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Cardiac Pharmacology: Difference between revisions
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''Heather Melrose, Jonas de Jong'' | |||
__TOC__ | |||
Cardiovascular disease including heart disease, arrhythmias and hypertension, is the leading cause of morbidity and mortality in the Western world. There are numerous devastating conditions affecting the heart and/or the vasculature, leading to high demand for cardiovascular drugs. This chapter focuses on some key therapeutic targets within the cardiovascular system and the drugs used to combat cardiovascular disease. | Cardiovascular disease including heart disease, arrhythmias and hypertension, is the leading cause of morbidity and mortality in the Western world. There are numerous devastating conditions affecting the heart and/or the vasculature, leading to high demand for cardiovascular drugs. This chapter focuses on some key therapeutic targets within the cardiovascular system and the drugs used to combat cardiovascular disease. | ||
==Renin-Angiotensin-Aldosterone System== | ==Renin-Angiotensin-Aldosterone System== | ||
[[Image:Renin-angiotensin-aldosterone_system.png|thumb|right|500px|RAAS schematic]] | |||
The renin-angiotensin-aldosterone system (RAAS) is an important hormone-based pathway within the body that regulates fluid balance and thus systemic blood pressure. The system is activated by decreases in blood volume or pressure detected in two ways: a drop in blood pressure detected by baroreceptors (pressure sensors) located in the carotid sinus or a drop in flow rate through the kidneys, detected by the juxtaglomerular apparatus. The body responds to these stimuli to effect a restoration in blood pressure via the actions of three hormones; renin, angiotensin and aldosterone. Following the detected drop in blood pressure, the enzyme renin is released from specialised cells within the kidney. The substrate of renin is the inactive precursor of angiotensin I, angiotensinogen. Angiotensin I is then enzymatically converted by angiotensin converting enzyme (ACE) into angiotensin II, a hormone with various actions throughout the body that ultimately increase blood pressure, restoring fluid balance within the body. | The renin-angiotensin-aldosterone system (RAAS) is an important hormone-based pathway within the body that regulates fluid balance and thus systemic blood pressure. The system is activated by decreases in blood volume or pressure detected in two ways: a drop in blood pressure detected by baroreceptors (pressure sensors) located in the carotid sinus or a drop in flow rate through the kidneys, detected by the juxtaglomerular apparatus. The body responds to these stimuli to effect a restoration in blood pressure via the actions of three hormones; renin, angiotensin and aldosterone. Following the detected drop in blood pressure, the enzyme renin is released from specialised cells within the kidney. The substrate of renin is the inactive precursor of angiotensin I, angiotensinogen. Angiotensin I is then enzymatically converted by angiotensin converting enzyme (ACE) into angiotensin II, a hormone with various actions throughout the body that ultimately increase blood pressure, restoring fluid balance within the body. | ||
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==Neural Control of the Cardiovascular System== | ==Neural Control of the Cardiovascular System== | ||
[[File:Sympathic_parasympathic.svg|thumb|400px|Interaction between the sympathic and parasympathic nervous system and the heart]] | |||
===Sympathetic (Adrenergic) Nervous System=== | ===Sympathetic (Adrenergic) Nervous System=== | ||
The adrenergic nervous system is a vital component of many processes throughout the body, including the cardiovascular system. Circulating catecholamines (e.g. adrenaline and noradrenaline) bind to and activate adrenergic receptors on cell membranes. Adrenergic receptors are a class of G-protein coupled receptors that elicit a variety of tissue-specific effects and exist in several subtypes. | The adrenergic nervous system is a vital component of many processes throughout the body, including the cardiovascular system. Circulating catecholamines (e.g. adrenaline and noradrenaline) bind to and activate adrenergic receptors on cell membranes. Adrenergic receptors are a class of G-protein coupled receptors that elicit a variety of tissue-specific effects and exist in several subtypes. | ||
====Vasculature==== | ====Vasculature==== | ||
The predominant receptor subtype present in blood vessels is the | The predominant receptor subtype present in blood vessels is the a1-adrenergic receptor, activation of which by catecholamine binding causes activation of the phospholipase-C (PLC), inositol triphosphate (IP3), diacylglycerol (DAG) intracellular signalling pathway. This ultimately results in myocyte contraction, vasoconstriction and consequent increases in systemic blood pressure. | ||
