Neuropharmacology: Drug Action, Dose-Response, Barriers, and Class Logistics
Drug Naming and Neuropharmacology Basics
Drug naming conventions
Chemical name: describes the chemical structure of the compound.
Trade name: brand name assigned by the pharmaceutical company (example discussions included heroin, clonase, Prozac as examples of trade/generic naming in class).
Generic name: descriptive, common name for the drug, often reflects its class or mechanism.
The instructor emphasized these three naming types and how they relate to classifying and identifying drugs.
Neurons and neurocommunication (context for drug action)
Drugs affect neurotransmission by altering release of neurotransmitters at synapses (e.g., release from boutons) and binding to receptors on the postsynaptic neuron.
The upcoming discussion in the lesson focuses on binding and receptor interactions as a core mechanism of drug effects.
Routes of Administration and Absorption
Routes of administration discussed
Inhalation
Oral (including ingestion)
Injection
Absorption through mucous membranes
Types of injection highlighted
Intravenous (IV)
Intraperitoneal (IP)
Subcutaneous (SC)
Intravenous/intravascular (discussed as fastest pathway in practice)
Relative speed of routes
Fastest: IV injection (intravenous) — peak effect occurs rapidly.
Inhalation often produces a rapid peak similar to injection.
Ingestion/absorption through mucous membranes are slower and more variable.
Factors affecting absorption (baseline points from previous discussion)
Drug dose is often expressed as:
Dose (mg) per body weight:
Physiological factors that influence absorption the most: sex, body size, age, and body water-to-fat ratio (water-to-fat ratio).
Higher water content generally means more dilute drug in the body; body composition affects concentration and distribution.
Notes on body composition example
Water-to-fat ratio influences how concentrated a drug is in the body after administration.
Lipid-soluble drugs tend to accumulate in fat stores; water-soluble drugs are less likely to be stored and are excreted more readily.
Dose-Response Concepts and Safety Metrics
Dose-response curve basics
X-axis: Dose of drug
Y-axis: Percentage of individuals showing a given effect (often represented as % of population with the effect)
Curves are typically sigmoidal (an inverted-S shape on some presentations): increasing dose increases effect up to a plateau.
Meaning of dose, effect, and safety thresholds
The curve helps illustrate safety and efficacy: where the desired effect occurs vs. where adverse effects begin.
Examples discussed included effects like slowed reaction time, ataxia, coma, and death depending on dose.
When ED and TD (or LD) curves overlap substantially, the therapeutic window is narrow and dosing is riskier.
Key definitions (percent-based dosing terminology)
ED
ED$_{50}$: dose producing the desired effect in 50% of the population.
ED${10}$, ED${90}$, etc., denote doses producing the effect in 10% or 90% of the population respectively.
TD
TD$_{50}$: dose producing toxic effects in 50% of the population.
TD${10}$, TD${90}$, etc., similarly defined for toxicity thresholds.
LD
LD$_{50}$: dose lethal in 50% of the population (used in animal studies).
Therapeutic index (margin of safety)
Definition: the ratio that compares the toxic/lethal dose to the effective dose.
Human focus: use TD${50}$ divided by ED${50}$ to yield the therapeutic index (TI).
Calculation:
Interpretation:
A low TI means a narrow safety margin (toxic effects occur not far above therapeutic effects).
A high TI means a wide safety margin (therapeutic effects occur far below toxic effects).
Example notes from lecture:
Barbiturates have a TI of about 2–3 (narrow safety margin).
Diazepam (Valium) has a TI around ~100 (wide safety margin).
Practical notes on TI calculations
TI can be calculated with different percentile points, as long as you use the same percentile for both the numerator and the denominator:
E.g., TI = TD${10}$ / ED${10}$ is valid and yields the margin at 10% thresholds, if that convention is used.
The formula TD${50}$/ED${50}$ is the standard interpretation for humans in class discussions.
In veterinary or animal studies, TI is often LD${50}$/ED${50}$ (lethal dose rather than toxic dose) due to ethical considerations.
Graphical interpretation of potency vs. efficacy
Potency: reflected by the left-right position of the ED/TD curves (which drug achieves the effect at a lower dose).
Efficacy: reflected by the height of the maximum effect (which drug achieves a higher ceiling of effect).
In the exercise, Drug A and Drug B were similarly potent (curves near each other on the x-axis); Drug C was more efficacious (higher maximum effect) but not necessarily more potent.
