Drug Administration and Absorption PDF

Module 3: Pharmacokinetics Lesson 1: Drug Administration and Absorption Learning Outcomes: — Identify the different routes of administration, its advantage and disadvantages — Determine which route is the most practical in a given situation — Describe the mechanism of drug ab...

Module 3: Pharmacokinetics Lesson 1: Drug Administration and Absorption Learning Outcomes: — Identify the different routes of administration, its advantage and disadvantages — Determine which route is the most practical in a given situation — Describe the mechanism of drug absorption Drug administration and absorption Routes of administration Alimentary or Enteral Parenteral (Subcutaneous, Intramuscular, Intravenous, Intradermal, Intraperitoneal, Epidural, Intraocular) Topical Inhalation Absorption Physiological Disposition of the Drugs — Refers to the movement and changes that undergoes within a body, from the time of its administration up top the time of elimination from the body — Includes — Absorption Allow the administered drug to reach its site of action to produce its effect — Distribution — Biotransformation Terminate the action of drug; drug effect may persist even drug action is terminated — Excretion  Parenteral Physical Disposition of Drugs administration Rectal administration Stomach Intravenous Intramuscular/ subcutaneous Absorption Bloodstream Absorption Intestines Plasma- free drug Site of Tissues action Metabolites Protein- bound drug Distribution Liver Biotransformation Kidneys (Urine) Lungs Feces Mammary glands Sweat glands Salivary glands Excretion Excretion Source: Pettes and Wannamaker. 2000 Drug absorption — Refers to the passage of drugs or other substances from the site of administration into the blood circulation — Drug crosses the cell (biological) membrane (semi- permeable) in order to reach the site of action Drug absorption — Means by which drug molecules cross the cell membrane — Diffusion — Passive: Requires concentration gradient — Facilitated — Active transport — Pinocytosis Drug absorption — Influenced by — Formulation — Physicochemical — Solid properties — Liquid — Water- or lipid- soluble — Colloid — Hydrophilic- IM — Gas — Lipophilic- Per os — Route of administration — pH (drug and environment) Drug absorption and physicochemical properties of drugs — Lipid solubility — Expressed in terms of partition coefficient; the ratio of drug solubility in oil to its solubility in water — Water-soluble drugs penetrate through aqueous channels — Lipid-soluble drugs cross membranes easier than the water-soluble ones — The higher the lipid solubility, the faster is the absorption rate Drug absorption and physicochemical properties of drugs — Degree of ionization in a given pH — Uncharged ones readily cross the membranes — pH of the drug — Absorption depends on the pH of the medium Drug absorption and drug formulation — Solid drug formulation needs to be absorbed through the gastrointestinal tract to reach the circulation — Injectable drugs have better absorption Drug absorption and routes of administration — General Principles — Drugs dissolve in body fluid (water). — Drugs enter the circulatory system as fluid enters the circulatory system. — Drugs must enter the circulatory system before they can be distributed to sites of action. — Drugs for enteric effects are an obvious exception. — Therefore, drugs are not IN the body until they are IN the bloodstream. Drug absorption and routes of administration — Parenteral route- other than the gastrointestinal tract Intravenous (IV) Intra-muscular (IM) Subcutaneous (SC) Intra-synovial Intra-peritoneal (IP) Intra-scleral Intra-thecal Intra-arterial Intranasal Intra-dermal Sub-conjunctival Intratracheal Drug absorption and routes of administration — Alimentary/ Enteral route - through the digestive tract — Oral- oldest route — Rectal — Miscellaneous routes — Inhalation — Topical Parenteral routes — Introduction into the bloodstream is equal to the actual rate of absorption — Drug concentration is directly proportional to absorption rate from intramuscular (IM) and subcutaneous (SC) sites — The greater the dose administered, the slower is the rate of absorption — Blood flow and diffusion limit absorption — Other factors affecting drug absorption — Ionization — Lipid solubility — Molecular weight Parenteral routes: Disadvantages — Asepsis is very important — May cause pain — Blood vessels may be penetrated with IM injection — Speed on onset of action is rapid (IV administration) — Discoloration of meat or abscess formation which is not good for food animals Intramuscular (IM) route: Advantages — More consistent absorption compared to — Oral route — Subcutaneous route — Depot or sustained effect is possible — Practical route for patients that are — Unconscious — Vomiting — Fractious Intramuscular (IM) route: Advantages — Last resort for dehydrated patients — Most common route of drug administration in large animals Intramuscular (IM) route: Disadvantages — Difficult in small patients — There is pain at site of injection — Muscle damage is possible — Exact blood and tissue levels may not be obtained IM route: Processes involved Drug in suspension or lipid solution is dissolved in tissue fluid ↓ Drug in tissue fluid diffuses into capillaries ↓ Drug in capillaries is carried to circulatory system Note: Any of the mentioned processes can affect rate of absorption. Subcutaneous (SC) route — Advantages: — Vasoconstrictor can be given at the site of injection to prolong the action — Allows administration of large drug volumes — Disadvantages: — Variable rate of absorption — Less rate of absorption compared to IM Intravenous (IV) route: Advantages — Accurate and rapid accumulation of blood and tissue levels — Allows administration of — Large drug volumes — Irritant drugs — Drugs that causes pain at the site of injection (IM) Intravenous (IV) route: Disadvantages — Administration requirements — Specific formulations — Good techniques — Toxic reactions are usually acute — May result in the formation of perivascular and intravascular thrombosis Intradermal (ID) route — Drug is administered within the skin — Very small needle should be used — Usually for skin testing procedures — TB test — Allergy test Different angles used in parenteral injection Intraperitoneal (IP) route — Advantage: Large absorptive surface than IM or SC — Disadvantages: — Drugs or vehicles may cause peritonitis — May result in organ damage due to needle puncture — Drugs may be injected into internal organs — Comment: generally restricted to laboratory animals © 2018 Newcastle University Intrathecal route — Advantages: direct delivery to the site of action — Disadvantages: — Difficult dose calculation — CSF volume is not proportional to body weight — Infection may be introduced Intrathecal route Intra-articular route: Advantages — Direct delivery to the site of action — High concentrations is achieved in the joint Photo Courtesy of Dr. Ramney. 