====Heart==== | ====Heart==== | ||
Although the heart is myogenic, that is the impetus for contraction is self-initiated, the output of the heart is influenced by the central nervous system. The net effect of the sympathetic system on the heart is to increase cardiac output. The adrenergic receptors found in the heart belong to the | Although the heart is myogenic, that is the impetus for contraction is self-initiated, the output of the heart is influenced by the central nervous system. The net effect of the sympathetic system on the heart is to increase cardiac output. The adrenergic receptors found in the heart belong to the ß-receptor subfamily and include ß1 and ß3 receptors. Catecholamine binding to ß1-receptors in the heart causes increases in cardiac output via a number of mechanisms: positive chronotropic effects, positive inotropic effects increased automaticity and conduction in both ventricular myocytes and the atrioventricular (AV) node. However ß3-receptor activation antagonises these actions, producing a negative inotropic effect and providing an inbuilt control system within the heart. | ||
Prolonged increase catecholamine levels in the circulation (e.g. when secreted from adrenal tumours or times of stress) can lead to chronic cardiovascular problems such as hypertension and arrhythmias. | Prolonged increase catecholamine levels in the circulation (e.g. when secreted from adrenal tumours or times of stress) can lead to chronic cardiovascular problems such as hypertension and arrhythmias. | ||
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==Platelet/Clotting System== | ==Platelet/Clotting System== | ||
[[File:Platelet_receptors.svg|thumb|400px|Platelet activation and inhibition operates through surface receptors on platelets. Feedback loops enhance platelet activation (e.g. ADP released by platelets increases platelet activation, through the ADP receptor)]] | |||
Platelets (also known as thrombocytes) are small cells lacking nuclei that are responsible for haemostasis, or blood clotting. Damage or injury leading to blood loss and exposure of extracellular collagen fibres is detected, activating platelets. Once activated, platelets become adhesive, sticking to both the damaged vessel wall and each other, forming a clump of cells, or ‘clot’, helping to dam the vessel leak. They then begin to secrete cytokines that encourage invasion of fibroblasts present in the surrounding tissue which form a more permanent patch, either by creating healthy tissue, or depositing extracellular matrix to form a scar. | Platelets (also known as thrombocytes) are small cells lacking nuclei that are responsible for haemostasis, or blood clotting. Damage or injury leading to blood loss and exposure of extracellular collagen fibres is detected, activating platelets. Once activated, platelets become adhesive, sticking to both the damaged vessel wall and each other, forming a clump of cells, or ‘clot’, helping to dam the vessel leak. They then begin to secrete cytokines that encourage invasion of fibroblasts present in the surrounding tissue which form a more permanent patch, either by creating healthy tissue, or depositing extracellular matrix to form a scar. | ||
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!Formula | !Formula | ||
|- | |- | ||
!Dose | |||
|Amount of active drug given to patient | |Amount of active drug given to patient | ||
|mg (D) | |align="center"|mg (D) | ||
|Drug Specific (From clinical studies) | |Drug Specific (From clinical studies) | ||
|- | |- | ||
!Concentration | |||
|Amount of drug in a given plasma volume | |Amount of drug in a given plasma volume | ||
|µg/ml (C) | |align="center"|µg/ml (C) | ||
|= D / Vd | |align="center"|= D / Vd | ||
|- | |- | ||
!EC<sub>50</sub> | |||
|The concentration of drug needed to elicit a response halfway between zero and maximal responses. | |The concentration of drug needed to elicit a response halfway between zero and maximal responses. | ||
|µg/ml ( | |align="center"|µg/ml (EC<sub>50</sub>) | ||
| | |align="center"|y = bottom + (Top-Bottom)/(1+ [x/EC50] Hill Coefficient) | ||
|- | |- | ||
!Volume of Distribution | |||
|The theoretical volume the drug would occupy if distributed uniformly throughout the tissues to elicit the current plasma concentration. | |The theoretical volume the drug would occupy if distributed uniformly throughout the tissues to elicit the current plasma concentration. | ||
|L (Vd) | |align="center"|L (Vd) | ||
|D / C | |align="center"|D / C | ||
|- | |- | ||
!Elimination Constant (Rate) | |||
|The rate at which the drug is removed from the body. | |The rate at which the drug is removed from the body. | ||
|h-1 (Ke) | |align="center"|h-1 (Ke) | ||
|ln(2) / t1/2 or CL / Vd | |align="center"|ln(2) / t1/2 or CL / Vd | ||
|- | |- | ||
!Bioavailability | |||
|How much of the administered dose is available for actual use by the body. | |How much of the administered dose is available for actual use by the body. | ||
