The pH scale is logarithmic and as a result, each whole pH value below 7 is ten times more acidic than the next higher value. For example, pH 4 is ten times more acidic than pH 5 and 100 times (10 times 10) more acidic than pH 6. The same holds true for pH values above 7, each of which is ten times more alkaline (another way to say basic) than the next lower whole value. For example, pH 10 is ten times more alkaline than pH 9 and 100 times (10 times 10) more alkaline than pH
A chemical substance that takes on oxygen or gives up electrons to another substance. Read more: Oxidation-Reduction Reaction - examples, body, used, water, process, life, plants, chemical, form, energy, gas, animals, carbon, oxygen, substance, plant, Redox and electron exchanges http://www.scienceclarified.com/Oi-Ph/Oxidation-Reduction-Reaction.html#ixzz0wPXCNZTp Reduction: A process in which a chemical substance gives off oxygen or takes on electrons. Read more: Oxidation-Reduction Reaction - examples, body, used, water, process, life, plants, chemical, form, energy, gas, animals, carbon, oxygen, substance, plant, Redox and electron exchanges http://www.scienceclarified.com/Oi-Ph/Oxidation-Reduction-Reaction.html#ixzz0wPXUgtyL
Faeces: Liver actively transport drugs and its metabolites into bile (Glucoronides). OATP – orgnic acids and OCT – organic bases. Other lipophillic drugs – by P-gp. Most lucoronides are deconjugated by bacteria and reabsorbed in intestine – enterohepatic circulation. Drugs – erythromycin, rifmpicin and tetracycline etc. Ultimate excretion occurs in urine Milk – not importnt for mother but for fetus. Basic drugs can pass to milk as it has slightly lower pH Drugs – Saliva – Lithium, KI, heavy metals and rifampicin
Although Cpss cn be calculated, its real value actually varies with individuls – deviation from averge ptients
Pharmacokinetics Dr. D. K. Brahma Department of Pharmacology NEIGRIHMS, Shillong
Pharmacokinetics is the quantitative study of drug movement in, through and out of the body. Intensity of effect is related to concentration of the drug at the site of action, which depends on its pharmacokinetic properties
Pharmacokinetic properties of particular drug is important to determine the route of administration, dose, onset of action, peak action time, duration of action and frequency of dosing
Relationship – Dynamics and Kinetics Dosage Regimen Concentration in Plasma Concentration at the site of action Absorption Distribution Metabolism Excretion Pharmacokinetics Pharmacodynamics Effect
It involves the invagination of a part of the cell membrane and trapping within the cell of a small vesicle containing extra cellular constituents. The vesicle contents can than be released within the cell, or extruded from the other side of the cell. Pinocytosis is important for the transport of some macromolecules (e.g. insulin through BBB).
Bioavailability refers to the rate and extent of absorption of a drug from dosage form as determined by its concentration-time curve in blood or by its excretion in urine. It is a measure of the fraction (F) of administered dose of a drug that reaches the systemic circulation in the unchanged form
Bioavailability of drug injected i.v. is 100%, but is frequently lower after oral ingestion, because:
The drug may be incompletely absorbed
The absorbed drug may undergo first pass metabolism in intestinal wall and/or liver or be excreted in bile.
Practical Significance – low safety margin drugs
Biovailability - AUC Plasma concentration (mcg/ml) Time (h) 0 5 10 15 AUC p.o. F = ------------ x 100% AUC i.v. AUC – area under the curve F – bioavailability
It is the passage of drug from the circulation to the tissue and site of its action.
The extent of distribution of drug depends on its lipid solubility, ionization at physiological pH (dependent on pKa), extent of binding to plasma and tissue proteins and differences in regional blood flow, disease like CHF, uremia, cirrhosis
Movement of drug - until equilibration between unbound drug in plasma and tissue fluids
BBB is lipoidal and limits the entry of non-lipid soluble drugs (amikacin, gentamicin, neostigmine etc.).
(Only lipid soluble unionized drugs penetrate and have action on the CNS)
Efflux carriers like P-gp (glycoprotein) present in brain capillary endothelial cell (also in intestinal mucosal, renal tubular, hepatic canicular, placental and testicular cells) extrude drugs that enter brain by other processes.
(Inflammation of meaninges of brain increases permeability of BBB)
Dopamine (DA) does not enter brain, but its precursor levodopa does. This is used latter in parkinsonism.
c) High degree of protein binding makes the drug long acting, because bound fraction is not available for metabolism, unless it is actively excreted by liver or kidney tubules
d) The drugs with high physicochemical affinity for plasma proteins (e.g. aspirin, sulfonamides, chloramphenicol) can replace the other drugs(e.g. acenocoumarol, warfarin) or endogenous compounds (bilirubin) with lower affinity – kernicterus sulfonamide-bilirubin
e) Generally expressed plasma concentrations of the drug refer to bound as well as free drug , e.g. MIC of AMAs
f) In hypoalbuminemia, binding may be reduced and high concentration of free drug may be attained (e.g. phenytoin).
Involve – cytochrome P-450 monooxygenases (CYP), NADPH and Oxygen
More than 100 cytochrome P-450 isoenzymes are identified and grouped into more than 20 families – 1, 2 and 3 …
Sub-families are identified as A, B, and C etc.
In human - only 3 isoenzyme families important – CYP1, CYP2 and CYP3
CYP 3A4/5 carry out biotransformation of largest number (30–50%) of drugs. In addition to liver, this isoforms are expressed in intestine (responsible for first pass metabolism at this site) and kidney too ..
Inhibition of CYP 3A4 by erythromycin, clarithromycin, ketoconzole, itraconazole, verapamil, diltiazem and a constituent of grape fruit juice is responsible for unwanted interaction with terfenadine and astemizole
Rifampicin, phenytoin, carbmazepine, phenobarbital are inducers of the CYP 3A4
This is cleavage of drug molecule by taking up of a molecule of water. Similarly amides and polypeptides are hydrolyzed by amidase and peptidases. Hydrolysis occurs in liver, intestines, plasma and other tissues.
Drug glucuronides, excreted in bile, can be hydrolyzed in the gut by bacteria, producing beta-glucoronidase - liberated drug is reabsorbed and undergoes the same fate - enterohepatic recirculation (e.g. chloramphenicol, phenolphthalein, oral contraceptives) and prolongs their action
Drug is absorbed glucuronidated or sulfatated in the liver and secreted through the bile glucuronic acid/sulfate is cleaved off by bacteria in GI tract drug is reabsorbed (steroid hormones, rifampicin, amoxycillin, contraceptives)
Anthraquinone, heavy metals – directly excreted in colon
Energy dependent active transport – reduces the free concentration of drugs – further, more drug dissociation from plasma binding – again more secretion (protein binding is facilitator for excretion for some drugs)