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Cardiac Pharmacology: Difference between revisions
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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: | 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.) | {| class="wikitable" border="0" cellpadding="0" cellspacing="0" | ||
CYP2C19 Clopidogrel | |- | ||
!Enzyme | |||
!Substrates (e.g.) | |||
!Inhibitors (e.g.) | |||
!Inducers (e.g.) | |||
|- | |||
|CYP2C19 | |||
|Clopidogrel | |||
Propranolol | Propranolol | ||
Warfarin Moclobemide | Warfarin | ||
|Moclobemide | |||
Chloramphenicol | Chloramphenicol | ||
Many anti-convulsants (Valproate) | Many anti-convulsants (Valproate) | ||
Proton pump inhibitors (Omeprazole) | Proton pump inhibitors (Omeprazole) | ||
|Rifampicin | |||
Carbamazepine | Carbamazepine | ||
Prednisone | Prednisone | ||
CYP3A4 Donepezil | |- | ||
|CYP3A4 | |||
|Donepezil | |||
Statins (Atorvastatin) | Statins (Atorvastatin) | ||
Ca-channel blockers (Nifedipine) | Ca-channel blockers (Nifedipine) | ||
| Line 225: | Line 234: | ||
Salmeterol | Salmeterol | ||
Warfarin | Warfarin | ||
Clopidogrel Protease inhibitors (Ritonavir) | Clopidogrel | ||
|Protease inhibitors (Ritonavir) | |||
Macrolides (Clarithromycin) | Macrolides (Clarithromycin) | ||
Chloramphenicol | Chloramphenicol | ||
| Line 232: | Line 242: | ||
Cimetidine | Cimetidine | ||
Some azole anti-fungals (Ketaconazole) | Some azole anti-fungals (Ketaconazole) | ||
Grapefruit juice Some anti-convulsants (Carbamazepine) | Grapefruit juice | ||
|Some anti-convulsants (Carbamazepine) | |||
Baribiturates (Phenobarbital) | Baribiturates (Phenobarbital) | ||
St. John’s Wort | St. John’s Wort | ||
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Glucocorticoids | Glucocorticoids | ||
Modafinil | Modafinil | ||
|- | |||
CYP2C9 Fluvastatin | |CYP2C9 | ||
|Fluvastatin | |||
Angiotensin receptor II agonists (losartan) | Angiotensin receptor II agonists (losartan) | ||
Warfarin | Warfarin | ||
Torasemide Some azole anti-fungals (Fluconazole) | Torasemide | ||
|Some azole anti-fungals (Fluconazole) | |||
Amiodarone | Amiodarone | ||
Antihistamines (Cyclizine) | Antihistamines (Cyclizine) | ||
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Fluvoxamine | Fluvoxamine | ||
Probenecid | Probenecid | ||
Sertraline Rifampicin | Sertraline | ||
|Rifampicin | |||
Secobarbital | Secobarbital | ||
CYP2D6 β-blockers (Propranolol) | |- | ||
|CYP2D6 | |||
|β-blockers (Propranolol) | |||
Class I anti-arrythmics (Flecainide) | Class I anti-arrythmics (Flecainide) | ||
Donepezil | Donepezil | ||
|SSRIs (Fluoxetine) | |||
Quinidine | Quinidine | ||
Sertraline | Sertraline | ||
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Metoclopramide | Metoclopramide | ||
Ranitidine | Ranitidine | ||
Mibefradil Rifampicin | Mibefradil | ||
|Rifampicin | |||
Dexamethasone | Dexamethasone | ||
Glutethimide | 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 | 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 General Use of Medicine] | ||
Cardiovascular Drugs | {| class="wikitable" border="0" cellpadding="0" cellspacing="0" | ||
Drug Category Drug Type | |- | ||
Examples (generic name) | |+Cardiovascular Drugs | ||
|- | |||
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). | !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 | Resistant Hypertension Furosemide: 40-80mg once daily ESC Guidelines (European Heart Journal | ||
doi:10.1093/eurheartj/ehs104): | doi:10.1093/eurheartj/ehs104): | ||