A drug concentration, however, can only be regarded as a guide around which to alter the dosage according to the patient's clinical condition. Serum drug concentration monitoring is particularly useful to ensure compliance and in helping to manage combinations of antiepileptic drugs that invariably interact.
Why is drug concentration important in clinical practice?
The drug concentration is complementary to and not a substitute for clinical judgement so it is important to treat the individual patient and not the laboratory value. Drug concentrations may be used as surrogates for drug effects so therapeutic drug monitoring may assist with dose individualisation.
What factors should be considered when interpreting drug concentration measurements?
When interpreting drug concentration measurements, factors that need to be considered include the sampling time in relation to the dose, the dosage history, the patient's response, and the desired clinical targets.
Why is it important to measure plasma concentration of a drug?
On the other hand, if it is difficult to measure the therapeutic effects of a drug, then measuring the plasma concentration helps to tailor the dose within the appropriate therapeutic range.
What is drug concentration in blood test?
Drug Concentration. Drug concentration is most often measured in blood (using serum, plasma or whole blood), since this is the main connective tissue that equilibrates with all the other tissues of the body.
What is the importance of drug concentration?
The drug concentration has a direct effect on the nasal drug absorption, that is, increase in the concentration of drug causes better absorption at the site of administration. This is more important for the drugs primarily having a passive diffusion mechanism of absorption of the drug.
Why is the drug dosing important in treatment?
The administered dose of a drug modulates whether patients will experience optimal effectiveness, toxicity including death, or no effect at all. Dosing is particularly important for diseases and/or drugs where the drug can decrease severe morbidity or prolong life.
What is drug concentration?
Drug concentration in the compartment is. defined as the amount of drug in a given volume, such. as mg/L: 1-1. Volume of distribution (V) is an important indicator of the extent of drug distribution into body fluids and tis- sues.
What is effective concentration of drug?
The effective drug concentration is the concentration of a drug at the receptor site. In patients, drug concentrations are more readily measured in the blood.
What is the purpose of therapeutic drug monitoring?
Therapeutic drug monitoring (TDM) is testing that measures the amount of certain medicines in your blood. It is done to make sure the amount of medicine you are taking is both safe and effective.
What are the things to consider in giving dosages to patients?
The Five Rights are:The right dose.The right medication.The right patient.The right route.The right time.
How does drug effect vary with drug concentration?
1), there is initially little change in effect as the concentration decreases. In this case, as drug concentration falls from 100 mg/L to 4 mg/L, the effect only falls from 99% to 80% of maximal effect. The decrease in effect is then approximately linear with time between 80% and 20% of maximal effect.
What is the importance of steady state concentration?
Within the PK, the steady-state is a concept of fundamental importance in pharmacology. It describes a dynamic equilibrium in which drug concentrations consistently stay within therapeutic limits for long, potentially indefinite, periods.
What is the minimum concentration of the drug for therapeutic effect?
Minimum effective concentration (MEC) is the minimum plasma concentration of a drug needed to achieve sufficient drug concentration at the receptors to produce the desired pharmacologic response, if drug molecules in plasma are in equilibrium with drug molecules in the various tissues (Figure 1.3).
What is concentration effect relationship?
Concentration–effect relationships concerns groups of patients and indicate the probability of a given response (therapeutic/toxic) at a given concentration.
How do you find effective concentration?
0:034:44Acids & Bases Fundamentals (14 of 35) Effective Concentration - YouTubeYouTubeStart of suggested clipEnd of suggested clipAnd the concentration of chlorine ion will be 0.1 moles per liter. And so the uh the 0.1 molarMoreAnd the concentration of chlorine ion will be 0.1 moles per liter. And so the uh the 0.1 molar hydrochloric acid solution will have a ph equal to 1 when we take the log of 0.1.
Why are drug concentrations measured in the blood?
