Lecture 65 Flashcards
Introduction to Pharmacology and Drug Development, Evaluation, and Control
pharmacology
- studies how xenobitics (substances foreign to the body) affect biological systems
- these xenobiotics may include drugs (intention to treat) used for medical purposes or chemicals encountered in the environment
- broadly divided into: medical pharmacology & toxicology, and environmental toxicology
- toxicology = why we use the medicine to treat
pg 1658
medical pharmacology
- examines drugs to prevent, diagnose, and treat disease or modify body processes
- focuses on understanding drug actions, therapeutic effects, safe dosages, and side effects to optimize treatments
pg 1659
environmental toxicology
- investigates the harmful effects of chemicals on living organisms from cells to ecosystems
- assesses the risks and impacts of environmental exposures, aiming to prevent and reduce chemical hazards
pg 1659
pharmacokinetics
- study of how the body processes drugs over time = effect of the body on the drug
- focusing on absorption, distribution, metabolism, and elimination (ADME) → sometimes add T (toxicity)
- determine the best method of administration for each patient
pg 1660
pharmacodynamics
studies biochemical, physiological, and molecular effects of drugs on the body = effect of the drug on the body
pg 1661
pharmacogenomics
relation of the individual’s genetic makeup to his/her response to specific drugs
pg 1661
clinical pharmacology
- involves pharmacodynamic and pharmacokinetic investigations on patients to evaluate the efficacy and safety of drugs
- pharmacodynamics: onset of action, duration of action, intensity of action
- pharmacokinetics: absorption phase, absorption rate = elimination rate, post-absorption phase, elimination phase
pg 1662
principles to remember
- all substances can under certain circumstances be toxic, even water
- botanical chemicals (in herbs and plant extracts) are similar to those in manufactured drugs but with more impurities
- dietary supplements should meet the same efficacy and safety standards as drugs, verified through randomized controlled trials
pg 1663
nature of drugs
- drugs induce changes in biological function through their chemical effects
- drug molecules are either agonists (activators) or antagonists (inhibitors) to specific receptors
- drugs can have therapeutic effects, side effects, or toxic effects (poisons)
pg 1664
therapeutic effect
primary intended effect of the drug (aspirin → analgesic)
pg 1664
side effect
- secondary effect of the drug
- unintended, usually predictable, and may be harmless or toxic
pg 1664
poisons
- almost exclusively harmful
- dose makes the poison → any substance can be harmful if taken in the wrong dosage
pg 1665
toxins
- biologic poisons = plants or animals
- inorganic poisons = lead and arsenic
pg 1665
immunopharmacology
study the effects of drugs on the immune response and production of antibodies
pg 1665
drug allergy
immunological reaction to a drug
pg 1665
tolerance
a decreasing response to repetitive drug doses
pg 1665
drug misuse
improper use of common medications in a way that leads to acute and chronic toxicity
pg 1666
drug abuse
inappropriate intake of drug (continually or periodically)
pg 1666
drug dependence
a person’s reliance on or need to take drug or substance
pg 1666
dose
quantity of the drug that achieves the therapeutic effect without causing harmful side effect
pg 1666
therapeutic index
measures the danger of poisoning → the higher the index, the safer the drug is
pg 1666
physical nature of drugs
the drug must have:
- appropriate size of the molecule
- electrical charges
- molecular shape
- atomic composition
- hydrophilicity (body is mostly water)
- hydrophobicity (lipophilicity) → needs to pass through lipid membranes
- to be absorbed, distributed in the body, interact with receptors, metabolized & excreted from the body at a reasonable rate = provide actions of appropriate duration
- these factors often determine the best route of administration
pg 1667
drug molecular size
- most drugs molecular weight between 100 to 1000 Da
- drugs»_space; 1000 Da do not diffuse readily between compartments of the body and must be administered directly into the compartment where they have their effect
pg 1668
drug reactivity and drug-receptor bonds
drugs interact with receptors by chemical forces or bonds
pg 1669
covalent bonds
- very strong and irreversible under biological conditions
- example: bond between the acetyl group of Aspirin and cyclooxygenase → blocks platelet aggregation for a long time and is reversed only by the synthesis of a new enzyme which takes several days (7-10 days for platelet turnover)
pg 1669
electrostatic bonding, weak hydrogen bonding, Van der Waals forces, hydrophobic bonds
- electrostatic bonding: strong linkages between permanently charged ionic molecules
- weak hydrogen bonding
- Van der Waals forces: very weak induced dipole interactions
- hydrophobic bonds: quite weak; between lipid-soluble drugs and the lipids of cell membranes or with receptor surfaces
pg 1670
drug shape
- a drug must have a certain configuration complementary to the receptor → lock and key effect
- active enantiomer at one receptor is NOT the active enantiomer at another receptor
- drugs containing both chiral forms are called racemic mixtures
pg 1671-1672
drug chirality
- 50% of drugs are chiral
- exist as enantiomeric pairs → same chemical and structural formula, but one is the mirror image of the other
- only the one that is correctly oriented will fit into the receptor
pg 1671
types of drug-receptor interactions
- agonist: drug binds to receptor = activation = effect
- full agonist: has high efficacy, producing a full response while occupying a relatively low proportion of receptors
- partial agonists: produce sub-maximal activation even when occupying the total receptor population
- competitive antagonist: binds to the same site as the agonist but does NOT activate it, thus blocking the agonist’s action
pg 1673
allosteric inhibition
- drugs binding allosterically to the same receptor as the agonist can enhance or inhibit the agonist’s action
- allosteric inhibition is typically not overcome by increasing the agonist dose
- allosteric activators increase the efficacy of the agonist or its binding affinity
pg 1674
drug groups
- several thousand drugs can be arranged into ~70 drugs
- many drugs within each group are similar in pharmacodynamic and pharmacokinetic properties
- 1 or 2 prototype drugs are the most important of the group
- other significant drugs in the group are variations of the prototype
pg 1675
new drug development and regulation
- the process of drug discovery and development from initial identification of a molecule to preclinical testing before human trials
1. discovery → synthesizing or extracting a new drug
2. target interaction → study interaction with biological targets
3. optimization → create analogs to improve
4. in vitro/in vivo testing
5. pharmacokinetics and safety → evaluate drug behavior and safety in animals
6. human testing → with regulatory approval (3 clinical phases)
7. drug approval for marketing
8. IRB makes sure rights and welfare of participants are protected
9. post-marketing surveillance
10. after patent expires, any company can produce drug (abbreviated new drug application - ANDA)
11. FDA approval to market drug as generic product
pg 1676-1678
trademark
drug’s proprietary trade name and is usually registered; legally protected as long as it is used
pg 1679
Food & Drug Administration (FDA)
- administrative body that oversees the drug evaluation process in the USA and grants approval for the marketing of new drug products
- if a drug is effective and unsafe, cannot be marketed in interstate commerce
- complete absence of risk in FDA approved drugs is impossible
- history of drug regulation in the USA reflects several health events that precipitated major shifts in public opinion
pg 1680
