Cardiovascular Flashcards
Furosemide
Loop Diuretic
How Loop Diuretics work?
Act in thick ascending limb of loop of Henle. Prevents Na+ and K+ reabsorption decreasing water reabsorption
Indications for Loop Diuretics
Peripheral oedema, pulmonary oedema and acute renal insufficiency
Contraindications for Loop Diuretics
Anuria Hypokalaemia Gout Type II DM Pregnancy
Side effects of Loop Diuretics
Ototoxicity (toxic to ear) GI disturbance Hypokalaemia Gout Rash Postural Hypotension
Possible interactions for Loop Diuretics
- ACEi increased risk of first dose hypotension
- Reduce excretion of lithium causing serum concentrations to rise
- Digoxin - hypokalaemia increases risk of toxicity from digoxin and antiarrythimic grus
- Theophylline- risk of hypokalaemia increased
Bendroflumethiazide, Chlortalidone, Metolazone
Thiazide Diuretic
Thiazide Diuretics
Act in distal convoluted tubule. Inhibits NaX reabsorption so decreases water reabsorption
Indications for Thiazide Diuretics
Hypertension
Oedema
Prophylaxis of Ca-containing renal stones
Nephrogenic diabetes insipidus
Contraindications for Thiazide Diuretics
Addison’s disease; hypercalcaemia; hyponatraemia; refractory hypokalaemia; symptomatic hyperuricaemia, hypotension, gout, TYype II DM , loop diuretic, pregnancy, poor renal function, breast feeding
Side effects for Thiazide Diuretics
Hypomagnesaemia, hypercalcaemia, postura hypotension, gout, hyperuricaemia, hyperlipidaemia, allergic vsculitis, hyperlipidaemia, a, allergic vasculitis, photosensitivity hyperglycaemia, erectile impotence, thrombocytopenia
Possible interactions for Thiazide Diuretics
NSAIDs, ACEI, Lithium- increasing plasma concentration, Digoxin, theophyllines
Spironolactone
Potassium Sparing Diuretic and Aldosterone Receptor Antagonist
How does Spironolactone work?
Competes for receptors in distal convoluted tubule. Inhibits Na+ reabsorption and K+ secretion so decreases water reabsorption. Results in sodium loss and potassium retention
Indications of Spironolactone
Ascite and oedema, heart failure, nephrotic syndrome, primary hyperaldosteronism (Conn’s syndrome)
Contra-indications of Spironalactone
Renal insufficiency, pregnancy, breast feeding, Addison’s disease
Side-effects of Spironolactone
Potassium sparing drugs, ACEi, ciclosporin, NSAIDs, digoxin, lithium
Atenolol
Beta-blocker drug
How do beta-blocker drugs work?
- Beta-adrenoreceptors form part of sympathetic pathway causing vasconstriction, increase force, rate, conductance and bronchodilation.
Blocking these receptors causes vasodilation, decreased force, rate, conductance and bronchoconstriction. They are negatively inotropic ( decreases contraction) and negatively chronotropic (decreases heart rate) - Antihypertensive as decreases renin production by kidneys
- Antiarrhythmic as decreases AP initiation of heart
Stimulation of B1 adrenoreceptors causes what
Increase in force, rate and conductance of the heart
Stimulation of B2 adrenorecptors causes what
Smooth muscle relaxation, bronchodilation, vasodilation
Stimulation of B3 adrenoreceptors causes what
Fat lipolysis
Indication of Beta-blockers
Hypertension, Angina, arrhythimas, Heart failure, Migarines, MI, Hyperthyroidism, Aortic Dissection, Pheochromocytoma, Anxiety, Glaucoma, Benign Essential Tremor
Contra-indications of Beta-blockers
Asthma, heart block, unstable heart failure, unstable angina, bradycardia, sick sinus syndrome, hypotension, metabolic acidosis, cardiogenic shock, pregnancy
Side effects of Beta Blockers
Bronchoconstriction, heart failure, Raynaud’s, sleep distturbances, erectile impotence, liver damage, rash and dry eyes
Interactions of Beta-blockers
Verpamil as can increase risk of asystole or catastrophic reduction of cardiac output, antihypertensives, anti-arrhythmic drugs, NSAIDs
How are beta- blockers eliminated?
50% urine and 50% faeces
Stimulation of Alpha-1 adrenoreceptors causes what
vasoconstriction, relaxes GIT
Stimulationof ALpha-2 adrenoreceptors causes what
Platelet aggregation, inhibits NA and Ach release at presynaptic terminals
Amlodipine
Calcium Channel Blocker
How do Calcium Channel Blockers work?
