Cardiac Pharmacology: Difference between revisions

Jump to navigation Jump to search

Cardiac Pharmacology (view source)

Revision as of 17:14, 23 May 2013

34,753 bytes added ,  23 May 2013
no edit summary
(Created page with "{{DevelopmentPhase}}")
 
No edit summary
Line 1: Line 1:
{{DevelopmentPhase}}
{{DevelopmentPhase}}
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==
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.
'''Angiotensin II causes increases in blood pressure by actions at various sites:'''
*'''Adrenal Glands:''' Angiotensin II augments release of the steroid hormone aldosterone, which acts locally to augment sodium retention and potassium secretion from the kidney. The net effect of this is water retention, thus restoring fluid balance.
*'''Kidneys:''' Angiotensin II also increases sodium retention via direct actions on renal proximal tubules, as well as affecting glomerular filtration rate and renal blood flow.
*'''Cardiovascular System:''' Angiotensin II is a potent endogenous vasoconstrictor, causing resistance arteries and veins to constrict, raising blood pressure. Furthermore in both the blood vessels and the heart, prolonged increases in Angiotensin II encourage cell growth and resultant hypertrophy.
*'''Central Nervous System:''' In the brain, Angiotensin II acts on the posterior pituitary gland, stimulating release of antidiuretic hormone (ADH, also known as Arginine Vasopressin (AVP)). ADH increases water reabsorption in the renal collecting ducts. Angiotensin II also acts on the subfornical organ within the brain to cause increased ''thirst'', encouraging water intake.
Chronic activation of the RAAS system can lead to deleterious remodelling and increased inflammation in the heart, vasculature and kidneys, as well as hypertension and chronic kidney disease.
==Neural Control of the Cardiovascular 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.
====Vasculature====
The predominant receptor subtype present in blood vessels is the α1-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====
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 β-receptor subfamily and include β1 and β3 receptors. Catecholamine binding to β1-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 β3-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.
===Parasympathetic Nervous System===
The parasympathetic system relies on the binding of the neurotransmitter acetylcholine (Ach) to muscarinic receptors, and has various roles throughout the body.
====Vasculature====
Although blood vessels do express muscarinic receptors, they do not receive cholinergic innervation; however application of exogenous Ach results in a swift and profound vasodilation.
====Heart====
Activation of muscarinic receptors (M2-subtype) in the heart by Ach released from the vagus nerve causes a reduction in cardiac output via opposite effects to adrenergic stimulation: negative chronotropic effects and decreases in AV node conduction as well as decreasing the force of atrial contractions.
==Platelet/Clotting System==
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.
There are several conditions in which abnormal clotting can be damaging to the body; excess clotting can lead to vascular blockage and ischaemia or stroke; less commonly, deficient clotting can lead to excess blood loss, for example in haemophilia. To combat these diseases, there are drugs that modulate the clotting process.
===Anti-coagulants===
Drugs that prevent clotting (anti-coagulants) are important in those with an increased risk of clotting-mediated damage such as a stroke or ischaemia.
As well being an analgesic and anti-pyretic, Aspirin is an anti-thrombotic agent given in low doses to those at risk of damage from clotting (e.g. following a heart attack). Aspirin’s anti-coagulant actions come from its suppression of key pro-clotting factors such as prostaglanding and thromboxanes via irreversible inactivation of the PTGS cyclooxygenase enzyme. This suppression of factors such as thromboxane A<sub>2</sub> reduces platelet aggregation and thus prevents clot formation.
P2Y<sub>12</sub> inhibitors such as clopidogrel exert their anti-coagulant effect via inhibition of the P2Y<sub>12</sub> subtype of the platelet ADP receptor. By blocking P2Y<sub>12</sub>, these drugs prevent activation of platelets and the formation of the fibrin network needed for clotting. 
Drugs such as abciximab and tirofiban prevent clotting via inhibition of the glycoprotein IIb/IIIa receptor preventing both platelet activation and aggregation.
