Cardiac Pharmacology: Difference between revisions

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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:
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
{| class="wikitable" border="0" cellpadding="0" cellspacing="0"
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
!Property
EC50 The concentration of drug needed to elicit a response halfway between zero and maximal responses. µg/ml (EC50)
!Description
            y=bottom+  (Top-Bottom)/(1+ [x/EC50]  Hill Coefficient)
!Standard units (Abbreviation)
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
!Formula
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)
|Dose
100 ×  (AUC (po)×D (iv))/(AUC (iv)×D (po))
|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
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
|Cmax or Cmin
Half-life The time it takes for a drug to reach half its original concentration h (t1/2) ln(2) / Ke
|The maximum (Cmax) /  minimum (Cmin) plasma drug concentration reached following drug administration
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
|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
==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:
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
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|-
!Drug
!Drugs that ↑drug action
!Drugs that ↓ drug action
|-
|Digoxin
|Diuretics
Antiarrhythmics
Antiarrhythmics
Macrolide antibiotics
Macrolide antibiotics
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Benzodiazepines
Benzodiazepines
Amiodarone
Amiodarone
Verapamil Rifampicin
Verapamil
|Rifampicin
Antacids (liquid)
Antacids (liquid)
Warfarin Furosemide
|-
|Warfarin
|Furosemide
Amiodarone
Amiodarone
Sulfa, macrolide and quinolone  
Sulfa, macrolide and quinolone  
  antibiotics
antibiotics
NSAIDs
NSAIDs
Azathioprine
|Azathioprine
Phenobarbitone
Phenobarbitone
Carbamazepine
Carbamazepine
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Vitamin K
Vitamin K
Raloxifene
Raloxifene
Clopidogrel Rifampicin
|-
|Clopidogrel
|Rifampicin
Caffeine
Caffeine
Methylxanthines
Methylxanthines
Phosphodiesterase inhibitors Statins
Phosphodiesterase inhibitors
|Statins
Calcium channel blockers
Calcium channel blockers
Warfarin
Warfarin
Proton pump inhibitors
Proton pump inhibitors
Furosemide
|-
NSAIDs
|Furosemide
|
|NSAIDs
Phenytoin
Phenytoin
Colesevelam
Colesevelam
ACE Inhibitors NSAIDs
|-
|ACE Inhibitors
|NSAIDs
Probenecid
Probenecid
Calcium channel blockers Indomethacin
Calcium channel blockers
|Indomethacin
Antacids
Antacids
β-blockers Amiodarone
|-
|β-blockers
|Amiodarone
Calcium channel blockers
Calcium channel blockers
Diltiazem
Diltiazem
Phenoxybenzamine Phenobarbital
Phenoxybenzamine
|Phenobarbital
Rifampicin
Rifampicin
Cimetidine
Cimetidine
Antacids (liquid)
Antacids (liquid)
NSAIDs
NSAIDs
Statins Amiodarone
|-
|Statins
|Amiodarone
Verapamil
Verapamil
Fibrates
Fibrates
Amprenavir
Amprenavir
Diltiazem Nevirapine
Diltiazem
|Nevirapine
Rifampicin
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:  
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.)
Enzyme Substrates (e.g.) Inhibitors (e.g.) Inducers (e.g.)
CYP2C19 Clopidogrel
CYP2C19 Clopidogrel
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