Pharmacokinetics sometimes abbreviated as PK, is a branch of pharmacology dedicated to determining the fate of substances administered to a. The pharmacokinetic term half-life (t1/2) refers to the time taken for half the initial dose of medicine administered to be eliminated from the body. 2. pharmacokinetics. 1. Clinical PharmacokineticsPharmacokinetics Dr. Deepak Kr. Gupta, B.D.S.; 2. Quantitative study of drug movement in.
The characteristics of a drug that predict its movement and availability at sites of action are its molecular size and structural features, degree of ionization, relative lipid solubility of its ionized and non-ionized forms, and its binding to serum and tissue proteins.
In most cases, a drug must traverse the plasma membranes of many cells to reach its site of action. Although barriers to drug movement may be a single layer of cells intestinal epithelium or several layers of cells and associated extracellular protein skin , the plasma membrane represents the common barrier to drug distribution. The plasma membrane consists of a bilayer of amphipathic lipids with their hydrocarbon chains oriented inward to the center of the bilayer to form a continuous hydrophobic phase and their hydrophilic heads oriented outward.
Individual lipid molecules in the bilayer vary according to the particular membrane and can move laterally and organize themselves with cholesterol e. Membrane proteins embedded in the bilayer serve as structural anchors, receptors, ion channels, or transporters to transduce electrical or chemical signaling pathways and provide selective targets for drug actions. In contrast to earlier proposals that cell membranes are fluid and thus proteins collide in an unordered fashion, we now understand that membranes are highly ordered and compartmented Pinaud et al.
These proteins may be associated with caveolin and sequestered within caveolae; they may be excluded from caveolae; or they may be organized in signaling domains rich in cholesterol and sphingolipid not containing caveolin or other scaffolding proteins i.
Cell membranes are relatively permeable to water either by diffusion or by flow resulting from hydrostatic or osmotic differences across the membrane, Please enter User Name Password Error: Please enter Password Forgot Username?
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Sign in via OpenAthens. Sign in via Shibboleth. Clinical Sports Medicine Collection. To achieve this goal, adequate concentrations of the medicine must be delivered to the target tissues so that therapeutic, yet nontoxic levels, are obtained.
Pharmacological and toxicological actions of medicines are primarily related to their plasma concentrations. Consequently, healthcare professionals involved with medicines must recognise the onset speed of medicine action as well as the intensity and duration of its effect. In turn, these are controlled by the following four fundamental pathways of drug movement and modification in the body:.
Pharmacokinetics influences the decided route of administration for a specific medication, the amount and frequency of each dose and its dosing intervals.
On the other hand, pharmacodynamics is the study of how a medicine acts on a living organism. This includes the pharmacological response and its duration and magnitude observed, relative to the medicines concentration at an active site in the organism; i.
Clinical pharmacokinetics is the application of pharmacokinetic and pharmacodynamic principles to the safe and effective therapeutic management of an individual patient. For example, a medicated dose with a half-life of 12 hours, would have 25 per cent of the medication left in the body after 24 hours.
Many medications are classified in terms of their half-lives. For example the benzodiazepines are classified in terms of:. Absorption from the site of administration permits entry of the therapeutic agent either directly or indirectly into plasma. Medicine-related factors include ionisation state, molecular weight, solubility, and formulation.
Small, nonionised, lipid-soluble medicines permeate plasma membranes most readily. Once absorbed, the medicine may then reversibly leave the bloodstream and distribute into the interstitial and intracellular fluids. Most medicines are protein bound to some extent; only an unbound medicine is free to carry out its pharmacological action s.
Depot Storage refers to lipophilic medicines which store in fat, calcium-binding drugs, etc. This can result in changes in the volume of distribution Vd , for some medicines causing unpredictable effects, particularly in frail older people.
The volume of distribution is the extent to which a medicine distributes out of the bloodstream and into the tissues of the body i. A decrease in Vd will result in higher plasma concentrations for hydrophilic medicines such as gentamicin, digoxin and lithium.
A higher proportion of body fat will increase Vd for lipophilic medicines such as diazepam causing an increase in plasma half-life. Before being excreted, the medicine is metabolised by the liver, kidney or other sites. It refers to the process of making the drug more polar more water-soluble , which may lead to medicine inactivation and excretion.
Metabolites may be more or less prodrug active than the parent medicine. The liver is the major source of these enzymes P enzymes , though they may be present in the gastrointestinal tract, heart, lung, brain and kidney.
Phase I reactions nonsynthetic involve minor structural modifications of the parent structure via oxidation, reduction or hydrolysis to produce smaller, more water-soluble metabolite. These are predominantly handled by enzymes known as the Cytochrom P enzymes. The most common causes of medicine-to-medicine interactions are pharmacokinetics, particularly metabolic ones. These are known as the cytochrome P interactions.
A large number of clinically important interactions arise from inhibition or induction of substrates medicines that are significantly metabolised by the given enzymes. Some cases first need to be metabolised to more water-soluble moieties examples include amiodarone, amitriptyline, amlodipine, amphotericin B, aripiprazole, aspirin, atomoxetine, atorvastatin, azithromycin, felodipine etc.
Others are excreted unchanged or relatively unchanged penicillins, cephalosporins, aminoglycosides, ganciclovir, milrinone, oseltamivir, risedronate, varenicline etc.
Pharmacokinetics and Pharmacodynamics – Medicines and the Body
and clinical pharmacokinetics. 2. Define pharmacodynamics and relate it to pharma- cokinetics. 3. Describe the concept of the therapeutic concentra- tion range. these drugs therapeutic drug level monitoring is required (Chapter 2). .. 94 7 k. 0 0 h t. V. 1 2. 0 /. d. CL. Basic pharmacokinetics. Pharmacokinetics is the study of the rates of absorption, distribution, metabolism .. ➢AUC proportional to Dose = Linear pharmacokinetics. Cl, Vd, MRT, t. 1/2.