The drug concentrations in the blood or plasma are routinely measured as surrogates for concentrations at the site of action, due to ease of accessibility. While the drug concentration in systemic circulation may somewhat reflect the concentration at the site of action when the target is in a peripheral, more accessible, tissue, their use as a surrogate for brain drug concentrations can be misleading. This is important particularly in the context of brain compared to other organs due to presence of the BBB that can severely restrict drug distribution to the brain [13, 14]. To differentiate the bioavailability estimated using drug concentrations at the site of action, brain in this discussion, from the traditional bioavailability determined using the systemic concentrations, we would like to use the term ‘targeted bioavailability’ [48] ( Fig. 2 ). Various factors can influence a compound's targeted bioavailability in the brain such as BBB permeability, drug transport by transport proteins, drug metabolism, protein binding, protein expression, receptor affinity, gene regulation and dosage regimen [48]. The findings from various studies testing different anti-cancer agents indicate that the concentrations of a drug in the brain can be remarkably different from systemic concentrations [13, 14, 49]. The relevance of the concentration–effect relationship should be judiciously assessed when using systemic concentrations, as the variability in pharmacodynamic measurements (i.e., drug response, and toxicity) may not be reflected by the variability observed in the pharmacokinetic measurements [48]. Therefore, the measurement of target site concentrations, when possible, is more appropriate to evaluate a pharmacokinetic–pharmacodynamic (PK–PD) relationship.
What is the most important determinant of clinical response to a drug?
Drug concentration is amongst the most important determinants of clinical response to a drug. Variability in pharmacokinetic profiles makes drug concentration s unpredictable: the greater the variability, the greater the magnitude of this problem.
What is the concentration effect?
The concentration effect results from two factors: a concentrating effect and an augmentation in effective ventilation. When an inhalational anesthetic is administered in a low concentration (1 vol%), uptake of half of this anesthetic results in a concentration of approximately 0.5 vol%. The net effect of the uptake of this small volume on the alveolar gas volume is small; ventilation is minimally affected. If, however, the anesthetic is administered in an 80 vol% concentration, uptake of half of the anesthetic contracts the residual gas volume. The net concentration is not 50 vol% of the original concentration but rather 66 vol%, because of the concentrating effect on the smaller residual gas volume. This effect, along with the additional ventilation that follows the contracted alveolar volume, leads to a concentration that exceeds 70 vol%. The only anesthetic administered today that is subject to the concentration effect is nitrous oxide.
How does nasal concentration affect the brain?
The drug concentration has a direct effect on the nasal drug absorption , that is, increase in the concentration of drug causes better absorption at the site of administration. This is more important for the drugs primarily having a passive diffusion mechanism of absorption of the drug. But, higher concentrations of the drug when administered in large volume can have opposite effect on the absorption of the drug; which may be as a result of local adverse effects. In some cases, it may cause nasal mucosa damage. The delivery of the dosing volume and their drug concentration is restricted by the size and shape of the nasal cavity. A volume of 25–200 µL/nostril and an upper limit of 25 mg/dose are recommended ( Kushwaha et al., 2011 ).
How does the dosing interval affect steady state concentration?
1. Dosing interval. The dosing interval affects steady-state concentration in a proportional way. The more frequently the drug is given, the higher the steady-state concentration values. 2. Dose. In the same way, higher doses will increase the C ss values, and lower doses will decrease them. The dose required to reach and maintain steady state ...
How many doses are left at the end of the dosing interval?
As a result, drug concentrations in the body remain constant (steady). Another way to think about steady state: After Dose 1: There are 0.5 doses left at the end of the dosing interval. This means we’re at 50% steady state.
How long does it take for a drug to reach steady state?
For most drugs, the time to reach steady state is four to five half-lives if the drug is given at regular intervals—no matter the number of doses, the dose size, or the dosing interval. A half-life is how long it takes for half of the drug to be eliminated from the body.
What is loading dose?
A loading dose is a higher dose administered on treatment initiation. It will still take the usual four to five half-lives to reach steady state, but the initial concentration will be closer to the eventual steady-state concentration—which means the therapeutic effect will happen faster.
What does CL mean in medical terms?
Drug clearance (CL) dictates the rate at which a drug is eliminated from the body. The slower the clearance, the more of the drug will remain in the system and the higher the C ss (and vice versa).
Can steady state concentration be affected by weight?
Steady-state concentration can be affected by various factors, from the patient’s weight to the frequency of doses, and while you can speed up the therapeutic effects of a drug with a loading dose, you can’t speed up the time to steady state.
