M1 Lecture 1: General Pharm

Question 1

what does “pharmakon” mean in greek

Answer 1

medicine (drug)

Question 2

what does “logos” mean in greek

Answer 2

study

Question 3

what is a drug

Answer 3

any substance received by a biological system that is not for nutrition purposes (chemicals, biologicals, herbals)

Question 4

pharmacodynamics

Answer 4

effects of drug on body (ex: to lower blood sugar, or blood pressure)

Question 5

pharmacokinetics

Answer 5

effects on body on drug (absorption, distribution, metabolism, excretion [ADME])

Question 6

pharmacogenomics

Answer 6

genetic factor that underlie variation of drug response (some ppl break down drugs faster/slower depending on the drug)

Question 7

2 mechanisms of drug action and what does each do

Answer 7

1. Mediated by receptors (most drugs): modulate an endogenous process (block cholesterol synthesis), stim or inhibit receptor (opioids - beta blockers)
2. Not mediated by receptors (only few drugs)

Question 8

what is a receptor

Answer 8

protein molecules, target for drug interactions
diff tissues will have a diff combination of receptors
both extra and intracellular receptors

Question 9

extracellular receptors

Answer 9

location: outer surface of cell membrane
water soluble drugs*

Question 10

intracellular receptors

Answer 10

location: inner surface of membrane inside cell, and within the cytoplasm or the nucleus
fat soluble drugs*

Question 11

4 types of drug receptors

Answer 11

regulatory proteins, transporters, enzymes, structural proteins

Question 12

regulatory proteins

Answer 12

“switch”
Regulates DNA transcription via expression of RNA polymerase
best described receptors
activated by endogenous ligands (hormones or neurotransmitters)
drug ex: propranolol - beta blocker

Question 13

transporters

Answer 13

“gatekeeper”
Transports substances across cell membranes
- proteins that transport endogenous (electrolytes and irons) substances across cell membranes
- drugs often inhibit the function of the transporter
drug ex: SSRIs - antidepressants

Question 14

enzymes

Answer 14

“overseer”
Increases rate of biological reactions
- proteins that catalyze a bio reaction
- drugs often inhibit the catalytic function of the enzyme
drug ex: statins - antineoplastic

Question 15

structural proteins

Answer 15

“skeleton”
Contributes to cell’s structure
- proteins that contribute to the cell structure
- drugs that bind to structural proteins in the cell and disrupt their normal function
drugs ex: vincristine - antineoplastic

Question 16

Drug-Receptor Interactions (D-R interactions)

Answer 16

• drugs acting on active sites: agonists/antagonists
  Direct action on binding site
  Agonist (full, partial, or inverse): produces intended response
  Antagonist (reversible or irreversible): produces no response
• drugs acting on allosteric sites: act on non-active sites, cause confrontational changes on the receptor
  Action on alternative sites of receptor
  Activator: promotes agonistic effect
  Inhibitor: prevents agonistic effect without binding to active site

Question 17

Full Agonists

Answer 17

Agonist boosts the effect: might be strong enough to fully use effect (full agonist is max effect)

Question 18

Partial Agonist

Answer 18

Partial agonist is slight boost

Question 19

Neutral Agonist

Answer 19

Neutral agonist (substance blocks effect but shows nothing)

Question 20

Inverse Agonist

Answer 20

Inverse agonist (opposite effect as agonist)

Question 21

Allosteric Activators

Answer 21

Activator: promotes agonistic effect

Potentiates the agonistic effect

(look at diagram on slide)
Active site is where a substrate would be, allosteric site is area might be affected by drug

Allosteric activator gets in contact with the allosteric site and changes it so the substance cannot bind with the changed active site

Question 22

Allosteric Inhibitors

Answer 22

Non-competitive Inhibition

prevents agonistic effect without binding to active site

Question 23

what are 4 receptors drugs are coupled with?

Answer 23

1. intracellular receptors (ex: steroid receptors)
2. enzyme-linked receptors (ex: insulin receptors)
3. ion channel receptors (ex: calcium channel blockers receptors)
4. g-protein coupled receptors (ex: adrenergic receptors)

Question 24

what does D-R coupling trigger

Answer 24

a series of events (=signalling pathways)
modulates endogenous homeostasis or function

Question 25

5 steps of D-R coupling and signalling mechanisms

Answer 25

1. intracellular: Signal crosses plasma membrane to act on receptor in cell 2. enzyme-linked: Signal binds to extracellular component of transmembrane protein to active enzyme activity. Signal binds to extracellular component of transmembrane protein, which is bound to tyrosine kinase enzyme intracellularly for activation 4. ion-channel: Signal binds, which opens ion channel 5. g-protein: Signal binds cell-surface receptor linked to effector enzyme on G-protein

Question 26

dose

Answer 26

measured quantity of therapeutic agent taken at one time

Question 27

drug response

Answer 27

pharmacodynamics response to drug

Question 28

drug-response relationship

Answer 28

more drug given, greater the response until a certain point lots of receptors - strong drug response few receptors - weak response no receptors - no response diff receptors - no response

Question 29

potency

Answer 29

dose required to produce response to a certain magnitude

Question 30

efficacy

Answer 30

maximal response that a drug can produce as we increase dose

Question 31

Therapeutic Index (TI)

Answer 31

quantitative measurement of relative safety of drug - comparison of amount of drug that causes the therapeutic effect to the amount that causes toxicity Higher TI = safer drug and vice versa

Question 32

how to calculate therapeutic index

Answer 32

TI = TD50 (toxic dose to 50% of subjects) / ED50 (Effective dose in 50% of subjects) its a ratio look at slide if need help

Question 33

therapeutic range

Answer 33

range where drug has desired effects on body drugs administered for therapeutic effect, not to cause adverse effects drugs with narrow therapeutic range require closer monitoring (larger range = safer)