|no units as expressing a fraction (f) | |no units as expressing a fraction (f) | ||
|100 × (AUC (po)×D (iv))/(AUC (iv)×D (po)) | |align="center"|100 × (AUC (po)×D (iv))/(AUC (iv)×D (po)) | ||
AUC = Area under curve po = oral administration iv = intravenous administration | AUC = Area under curve po = oral administration iv = intravenous administration | ||
|- | |- | ||
!Cmax or Cmin | |||
|The maximum (Cmax) / minimum (Cmin) plasma drug concentration reached following drug administration | |The maximum (Cmax) / minimum (Cmin) plasma drug concentration reached following drug administration | ||
|µg/ml (Cmax or Cmin) | |align="center"|µg/ml (Cmax or Cmin) | ||
|Identified via direct measurement of plasma C | |Identified via direct measurement of plasma C | ||
|- | |- | ||
!tmax | |||
|The time it takes for a drug to reach Cmax following administration | |The time it takes for a drug to reach Cmax following administration | ||
|h (tmax) | |align="center"|h (tmax) | ||
|Identified via direct measurement of plasma C over time | |Identified via direct measurement of plasma C over time | ||
|- | |- | ||
!Half-life | |||
|The time it takes for a drug to reach half its original concentration | |The time it takes for a drug to reach half its original concentration | ||
|h (t1/2) | |align="center"|h (t1/2) | ||
|ln(2) / Ke | |align="center"|ln(2) / Ke | ||
|- | |- | ||
!Drug Clearance | |||
|The volume of plasma cleared of the drug over a set time | |The volume of plasma cleared of the drug over a set time | ||
|l/h (CL) | |align="center"|l/h (CL) | ||
|Vd x Ke or D / Area under curve | |align="center"|Vd x Ke or D / Area under curve | ||
|} | |} | ||
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|- | |- | ||
!Drug | !Drug | ||
!Drugs that | !Drugs that <big>↑</big> drug action | ||
!Drugs that ↓ drug action | !Drugs that <big>↓</big> drug action | ||
|- | |- | ||
!Digoxin | |||
|Diuretics | |valign="top"| | ||
Antiarrhythmics | *Diuretics | ||
Macrolide antibiotics | *Antiarrhythmics | ||
Cholestyramine | *Macrolide antibiotics | ||
Keto- and intraconazole | *Cholestyramine | ||
Calcium antagonists | *Neomycin | ||
Cyclosporine, indomethacin | *Keto- and intraconazole | ||
HMG CoA reductase inhibitors | *Calcium antagonists | ||
Benzodiazepines | *Cyclosporine, indomethacin | ||
Amiodarone | *HMG CoA reductase inhibitors | ||
Verapamil | *Benzodiazepines | ||
|Rifampicin | *Amiodarone | ||
Antacids (liquid) | *Verapamil | ||
|valign="top"| | |||
*Rifampicin | |||
*Antacids (liquid) | |||
|- | |- | ||
!Warfarin | |||
|Furosemide | |valign="top"| | ||
Amiodarone | *Furosemide | ||
Sulfa | *Amiodarone | ||
antibiotics | *Sulfa | ||
NSAIDs | *Macrolide and quinolone antibiotics | ||
|Azathioprine | *NSAIDs | ||
Phenobarbitone | |valign="top"| | ||
Carbamazepine | *Azathioprine | ||
Dexamethasone | *Phenobarbitone | ||
Prednisolone | *Carbamazepine | ||
Rifampicin | *Dexamethasone | ||
Vitamin K | *Prednisolone | ||
Raloxifene | *Rifampicin | ||
*Vitamin K | |||
*Raloxifene | |||
|- | |- | ||
!Clopidogrel | |||
|Rifampicin | |valign="top"| | ||
Caffeine | *Rifampicin | ||
Methylxanthines | *Caffeine | ||
Phosphodiesterase inhibitors | *Methylxanthines | ||
|Statins | *Phosphodiesterase inhibitors | ||
Calcium channel blockers | |valign="top"| | ||
Warfarin | *Statins | ||
Proton pump inhibitors | *Calcium channel blockers | ||
*Warfarin | |||
*Proton pump inhibitors | |||
|- | |- | ||
!Furosemide | |||
| | | | ||
|NSAIDs | |valign="top"| | ||
Phenytoin | *NSAIDs | ||
Colesevelam | *Phenytoin | ||
*Colesevelam | |||
|- | |- | ||
!ACE Inhibitors | |||
|NSAIDs | |valign="top"| | ||
Probenecid | *NSAIDs | ||
Calcium channel blockers | *Probenecid | ||
|Indomethacin | *Calcium channel blockers | ||
Antacids | |valign="top"| | ||
*Indomethacin | |||
*Antacids | |||
|- | |- | ||
!ß-blockers | |||
|Amiodarone | |valign="top"| | ||
Calcium channel blockers | *Amiodarone | ||
Diltiazem | *Calcium channel blockers | ||
Phenoxybenzamine | *Diltiazem | ||
|Phenobarbital | *Phenoxybenzamine | ||
Rifampicin | |valign="top"| | ||
Cimetidine | *Phenobarbital | ||
Antacids (liquid) | *Rifampicin | ||
NSAIDs | *Cimetidine | ||
*Antacids (liquid) | |||
*NSAIDs | |||
|- | |- | ||
!Statins | |||
|Amiodarone | |valign="top"| | ||
Verapamil | *Amiodarone | ||
Fibrates | *Verapamil | ||
Amprenavir | *Fibrates | ||
Diltiazem | *Amprenavir | ||
|Nevirapine | *Diltiazem | ||
Rifampicin | |valign="top"| | ||
*Nevirapine | |||
*Rifampicin | |||
|} | |} | ||
| Line 208: | Line 227: | ||
!Inducers (e.g.) | !Inducers (e.g.) | ||
|- | |- | ||
!CYP2C19 | |||
|Clopidogrel | |valign="top"| | ||
Propranolol | *Clopidogrel | ||
Warfarin | *Propranolol | ||
|Moclobemide | *Warfarin | ||
Chloramphenicol | |valign="top"| | ||
Many anti-convulsants (Valproate) | *Moclobemide | ||
Proton pump inhibitors (Omeprazole) | *Chloramphenicol | ||
|Rifampicin | *Many anti-convulsants (Valproate) | ||