==Pharmacokinetics==
When administering drugs to a patient, it is crucial to know several facts about the drug in order to maximise efficacy and minimise side-effects/toxicity. These include information about what dose is effective, how long the drug remains active in the body, how quickly it is broken down/removed from the body, and how easily the body can absorb/use that drug. The following table details these pharmacokinetic properties and how they are calculated:
Property Description Standard units (Abbreviation) Formula
Dose Amount of active drug given to patient mg (D) Drug Specific (From clinical studies)
Concentration Amount of drug in a given plasma volume µg/ml (C) = D / Vd
EC50 The concentration of drug needed to elicit a response halfway between zero and maximal responses. µg/ml (EC50)
            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. L (Vd) D / C
Elimination Constant (Rate) The rate at which the drug is removed from the body. h-1 (Ke) ln(2) / t1/2  or  CL / Vd
Bioavailability How much of the administered dose is available for actual use by the body. no units as expressing a fraction (f)
100 ×  (AUC (po)×D (iv))/(AUC (iv)×D (po))
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 µg/ml (Cmax or Cmin) Identified via direct measurement of plasma C
tmax The time it takes for a drug to reach Cmax following administration h (tmax) Identified via direct measurement of plasma C over time
Half-life The time it takes for a drug to reach half its original concentration h (t1/2) ln(2) / Ke
Drug Clearance The volume of plasma cleared of the drug over a set time l/h (CL) Vd x Ke  or  D / Area under curve
Common Drug-Drug Interactions
It is important to be aware of the interactions that can occur between concomitantly administered drugs, as they may effect efficacy and/or toxicity, or produce adverse side effects. Such interactions could for example affect drug absorption, drug bioavailability or efficacy, or combine to produce unwanted metabolites, as well as possibly having effects on clinical analyses. If a combination of two drugs decreases the effect of one or both of them, the interaction is termed an antagonistic effect; however if, conversely, a combination of two drugs enhances the effect of one or both of them, the interaction is termed a synergistic effect. Drugs that act on the cardiovascular system are high in interactivity, which is an issue as cardiovascular patients normally receive more than one drug. Some common drug—drug interactions related to cardiovascular drugs are listed below:
Drug Drugs that ↑drug action Drugs that ↓ drug action
Digoxin Diuretics
Antiarrhythmics
Macrolide antibiotics
Cholestyramine, neomycin
Keto- and intraconazole
Calcium antagonists
Cyclosporine, indomethacin
HMG CoA reductase inhibitors
Benzodiazepines
Amiodarone
Verapamil Rifampicin
Antacids (liquid)
Warfarin Furosemide
Amiodarone
Sulfa, macrolide and quinolone
  antibiotics
NSAIDs
Azathioprine
Phenobarbitone
Carbamazepine
Dexamethasone
Prednisolone
Rifampicin
Vitamin K
Raloxifene
Clopidogrel Rifampicin
Caffeine
Methylxanthines
Phosphodiesterase inhibitors Statins
Calcium channel blockers
Warfarin
Proton pump inhibitors
Furosemide
NSAIDs
Phenytoin
Colesevelam
ACE Inhibitors NSAIDs
Probenecid
Calcium channel blockers Indomethacin
Antacids
β-blockers Amiodarone
Calcium channel blockers
Diltiazem
Phenoxybenzamine Phenobarbital
Rifampicin
Cimetidine
Antacids (liquid)
NSAIDs
Statins Amiodarone
Verapamil
Fibrates
Amprenavir
Diltiazem Nevirapine
Rifampicin
There are several mechanisms by which drugs are broken down by the body, usually via degradation by enzymes. One common family of enzymes involved in drug metabolismis the cytochrome P450 (CYP) family; a large, diverse group of enzymes that encourage oxidation of a variety of substrates, both endogenous (e.g. steroid hormones) and exogenous (e.g.  toxins and drugs). CYP enzymes account for up to 75% of drug metabolism, aiding some drugs to form their active compounds but mostly deactivating drugs into inactive metabolites to be excreted. CYP enzymes can influence drug actions in several ways; they can increase drug metabolism (either increasing action via formation of the active by-product or decreasing action by metabolism of the active drug) or their action can be inhibited by drugs that compete for access to the CYP enzymes active site, preventing the normal interaction between drug and enzyme. Many drugs exert their interactions with other drugs viainterference with the CYP system. For example, if Drug A is metabolised by CYP and Drug B inhibits CYP activity, co-administration will result in a decreased bioavailability of Drug A. In humans there are 18 families and 43 subfamilies of the CYP group of enzymes, which target different substrates. Some CYP enzymes important in cardiovascular medicine, their cardiovascular-drug substrates and some of their interactions are shown in the table below:
Enzyme Substrates (e.g.) Inhibitors (e.g.) Inducers (e.g.)