Blocks L-type voltage-gated calcium channels preventing entry of Ca2+ and depolarisation of tissues.
Vasodilates and lowers blood pressure
Effect of CCB on myocardial cells
Reduces contractility and anti-dysrhytmic action
Effect of CCB on Vascular smooth muscle
Vasodilation
Arterial dilation: reduces resistance and pressure
Venous dilation: increase in venous pooling, reduced flow to heart, reduces end-diastolic pressure
Indications of Amlodipine
Hypertension, Angina, Raynauds, Migraine,
Contraindications of Amlodipine
Pregnancy, breast feeding, heart failure, unstable angina, bradycardia,
Side effects of Amlodipine
Flushing, headache, peripheral oedema, bradycardia, SA block, palpitations
Interactions of CCB
other hypotensives, cyclosporin, digoxin, theophylline, grapefruit juice (except amlodipine)
Elimination of CCB
1st pass metabolism
Patient information for CCB
Ankle swelling or headache
Stop drinking grapefruit juice
Diltiazem
Benzthiazepine Calcium channel blocker
L-type Voltage Gated Calcium Channels
responsible for excitation-contraction coupling of skeletal, smooth, and cardiac muscle, hormonesecretion in endocrine cells and conduction of cardiac pacemaker signals
Indications for Dilitiazem
Angina, Hypertension, Cardiac Arrhythmias
Ramipril
Angiotensin Converting Enzyme Inhibitor (ACEi)
How do ACE inhibitors work?
ACE inhibitor inhibits ACE
Reduces formation of Angiotensin 2
Reduces vasoconstriction, aldosterone secretion, water retention
BP decreases
Indications for ACE inhibitors
Hypertension, Symptomatic heart failure, following MI, diabetic nephropathy
Contra-indications of ACE inhibitors
Pregnancy, Angioedema, renovascular disease
Side effects of ACE inhibitors
Persistent dry cough, hypotension, hypersensitivity, renal impairment, hyperkalaemia
Interactions of ACE inhibiotrs
Diuretics- increase risk of hyperkalaemia
NSAIDS- increase risk of renal impairment
Patient information for ACE inhibitors
Avoid in pregnancy as may effect fetal BP and renal function
Patients should take 1st dose to avoid 1st dose hypotension
Losartan
Angiotensin Receptor Blocker (ARBs)
How do ARBs work
ARB inhibits angiotensin II type I receptors
Reduces vasoconstriction, aldosterone secretion, H2O retention
BP decreases
Indication of ARBs
Alternative to ACEi as causes less frequent coughs, hypertension, heart failure, MI, Diabetic nephropathy
Contraindications of ARBs
Pregnancy, Angioedema, renovascular disease, fixed cardiac output, peripheral vascular disease, hyperkalaemia
Interactions of ARBs
Diuretics, NSAIDs
Isosorbide mononitrate
Nitrates/ Nitrovasodilators. Like GTN but slower onset and longer half-time than GTN
How do Nitrates work?
Administered as a prodrug. Nitrates undergoes a chemical reduction by enzymes releasing NO. This stimulates guanylate cyclase pathway in smooth muscle cells causing vascular smooth muscle relaxation and vasodilation. This reduces preload and afterload so heart requires less oxygen
Indications for Nitrates
Angina Pectoris
Short term reduction of BP
Pulmonary Oedema
Chronic Heart Failure
Contraindications for Nitrates
Hypovolaemia and Hypotension Cardiac Disease e.g. mitral stenosis, hypertrophic cardiomyopathy Bleeding and haemorrhage Anaemia Close-angle Glaucoma Pregnancy
Side effects of nitrates
Throbbing headache Dizziness Postural hypotension Tachycardia Methaemoglobinaemia
Interactions of nitrates
Sildenafil (Viagra) - risk of severe hypotension
Other antihypertensives
Antimuscarinic drugs - cause of dry mouth, reduce absorption of sublingual nitrates
PDE5 inhibitors- block deactivation of cGMP whilst nitrates increase cGMP levels, leads to venous pooling
Patient Information of Nitrates
Nitrate free period required everyday (min 4-8hours) to prevent nitrate tolerance
Tolerance reversed within 18hours of stopping nitrates
Digoxin
Cardiac glycoside (digitalis)
How does Digoxin work?
Inhibits Na/ K pump so increases intracellular Na concentration. This causes Ca+ to be pumped out of cell increasing force of contraction.