Where is drug concentration measured?
The drug concentration is usually measured in blood; however, it can also be measured in other body fluids like sweat, urine, and saliva. Therapeutic drug monitoring is used for treatment as well as for diagnostic purposes. It is easier to correlate the relationship between the drug’s therapeutic or adverse effect on its concentration in the blood, ...
What drugs are used for drug monitoring?
Some classes of drugs which are already being used for therapeutic drug monitoring include: Anti-arrhythmics - e.g., digoxin - for heart failure. Anti-maniacs or mood stabilizers - e.g., lithium and tricyclic antidepressants– for acute and maintenance dose for psychotic disorders. Immunosuppressants - e.g., sirolimus.
What is a suitable candidate for therapeutic drug monitoring?
A drug becomes a suitable candidate for therapeutic drug monitoring if it meets the following criteria: The therapeutic effect cannot be readily assessed based on clinical observation, e.g., for anticonvulsants like phenytoin or antidepressants, the relationship between dose and plasma concentration is unpredictable.
What is therapeutic drug monitoring?
Therapeutic drug monitoring helps in designing patient-specific dosage regimen ; it aids in enhancing the efficacy of drugs, to reduce the toxicity of drugs and for diagnostic purposes, by individualizing drug therapy.
What is TDM in medicine?
Therapeutic drug monitoring (TDM) is the practice of measuring the concentration of drug in the bloodstream, at pre-defined intervals. It helps to individualize the dosage regimen for patients and thus maintain the desired level of drug substance in patients’ body. The drug concentration is usually measured in blood; however, ...
What is therapeutic failure?
Therapeutic failure. Wide variation in metabolism of drugs. A poorly defined clinical endpoint. For diagnosis of suspected toxicity and to detect drug abuse. The drug assay methods are expensive; hence, it is important to understand the benefits of therapeutic drug monitoring and its advantage for that drug.
Can therapeutic effects be assessed?
The therapeutic effect cannot be readily assessed based on clinical observation, e.g., for anticonvulsants like phenytoin or antidepressants, the relationship between dose and plasma concentration is unpredictable. Proven range of target drug concentration in blood.
Why is drug monitoring important?
For selected drugs therapeutic drug monitoring aims to enhance drug efficacy, reduce toxicity or assist with diagnosis. Despite its apparent advantages, it has inherent limitations. Some large hospitals have services which provide support with drug monitoring and interpretation of results.
What is the purpose of monitoring therapeutic drugs?
The monitoring of therapeutic drugs involves measuring drug concentrations in plasma, serum or blood. This information is used to individualise dosage so that drug concentrations can be maintained within a target range. 1
Why is drug assay important?
Drug assays are costly, so the reason for monitoring and the additional information to be gained (if any) should be carefully considered. For some drugs, therapeutic drug monitoring helps to increase efficacy (vancomycin), to decrease toxicity (paracetamol) and to assist diagnosis (salicylates). Routine monitoring is not advocated for most drugs. Only clinically meaningful tests should be performed. 1
How long should digoxin be monitored?
Correct sample timing should also take into account absorption and distribution. For example, digoxin monitoring should not be performed within six hours of a dose, because it will still be undergoing distribution and so plasma concentrations will be erroneously high. 1-3.
What is therapeutic drug monitoring?
Therapeutic drug monitoring involves not only measuring drug concentrations, but also the clinical interpretation of the result. This requires knowledge of the pharmacokinetics, sampling time, drug history and the patient's clinical condition.
What are the limitations of drug monitoring?
Apart from the limited number of drugs amenable to therapeutic drug monitoring, there are also inherent limitations, including the scientific accuracy of the drug assays, laboratory variability in reporting, limited accessibility in rural Australia and the validity of suggested target ranges 1 , 3
Which drugs are most commonly monitored?
availability of cost-effective drug assay. The most commonly monitored drugs are probably carbamazepine, valproate and digoxin. However, there is little evidence that monitoring concentrations of anticonvulsants improves clinical outcomes when the drugs are used to treat mood disorders. Table 1shows some of the drugs that meet these criteria.