CYP2C19 Clopidogrel
Propranolol
Warfarin Moclobemide
Chloramphenicol
Many anti-convulsants (Valproate)
Proton pump inhibitors (Omeprazole)
Rifampicin
Carbamazepine
Prednisone
CYP3A4 Donepezil
Statins (Atorvastatin)
Ca-channel blockers (Nifedipine)
Amiodarone
Dronedarone
Quinidine
PDE5 Inhibitors (Sildenafil)
Kinins
Caffeine
Eplerenone
Propranolol
Salmeterol
Warfarin
Clopidogrel Protease inhibitors (Ritonavir)
Macrolides (Clarithromycin)
Chloramphenicol
Nefazodone
Some Ca-channel blockers (Verapamil)
Cimetidine
Some azole anti-fungals (Ketaconazole)
Grapefruit juice Some anti-convulsants (Carbamazepine)
Baribiturates (Phenobarbital)
St. John’s Wort
Some reverse transcriptase inhibitors (Efavirenz)
Some Hypoglycaemics (Pioglitazone)
Glucocorticoids
Modafinil
CYP2C9 Fluvastatin
Angiotensin receptor II agonists (losartan)
Warfarin
Torasemide Some azole anti-fungals (Fluconazole)
Amiodarone
Antihistamines (Cyclizine)
Chloramphenicol
Fluvastatin
Fluvoxamine
Probenecid
Sertraline Rifampicin
Secobarbital
CYP2D6 β-blockers (Propranolol)
Class I anti-arrythmics (Flecainide)
Donepezil
SSRIs (Fluoxetine)
Quinidine
Sertraline
Terbinafine
Amiodarone
Cinacalcet
Ritonavir
Antipsychotics (Haloperidol)
Antihistamines (Promethazine)
Metoclopramide
Ranitidine
Mibefradil Rifampicin
Dexamethasone
Glutethimide
In addition to drug-drug interactions, the actions of many drugs are also affected by food or drink. For example, care should be taken with alcohol consumption with many kinds of drugs, as it can put stress on the liver which is already working hard to metabolise drugs in the body. Grapefruit juice too can cause issues, as it is known to inhibit CYP3a. For more information of interactions between drugs and food/drinks see this guide: http://www.fda.gov/downloads/Drugs/ResourcesForYou/Consumers/BuyingUsingMedicineSafely/EnsuringSafeUseofMedicine/GeneralUseofMedicine/UCM229033.pdf
Cardiovascular Drugs
Drug Category Drug Type
Examples (generic name)
Indications Typical Dosage Guidelines/Class of Indication Side Effects (Prevalence %)
Anti-hypertensives Diuretics Furosemide Oedema Furosemide: 20-40mg once daily 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 ESC Guidelines (European Heart Journal
doi:10.1093/eurheartj/ehs104):
Hypertension in symptomatic (NYHA class II-IV) HF and LVD: Class IC
ACE Inhibitors Captopril, Monopril Hypertension Captopril: 12.5mg twice daily ESC and EASD Guidelines (European Heart Journal doi: 10.1093/eurheart/ehl261)
Hypertension: Class IA
ESC Guidelines (European Heart Journal
doi:10.1093/eurheartj/ehs104):
Hypertension in symptomatic (NYHA class II-IV) HF and LVD: Class IA
ESC Guidelines: (European Heart Journal
doi:10.1093/eurheartj/ehs092):
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 ESC Guidelines (European Heart Journal (2012) 33, 2569–2619
doi:10.1093/eurheartj/ehs215):
Post STEMI: Class IA
ESC and EASD Guidelines (European Heart Journal doi: 10.1093/eurheart/ehl261)
Diabetic patients: Class IC
ESC Guidelines (European Heart Journal
doi:10.1093/eurheartj/ehs104):
Symptomatic (NYHA class II-IV) HF: Class IA
Acute heart failure with ACS: Class IA
Prophylaxis Following MI Captopril: 6.25mg once daily
Diabetic nephropathy Captopril: 75-100mg once daily
Angiotensin Receptor Blockers Losartan. Candesartan Hypertension Losartan: 50mg once daily ESC and EASD Guidelines (European Heart Journal doi: 10.1093/eurheart/ehl261)
Hypertension: Class IA
ESC Guidelines: (European Heart Journal
doi:10.1093/eurheartj/ehs092):
Hypertension in diabetics: Class IA gastro-intestinal disturbances (<3%), dizziness (14%), angina, palpitation, oedema, dyspnoea, headache (14%), malaise, urticaria, pruritus, rash;
