Pharmacology: Basic Concepts Flashcards
Pharmacology
Study of drugs and their interactions with living systems
Therapeutics
The use of drugs to diagnose, prevent pregnancy, or treat disease states
Pharmacokinetics
The study of how living systems process drugs
Pharmacodynamics
The study of how drugs affect living systems
Pharmacogenomics
The study of how genetics affect our drug response
ADME: what does it stand for and does it fall under pharmacokinetics or pharmacodynamics?
Absorption, Distribution, Metabolism, Excretion
Pharmacokinetics
Drug-receptor interactions, patient’s functional state, placebo effects… these fall under pharmacokinetics or pharmacodynamics?
Pharmacodynamics
Schedule I Drugs
High abuse potential with no accepted medical uses
Schedule II drugs
High abuse potential WITH accepted medical uses (opiates, methylphenidate)
Schedule III drugs
Abuse potential, but less than I or II
(Codeine, steroids, pseudoephedrine - IN OREGON ONLY). Can differ from one state to the next.
Schedule IV drugs
Include benzos
Schedule V drugs
Include cough medicine
Pregnancy Categories A, B, C, D, X
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
Clinical trial Phase I purpose
First in human studies
Healthy volunteers
Know what they’re taking.
Goal is to assess safety and tolerability
Clinical Trial Phase II
First in patient studies
Patients receive drug
Randomized, controlled, maybe blind
Goal: correct dose and efficacy
Clinical Trials phase 3
Hundreds of thousands of patients
Randomized, controlled, maybe blind
Best phase to gather info from.
Clinical Trials phase IV
Post-marketing surveillance.
DDIs, AEs.
Simple Occupancy Theory
The number of places a drug binds to a receptor is proportional to the intensity of the effects.
Modified Occupancy Theory
Strength of the attraction between drug and receptor affects the potency of the drug. Drugs with lower affinity require higher concentrations to bind.
Intrinsic activity
The ability of a drug to activate a receptor to produce an effect
Noncompetitive antagonists
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.
Competitive antagonists
Compete for receptors with equal affinity as the agonists.
Bind reversibly, so whichever has the most creates the strongest effect.
Partial agonists
Can’t produce a 100% effect, no matter how much you give.
Receptorless drugs
Antacids, laxatives, chelating agents
Dose response curve: Pharmacodynamics or Pharmacokinetics?
What’s the x-variable and what’s the y-variable?
Pharmacodynamics.
X-variable: concentration of the drug
Y-variable: effect or response
Relative potency
-does it affect maximal efficacy?
The amount of a drug needed to produce an effect.
Has nothing to do with maximal efficacy.
EC50
The concentration of a drug that produces a specific response intensity in 50% of the population
ED50
The dose of a drug that produces the same response in 50% of the population.
Aka: “median effective dose”
The smaller the ED50, the _____ potent
More
Therapeutic Index or Therapeutic window
How to calculate?
How safe a drug is.
The higher the TI, the safer the drug.
Toxic dose/(dose needed for therapeutic response)
LD50/ED50
Factors in bioavailability of a drug
Rate of dissolution Surface area Blood flow Lipid solubility of a drug Ph partitioning Route of administration
Ion trapping
Acidic drugs accumulate on the alkaline side of a membrane, while basic drugs accumulate on the acidic side of a membrane
Percutaneous route
Lipid soluble
Massaging increases absorption
When can non-lipid soluble drugs enter the BBB?
Only when they have a transport system to get across. All other drugs must be lipid-soluble.
ABC transporters - what does it stand for? What do they rely on?
ATP Binding Cassette transporter
Rely on ATP
Use P-glycoproteins (site of many DDIs). If blocked, can affect absorption.
SLC transporters
Solute Carrier Transporters
Don’t use ATP.
Facilitated transport and ion-coupled secondary active transport.
Protein bound drugs - what does this mean?
Bound to albumin
Won’t cross membranes if bound (bonds are reversible)
Where does metabolism of drugs usually happen? What does it mean?
At the liver, usually. Means the enzymatic alteration of the structure of the drug. Form metabolites (usually inactive, but sometimes active).
Prodrug
When a drug becomes active AFTER metabolism by the liver.
Phase I of drug metabolism - what is it?
Chemical process - oxidation/reduction/hydrolysis
-modifies functional group or breaks into smaller pieces
Phase II of drug metabolism - what is it?
Conjugation with an endogenous substance. Allows for better excretion by forming a more polar molecule.
What are drug-metabolizing enzymes? Which are the major ones?
The enzymes that metabolize in Phase I. Cytochrome P450s (P450 or CYP): major hepatic enzymes
Transferases - what do they do? What phase of drug metabolism are they associated with?
Transfer endogenous substances onto drugs.
Phase II of drug metabolism.
Why does the first pass effect happen? What is the bioavailability of oral meds as a result?
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.
What is enterohepatic recirculation?
Repeating cycle that brings drug from liver to bile to GI tract and back. Requires glucaronidation.
What are the 3 processes of renal excretion?
- Glomerular filtration
- Passive tubular reabsorption
- Active tubular secretion (needs ATP)
What is the time-concentration curve?
Demonstrates the relationship between the time after administration and the drug concentration in the body
What is the Therapeutic Range? What’s the equation?
In the time-concentration curve, the range between minimum toxic concentration and the minimum effective concentration.
MTC-MEC
How many half-lives are needed to eliminate a drug from the system?
4
What happens to the half-life of a drug in renal failure?
The half-life increases
Direct chemical or physical interactions between drugs consist of what? What are two big rules?
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.
Pharmacokinetic interactions consist of what?
Medications that alter another’s ADM or E.
Ex:
-affect transporters like p-glycoproteins
-affect metabolism like CYP enzymes (induce or inhibit)
Pharmacodynamic drug interactions - where are they likely to happen?
Can be at same receptor (usually inhibitory)
Or at separate sites (potentiative or inhibitory)
What’s the problem with grapefruit juice?
It can inhibit CYP3A4 metabolism of certain drugs.
What effect does St John’s Wort tend to have on drugs?
It induces drug-metabolizing enzymes, reducing blood levels of many drugs.
Iatrogenic disease
Drug induced disease (like Parkinson’s symptoms created by antipsychotics)
If you’re checking for aspartate aminotransferase and alanine aminotransferase, you’re checking what?
LFTs
What’s the difference between pharmacogenetics and pharmacogenomics?
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.
Genetic polymorphism
Variation in genetic code. (Ex: CYP2D6 and codeine metabolism). Can affect protein structure, metabolism speed, qty, or nothing at all.
