Pharmacology Flashcards
Molecular Weight
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
Drug Solubility
> max concentration of a substance that may be completely dissolved in a given solvent at a given temp/pressure
Solute/Solvent Properties
Want it to be able to cross the lipid bilayer (soluble in lipids) and want it to be circulated (soluble in water) –> IDEAL = BOTH
4 elements of pharmakokinetics
Absorption
Distribution
Metabolism
Excretion
paracellular pathway
Go between tight gaps btwn cells
>Dictated by: concentration gradient and gap presence
>Benefit: drugs do not need to be lipid soluble
Transcellular Pathways for drugs
- Simple Diffusion (i.e. lipid soluble drugs)
- Facilitated Diffusion (piggyback on another carrier)
- Active Transport (requires ATP) - lots of drugs can block receptors and pumps in this method (SSRIs)
- Vasicular Transport (little pockets)
Steps of Absorption
- Administration
- Dissolution (how drug is broken down)
- Absorption
- Distribution
- Excretion
Dissolution
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
Absorption
drug crossing in to bloodstream
Bioavailability
The extent and rate at which the active moiety (drug/metabolite) enters systemic circulation
(ex: IV = 100% bioavailability)
Causes of Low Bioavailability
- 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 - 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) - Age, sex, physical activity, genetic phenotype, stress, disorders, previous GI surgery
Distribution
from systemic circulation to tissues
2 main fluid compartments of your body
ECF = plasma and interstitial
ICF
*These 2 are in constant equilibrium
Third Spacing
fluid with no functional purpose besides lubrication (i.e. pleural fluid)
2 phases of distribution
1st Phase: hits major organs first and fast
2nd Phase: drug in circulation and drug in tissue reaches equilibrium
How do you measure absorption?
Bioavailability
How do you measure distribution?
Vd (volume of distribution)
What factors influence distribution?
- Acid drugs = hang out near plasma proteins VS. Basic drugs = hang out near tissue** - less important
- Protein Binding makes drugs less effective
- Sex (male vs female) - physiological and hormonal differences
- Age
- Body fat/size of patient - DOSING
- Relative blood flow, CO and perfusion rates
- Capillary permeability
- Lipid solubility
- pH (drug pKa)
1st phases of metabolism
Phase 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
2nd phases of metabolism
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)
