Introductory course to pharmacology and pharmacokinetics, covering drug absorption, distribution, elimination, dosage, and response. Notes summarize lecture slides and concepts discussed in class. From 2020, taught by Dr. Cindy Woodland
Pharmacology = study of drugs, how substances interact with biological systems, fates+actions in body
Drug = substance used in diagnosis, treatment, mitigation, prevention of disease/disorder
Pharmacokinetics (PK): what body does to drug; ADME: absorption, distribution, metabolism, excretion
Pharmacodynamics (PD): what drug does to body; actions/effects of drug
Drug Nomenclature
1. Chemical Name - recognized worldwide, used in early development
2. Drug Company Code Name - used by companies during early development
3. Non-Proprietary (Generic) Name - official or approved name in pharmacopoeias
4. Proprietary (Brand) Name - assigned by manufacturer, registered trademark
5. Street Name - assigned by public; useful for physicians to know these
Drug Development + Regulation in Canada
A. Synthesis of a compound (up to 4 yrs)
B. Preclinical Testing (3-5 yrs) - animal studies, structure-activity relationships, in vitro assays
C. Clinical Trial Application - must be approved by Health Canada
D. Clinical Trials
1. Phase I (6-9 months) - first human subjects, healthy volunteers, establish pharmacokinetic
parameters + some examination of safety
2. Phase II (6m - 3 yrs) - first patients (usually male), proof-of-concept, dosing adjustments, some
examination of safety
3. Phase III (1-5 yrs) - thousands of patients, comparisons with placebo or standard drug,
examination of safety + efficacy
E. New Drug Submission (NDS) to Health Canada
-contains information about safety, efficacy, and quality of product
-results from preclinical + clinical tests, production, packaging + labelling, adverse effects
F. (Abbreviated NDS)
-generic companies don’t need to show drug efficacy, just need to prove product is the same as
the approved brand-name drug
G. (Supplemental NDS) - used when manufacturer wants to change drug already authorized for sale
(change dosage, intended effects, etc.)
H. Notice of Compliance - NOC+DIN needed to sell product in Canada (if failed, will receive NON)
Note: DIN = drugs in Canada, NPN = natural health products
I. Patented Medicine Prices Review Board (PMPRB) - establishes max price of patented drug, no
regulation over generic drugs
J. Phase IV - post-marketing surveillance, looking mostly for safety
-Patent Act: gives manufacturers 17 years patent protection from date of issue, or 20 years from filing date
Study Design
-Cohort Design: prospective; following groups with different exposure and want to see outcome
-Case-Control Design: compare unaffected and affected populations, look at differing exposures
,LECTURE 2: Drug Properties and Permeation
Concentration-Time Curves
Focus: Oral Drug Absorption
-mainly absorbed by small intestine; very large surface area + rich blood flow
-intestinal barriers: stomach pH very acidic, may destroy drugs
-drugs can be given enteric coating to protect from this environment (intestine made of enterocytes)
-intestinal epithelial cells have tight junctions
Factors Affecting Rate of Drug Diffusion
-properties + concentration of drug, surface area for permeation, contact time, blood flow
, LECTURE 3: Drug Absorption
Mechanisms of Drug Permeation
-Passive Diffusion: water-soluble drugs through aqueous pore, or lipid-soluble drug dissolved in membrane
-Facilitated Diffusion: harder for charged drugs
-Active Transport: requires ATP
-Transcytosis: large drugs typically endocytosed
Drug Properties that affect Permeability
-Size + Structure: water soluble (250-450 Da can diffuse), lipid soluble (<1000 Da can diffuse)
-Water + Lipid Solubility: determined by partition coefficient (P)
-P: (oil/water) or (membrane/buffer); value of P increases with hydrophobicity (lipid solubility)
-lipophilic drugs generally more soluble, but still need to cross unstirred water layer of membrane
-Ionization: uncharged form of drug better able to cross cell membranes
-acidic drugs: pH > pKa = more drug in charged form (A-), reduced absorption
-basic drugs: pH > pKa = more drug in uncharged form (B), increased absorption
-Drug Transporters: often found on basal/apical membranes of hepatocytes, enterocytes, renal tubular cells,
brain capillary cells
-uptake transporters: SLC superfamily (OATs, OATPs, OCTs, OCTNs)
-efflux transporters: ABC superfamily (MDRs, MRPs, BCRP)
Example: P-glycoprotein (MDR1) -known substrate: Digoxin
-part of ABC superfamily; removes drugs from tumour cells (often overexpressed in cancer patients)
-also expressed in numerous healthy cells; need inhibitor that only targets cancer cells
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