Pharmacology

Question 1

Molecular Weight

Answer 1

A significant factor that determines ease of entry into certain body spaces
>Lower Weight = smaller molecules = easier for drug to move into body
>use larger drug in lactating women to prevent accumulation in breast milk

Question 2

Drug Solubility

Answer 2

> max concentration of a substance that may be completely dissolved in a given solvent at a given temp/pressure

Question 3

Solute/Solvent Properties

Answer 3

Want it to be able to cross the lipid bilayer (soluble in lipids) and want it to be circulated (soluble in water) –> IDEAL = BOTH

Question 4

4 elements of pharmakokinetics

Answer 4

Absorption
Distribution
Metabolism
Excretion

Question 5

paracellular pathway

Answer 5

Go between tight gaps btwn cells
>Dictated by: concentration gradient and gap presence
>Benefit: drugs do not need to be lipid soluble

Question 6

Transcellular Pathways for drugs

Answer 6

1. Simple Diffusion (i.e. lipid soluble drugs)
2. Facilitated Diffusion (piggyback on another carrier)
3. Active Transport (requires ATP) - lots of drugs can block receptors and pumps in this method (SSRIs)
4. Vasicular Transport (little pockets)

Question 7

Steps of Absorption

Answer 7

1. Administration
2. Dissolution (how drug is broken down)
3. Absorption
4. Distribution
5. Excretion

Question 8

Dissolution

Answer 8

How a drug is broken down

• Drugs can be manipulated to dissolve where we want it to dissolve (coated pills to pass through stomach to small intestine)
• Problems: if you need fast acting, a pill won’t work

Question 9

Absorption

Answer 9

drug crossing in to bloodstream

Question 10

Bioavailability

Answer 10

The extent and rate at which the active moiety (drug/metabolite) enters systemic circulation
(ex: IV = 100% bioavailability)

Question 11

Causes of Low Bioavailability

Answer 11

1. Insufficient Absorption
   (i. e. drug binds with another molecule and makes it polar OR drug is a large molecule) OR Lack of time to absorb
2. First Pass Metabolism
   (i. e. goes through liver filtration first - metabolized before target site. Gets drug out of the system quicker. Issue is PO meds)
3. Age, sex, physical activity, genetic phenotype, stress, disorders, previous GI surgery

Question 12

Distribution

Answer 12

from systemic circulation to tissues

Question 13

2 main fluid compartments of your body

Answer 13

ECF = plasma and interstitial
ICF
*These 2 are in constant equilibrium

Question 14

Third Spacing

Answer 14

fluid with no functional purpose besides lubrication (i.e. pleural fluid)

Question 15

2 phases of distribution

Answer 15

1st Phase: hits major organs first and fast

2nd Phase: drug in circulation and drug in tissue reaches equilibrium

Question 16

How do you measure absorption?

Answer 16

Bioavailability

Question 17

How do you measure distribution?

Answer 17

Vd (volume of distribution)

Question 18

What factors influence distribution?

Answer 18

1. Acid drugs = hang out near plasma proteins VS. Basic drugs = hang out near tissue** - less important
2. Protein Binding makes drugs less effective
3. Sex (male vs female) - physiological and hormonal differences
4. Age
5. Body fat/size of patient - DOSING
6. Relative blood flow, CO and perfusion rates
7. Capillary permeability
8. Lipid solubility
9. pH (drug pKa)

Question 19

1st phases of metabolism

Answer 19

Phase 1:

1. Oxidation (phase 1): a. CYP 2D6, CYP3A4 –> enzymes that catalyze the oxidation of many drugs
   i. Inhibitor = a lot of drug interactions
   ii. Inducer = less side effects/interaction (decreases effectiveness)
   b. The drug is oxidized (little change to the polarity)
   c. Can change it to be inactive without significant alteration to chemical structure
   i. Can be induced or inhibited by many drugs and substances resulting in drug interactions

Question 20

2nd phases of metabolism

Answer 20

Conjugation:

a. Addition of a functional group to the drug that makes it very polar
b. Increases clearance
c. Glucuronidation (most common phase II rxn - in liver)