be paroxysmal, persistent or permanent
- First line therapy is to remove underlying cause (pneumonia, thyroid imbalance, alcohol, caffeine, medications)
When to start drug therapy in atrial fibrillation
When to start treatment
- Nature of arrhythmia is life threatening
- Systemic symptoms or hemodynamic effects
- Presence of underlying heart disease (heart failure, coronary artery disease or valvular heart disease)
First line drug therapy for atrial fibrillation
Beta blocker (atenolol or metoprolol)
OR
Non-dihydropyridine CCB (diltiazem or verapamil)
- Do not use these together as both slow the heart rate and force of contraction allowing more time for heart to fill
Digoxin (AF treatment)
- MOA
- Indications
- Adverse effects
MOA
- Slows heart rate and reduces AV node conduction by increased vagal tone and reduction in sympathetic activity
Indications
- Patients with comorbidity of heart failure and require ventricular rate control as it increases the force of myocardial contraction by increasing release and availability of stored intracellular calcium
- Effective in elderly/non active patient
- Not strong enough in active younger patients
- AF and Atrial flutter
- Heart failure
- Narrow therapeutic index - regularly assess for toxicity
Adverse effects
- Common include anorexia, nausea, vomiting, diarrhea, visual disturbances, drowsiness, dizziness, headache, rash, bradycardia, arrhythmia
Digoxin (AF treatment) contraindications and cautions
Pregnancy - safe
Geriactric - may be preferred but care if renal function is reduced
Renal reduced dose in renal impairment
Avoid using with drugs that slow cardiac conduction
Precautions
- Hypo/Hyperthyroidism
- Electrolyte imbalances
Amiodarone (AF treatment)
- MOA
MOA
- Slows how quickly the heart can contract by acting on refractory period of muscle contraction, or how quickly the muscle cells can recover from one contraction to contract again
- Also has some beta blocking activity
Amiodarone (AF treatment)
- Adverse effects
Lots of serious adverse effects (closely monitor)
- Thyroid dysfunction
- Pulmonary toxicity
- Liver dysfunction
- Ocular effects
- Neurotoxicity
Amiodarone (AF treatment)
- Contraindications/cautions
Pregnancy/Breastfeeding - Do not use
Elderly - more likely to have bradycardia
Avoid in patients with bradycardia or prolonged QT intervals
Renal impairment
Precautions
- Thyroid disorders
- Lung disease
AF treatment - Non drug therapy
- Artificial pacemakers
- Implantable cardiac defibrillators
- Cardio version
- Catheter ablation
- Surgery
Describe the coagulation cascade in terms of the blood vessel
- Damaged blood vessel (triggers release of clotting factors)
- Formation of platelet plug (vasoconstriction limits blood flow and platelets form a sticky plug)
- Development of clot (Fibrin strands adhere to plug to form insoluble clot)
Coagulation cascade in terms of clotting factors
- Extrinsic pathway
- Intrinsic pathway
- Common pathway
Extrinsic pathway
- Damage to tissue outside vessel
- Tissue thromboplastin
- Converts inactive Factor X to activated Factor X
Intrinsic pathway
- Damage to blood vessel
- Cascade of clotting factors (produced using vitamin K)
- Converts inactive Factor X to active Factor X
Common pathway
- Once both extrinsic and intrinsic pathway produce active factor X prothrombin is converted into thrombin
- Thrombin then converts fibrinogen to fibrin
- Fibrin and Factor XIII produces a blood clot
What are anticoagulants?
- Target clotting factors
- Work in venous system
- They are not blood thinners they just prevent the formation of clots
- Considered a more aggressive therapy than anti platelet therapy
When are anticoagulants used?
What are the common anticoagulant drugs?
