Tutorial 1 January 18, 2013

Contact Details Two TAs Julian Chesterman julian.chesterman@chee.queensu.ca Biosciences 1424 Cody Brown c.brown@queensu.ca HMRC 5-201

Quick Overview of Course to Date Definition of drug/objectives of drug dosage formulation Drug - substance or mixture of substances advertised for treatment or prevention of disease or symptoms, e.g. Aspirin Drug dosage – include excipients to facilitate/control delivery of drug, protect drug from degradation, conceal taste/odor Want predictable and repeatable therapeutic response

Plasma Concentration (Cp) Key Definitions Bioavailability: extent of absorption and the rate at which an administered dose reaches systemic circulation in its active form Therapeutic Window: Time after Administration Plasma Concentration (Cp) Minimum Effective Concentration Minimum Toxic Concentration

Hepatic First Pass Effect Everything absorbed in the intestines enters the portal vein and is transported directly to the liver Liver (poison filter) is responsible for metabolizing chemicals in the blood Consequently a portion of the drug will be metabolized before it ever reaches systemic circulation

Routes of Administration –Pros/Cons Oral Pro: Patient Compliance Con: Hepatic first-pass effect/Too slow for emergencies Rectal Pro: Avoids some hepatic first-pass effect Con: Low buffering capacity of fluid

Routes of Administration –Pros/Cons Buccal/Sublingual Pro: Rapid absorption/no first-pass effect Con: Bad taste of drugs/small doses Parenteral (Intravenous/Subcutaneous, etc.) Pro: 100% available/rapid delivery (emergencies) Con: Patient compliance (fear of needles/need for training)

Routes of Administration –Pros/Cons Transdermal Pro: Convenient/sustained release (good for drugs with narrow therapeutic window or requiring frequent delivery by other methods) Con: Drug must be potent and effective when delivered slowly Nasal Pro: bioavailability similar to injection for some drugs Con: Formulation complexity/shelf-life

Routes of Administration –Pros/Cons Pulmonary Pro: Large surface area and thin membrane Con: More complex to formulate

Drug Absorption Simple diffusion Because viscosity of the phospholipid bilayer is 100 to 1000 times higher than that of water, movement across cell membranes (hydrophobic region) is the rate-limiting step in drug absorption by simple diffusion (Stokes-Einstein equation). Not all molecules can diffuse across phospholipid bilayer.

Drug Absorption Facilitated Diffusion: Transport across cell membrane via carrier proteins. Transport from high concentration to low concentration. Active Transport: Transport across cell membrane against a concentration gradient . Requires expenditure of energy by cell.