Carbamazepine | *Proton pump inhibitors (Omeprazole) | ||
Prednisone | |valign="top"| | ||
*Rifampicin | |||
*Carbamazepine | |||
*Prednisone | |||
|- | |- | ||
!CYP3A4 | |||
|Donepezil | |valign="top"| | ||
Statins (Atorvastatin) | *Donepezil | ||
Ca-channel blockers (Nifedipine) | *Statins (Atorvastatin) | ||
Amiodarone | *Ca-channel blockers (Nifedipine) | ||
Dronedarone | *Amiodarone | ||
Quinidine | *Dronedarone | ||
PDE5 Inhibitors (Sildenafil) | *Quinidine | ||
Kinins | *PDE5 Inhibitors (Sildenafil) | ||
Caffeine | *Kinins | ||
Eplerenone | *Caffeine | ||
Propranolol | *Eplerenone | ||
Salmeterol | *Propranolol | ||
Warfarin | *Salmeterol | ||
Clopidogrel | *Warfarin | ||
|Protease inhibitors (Ritonavir) | *Clopidogrel | ||
Macrolides (Clarithromycin) | |valign="top"| | ||
Chloramphenicol | *Protease inhibitors (Ritonavir) | ||
Nefazodone | *Macrolides (Clarithromycin) | ||
Some Ca-channel blockers (Verapamil) | *Chloramphenicol | ||
Cimetidine | *Nefazodone | ||
Some azole anti-fungals (Ketaconazole) | *Some Ca-channel blockers (Verapamil) | ||
Grapefruit juice | *Cimetidine | ||
|Some anti-convulsants (Carbamazepine) | *Some azole anti-fungals (Ketaconazole) | ||
Baribiturates (Phenobarbital) | *Grapefruit juice | ||
St. John’s Wort | |valign="top"| | ||
Some reverse transcriptase inhibitors (Efavirenz) | *Some anti-convulsants (Carbamazepine) | ||
Some Hypoglycaemics (Pioglitazone) | *Baribiturates (Phenobarbital) | ||
Glucocorticoids | *St. John’s Wort | ||
Modafinil | *Some reverse transcriptase inhibitors (Efavirenz) | ||
*Some Hypoglycaemics (Pioglitazone) | |||
*Glucocorticoids | |||
*Modafinil | |||
|- | |- | ||
!CYP2C9 | |||
|Fluvastatin | |valign="top"| | ||
Angiotensin receptor II agonists (losartan) | *Fluvastatin | ||
Warfarin | *Angiotensin receptor II agonists (losartan) | ||
Torasemide | *Warfarin | ||
|Some azole anti-fungals (Fluconazole) | *Torasemide | ||
Amiodarone | |valign="top"| | ||
Antihistamines (Cyclizine) | *Some azole anti-fungals (Fluconazole) | ||
Chloramphenicol | *Amiodarone | ||
Fluvastatin | *Antihistamines (Cyclizine) | ||
Fluvoxamine | *Chloramphenicol | ||
Probenecid | *Fluvastatin | ||
Sertraline | *Fluvoxamine | ||
|Rifampicin | *Probenecid | ||
Secobarbital | *Sertraline | ||
|valign="top"| | |||
*Rifampicin | |||
*Secobarbital | |||
|- | |- | ||
!CYP2D6 | |||
| | |valign="top"| | ||
Class I anti-arrythmics (Flecainide) | *ß-blockers (Propranolol) | ||
Donepezil | *Class I anti-arrythmics (Flecainide) | ||
|SSRIs (Fluoxetine) | *Donepezil | ||
Quinidine | |valign="top"| | ||
Sertraline | *SSRIs (Fluoxetine) | ||
Terbinafine | *Quinidine | ||
Amiodarone | *Sertraline | ||
Cinacalcet | *Terbinafine | ||
Ritonavir | *Amiodarone | ||
Antipsychotics (Haloperidol) | *Cinacalcet | ||
Antihistamines (Promethazine) | *Ritonavir | ||
Metoclopramide | *Antipsychotics (Haloperidol) | ||
Ranitidine | *Antihistamines (Promethazine) | ||
Mibefradil | *Metoclopramide | ||
|Rifampicin | *Ranitidine | ||
Dexamethasone | *Mibefradil | ||
Glutethimide | |valign="top"| | ||
*Rifampicin | |||
*Dexamethasone | |||
*Glutethimide | |||
|} | |} | ||
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|- | |- | ||
|+Cardiovascular Drugs | |+Cardiovascular Drugs | ||
|- | |- | ||
!Drug Type | !Drug Type | ||
!Examples (generic name) | !Examples (generic name) | ||
!Indications | !Indications | ||
!Typical Dosage | !Typical Dosage | ||
!Guidelines/Class of Indication !Side Effects (Prevalence %) | !Guidelines / Class of Indication | ||
!Side Effects (Prevalence %) | |||
|- | |||
|colspan="6" bgcolor="#E6E6FA"|:'''Anti-hypertensives''' | |||
|- | |||
|rowspan="2"|Diuretics | |||
|rowspan="2"|Furosemide | |||
|Oedema | |||
|Furosemide: 20-40mg once daily | |||
| | |||
|rowspan="2" valign="top"|Mild gastro-intestinal disturbances, pancreatitis, hepatic encephalopathy, postural hypotension, temporary increase in serum-cholesterol and triglyceride concentration, hyperglycaemia, acute urinary retention, electrolyte disturbances, metabolic alkalosis, blood disorders, hyperuricaemia, visual disturbances, tinnitus and deafness, and hypersensitivity reactions (including rash, photosensitivity, and pruritus). | |||
|- | |||
|Resistant Hypertension | |||
|Furosemide: 40-80mg once daily | |||
|Hypertension in symptomatic (NYHA class II-IV) HF and LVD: Class IC <cite>Esc1</cite> | |||
|- | |- | ||
| | |rowspan="4"|ACE Inhibitors | ||
| | |rowspan="4"|Captopril, Monopril | ||
|Hypertension | |||
|Captopril: 12.5mg twice daily | |||
|Hypertension: Class IA <cite>Esc2</cite> | |||
Hypertension: Class IA | |||
Hypertension in symptomatic (NYHA class II-IV) HF and LVD: Class IA <cite>Esc1</cite> | |||
Hypertension in symptomatic (NYHA class II-IV) HF and LVD: Class IA | |||
Hypertension in diabetics: Class IA <cite>Esc3</cite> | |||