- Patients at high risk of stroke or who have already had a stroke/pulmonary embolism/VTE (include patients with AF)
- Acute coronary syndrome
Common drugs include
- Warfarin
- Newer oral anticoagulants (NOACs) such as Factor Xa inhibitors
- Heparin
- Low molecular weight heparin (LMWH)
Anticoagulant practice points
- Counseling to ensure patient understands how to take/inject their medication as well as check for signs of bleeding
- Avoid other drugs which cause bleeding
- Monitor signs of bleeding
- Surgery must be ceased prior to surgery
Anticoagulants - Warfarin
- MOA and points
MOA
- Vitamin K antagonist therefore inhibits synthesis of clotting factors including Factor X
- As it works high up in cascade it is associated with high risk of bleeding
- Many interactions including green leafy vegetables (high in vitamin K)
- INR (clotting time) needs to be monitored no more than 4 weeks apart
- Compliance as it must be taken at same time everyday
- Avoid in pregnancy
- Brands should never be substituted (Marevan and Coumadin)
Anticoagulants - Heparin/LMWH
- MOA
- Route
- Monitoring
- Drugs
- Pharmacokinetics
- Cautions
- Contraindications
- Adverse effects
- Use in pregnancy and breastfeeding
MOA
- Inactivate thrombin and Factor Xa with Heparin inhibiting both equally while LMWH inhibit thrombin more than Factor Xa
- Only available via injection
- LWMH can be used as outpatient therapy
- Heparin usually requires hospital monitoring
- Drugs include Enoxaparin and Dalteparin
- Faster onset and shorter half life than Warfarin
- LWMH cautioned in RF
- Contraindicated in severe hepatic impairment or disease
- Can cause thrombocytopenia (Heparin induced thrombocytopenia - HIT)
- Used to treat/prevent thromboembolism in pregnancy and safe for breastfeeding
Anticoagulants - Factor Xa Inhibitors
- MOA
- Adverse effect
- Route and adherance
- Drugs
- Practice points
MOA
- Selectively inhibit Factor Xa
Adverse effect
- Bleeding (it is better tolerated than Heparin)
Route and adherance
- Oral and requires compliance with same time per day administration
Drugs include
- Apixaban
- Rivaroxaban
Practice points
- Not suitable for severe RF
- No antidote - not suitable if high risk of bleeding
- Shorter half life than Warfarin
- Interaction are increasing in number being identified
Anticoagulants - Direct thrombin inhibitors
- MOA
- Caution
- Route
- Drugs
MOA
- Directly and selectively inhibit thrombin (lower in cascade)
Caution
- Renal and liver failure
Route
- Oral but capsules cannot be opened (do not crush or chew)
Drugs
- Dabigatran
What are antiplatelets?
What are common antiplatelet drugs?
Work to inhibit the ability of platelets to stick together - still circulate but cannot help form a blood clot
* They are not blood thinners
Work in arterial system
Drugs include
- Aspirin
- Clopidogrel
- Dypirimadole
Uses of antiplatelets
- Prevent stroke
- ACS
- Aspirin used for CVD prevention in long term management of MI
Platelet plug formation
- Platelets adhere to collagen
- Activation of thromboxane A2 receptor by Thromboxane A2 which is activated by arachidonic acid via COX-1
- Activation of ADP receptor
- Activation of IIb/IIIa receptor allowing aggregation of platelets at these receptors via fibrinogen cross linking
See Diagram
Antiplatelets - Aspirin
- MOA
- Combination products
- ADR
MOA
- Inhibit platelet aggregation by irreversibly inhibiting cyclo-oxygenase (COX) which stops synthesis of thromboxane A2
- Works for lifetime of platelet (up to 3 months)
Combination products
- Aspirin + Clopidogrel
- Aspirin + Dypirimadole
ADR (lots)
- Gastric upset, GI bleeds, ulcer, severe skin reaction, hemorrhage
Antiplatelets - Clopidogrel
- MOA
- ADR
- Interaction
MOA
- Bind to platelet ADP receptor to inhibit platelet aggregation for the life of the platelet
- It is a pro drug and needs to be activated by CYP enzymes
ADR
- Usually well tolerated but there are some rare side effects including skin reactions, multi-organ hypersensitivity, anaemia, thrombocytopenia, neutropenia
