Pharmacology: Basic Concepts

Question 1

Pharmacology

Answer 1

Study of drugs and their interactions with living systems

Question 2

Therapeutics

Answer 2

The use of drugs to diagnose, prevent pregnancy, or treat disease states

Question 3

Pharmacokinetics

Answer 3

The study of how living systems process drugs

Question 4

Pharmacodynamics

Answer 4

The study of how drugs affect living systems

Question 5

Pharmacogenomics

Answer 5

The study of how genetics affect our drug response

Question 6

ADME: what does it stand for and does it fall under pharmacokinetics or pharmacodynamics?

Answer 6

Absorption, Distribution, Metabolism, Excretion

Pharmacokinetics

Question 7

Drug-receptor interactions, patient’s functional state, placebo effects… these fall under pharmacokinetics or pharmacodynamics?

Answer 7

Pharmacodynamics

Question 8

Schedule I Drugs

Answer 8

High abuse potential with no accepted medical uses

Question 9

Schedule II drugs

Answer 9

High abuse potential WITH accepted medical uses (opiates, methylphenidate)

Question 10

Schedule III drugs

Answer 10

Abuse potential, but less than I or II

(Codeine, steroids, pseudoephedrine - IN OREGON ONLY). Can differ from one state to the next.

Question 11

Schedule IV drugs

Answer 11

Include benzos

Question 12

Schedule V drugs

Answer 12

Include cough medicine

Question 13

Pregnancy Categories A, B, C, D, X

Answer 13

A: no risk to fetus in 1st trimester
B: no well controlled human studies, but no risk in animal studies
C: animal studies have adverse effects, but in humans benefits outweigh risks
D: Fetal risk. Only really ok if no safer alternative
X: Fetal abnormalities. Don’t use

Question 14

Clinical trial Phase I purpose

Answer 14

First in human studies
Healthy volunteers
Know what they’re taking.
Goal is to assess safety and tolerability

Question 15

Clinical Trial Phase II

Answer 15

First in patient studies
Patients receive drug
Randomized, controlled, maybe blind
Goal: correct dose and efficacy

Question 16

Clinical Trials phase 3

Answer 16

Hundreds of thousands of patients
Randomized, controlled, maybe blind
Best phase to gather info from.

Question 17

Clinical Trials phase IV

Answer 17

Post-marketing surveillance.

DDIs, AEs.

Question 18

Simple Occupancy Theory

Answer 18

The number of places a drug binds to a receptor is proportional to the intensity of the effects.

Question 19

Modified Occupancy Theory

Answer 19

Strength of the attraction between drug and receptor affects the potency of the drug. Drugs with lower affinity require higher concentrations to bind.

Question 20

Intrinsic activity

Answer 20

The ability of a drug to activate a receptor to produce an effect

Question 21

Noncompetitive antagonists

Answer 21

Bind irreversibly to an allosteric site
Fewer available receptors reduces the maximum possible effect.
Adding more agonist doesn’t help because the receptor sites have changed.

Question 22

Competitive antagonists

Answer 22

Compete for receptors with equal affinity as the agonists.

Bind reversibly, so whichever has the most creates the strongest effect.

Question 23

Partial agonists

Answer 23

Can’t produce a 100% effect, no matter how much you give.

Question 24

Receptorless drugs

Answer 24

Antacids, laxatives, chelating agents

Question 25

Dose response curve: Pharmacodynamics or Pharmacokinetics? | What’s the x-variable and what’s the y-variable?

Answer 25

Pharmacodynamics. X-variable: concentration of the drug Y-variable: effect or response

Question 26

Relative potency | -does it affect maximal efficacy?

Answer 26

The amount of a drug needed to produce an effect. | Has nothing to do with maximal efficacy.

Question 27

EC50

Answer 27

The concentration of a drug that produces a specific response intensity in 50% of the population

Question 28

ED50

Answer 28

The dose of a drug that produces the same response in 50% of the population. Aka: “median effective dose”

Question 29

The smaller the ED50, the _____ potent

Answer 29

More

Question 30

Therapeutic Index or Therapeutic window | How to calculate?