Left ventricular hypertrophy Losartan: 12.5-150mg daily ESC Guidelines (European Heart Journal (2012) 33, 2569–2619
doi:10.1093/eurheartj/ehs215):
LVH:  Class IB
Diabetic nephropathy Losartan: 50mg daily
Alpha Blockers Prazosin, Doxazosin Hypertension Prazosin: 1-10mg 2-3 times daily 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
Beta Blockers Atenolol, Propranolol Hypertension Atenolol: 25-50mg daily 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 ESC and EASD Guidelines (European Heart Journal doi: 10.1093/eurheart/ehl261)
ACS: Class IIaB
ESC Guidelines (European Heart Journal
doi:10.1093/eurheartj/ehs104):
Angina in symptomatic (NYHA class II-IV) HF and LVD: Class IA
Arrhythmias Atenolol: 50-100mg daily ESC Guidelines (European Heart Journal (2012) 33, 2569–2619
doi:10.1093/eurheartj/ehs215):
Atrial fibrillation: Class IA
Polymorphic VT: Class IB
ESC Guidelines (European Heart Journal
doi:10.1093/eurheartj/ehs104):
Symptomatic (NYHA class II-IV) HF, LVD and AF: Class IA
Management of VA in HF: Class IA
ACC/AHA/ESC Guidelines (Blomström-Lundqvist and Scheinman et al. 2003):
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
Migraine Atenolol: 50-200mg daily
Calcium Channel Blockers Nifedipine, Verapamil, Diltiazem Hypertension Nifedipine: 20-30mg once daily ESC Guidelines (European Heart Journal
doi:10.1093/eurheartj/ehs104):
Hypertension in symptomatic (NYHA class II-IV) HF and LVD: Class IA 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 ESC Guidelines (European Heart Journal
doi:10.1093/eurheartj/ehs104):
Angina in symptomatic (NYHA class II-IV) HF and LVD: Class IIaA
Anti-Arrhythmics Class I (sodium channel blockers) Flecainide, Lidocaine, Procainamide Ventricular Arrhythmias Flecainide: 50-100mg twice daily ESC Guidelines(European Heart Journal (2012) 33, 2569–2619
doi:10.1093/eurheartj/ehs215):
Sustained VT and VF: Class IIbC
ACC/AHA/ESC Guidelines (Blomström-Lundqvist and Scheinman et al. 2003):
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 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 ESC Guidelines(European Heart Journal (2012) 33, 2569–2619
doi:10.1093/eurheartj/ehs215):
Sustained VT and VF: Class IIaC
Polymorphic VT: Class IC
ESC Guidelines (European Heart Journal
doi:10.1093/eurheartj/ehs104):
Management of VA in HF: Class IA
Prevention of VA in HF: Class IIbB
ACC/AHA/ESC Guidelines (Blomström-Lundqvist and Scheinman et al. 2003):
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 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
Class IV (Calcium channel blockers) (See above) (See above) (See above) (See above)
- Digoxin Supra-ventricular Arrhythmias Acute: 0.75-1.5mg over 24 hours
Maintenance: 125-150µg daily ACC/AHA/ESC Guidelines (Blomström-Lundqvist and Scheinman et al. 2003):
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 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 ESC Guidelines (European Heart Journal
doi:10.1093/eurheartj/ehs104):
Symptomatic (NYHA class II-IV) HF: Class IIbB
ESC Guidelines Symptomatic (NYHA class II-IV) HF, LVD and AF: Class IB
Acute HF with AF and VT: Class IC
Anti-platelet Drugs - Aspirin Prevention of thrombotic cerebro- or cardio-vascular disease 75mg once/day ESC and EASD Guidelines (European Heart Journal doi: 10.1093/eurheart/ehl261)
Prevention in AF: Class IC
Prevention in diabetic patients: IIaB
ESC Guidelines (European Heart Journal
doi:10.1093/eurheartj/ehs104):
Prevention in Symptomatic (NYHA class II-IV) HF and AF: Class IIA
ESC Guidelines: (European Heart Journal
doi:10.1093/eurheartj/ehs092):
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
ESC Guidelines: (European Heart Journal
doi:10.1093/eurheartj/ehs092):
Post-MI: Class Ia
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%).
