Lecture 65

Question 1

pharmacology

Answer 1

• 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

Question 2

medical pharmacology

Answer 2

• 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

Question 3

environmental toxicology

Answer 3

• 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

Question 4

pharmacokinetics

Answer 4

• 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

Question 5

pharmacodynamics

Answer 5

studies biochemical, physiological, and molecular effects of drugs on the body = effect of the drug on the body

pg 1661

Question 6

pharmacogenomics

Answer 6

relation of the individual’s genetic makeup to his/her response to specific drugs

pg 1661

Question 7

clinical pharmacology

Answer 7

• 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

Question 8

principles to remember

Answer 8

1. all substances can under certain circumstances be toxic, even water
2. botanical chemicals (in herbs and plant extracts) are similar to those in manufactured drugs but with more impurities
3. dietary supplements should meet the same efficacy and safety standards as drugs, verified through randomized controlled trials

pg 1663

Question 9

nature of drugs

Answer 9

• 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

Question 10

therapeutic effect

Answer 10

primary intended effect of the drug (aspirin → analgesic)

pg 1664

Question 11

side effect

Answer 11

• secondary effect of the drug
• unintended, usually predictable, and may be harmless or toxic

pg 1664

Question 12

poisons

Answer 12

• almost exclusively harmful
• dose makes the poison → any substance can be harmful if taken in the wrong dosage

pg 1665

Question 13

toxins

Answer 13

• biologic poisons = plants or animals
• inorganic poisons = lead and arsenic

pg 1665

Question 14

immunopharmacology

Answer 14

study the effects of drugs on the immune response and production of antibodies

pg 1665

Question 15

drug allergy

Answer 15

immunological reaction to a drug

pg 1665

Question 16

tolerance

Answer 16

a decreasing response to repetitive drug doses

pg 1665

Question 17

drug misuse

Answer 17

improper use of common medications in a way that leads to acute and chronic toxicity

pg 1666

Question 18

drug abuse

Answer 18

inappropriate intake of drug (continually or periodically)

pg 1666

Question 19

drug dependence

Answer 19

a person’s reliance on or need to take drug or substance

pg 1666

Question 20

dose

Answer 20

quantity of the drug that achieves the therapeutic effect without causing harmful side effect

pg 1666

Question 21

therapeutic index

Answer 21

measures the danger of poisoning → the higher the index, the safer the drug is

pg 1666

Question 22

physical nature of drugs

Answer 22

the drug must have:

1. appropriate size of the molecule
2. electrical charges
3. molecular shape
4. atomic composition
5. hydrophilicity (body is mostly water)
6. 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

Question 23

drug molecular size

Answer 23

• most drugs molecular weight between 100 to 1000 Da
• drugs&raquo_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

Question 24

drug reactivity and drug-receptor bonds

Answer 24

drugs interact with receptors by chemical forces or bonds

pg 1669

Question 25

covalent bonds

Answer 25

* 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) ## Footnote pg 1669

Question 26

electrostatic bonding, weak hydrogen bonding, Van der Waals forces, hydrophobic bonds

Answer 26

* *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 ## Footnote pg 1670

Question 27

drug shape

Answer 27

* 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 ## Footnote pg 1671-1672

Question 28

drug chirality

Answer 28

* 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* ## Footnote pg 1671

Question 29

types of drug-receptor interactions

Answer 29

* *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 ## Footnote pg 1673

Question 30

allosteric inhibition

Answer 30

* 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 ## Footnote pg 1674

Question 31

drug groups

Answer 31

* 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 ## Footnote pg 1675

Question 32

new drug development and regulation

Answer 32

* 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 ## Footnote pg 1676-1678

Question 33

trademark

Answer 33

drug's proprietary trade name and is usually registered; legally protected as long as it is used ## Footnote pg 1679

Question 34

Food & Drug Administration (FDA)

Answer 34

* 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 ## Footnote pg 1680