2011. http://www.doctorramey.com/joint-therapies/ Intra-articular route: Disadvantages — Joint space may be difficult to hit (species difference: joint space size varies) — Difficult to calculate dose — Joint space volume is affected by diseases — May result in irritation/damage of joint surfaces/ capsules — Infection may be introduce instead, especially if not performed aseptically Drugs administered per os (Riviere and Papich, 2009) Processes after oral administration Per os Disintegration Dissolution administration Drug must still be non-ionized for absorption across the lipid membranes of the mucosa Drug factors affecting absorption — Disintegration — Barrier diffusion — Excipients/ vehicles — Solubility — Compaction pressure — Transit time — Enteric coatings, capsules — Homogeneity — Dissolution — Particle size/ surface area — Binding/ complexation to inert filler ingredients — Local pH, buffers — Boundary layers Drugs administered per os — Absorption is more complicated compared to parenteral routes — Factors affecting rate of absorption — pH differences in GIT segments — Surface area for absorption — Gastrointestinal secretions (juices, enzymes, bile and mucus) — Blood flow (perfusion) — Microbial population present (capable of pre-systemic metabolism) — Presence of food in the stomach — Species difference (nature of epithelial membranes) — Gastric motility Drugs administered per os — Used in conjunction with other drug forms — Balling gun is used to administer drugs orally in large animals Oral administration: Advantages — Safest — Convenient and economical — Sterilization not needed — Different drug forms are available Oral administration: Disadvantages — Drugs may be destroyed by — Acidic environment by the stomach — Digestive enzymes — Bacterial enzymes (ruminants) — Degree of absorption and bioavailability is variable, due to — Physiology — Presence of food — Disease — Presence of first-pass effect Oral administration: Disadvantages — Efficiently metabolized drugs are eliminated by the liver before they reach the bloodstream (first-pass effect) — Drugs may affect the normal gut flora — Drugs may cause irritation Oral administration: Disadvantages — Presence of antimuscarinic and narcotic drugs — May causes delay in gastric emptying → delay in absorption rate → prolonged drug onset of action — Increased gut motility — Shortens transit time → decrease drug contact time → less absorption Oral administration: Species differences — Stomach- in most species (abomasum- ruminants, 3rd compartment- camelids) — pH is so extreme — Absorptive surface is flat — Site of mechanical preparation of drugs Oral administration: Species differences — Rumenoreticulum (compartments 1 and 2 for camelids) — Epithelium: stratified squamous epithelium — pH is influenced by diet — Bacterial flora is involved in metabolism — Large volume of fluid is present Oral administration: Species differences — Small intestine — Absorptive surface is large — pH is relatively normal — Colon/ rectum — Accessible — Absorptive surface is also large Location of processes involved in the absorption of orally administered drugs Primary Secondary Process location(s) location(s) Duodenum for Breaking up of tablets Stomach enteric coated forms Dissolution of drugs from Stomach Duodenum suspension Absorption of drugs in lipid Small intestine suspension by the lacteals (all segments) Absorption of drugs in Duodenum, Stomach, ileum, solution through the mucosa jejunum colon Topical application — Application of drugs to various body surfaces — Provide local rather than systemic effects — Degree of absorption is dependent on lipid solubility of the drug and biological differences in skin — Area to be administered should be clipped — Facilitate better absorption — Ease of application Topical application — Application frequency depends on — Disease or disorder — Drug — Type of formulation Topical application — Aside from the skin, drugs can be applied to the following — Eyes — Remove foreign objects — Treat infections — Ears — Soften earwax and facilitate its removal — Treatment — Superficial infections — Earmites  Topical application: Advantages — For systemic problems — Application is painless — Example: mass medication in cattle or pig — For skin problems — Reduces systemic effects — Enhances skin effects Degree of absorption is dependent on lipid solubility of the drug. Topical application: Disadvantages — Patients tend to groom themselves — Application: topical, absorption: oral! — May result in toxic skin reactions — Blood flow to the skin is variable thereby influencing the rate of absorption and drug activity Factors affecting drug absorption through topical application — Lipid solubility and molecular size — Skin hydration and abrasion — Area of application — Drug penetration varies between body regions — Scrotal>forehead>axilla=scalp>back=abdomen>palm and plantar (humans) — Thickness — Hair follicle density — Lipid composition — Blood flow — Ambient and patient temperature Inhalation — For administration of dry powders, so nebulized particles are delivered as fine droplets — Used for volatile or gaseous anesthetics with the use of gas anesthetic machine — Response is rapid due to — Large surface area of the lungs — Large blood flow to the lungs  Source: DVM 360. Inhalant therapy: Finding its place in small-animal practice. Retrieved from http://veterinarymedicine.dvm360.com/vetmed/ArticleStandard/Article/detail/608394 on 28 July 2014. Source: Agri-Pro Enterprises of Iowa, Inc. Air Muzzle© Restraint. Retrieved from http://www.agri- pro.com/products/index.cfm?air_muzzle_restraint&show=product&productI D=270979 on 28 July 2014. References: — The Merck Manual Online (www.merck.com) — Ahrens, F. A. 1996. Pharmacology. Williams and Wilkins, USA. — Wannamaker, B.P. and Pettes, C.L. Applied Pharmacology for the Veterinary Technicians. 2nd Ed. W.B. Saunders Company, USA