Drug Elimination and Bioavailability (PDF)

 Drug elimination Medical absorption is the movement of a drug from its site of administration into the blood oral drugs enter the stomach where they are either dissolved and pass through the cell membranes of the epithelial cells lining the stomach or travel undissolved through the stom...

 Drug elimination Medical absorption is the movement of a drug from its site of administration into the blood oral drugs enter the stomach where they are either dissolved and pass through the cell membranes of the epithelial cells lining the stomach or travel undissolved through the stomach to the small intestine which is the main side of absorption Drugs will dissolve and pass through the intestinal wall and oral drugs then travele through the portal of Venus system to deliver.  and this is where the first pass effect occurs during this process the liver will metabolize the drug and that's some of it inactivating it or excreting it into the bile for illuminating from the body  As for the remaining amount of active drug it will leave the liver and it's ntering the general circulation reaching its targeted organs. If the drug was administered in a different way for example the intravenous injection then the drug will pass directly into the bloodstream and that will result in passing the liver elimination.  Drugs administered into a muscle the drug enters either a muscle or subcutaneous tissue and here it passes through the gap junctions into the capillary walls and then into the general circulation reaching its destinated organ also that helps them bypassing the GI track As for the bio availability it is basically the amount of dose of a drug that is actually absorption into the bloodstream so the bio availability will which you be less than 100 because of the first pass effect of the liver to compare if the drug was administered through an IV it will be 100% because its not exposed to the first pass of the liver different drugs have different bioavailability because they're not absorbed in the same rate. Watch presentation https://youtu.be/Y2N8iQ2Khxg Ibuprofen This drug by it's trade names: Nurofen or Advil. They are part of a class of drugs called NSAIDS - that's Non Steroidal Anti-Inflammatory Drugs. They are COX inhibitors. It's good for headaches, fever and booboos. Analgesia and antipyretic, and also anti-swelling! Ibuprofen works as a pain killer (analgesic), how it can low temperature (antipyretic), and how it can stop swelling.  Nonsteroidal anti-inflammatory drugs (NSAIDs) are a drug class FDA-approved for use as antipyretic, anti-inflammatory, and analgesic agents. These effects make NSAIDs useful for treating muscle pain, dysmenorrhea, arthritic conditions, pyrexia, gout, migraines, and used as opioid-sparing agents in certain acute trauma cases. NSAIDs are typically divided into groups based on their chemical structure and selectivity: acetylated salicylates (aspirin), non-acetylated salicylates (diflunisal, salsalate), propionic acids (naproxen, ibuprofen, acetic acids (diclofenac, indomethacin), enolic acids (meloxicam, piroxicam) anthranilic acids (meclofenamate, mefenamic acid), naphthylalanine (nabumetone), and selective COX-2 inhibitors (celecoxib, etoricoxib).  Non-selective NSAIDs Diclofenac Diflunisal Etodolac Fenoprofen Flurbiprofen Ibuprofen Indomethacin Ketoprofen Ketorolac Mefenamic acid Meloxicam Nabumetone Naproxen Oxaprozin Piroxicam Sulindac Tolmetin COX-2 Selective NSAIDs Celecoxib Rofecoxib Valdecoxib Mechanism The main mechanism of action of NSAIDs is the inhibition of the enzyme cyclooxygenase (COX). Cyclooxygenase is required to convert arachidonic acid into thromboxanes, prostaglandins, and prostacyclins. The therapeutic effects of NSAIDs are attributed to the lack of these eicosanoids. Specifically, thromboxanes play a role in platelet adhesion, prostaglandins cause vasodilation, increase the temperature set-point in the hypothalamus, and play a role in anti-nociception. There are two cyclooxygenase isoenzymes, COX-1 and COX-2. COX-1 gets constitutively expressed in the body, and it plays a role in maintaining gastrointestinal mucosa lining, kidney function, and platelet aggregation. COX-2 is not constitutively expressed in the body; and instead, it inducibly expresses during an inflammatory response.  Most of the NSAIDs are nonselective and inhibit both COX-1 and COX-2. However, COX-2 selective NSAIDs (ex. celecoxib) only target COX-2 and therefore have a different side effect profile. Importantly, because COX-1 is the prime mediator for ensuring gastric mucosal integrity and COX-2 is mainly involved in inflammation, COX-2 selective NSAIDs should provide anti-inflammatory relief without compromising the gastric mucosa. Area under the curve The AUC is directly proportional to the dose when the drug follows linear kinetics. The AUC is inversely proportional to the clearance of the drug. That is, the higher the clearance, the less time the drug spends in the systemic circulation and the faster the decline in the plasma drug concentration. Therefore, in such situations, the body exposure to the drug and the area under the concentration-time curve are smaller. Labetalol lowers the blood pressure primarily by blocking peripheral arteriolar alpha-adrenoceptors thus reducing peripheral resistance and, by concurrent beta-blockade, protects the heart from reflex sympathetic drive that would otherwise occur. Cardiac output is not significantly reduced at rest or after moderate exercise. Increases in systolic blood pressure during exercise are reduced but corresponding changes in diastolic pressure are essentially normal. Labetalol antagonises alpha- and beta-adrenoceptors concurrently by competitive inhibition; it has no intrinsic sympathomimetic activity and less pronounced membrane stabilising activity than propranolol.  