Answer 30

How safe a drug is. The higher the TI, the safer the drug. Toxic dose/(dose needed for therapeutic response) LD50/ED50

Question 31

Factors in bioavailability of a drug

Answer 31

``` Rate of dissolution Surface area Blood flow Lipid solubility of a drug Ph partitioning Route of administration ```

Question 32

Ion trapping

Answer 32

Acidic drugs accumulate on the alkaline side of a membrane, while basic drugs accumulate on the acidic side of a membrane

Question 33

Percutaneous route

Answer 33

Lipid soluble | Massaging increases absorption

Question 34

When can non-lipid soluble drugs enter the BBB?

Answer 34

Only when they have a transport system to get across. All other drugs must be lipid-soluble.

Question 35

ABC transporters - what does it stand for? What do they rely on?

Answer 35

ATP Binding Cassette transporter Rely on ATP Use P-glycoproteins (site of many DDIs). If blocked, can affect absorption.

Question 36

SLC transporters

Answer 36

Solute Carrier Transporters Don’t use ATP. Facilitated transport and ion-coupled secondary active transport.

Question 37

Protein bound drugs - what does this mean?

Answer 37

Bound to albumin | Won’t cross membranes if bound (bonds are reversible)

Question 38

Where does metabolism of drugs usually happen? What does it mean?

Answer 38

``` At the liver, usually. Means the enzymatic alteration of the structure of the drug. Form metabolites (usually inactive, but sometimes active). ```

Question 39

Prodrug

Answer 39

When a drug becomes active AFTER metabolism by the liver.

Question 40

Phase I of drug metabolism - what is it?

Answer 40

Chemical process - oxidation/reduction/hydrolysis | -modifies functional group or breaks into smaller pieces

Question 41

Phase II of drug metabolism - what is it?

Answer 41

Conjugation with an endogenous substance. Allows for better excretion by forming a more polar molecule.

Question 42

What are drug-metabolizing enzymes? Which are the major ones?

Answer 42

``` The enzymes that metabolize in Phase I. Cytochrome P450s (P450 or CYP): major hepatic enzymes ```

Question 43

Transferases - what do they do? What phase of drug metabolism are they associated with?

Answer 43

Transfer endogenous substances onto drugs. | Phase II of drug metabolism.

Question 44

Why does the first pass effect happen? What is the bioavailability of oral meds as a result?

Answer 44

Because the drug goes from the GI tract to the liver before entering systemic circulation. Oral meds have a 0.5 bioavailability because of this.

Question 45

What is enterohepatic recirculation?

Answer 45

Repeating cycle that brings drug from liver to bile to GI tract and back. Requires glucaronidation.

Question 46

What are the 3 processes of renal excretion?

Answer 46

1. Glomerular filtration 2. Passive tubular reabsorption 3. Active tubular secretion (needs ATP)

Question 47

What is the time-concentration curve?

Answer 47

Demonstrates the relationship between the time after administration and the drug concentration in the body

Question 48

What is the Therapeutic Range? What’s the equation?

Answer 48

In the time-concentration curve, the range between minimum toxic concentration and the minimum effective concentration. MTC-MEC

Question 49

How many half-lives are needed to eliminate a drug from the system?

Answer 49

4

Question 50

What happens to the half-life of a drug in renal failure?

Answer 50

The half-life increases

Question 51

Direct chemical or physical interactions between drugs consist of what? What are two big rules?

Answer 51

Usually in an IV solution. Big rules: don’t administer if you see precipitate. Never combine drugs in the same container unless you know a reaction won’t occur.

Question 52

Pharmacokinetic interactions consist of what?

Answer 52

Medications that alter another’s ADM or E. Ex: -affect transporters like p-glycoproteins -affect metabolism like CYP enzymes (induce or inhibit)

Question 53

Pharmacodynamic drug interactions - where are they likely to happen?

Answer 53

Can be at same receptor (usually inhibitory) | Or at separate sites (potentiative or inhibitory)

Question 54

What’s the problem with grapefruit juice?

Answer 54

It can inhibit CYP3A4 metabolism of certain drugs.

Question 55

What effect does St John’s Wort tend to have on drugs?

Answer 55

It induces drug-metabolizing enzymes, reducing blood levels of many drugs.

Question 56

Iatrogenic disease

Answer 56

Drug induced disease (like Parkinson’s symptoms created by antipsychotics)

Question 57

If you’re checking for aspartate aminotransferase and alanine aminotransferase, you’re checking what?

Answer 57

LFTs

Question 58

What’s the difference between pharmacogenetics and pharmacogenomics?

Answer 58

Pharmacogenetics refers to differences in a single gene and how it alters drug responses, while pharmacogenomics refers to differences in multiple genes and how it affects drug response.

Question 59

Genetic polymorphism

Answer 59

Variation in genetic code. (Ex: CYP2D6 and codeine metabolism). Can affect protein structure, metabolism speed, qty, or nothing at all.