|rowspan="4" valign="top"|Hypotension (2.4%), renal impairment, persistent dry cough, angioedema, rash pancreatitis, upper respiratory-tract symptoms (2-10%), gastro-intestinal symptoms (1-2%), altered liver function tests, cholestatic jaundice, hepatitis, fulminant hepatic necrosis and failure, hyperkalaemia (2%), hypoglycaemia, blood disorders including thrombocytopenia, leucopenia, neutropenia, headache (3%), dizziness (2-12%), fatigue, malaise, taste disturbance, paraesthesia, bronchospasm, fever, serositis, vasculitis, myalgia (3%), arthralgia, positive antinuclear antibody, raised erythrocyte sedimentation rate, eosinophilia, leucocytosis, and photosensitivity. | |||
Hypertension in diabetics: Class IA Hypotension (2.4%), renal impairment, persistent dry cough, angioedema, rash pancreatitis, upper respiratory-tract symptoms (2-10%), gastro-intestinal symptoms (1-2%), altered liver function tests, cholestatic jaundice, hepatitis, fulminant hepatic necrosis and failure, hyperkalaemia (2%), hypoglycaemia, blood disorders including thrombocytopenia, leucopenia, neutropenia, headache (3%), dizziness (2-12%), fatigue, malaise, taste disturbance, paraesthesia, bronchospasm, fever, serositis, vasculitis, myalgia (3%), arthralgia, positive antinuclear antibody, raised erythrocyte sedimentation rate, eosinophilia, leucocytosis, and photosensitivity. | |- | ||
|Heart Failure | |||
|Captopril: 12.5mg 3 times daily | |||
Post STEMI: Class IA | |Post STEMI: Class IA <cite>Esc4</cite> | ||
Diabetic patients: Class IC <cite>Esc2</cite> | |||
Diabetic patients: Class IC | |||
Symptomatic (NYHA class II-IV) HF: Class IA; Acute heart failure with ACS: Class IA <cite>Esc1</cite> | |||
|- | |||
Symptomatic (NYHA class II-IV) HF: Class IA | |Prophylaxis Following MI | ||
|Captopril: 6.25mg once daily | |||
| | |||
|- | |||
|Diabetic nephropathy | |||
|Captopril: 75-100mg once daily | |||
| | |||
|- | |||
|rowspan="3"|Angiotensin Receptor Blockers | |||
|rowspan="3"|Losartan, Candesartan | |||
|Hypertension | |||
|Losartan: 50mg once daily | |||
|Hypertension: Class IA <cite>Esc2</cite> | |||
Hypertension in diabetics: Class IA <cite>Esc3</cite> | |||
|rowspan="3" valign="top"|Gastro-intestinal disturbances (<3%), dizziness (14%), angina, palpitation, oedema, dyspnoea, headache (14%), malaise, urticaria, pruritus, rash; | |||
|- | |||
|Left ventricular hypertrophy | |||
|Losartan: 12.5-150mg daily | |||
|LVH: Class IB <cite>Esc4</cite> | |||
|- | |||
|Diabetic nephropathy | |||
|Losartan: 50mg daily | |||
| | |||
|- | |||
|rowspan="3"|Alpha Blockers | |||
|rowspan="3"|Prazosin, Doxazosin | |||
|Hypertension | |||
|Prazosin: 1-10mg 2-3 times daily | |||
| | |||
|rowspan="3" valign="top"|Drowsiness, hypotension (notably postural hypotension) (10-70% initially), syncope (1%), asthenia, dizziness, depression, headache (8-18%), dry mouth, gastro-intestinal disturbances, oedema, blurred vision (<5%), intra-operative floppy iris syndrome, rhinitis (<4%), erectile disorders (including priapism), tachycardia and palpitations (7-14%), gastrointestinal side-symptoms (4-5%), hypersensitivity reactions including rash, pruritus and angioedema. | |||
|- | |||
|Congestive Heart Failure | |||
|Prazosin: 4-20mg daily | |||
| | |||
|- | |||
|Raynaud’s Syndrome | |||
|Prazosin: 1-2mg daily | |||
| | |||
|- | |||
|rowspan="4"|Beta Blockers | |||
|rowspan="4"|Atenolol, Propranolol | |||
|Hypertension | |||
|Atenolol: 25-50mg daily | |||
| | |||
|rowspan="4" valign="top"|Gastro-intestinal disturbances (2-4%); bradycardia, heart failure, hypotension, conduction disorders, peripheral vasoconstriction, bronchospasm, dyspnoea; headache, fatigue, sleep disturbances (2-5%), paraesthesia, dizziness (2-5%), vertigo, psychoses; sexual dysfunction; purpura, thrombocytopenia; visual disturbances; exacerbation of psoriasis, alopecia; rarely rashes and dry eyes. | |||
|- | |||
|Angina | |||
|Atenolol: 100mg once/twice daily | |||
|ACS: Class IIaB <cite>Esc2</cite> | |||
Angina in symptomatic (NYHA class II-IV) HF and LVD: Class IA <cite>Esc1</cite> | |||
|- | |||
|Arrhythmias | |||
|Atenolol: 50-100mg daily | |||
|Atrial fibrillation: Class IA; Polymorphic VT: Class IB <cite>Esc4</cite> | |||
Symptomatic (NYHA class II-IV) HF, LVD and AF: Class IA; Management of VA in HF: Class IA <cite>Esc1</cite> | |||
Atrial | SVT: Class IIbC; Wide QRS-complex tachycardia of unknown origin: Class IIIC; Sinus tachycardia: Class IC; Poorly tolerated AVNRT with haemodynamic intolerance: Class IIaC; Recurrent symptomatic AVNRT: Class IC; Documented PSVT with only dual AV-nodal pathways or single echo beats demonstrated during electrophysiological study and no other identified cause of arrhythmia: Class IC; Infrequent, well tolerated AVNRT: Class IB; Focal junction tachycardia: Class IIaC; Nonparoxysmal junctional tachycardia: Class IIaC; WPW Syndrome: Class IIaC; AVRT, poorly tolerated: Class IIbC; Since or infrequent AVRT episode(s): Class IIaB; Acute treatment of Focal Atrial Tachycardia: Class IIaC; Prophylactic therapy for AT: Class IC; AF (Poorly tolerated): Class IIaC; AF (Stable flutter): Class IC; Prophylaxis of SVT during pregnancy: Class IIaB <cite>Acc5</cite> | ||