Interactions
- Grapefruit juice (blocks CYP enzyme from working)
Antiplatelet - Dypirimadole
- MOA
- ADR
- Contraindications
MOA
- Helps inhibit platelet function by inhibiting the platelet phosphodiesterase, which is necessary for activation of the platelet
ADR
- Commonly causes headache, GI upset, hypotension and tachycardia
Contraindications
- Avoid use in patients with unstable angina or recent MI
Cholesterol
- Low Density Lipoproteins
- High density Lipoproteins
LDL
- Carry cholesterol from liver to peripheral tissue for physiological function
- Carry excess cholesterol to vascular tissue where atherosclerosis is likely to develo
- Bad cholesterol
HDL
- Carry cholesterol from vascular tissue to liver for removal
- Remove cholesterol from tissue where atherosclerosis is likely to develop
- Good cholesterol
Target lipid levels for patients on lipid modifying therapy
LDL cholesterol = <2.0mmol/L
Non-HDL cholesterol = <2.5mmol/L
Total cholesterol = <4 mmol/L
HDL cholesterol = >1mmol/L
Triglycerides = <2.0mmol/L
Dietary modification of cholesterol
- Reduce saturated and trans fats (replace with monounsaturated and poly saturated fats)
- Increase soluble fibre
- Introduce plant sterol enriched milk, margarine, cheese produces
- Limit alcohol
- Lose weight
Initiating drug therapy for cholesterol
- Consider treatable secondary causes of raised blood lipid before commending drug therapy
- First line = statins
- If not adequately controlled add one or more of Ezetimibe, Bile acid binding resin, Nicotinic acid
- If intolerant to statins consider Ezetimibe, Bile acid resin or nicotinic acid
- For raised triglycerides consider Fenofibrate, nicotinic acid or fish oil
Synthesis of cholesterol
- Hydroxy-methylglutaryl coenzyme A converted to cholesterol by HMG CoA reductase (rate limiting step)
- Cholesterol also brought into liver from fats and diet
- Cholesterol produces steroid hormones, bile salts and membranes
- Low liver cholesterol synthesis increases synthesis of LDL receptors (reuptake of LDL into liver)
See Diagram
Cholesterol control - Statins
- MOA
- Drugs
MOA
- Block action of HMG CoA reductase
- Stops body from making excess cholesterol
- As body is not making as much on its won it increases uptake from diet which further lowers LDL levels
Drugs include
- Simvastatin
- Atorvastatin
- Rosuvastatin
Cholesterol control - statins
- Indications
- ADR
Indications
- Hypercholesterolaemia
- High risk of coronary heart disease, with or without hypercholesterolaemia
ADR
- Common include myalgia, mild transient GI symptoms, headache, sleep disturbance, dizziness, elevated aminotransferase concentration
- Rare include myopathy and rhabdomyolysis
Must monitor for liver dysfunction and muscle problems
- Risk factors for myopathy and rhabdomyolysis are pre-existing muscle, liver, kidney disease, high dose, interacting drugs, illness, elderly/frail
Cholesterol control - statins
- Contraindications and cautions
Pregnancy
- Contraindicated for use in 1st trimester causes fetal malformation
Hepatic
- Use cautiously and start at low dose
Geriatric
- Increased risk of myopathy
Renal impairment
- Increased risk of myopathy and rhabdomyolysis
- Start at low dose
Drug interactions - lots due to CYP enzyme metabolism (substrate of CYP3A4)
Cholesterol control - Ezetimibe
- MOA
- Line of therapy
- ADR
MOA
- Reduces absorption of cholesterol from diet by inhibiting the transport of cholesterol across intestinal wall
- Increase uptake of LDL that does get through back into liver and away from peripheral tissue
Line of therapy
- Usually in combination with statin, only used as single therapy if statins are not tolerated
ADR
- Diarrhea, myalgia/myopathy, raised liver enzymes, pancreatitis
Cholesterol control - Ezetimibe
- Contraindications and cautions
Pregnancy
- No data; avoid
Hepatic
- Do not use
Not to be used with fibrates or in patients with pancreatitis or gall bladder disease
