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PowerPoint Presentation Semester 1 2020 • Welcome to BIOL 122 ! •Human Biological Science 2 •Introduction to Unit •Week 1- Lecture A • Important information about the BIOL122 • will be given at the lecture • Not to be missed! Semester 1 2020 Pharmacokinetics - Dr Hemant Mehta 20/02/2020 1 Pharmacokinetics BIOL 122 Dr H Mehta Pharmacokinetics • Study of the absorption, distribution, metabolism, and excretion of drugs, “ie. what the body does to the drug” • Movement of drug inside the body – how the body handles the drug (influenced by the route of administration) Drug absorption: the process of drug transport from site of administration to systemic circulation by crossing biological membrane. Drug transport processes: • Passive transport Most drugs transport by simple diffusion (movement from high to low concentration; no carrier protein; no energy required) • Specialised transport - Active transport - Facilitated diffusion - Endocytosis - Exocytosis 20/02/2020 2 Bioavailability: the rate and amount of drug that is absorbed from a given dosage form and reaches the systemic circulation. 1st pass hepatic metabolism: metabolism of drugs upon first passage through the liver (can inactivate drug molecule before reaching the systemic circulation) The mode of entry of a drug into the body determines the character, speed, dose and degree of action. Absorption and hepatic first pass determine the bioavailability of a drug to produce a therapeutic effect. Factors affecting drug absorption & bioavailability • Physico-chemical properties of drug (molecular size, solubility, pH) • Nature of the dosage form (eg. particle size, disintegration and dissolution of drug) • Physiological factors (eg. GI transit time, surface area, blood supply to site of absorption, rate of gastric emptying, peristaltic activity) • Disease states (Absorption and first pass metabolism may be affected in conditions like malabsorption, liver cirrhosis) Drug absorption depends on chemical structure of drug and nature of the absorbing surface Drug molecular weight: the smaller in size, the more absorption • Many drugs are absorbed by simple diffusion • small molecules diffuse more rapidly than large molecules 20/02/2020 3 Drug solubility: Drug solubility determines the degree and time taken to cross cell membranes. - non-ionised (ie. non-polar) drugs are lipid soluble; these lipophilic substances diffuse across cell membranes easily and rapidly. Lipid-soluble drugs are absorbed effectively. - ionised (polar) drugs are water soluble; (hydrophilic substances don’t cross cell membranes readily) The more lipid soluble the drug … more absorption The more water soluble the drug … less absorption pH: • Drugs are weak acids or weak bases, and tend to dissociate in body fluids depending on pH of local environment. GIT is a major site of drug absorption; it has a variable pH (stomach: pH 3 & duodenum: pH 8). • Acidic drugs (eg. aspirin) are better absorbed in the stomach • Basic drugs (eg. morphine) are better absorbed in the small intestine. Physiological factors affecting drug absorption • Rate of gastric emptying: Rapid gastric emptying rate → faster drug absorption • Peristaltic activity: Slow peristaltic activity → slower but more complete absorption of drugs. 20/02/2020 4 Nature of absorbing surface Number of cell layers: rapid absorption across thin respiratory membrane than across skin (multiple cell layers) Surface area of the administration site is also important: a large surface area results in greater & rapid absorption. Absorption of orally-taken drugs usually mainly takes place in the small intestines. Respiratory medication is best given by inhalation, as the large surface area of lungs (thin respiratory membrane) lead to rapid, effective absorption into pulmonary bloodstream. Blood supply to site of absorption High blood flow: facilitates drug absorptive process; poor blood flow: impedes absorption. Drugs administered into highly vascular tissues (eg. muscle, or directly into circulation) are readily absorbed. Drugs administered into less vascularised tissues (eg. subcutaneous layer) are poorly absorbed. Circulatory disorders (such as shock) significantly ↓drug absorption. Dosage forms and routes of administration Ointment A medical preparation applied topically (to the skin) that has an oil base (a cream is water-soluble). Capsule A gelatinous casing enclosing a dose of a drug. Tablet A small solid form of medication intended for oral use. Drug suspension A preparation of drug suspended in a liquid. Enteric coated A waxy coating applied to oral medication that prevents release until the small intestine is reached. Nebuliser A pump to administer medication in the form of mist to the lungs. 