|- | |||
|Migraine | |||
|Atenolol: 50-200mg daily | |||
| | |||
|- | |||
|rowspan="3"|Calcium Channel Blockers | |||
|rowspan="3"|Nifedipine, Verapamil, Diltiazem | |||
|Hypertension | |||
|Nifedipine: 20-30mg once daily | |||
|Hypertension in symptomatic (NYHA class II-IV) HF and LVD: Class IA <cite>Esc1</cite> | |||
|rowspan="3" valign="top"|Gastro-intestinal disturbance (2-11%); hypotension (1-5%), oedema (7-29%), vasodilatation, palpitation; headache (7-35%), dizziness (3-27%), lethargy (4-6%), asthenia (10-12%); less commonly tachycardia (<1-7%), syncope (<1%), chills, nasal congestion, dyspnoea (<3%), anxiety, sleep disturbance (<2%), vertigo (<3%), migraine, paraesthesia, tremor (1-8%), polyuria, dysuria, nocturia, erectile dysfunction (<2%), epistaxis, myalgia, joint swelling, visual disturbance (<2%), sweating (<2%), hypersensitivity reactions (<1%); rarely anorexia, gum hyperplasia, mood disturbances, hyperglycaemia, male infertility, purpura (<1%), and photosensitivity reactions (<1%); also reported dysphagia, intestinal obstruction, intestinal ulcer, bezoar formation, gynaecomastia, agranulocytosis, and anaphylaxis; | |||
|- | |||
|Raynaud’s Syndrome | |||
|Nifedipine: 5-20mg 3 times daily | |||
| | |||
|- | |||
|Angina (prophylaxis) | |||
|Nifedipine: 5-20mg 3 times daily | |||
|Angina in symptomatic (NYHA class II-IV) HF and LVD: Class IIaA <cite>Esc1</cite> | |||
|- | |||
|colspan="6" bgcolor="#E6E6FA"|'''Anti-Arrhythmics''' | |||
|- | |||
|Class I (sodium channel blockers) | |||
|Flecainide, Lidocaine, Procainamide | |||
|Ventricular Arrhythmias | |||
|Flecainide: 50-100mg twice daily | |||
|Sustained VT and VF: Class IIbC <cite>Esc4</cite> | |||
Pre-excited SVT/AF: Class IB; Wide QRS-complex tachycardia of unknown origin: Lidocaine (Class IIbB) / Procainamide (Class IB); Wide QRS-complex tachycardia of unknown origin with LVD: Class IB; Focal junction tachycardia: Class IIaC; WPW Syndrome: IIaC; AVRT, poorly tolerated: IIaC; Single or infrequent AVRT episode(s): Class IIbC; Acute treatment of Focal Atrial Tachycardia: Class IIaC; Prophylactic therapy for AT: Class IIaC; AF (Stable flutter): Class IIbA; Prophylaxis of SVT during pregnancy: Class IIbB <cite>Acc5</cite> | |||
|Oedema, pro-arrhythmic effects (1-13%); dyspnoea; nervous-system side-effects including dizziness, asthenia, fatigue, fever; visual disturbances (13-28%); rarely pneumonitis, hallucinations, depression, confusion, amnesia, dyskinesia, convulsions, peripheral neuropathy; also reported gastro-intestinal disturbances (1-4%), anorexia, hepatic dysfunction, flushing, syncope, drowsiness, tremor, vertigo, headache, anxiety, insomnia, ataxia, paraesthesia, anaemia, leucopenia, thrombocytopenia, corneal deposits, tinnitus, increased antinuclear antibodies, hypersensitivity reactions (including rash, urticaria, and photosensitivity), increased sweating. | |||
|- | |||
|Class II (Beta blockers) | |||
|(See above) | |||
|(See above) | |||
|(See above) | |||
| | |||
|(See above) | |||
|- | |||
|Class III (Potassium channel blockers) | |||
|Amiodarone, Sotalol | |||
|Ventricular, Arrhythmias | |||
|Amiodarone: 200mg 2-3 times daily | |||
|Sustained VT and VF: Class IIaC; Polymorphic VT: Class IC <cite>Esc4</cite> | |||
Management of VA in HF: Class IA; Prevention of VA in HF: Class IIbB <cite>Esc1</cite> | |||
SVT: Class IIBC; Wide QRS-complex tachycardia of unknown origin: Class IB; Wide QRS-complex tachycardia of unknown origin with LVD: Class IB; Recurrent AVNRT unresponsive to beta blocker or calcium-channel blocker and patient not desiring RF ablation: Class IIbC; Focal junction tachycardia: Class IIaC; WPW Syndrome: IIaC; AVRT, poorly tolerated: Class IIaC; Since or infrequent AVRT episode(s): Class IIbB; Acute treatment of Focal Atrial Tachycardia: Class IIaC; Prophylactic therapy for AT: Class IIaC; AF (Poorly tolerated): Class IIbC; AF (Stable flutter): Class IIbC; Prophylaxis of SVT during pregnancy: Class IIIC <cite>Acc5</cite> | |||
|Gastro-intestinal disturbances (2-20%)), taste disturbances, hepatic disturbances (up to 50%); bradycardia; pulmonary toxicity (1-17%); tremor (9-59%), sleep disorders; hypothyroidism (5-10%), hyperthyroidism (5-10%); reversible corneal microdeposits (up to 98%); phototoxicity, persistent slate-grey skin discoloration (1-7%), injection-site reactions; less commonly onset or worsening of arrhythmia, conduction disturbances, peripheral neuropathy (1-105) and myopathy; very rarely sinus arrest, bronchospasm, ataxia (2-37%), benign intracranial hypertension, headache, vertigo, epididymo-orchitis, impotence, haemolytic or aplastic anaemia, thrombocytopenia, rash, hypersensitivity including photosensitivity (2-20%), anaphylaxis on rapid injection, hypotension (10-30%), respiratory distress syndrome, sweating, and hot flushes | |||