The beta-blockade is non-selective. The precise relationship between alpha- and beta-blocking effects in contributing to the antihypertensive action is unknown. At therapeutic doses, labetalol is less active at alphaadrenoceptors than beta-adrenoceptors; the ratio of beta:alpha antagonism is 3:1 after oral and 6.9:1 after intravenous administration.  Adequate vasodilatation is achieved with incomplete blockade of the alpha-adrenoceptors in the arterioles. Reductions in blood pressure and systemic arterial resistance have been found to be linearly related to labetalol plasma concentration, while a quadratic reduction in cardiac output was observed with no reduction in heart rate. There is evidence from a small trial that, after the same dose, elderly patients exhibited a larger decrease in blood pressure than younger patients.  After intravenous administration, labetalol is rapidly and extensively distributed into extravascular tissues. About 50% of labetalol in the blood is protein bound. A 100 mg intravenous dose gave an AUC of 675-2470 ng/mL/hr; the area under the curve of an intravenous 0.5 mg/kg dose was reduced by about 17% when administered after a meal but the clinical effect of this is unknown  Labetalol is metabolised mainly through conjugation to inactive glucuronide metabolites, which are excreted both in the urine and via the bile into the faeces. Excretion Elimination half-lives of 3.5-6.3 hours  Nifedipine is almost completely absorbed from the gastrointestinal tract as shown by plasma levels after sublingual, oral, and rectal administration. Because of presystemic metabolism, the bioavailability is about 56% to 77%. After oral administration of 10 mg, the mean plasma concentration of nifedipine reaches maximum values of 160 +/- 49 micrograms/liter after 30 to 60 minutes. After 8 hours, the mean concentration drops to 3.4 +/- 1.2 micrograms/liter. After intravenous administration (0.015 mg/kg) biphasic elimination occurs, the half-life of the alpha-phase being about 13 minutes and of the beta- phase 1.26 +/- 0.55 hours in healthy volunteers. After oral administration of higher doses (40 mg) and after continuous infusion over 24 hours, a third phase with a half-life of about 8 hours can be seen.  The apparent volume of distribution of the central compartment (Vce) is 0.294 +/- 0.1 l/kg, and the total body clearance amounts to 0.45 +/- 0.1 liter/hr. kg. Nifedipine is eliminated from the body by hepatic metabolism to the major metabolites 2,6-dimethyl-4-(2-nitrophenyl)-5-methoxycarbonyl-pyridine-3- carboxylic acid (M I) and the corresponding 2-hydroxymethyl- pyridinecarboxylic acid (M II). Methods for the quantitative detection of unchanged nifedipine in the presence of the pyridine analog in plasma (HPLC) and of the main metabolites in plasma and urine (GLC) have been developed. A simple semiquantitative method for detecting metabolites in urine (HPTLC) can be used to monitor patient compliance.  The therapy of rheumatism began thousands of years ago with the use of decoctions or extracts of herbs or plants such as willow bark or leaves, most of which turned out to contain salicylates. Following the advent of synthetic salicylate, Felix Hoffman, working at the Bayer company in Germany, made the acetylated form of salicylic acid in 1897. This drug was named "Aspirin" and became the most widely used medicine of all time Aspirin In 1971, Vane discovered the mechanism by which aspirin exerts its anti-inflammatory, analgesic and antipyretic actions. He proved that aspirin and other non-steroid anti-inflammatory drugs (NSAIDs) inhibit the activity of the enzyme now called cyclooxygenase (COX) which leads to the formation of prostaglandins (PGs) that cause inflammation, swelling, pain and fever. However, by inhibiting this key enzyme in PG synthesis, the aspirin-like drugs also prevented the production of physiologically important PGs which protect the stomach mucosa from damage by hydrochloric acid, maintain kidney function and aggregate platelets when required  This conclusion provided a unifying explanation for the therapeutic actions and shared side effects of the aspirin-like drugs. Twenty years later, with the discovery of a second COX gene, it became clear that there are two isoforms of the COX enzyme. The constitutive isoform, COX-1, supports the beneficial homeostatic functions, whereas the inducible isoform, COX-2, becomes upregulated by inflammatory mediators and its products cause many of the symptoms of inflammatory diseases such as rheumatoid and osteoarthritis.