20/02/2020 5 Oral route • Most drugs are administered by the oral route Advantages: - safest - most convenient - least expensive Disadvantages: - slower acting than other routes such as injectables - oral route not suitable for those with GI intolerance or ‘nil by mouth’ status, or who are unconscious • Give oral drug with caution to those who have difficulty swallowing, eg. stroke (CVA) patient Routes of drug administration Sublingual • Under the tongue • Drug diffuses through the mucous membrane beneath tongue and into venous circulation • Bypasses liver and hepatic metabolism eg. anginine (for treatment of angina) www.answers.com/topic/sublingual Inhalational route eg. nasal/respiratory • Through the nose or inhaled • Drugs delivered directly to lungs • Have to be atomised (small droplets in air) Eg. Ventolin • Also quickly absorbed into bloodstream through mucous membranes Eg. psychoactive drugs www.buzzle.com/.../nasal-spray-side-effects.html http://www.answers.com/topic/sublingual http://www.buzzle.com/articles/nasal-spray-side-effects.html 20/02/2020 6 Transdermal • Drugs are delivered bodywide through the skin by wearing a skin patch • Continuous slow absorption • Useful for drugs that are quickly eliminated from the body Eg. anginine, nicotine publications.nigms.nih.gov/.../chapter1.html Intravenous • Injection into a vein • Fastest way to deliver liquids and medicines • Immediate effect because no barrier to absorption, eg. morphine, chemotherapeutic agents… • Use any identifiable vein (arm most common) Parenteral A route of administration that requires piercing the skin or mucous membrane and bypasses the GIT. Intravenous Drug injected directly into a vein to produce rapid action; can be given as bolus (eg. morphine, dopamine) or as continuous infusion (eg. fluids during shock or dehydration). Intrathecal Injected into subarachnoid space of spinal cord, eg. spinal anaesthetics. Intra-articular Injected directly into a joint, eg. hydrocortisone. http://publications.nigms.nih.gov/medbydesign/chapter1.html 20/02/2020 7 • Intradermal Injection into the layers of the skin, eg. BCG vaccine. • Subcutaneous Non-irritant substances are given into subcutaneous tissue, eg. insulin. • Depot form of drug Drug formulation where drug is injected i.m. or inserted under the skin and is slowly released over a period of time (eg. vaccines). This drug delivery method is mainly used for contraception and in mental health. Depot injection • Subcutaneous or intramuscular injections • Usually solid or oil-based • Long acting, slow release drugs • Reduction in frequency of dosing (helps with compliance) Eg. Fluanoxal for schizophrenia Subcutaneous • Under the skin • Avoids gastric digestion • Highly effective for insulin • Areas of injection are outer area of upper arm, above and below the waist, front of thigh, upper area of buttock www.dana-farber.org/can/patient-instruction/h... www.hghnews.us/p/175.html www.answers.com/topic/injection http://www.dana-farber.org/can/patient-instruction/html/instructions-for-subcutaneous-injection.html http://www.hghnews.us/p/175.html http://www.answers.com/topic/injection 20/02/2020 8 Intramuscular - Injected into the muscle • - Used for medicines (soluble substances, mild irritants, suspensions, and colloids) administered in small amounts, eg. vaccines, penicillin • - Slow absorption - Given in deltoid or vastus lateralis muscles www.answers.com/topic/injection Pessary A drug delivery system that contains a drug and is inserted into the vagina. Therapeutic pessaries may also be used to support the pelvic floor. Suppository A drug delivery system that is inserted into the rectum. It is inserted as a solid and will dissolve in the body to release the drug. Rectal • Insertion of suppositories into rectum; • drug is mixed with a waxy substance that dissolves or liquefies after it is inserted into the rectum; • rectum's wall is thin and its blood supply rich so drug is readily absorbed; • prescribed for people who cannot take a drug orally because they have nausea, cannot swallow, or have restrictions on eating, as is required after many surgical operations, eg. Stemetil http://en.wikipedia.org/wiki/File:Anorectum.gif http://upload.wikimedia.org/wikipedia/commons/c/ce/Suppositories_three_different_sizes_2.jpg http://www.answers.com/topic/injection 20/02/2020 9 Drug distribution After absorption of drug into blood circulation, it travels to its site of action. As the drug has to be lipophilic for absorption to take place, solubility in plasma may be limited. Many drugs become bound to plasma protein (“drug reservoir”: prolongs drug presence in body). Another drug reservoir in the body is the adipose (fat) tissue. Protein binding • Bloodstream has a remarkable ability to transport relatively insoluble substances (eg. sex hormones such as androgens) which are lipophilic and yet are transported efficiently in the blood. This is because they are transported attached to blood proteins such as albumin and globulins. • Many drugs are highly (99.9%) protein-bound; only the 0.1% free (unbound) drug is pharmacologically active. As the free form is used up, more is released from the protein-bound form. Protein binding acts as a temporary store of a drug and tends to prevent large fluctuations in concentration of unbound drug in the body fluids. - High protein bound drugs are usually long acting - Low protein bound drug: usually short acting 20/02/2020 10 Adipose tissue binding Body fat deposits also bind drugs. Fat tissue is an important reservoir for lipophilic drugs. Lipid-soluble drugs are absorbed into adipose tissue, and slowly released into bloodstream, hence prolonging their presence in the body. Eg. Tetrahydrocannabinol (THC: active constituent in marijuana) is lipophilic, and is readily taken up into body fat. After