Wide QRS-complex tachycardia of unknown origin: | |- | ||
Wide QRS-complex tachycardia of unknown origin with LVD: Class IB | |Class IV (Calcium channel blockers) | ||
Focal junction tachycardia: Class IIaC | |(See above) | ||
WPW Syndrome: IIaC | |(See above) | ||
AVRT, poorly tolerated: IIaC | |(See above) | ||
| | |||
Acute treatment of Focal Atrial Tachycardia: Class IIaC | |(See above) | ||
Prophylactic therapy for AT: Class IIaC | |- | ||
AF (Stable flutter): Class | |rowspan="2"| | ||
Prophylaxis of SVT during pregnancy: Class | |rowspan="2"|Digoxin | ||
|Supra-ventricular Arrhythmias | |||
|Acute: 0.75-1.5mg over 24 hours; Maintenance: 125-150µg daily | |||
|SVT: Class IIbC; WPW Syndrome: Class IIIC; AVRT, poorly tolerated: Class IIIC; Since or infrequent AVRT episode(s): Class IIIC; Prophylaxis of SVT during pregnancy: Class IC <cite>Acc5</cite> | |||
|rowspan="3" valign="top"|Gastro-intestinal disturbances (vomiting, diarrhoea, anorexia, abdominal pain) (25%); arrhythmias (up to 50%), AV conduction disturbances (50%); nervous system disturbances (dizziness, apathy, confusion, headache, fatigue, weakness) (25%); blurred or yellow vision; rash, eosinophilia, depression, anorexia, intestinal ischaemia and necrosis, psychosis, gynaecomastia on long-term use, and thrombocytopenia. | |||
|- | |||
|Heart Failure | |||
|62.5-125 µg daily | |||
|Symptomatic (NYHA class II-IV) HF: Class IIbB | |||
Symptomatic (NYHA class II-IV) HF, LVD and AF: Class IB; Acute HF with AF and VT: Class IC <cite>Esc1</cite> | |||
|- | |||
|colspan="6" bgcolor="#E6E6FA"|'''Anti-platelet Drugs''' | |||
Prevention of | |- | ||
|rowspan="7"| | |||
|rowspan="2"|Aspirin | |||
|Prevention of thrombotic cerebro- or cardio-vascular disease | |||
|75mg once/day | |||
|Prevention in AF: Class IC; Prevention in diabetic patients: IIaB <cite>Esc2</cite> | |||
Prevention in Symptomatic (NYHA class II-IV) HF and AF: Class IIA <cite>Esc1</cite> | |||
Symptomatic (NYHA class II-IV) HF | |||
Prevention in hypertensive patients with CV events: Class IA; Prevention in hypertensive patients without CV history but with reduced renal function/high risk: Class IIbA <cite>Esc3</cite> | |||
Prevention in | |||
Post-MI: Class Ia <cite>Esc3</cite> | |||
|rowspan="2" valign="top"|Bronchospasm (10-30% in asthmatics); gastro-intestinal irritation (up to 83%), gastro-intestinal haemorrhage (occasionally major), also other haemorrhage (e.g. intracranial (0.5%), subconjunctival), chest pain (8.3%), oedema (4.5%), hypertension (4.3%). | |||
Prevention | |- | ||
Prevention in | |Pain / pyrexia | ||
|300-600mg every 4-6 hours as necessary | |||
| | |||
|- | |||
|rowspan="3"|Clopidogrel | |||
|Prevention of thrombotic events (esp. when warfarin not tolerated) | |||
|75mg once/day | |||
|Prevention in diabetic patients: IIaB; Primary and secondary prevention of stroke: Class IB <cite>Esc2</cite> | |||
Prevention in Symptomatic (NYHA class II-IV) HF and AF: Class IIA <cite>Esc1</cite> | |||
Acute phase of coronary artery syndrome: Class IB; Non-cardioembolic cerebral ischaemic events: Class IA <cite>Esc3</cite> | |||
|rowspan="3" valign="top"|Dyspepsia (5.2%), abdominal pain (5.6%), diarrhoea (4.5%); bleeding disorders including gastro-intestinal (2.0%) and intracranial (0.4%), nausea (3.4%), vomiting, gastritis, flatulence, constipation, gastric and duodenal ulcers, headache (7.6%), epistaxis (2.9%), dizziness (6.2%), paraesthesia, leucopenia, decreased platelets (very rarely severe thrombocytopenia), eosinophilia, rash (4.2%), pruritus (3.3%), vertigo, colitis, pancreatitis, hepatitis (<1%), acute liver failure, hypertension (4.3%), chest pain (8.3%), oedema (4.1%), vasculitis, confusion, hallucinations, taste disturbance, cough (3.9%), fatigue (4.8%) stomatitis, bronchospasm, interstitial pneumonitis, pyrexia (2.2%), blood disorders including thrombocytopenic purpura (5.3%), agranulocytosis, neutropenia (0.04%) and pancytopenia and hypersensitivity-like reactions (<0.1%)including fever, glomerulonephritis, arthralgia, Stevens-Johnson syndrome, toxic epidermal necrolysis, lichen planus. | |||
Prevention in Symptomatic (NYHA class II-IV) HF and AF: Class IIA | |- | ||
|Acute myocardial infarction | |||
|300mg daily initially then 75mg once/day | |||
|Post STEMI: Class IA <cite>Esc4</cite> | |||
|- | |||
|Acute coronary syndrome | |||
|300mg daily initially then 75mg once/day | |||
|ACS: Class IIaC <cite>Esc2</cite> | |||
|- | |||
|Prasugrel | |||
|Prevention of thrombotic events. | |||
|60mg bolus then 5-10mg once daily | |||
|Prevention in Symptomatic (NYHA class II-IV) HF and AF: Class IIA <cite>Esc1</cite> | |||
Prevention in Symptomatic (NYHA class II-IV) HF and AF: Class IIA | Acute phase of coronary artery syndrome: Class IB <cite>Esc3</cite> | ||
