Tutorial 1

January 18, 2013

Contact Details

• Two TAs– Julian Chesterman

julian.chesterman@chee.queensu.caBiosciences 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

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

Not all molecules can diffuse acrossphospholipid bilayer.

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).

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.