Pain / pyrexia 300-600mg every 4-6 hours as necessary
- Clopidogrel Prevention of thrombotic events (esp. when warfarin not tolerated) 75mg once/day ESC and EASD Guidelines (European Heart Journal doi: 10.1093/eurheart/ehl261)
Prevention in diabetic patients: IIaB
Primary and secondary prevention of stroke: Class IB
ESC Guidelines (European Heart Journal
doi:10.1093/eurheartj/ehs104):
Prevention in Symptomatic (NYHA class II-IV) HF and AF: Class IIA
Prevention in Symptomatic (NYHA class II-IV) HF and AF: Class IIA
ESC Guidelines: (European Heart Journal
doi:10.1093/eurheartj/ehs092):
Acute phase of coronary artery syndrome: Class IB
Non-cardioembolic cerebral ischaemic events: Class IA 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
Acute myocardial infarction 300mg daily initially then 75mg once/day ESC Guidelines(European Heart Journal (2012) 33, 2569–2619
doi:10.1093/eurheartj/ehs215):
Post STEMI: Class IA
Acute coronary syndrome 300mg daily initially then 75mg once/day ESC and EASD Guidelines (European Heart Journal doi: 10.1093/eurheart/ehl261)
ACS: Class IIaC
- Prasugrel Prevention of thrombotic events. 60mg bolus then 5-10mg once daily ESC Guidelines (European Heart Journal
doi:10.1093/eurheartj/ehs104):
Prevention in Symptomatic (NYHA class II-IV) HF and AF: Class IIA
ESC Guidelines: (European Heart Journal
doi:10.1093/eurheartj/ehs092):
Acute phase of coronary artery syndrome: Class IB
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 ESC Guidelines (European Heart Journal
doi:10.1093/eurheartj/ehs104):
Prevention in Symptomatic (NYHA class II-IV) HF and AF: Class IIA
ESC Guidelines: (European Heart Journal
doi:10.1093/eurheartj/ehs092):
Acute phase of coronary artery syndrome: Class IB
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
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) 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 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)
Lipid-Lowering Drugs Statins Simvastatin, Atorvastatin Primary hyper-cholesterolaemia, combined hyperlipidaemia Simvastatin: 10-20mg once daily ESC and EASD Guidelines (European Heart Journal doi: 10.1093/eurheart/ehl261)
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
ESC Guidelines: (European Heart Journal
doi:10.1093/eurheartj/ehs092):
Hypertension in diabetics: Class IA
ACS: Class IA 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 ESC and EASD Guidelines (European Heart Journal doi: 10.1093/eurheart/ehl261)
HeFH: Class IC
Prevention of cardiovascular events 20-40mg once daily ESC and EASD Guidelines (European Heart Journal doi: 10.1093/eurheart/ehl261):
Class IA
Fibrates Gemfibrozil Hyperlipidaemias of types IIa, IIb, III, IV and V Gemfibrozil: 0.9-1.2mg daily ESC and EAS Guidelines (European Heart Journal (2011) 32, 1769–1818
doi:10.1093/eurheartj/ehr158)
Low HDL-C: Class IIbB
Transplant patients (with HTG, low HDL-C): Class IIbC 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 ESC and EAS Guidelines (European Heart Journal (2011) 32, 1769–1818
doi:10.1093/eurheartj/ehr158)
Transplant patients (with high LDL-C): Class IIbC 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
NiloferT
467

edits

Retrieved from "https://www.textbookofcardiology.org/wiki/Special:MobileDiff/2398"

Navigation menu