Increases vagal activity and decreases AV node conduction so increases stroke volume and decreases heart rate
Indications of Digoxin
Rate control for AF
Heart Failure
Contra-indications for Digoxin
- Second degree/ Complete Heart Block- slows conduction via AV node
- Supraventricular Tachycardia (SVT) associated with Wolff-Parkinson- White syndrome
- Hypokalaemia - risk of arrhythmias so give potassium supplements
- Pregnancy
- Renal Insufficiency
Side effects of Digoxin
Cardiac Arrhythmias/ Heart Block
HTN
Digoxin toxicity: N&V, diarrhoea, abdominal pain, visual disturbances, confusion, delirium, arrhythmias, heart block
Possible interactions of Digoxin
- Drugs that impair renal function e.g. NSAIDs, ACEi
- Diuretics can cause hypokalaemia resulting in digoxin toxicity without a change in plasma concentration
- Antiarrhythmic drugs e.g. beta blockers, amiodarone, verapamil, diltiazem
- Amiodarone, quinidine, spironolactone, verpamil
Patient information for Digoxin
Effective dose can be close to toxic dose so close monitoring is neeed
Pregnancy and breast feeding require small dose
Amiodarone
Antiarrhythmic
How does Amiodarone work?
Prolongs the action potential and refractory period throughout the heart. Often last drug of choice
Indications for Amiodarone
Tachycardia
AF and flutter
VF or pulseless VT - Emergency
Contraindications for Amiodarone
Sinus bradycardia, SA disease, Heart Block
Thyroid disease
Pregnancy, breast feeding
Heart Failure/ Cardiomyopathy bolus IV administration
Side effects of Amiodarone
Corneal lipofuscin microdeposits (almost 100% of patients will get this) Sunlight sensitivity Pneumonitis Peripheral neuropathy Hypo/Hyperthyroidism Hepatotoxicity Hypersensitivity/ Vasculitis Haemolytic or aplastic anaemia
Interactions of Amiodarone
- Warfarin- inhibits metabolism increasing effect
- Digoxin- reduces excretion increasing effect
- Drugs that reduced heart rate: CCB, beta blockers
- Drug that prolongs QT interval: antiarrhythmics, co-amoxiclav Erythromycin, antipsychotics, lithium, TCA, Phenytoin
Half life of Amiodarone
Very long half life up to 1 month so interactions can occur after stopping drug
Patient information for Amiodarone
- Before starting, measure TFT, LFTs, ECG and CXR
- Measure TFT and LFT every 6 months
- Patients may become more sensitive to the sun so should use SPF
Aspirin
Anti-platelet, NSAID
How does Aspirin work?
Irreversible COX-inhibitor. Irreversibly inhibits COX-1 and modifies the activity of COX-2
Mechanism of Aspirin
Aspirin is a weak acid so is protonated in the stomach and crosses the mucosa, most absorption is in the ileum, hydrolysed by esterase to form salicylate. Salicylate enters active site of COX-1 and 2 and acetylates serine 530, irreversibly activating them. Reduces PGE2 and TXA2 production.
Indications of Aspirin
Primary and secondary prevention of atherosclerotic diseae Analgesia Anti-Inflammatory Pyrexia Dysmenorrhoea Headaches and Migraine
Contraindications of Aspirin
Haemophilia Active peptic ulceration Uncontrolled hypertension Renal/ Hepatic bleeding Pregnancy Asthma Renal insufficiency G6PD deficiency Children under 16
Side effects of aspirin
Intracranial bleeding GI disturbance Tinnitus due to salicylism Hypersensitivity Bronchospasm Asthma Nasal Polyps Thrombocytopenia
Interactions of aspirin
Displaces warfarin from plasma increasing its effect
Antagonises effect of diureics and causes fluid retention at higher doses
Ibuprofen inhibits anti-platelet action of aspirin
Reduces excretion of methotrexate increasing risk of toxicity
Elimination of Aspirin
75% metabolised by liver
25% oxidised
25% excreted unchanged
Clopidogrel
Anti-platelet
How does Clopidogrel work
ADP receptor antagonist
Inhibits ADP receptors on platelets that stimulate platelet aggregation so inhibits thrombus formation
Indications for Clopidogrel
Prevention of atherosclerotic disease: MI, angina, storke with aspirin
Following Angioplasty with aspirin
Contraindication for Clopidogrel
Active Bleeding Conditions Haemophillia or other bleeding disorders Active peptic ulceration Renal/hepatic insufficiency Pregnancy
Side effects of Clopidogrel