Essential questions for comparing drugs:
Which is more potent? The one with the curve shifted left (lower ED$_{50}$).
Which is more efficacious? The one reaching a greater maximum effect.
Example scenario and quick calculations
Hypothetical numbers: Suppose an ED${50}$ is at 4.0 and a TD${50}$ is at 40.0.
TI =
If a more conservative approach uses ED${10}$ and TD${10}$, you would compute TI with those same percentiles:
TI =
High TI (e.g., Valium) indicates a large separation between effective and toxic doses; low TI (e.g., barbiturates) indicates a narrow separation and higher risk.
Blood-Brain Barrier (BBB) and Barrier Types
Blood-brain barrier (BBB) function and structure
BBB is a semipermeable barrier that protects the brain by restricting which substances can cross from the bloodstream into brain tissue.
Structure: brain capillaries lined by endothelial cells with tight junctions; astrocyte glial end-feet cover and interact with the capillaries to regulate permeability.
Endothelial cells and astrocyte feet collectively limit passage of many substances.
Permeability principles
Small molecules (e.g., oxygen, CO$_2$) readily cross.
Lipid-soluble (fat-soluble) molecules cross more easily than water-soluble molecules.
Water-soluble molecules cross poorly unless transported or extremely small.
Lipid-soluble vs. water-soluble drugs (examples)
Lipid-soluble: dissolve in fat; can cross membranes easily; can accumulate in adipose tissue; examples discussed include cannabis (stored in fat) and heroin (described as highly lipid-soluble, explaining rapid brain entry and a rush).
Water-soluble: not stored in fat; excreted more readily; vitamins like Vitamin C are typically water-soluble.
Important caveat from lecture examples
An example in the notes described iron as lipid-soluble and stored in fat; this is not accurate in physiological terms (iron is not lipid-soluble). It’s important to verify this point when studying; iron is typically transported differently and is not stored as a lipid-soluble compound. Use this note as a correction cue when reviewing with peers or instructors.
Placental Barrier
The placental barrier is analogous to the BBB in concept but differs in permeability
It is more permissive than the BBB, allowing more water-soluble molecules to cross from mother to fetus.
This implies that drugs affecting the brain in the mother may also affect the fetal brain via placental transfer.
Practical implication
Pregnant individuals must consider placental transfer when evaluating drug safety for the fetus; some substances cross more readily due to placental barrier properties.
Real-World Examples and Mechanistic Links
Heroin vs. morphine and lipid solubility
Both are opioids with analgesic properties, but heroin is more lipid-soluble due to structural modifications.
Higher lipid solubility allows heroin to cross the BBB more rapidly, producing a swift brain “rush.”
Morphine is less lipid-soluble, leading to slower brain onset and different user experience.
Why lipid solubility matters for addiction potential
Rapid entry into the brain via high lipid solubility can lead to faster onset of euphoria or reward, contributing to higher addiction potential for certain drugs.
Exam Preparation and Class Logistics (as discussed in transcript)
Upcoming schedule overview (tentative)
Lecture today, another lecture on Wednesday, followed by Friday review or finishing up the lecture.
Friday class may include exam breakdown; plan accordingly.
Class assignment and online quiz
A homework/quiz is available on soccerdiv.com (or the corresponding app).
The assignment is described as containing multiple questions (notes indicate six questions, with a mention of four questions in another part of the transcript; verify the exact number before submission).
Students should include their name when completing the assignment.
Quick Reference: Key Formulas and Concepts
Dose per body weight
Therapeutic index
For animals:
Percentile-based TI adjustments
You can compute TI at other percentages: where p = 10, 50, 90, etc.
Dose-response interpretation
Leftward shift = higher potency
Higher plateau = greater efficacy
Narrow TI = higher safety risk; wide TI = safer dosing window
BBB permeability rules (summary)
Small molecules pass easily
Lipid-soluble molecules cross readily
Water-soluble molecules cross with difficulty
Gases (O$2$, CO$2$) pass freely
Notes and cautions for study discipline
Always distinguish between lipid-soluble vs water-soluble properties when predicting CNS penetration.
Remember the different barriers and their implications for drug safety in special populations (e.g., pregnancy with placental transfer).
Be able to explain the difference between potency vs efficacy using graph interpretation and be able to identify the implications for choosing a drug in therapeutic contexts.
Verify ambiguous points from the lecture (e.g., exact assignment count on soccerdiv) with the instructor or updated slides.