|Haemorrhage (11.3%) (including gastro-intestinal (1.5%) and intracranial), haematoma, haematuria, hypertension (7.5%), hypotension (3.9%), headache (5.5%), back pain (5.0%), dyspnoea (4.9%), nausea (4.6%), dizziness (4.1%), cough (3.9%), fatigue (3.7%), chest pain (3.1%), arrhythmias including atrial fibrillation (2.9%) and bradycardia (2.9%), rash (2.8%), pyrexia (2.7%), oedema (2.7%), diarrhoea (2.3%), hypercholesterolaemia/hyperlipidaemia (7.5%), anaemia, rash,hypersensitivity reactions including angioedema (0.06%), thrombocytopenia (0.06%), thrombotic thrombocytopenic purpura. | |||
|- | |||
|Ticragelor | |||
|Prevention of thrombotic events. | |||
|180mg bolus then 90mg twice daily | |||
|Prevention in Symptomatic (NYHA class II-IV) HF and AF: Class IIA <cite>Esc1</cite> | |||
Acute phase of coronary artery syndrome: Class IB <cite>Esc3</cite> | |||
|Dyspnoea (13.8%), haemorrhage, bruising; nausea (4.3%), vomiting, diarrhoea (3.7%), hypertension (3.8%), hypotension (3.2%), back pain (3.6%), abdominal pain, dyspepsia, gastritis, dizziness (4.5%), chest pain (3.7%), headache (6.5%), cough (4.9%), rash, pruritus, fatigue (3.2%), constipation, arrhythmias including atrial fibrillation (4.2%), paraesthesia, confusion, hyperuricaemia, raised serum creatinine (7.4%), vertigo. | |||
Acute phase of coronary artery syndrome: Class IB | |- | ||
|colspan="6" bgcolor="#E6E6FA"|'''Vitamin K Antagonists''' | |||
|- | |||
| | |||
|Warfarin | |||
|Prevention of thrombotic/ embolic events (esp. after prosthetic valve insertion) | |||
|5-10mg initially then tailored to individual (usually 3-9mg once daily at the same time) | |||
| | |||
|valign="top"|Haemorrhage, nausea, vomiting, diarrhoea, jaundice, hepatic dysfunction, pancreatitis, pyrexia, alopecia, purpura, rash, ‘purple toes’, skin necrosis (increased risk in patients with protein C or protein S deficiency) | |||
|- | |||
| | |||
|Acenocoumarol | |||
|Prevention of thrombotic/ embolic events (esp. after prosthetic valve insertion) | |||
|4mg initially, followed by 1-8mg daily | |||
| | |||
|valign="top"|Haemorrhage, nausea, vomiting, diarrhoea, jaundice, hepatic dysfunction, pancreatitis, pyrexia, alopecia, purpura, rash, ‘purple toes’, skin necrosis (increased risk in patients with protein C or protein S deficiency) | |||
|- | |||
|colspan="6" bgcolor="#E6E6FA"|'''Lipid-Lowering Drugs''' | |||
|- | |||
|rowspan="3"|Statins | |||
|rowspan="3"|Simvastatin, Atorvastatin | |||
|Primary hyper-cholesterolaemia, combined hyperlipidaemia | |||
|Simvastatin: 10-20mg once daily | |||
|Dyslipidaemia: Class IA; Low HDL-C: Class IIbB; Elderly patients with CVD: IB; Elderly patients with no CVD but CV risk factors: IIbB; Type I diabetes: IC; Patients with CKD: IIaC; Transplant patients: Class IIaB; PAD: Class IA; HIV patients: IIaC <cite>Esc2</cite> | |||
Hypertension in diabetics: Class IA; ACS: Class IA <cite>Esc3</cite> | |||
|rowspan="3" valign="top"|Oedema (2.7%), abdominal pain (5.9%), nausea (5.4%), atrial fibrillation (5.7%), constipation (2.2%), gastritis (4.9%), diabetes mellitus (4.2%), myalgia (3.7%), headache (2.5%), insomnia (4.0%), vertigo (4.5%), bronchitis (6.6%), sinusitis (2.3%), eczema (4.5%), urinary tract infection (3.2%) | |||
|- | |||
|Familial hyper-cholesterolaemia | |||
|Simvastatin: 40mg once daily | |||
|HeFH: Class IC <cite>Esc2</cite> | |||
|- | |||
|Prevention of cardiovascular events | |||
|20-40mg once daily | |||
|Class IA <cite>Esc2</cite> | |||
|- | |||
|rowspan="2"|Fibrates | |||
|Gemfibrozil | |||
|Hyperlipidaemias of types IIa, IIb, III, IV and V | |||
|Gemfibrozil: 0.9-1.2mg daily | |||
|Low HDL-C: Class IIbB; Transplant patients (with HTG, low HDL-C): Class IIbC <cite>Esc6</cite> | |||
|Gastro-intestinal disturbances including dyspepsia (19.6%), nausea (4%), abdominal pain (9.8%), diarrhoea (7.2%), vomiting (1.2%); headache (1.2%), fatigue (3.8%), vertigo (1.5%), eczema, rash (1.7%), atrial fibrillation (0.7%), pancreatitis, appendicitis, disturbances in liver function including hepatitis and cholestatic jaundice, dizziness, paraesthesia, sexual dysfunction, thrombocytopenia, anaemia, leucopenia, eosinophilia, bone-marrow suppression, myalgia, myopathy, myasthenia, myositis accompanied by increase in creatine kinase, blurred vision, exfoliative dermatitis, alopecia, and photosensitivity | |||
|- | |||
|Ezetimibe | |||
|Primary and familial hyper-cholesterolaemia | |||
|10mg once daily | |||
|Transplant patients (with high LDL-C): Class IIbC <cite>Esc6</cite> | |||
|Gastro-intestinal disturbance including diarrhoea (4.1%) and abdominal pain (3.0%); headache, fatigue (2.4%); myalgia, arthralgia (3.0%), sinusitis (3.6%), pharyngitis (2.3%), viral infection (2.2%), coughing (2.3%), hypersensitivity reactions including rash, angioedema, and anaphylaxis, hepatitis,pancreatitis, cholelithiasis, cholecystitis, thrombocytopenia, raised creatine kinase, myopathy, and rhabdomyolysis | |||
|} | |||
==References== | |||
<biblio> | |||
#Esc1 pmid=22611136 | |||
#Esc2 pmid=17220161 | |||
#Esc3 pmid=22555213 | |||
#Esc4 pmid=22922416 | |||
#Acc5 pmid=14557344 | |||
#Esc6 pmid=21712404 | |||
</biblio> | |||