Increase risk of bleeding Abdominal PAin Nausea Dizziness/Vertigo Paraesthesia Hepatic/biliary damage
Interactions of Clopidogrel
With aspirin, anti-platelet effect and risk of bleeding increases
Caution with warfarin due to increase risk of bleeding
Fibrinolytics
Streptokinase
Tissue Plasminogen Activator (TPA)
Urukinase (UA)
Streptokinase drugs
Alteplase, Reteplase, Tenecteplase
Mechanism of Streptokinase
Combines with plasminogen to form an active complex which activates plasminogen to plasmin which breaks fibrin down
Indications for Streptokinase
Elevated ST elevation Acute MI Acute Stroke DVT/PE Unblock venous catheters/thromboses arteriovenous shunts
Contraindications for Streptokinase
Active Bleeding Haemophilia Active Peptic Ulceration Pregnancy Surgery or trauma in last 12 weeks Pericarditis/ Inefective endocarditis Acute pancreatitis
Side effects of Streptokinase
Bleeding
Hypotension in MI
Allergic Reaction
Nausea and Vomiting
When to give Alteplase, Reteplase, Streptokinase, Tenecteplase
Alteplase: within 6-12 hours of symptom onset
Reteplase and Streptokinase: within 12 hours of onset
Tenecteplase: 6 hours of onset
Tinzaparin
Enoxaparin
Dalteparin
Low Molecular Weight Heparin (LMWH)
Mechanism of Unfractionated Heparins (UF)
Activates antithrombin in turn inactivating clotting factor Xa and thrombin
Mechanism of LMWH
Inhibits factor Xa
Fondaparinux
Inhibits factor Xa only
Indications for LMWH/UF
- Venous Thromboembolism: DVT, PE
- Acute Coronary Syndrome: LMWH and Fondaparinux are first-line choice
- Prophylaxis against thromboembolic disease
Contraindication for LMWH/UF
Haemophilia
Thrombocytopenia
Side effects of LMWH/UF
Bruising Haemorrhage Osteoporosis Hypoaldosteronism/ Hyperkalaemia Thrombocytopenia
Elimination of Heparins
Around 1 hour
Eliminated by renal excretion
Use UH in renal failure
Drug for Heparin overdose or to reverse the effects of Heparin
Protamine Sulphate
Warfarin
Oral Anticoagulant
Mechanism of Warfarin
Inhibits Vitamin K-dependent coagulation factors and cofactors (1972).
Inhibits Vitamin K epoxide reductase preventing reactivation of Vitamin K and coagulation factor synthesis
INR ranges for people on Warfarin
2.0-3.0
For healthy people an INR < 1.1 is normal
Indications for Warfarin
Prevention of thromboembolic disease: DVT, PE, AF, prosthetic heart valves, after heart valve replacement
Contraindications for Warfarin
Haemophilia Thrombocytopenia Active Peptic Ulceration Uncontrolled HPT Renal/ Hepatic insufficiency Pregnancy Following trauma or surgery
Side effects of Warfarin
Haemorrhage Hypersensitivity Alopecia Diarrhoea Hepatic Dysfunction Pancreatitis
Interactions of Warfarin
Cytochrome P450 inhibitors decrease warfarin metabolism and increase bleeding risk
Cytochrome P450 inducers increase warfarin metabolism and risk of clots
Antibiotics can increase anticoagulation by killing gut flora that synthesise vitamin K
Cytochrome P450 inhibitors
Fluconasole
Macrolides
Protease Inhibitors
Cytochrome P450 inducers
Phenytoin
Carbamazepine
Rifampicin
Dosage of Warfarin
5-10mg OD
Rivaroxaban
Anticoagulant. Inhibitor of activated factor Xa.
Indications for Rivaroxaban
Prevention of stroke and systemic embolism in patients
Contraindicatons for Rivaroxaban
Active bleeding Antiphospholipid syndrome Malignant neoplasms Oesophageal varices Following an ACS event
Simvastatin
Statin - HMG CoA reductase inhibitors
Mechanism for Simvastatin
- Statins reduce serum cholesterol levels by Inhibiting HMG CoA reductase, the enzyme involved in cholesterol synthesis.
- Indirectly reduce triglycerides
Indications for Simvastatin
- Primary and Secondary prevention of Cardiovascular Disease
- Hyperlipidaemia
Contraindications for Simvastatins
Pregnancy and breast feeding
Renal/Hepatic Insufficiency
High alcohol intake
Risk factors of myopathy/rhabdomyolysis
Side effects of Simvastatin
Headache
GI disturbances ie Abdominal cramps
Myopathy and Rhabdomyolysis
Increase liver enzymes
Interactions of Simvastatin
Metabolism of Statins reduced by Cytochrome P450 inhibitors
Grapefruit Juice may increase statin levels by inhibiting Cytochrome P450 enzymes involved in metabolism
