Video Summary - Tema 2. FARMACOCINÉTICA; Absorción.

Main ideas and concepts (Topic 2: Pharmacokinetics — Absorption)

After administration, a drug must:

reach its site of action
achieve an adequate concentration to produce an effect
then be eliminated

Pharmacokinetics studies four major processes that generally occur for drugs:

Absorption
Distribution
Metabolism
Excretion

These processes happen simultaneously (a drug can be absorbed while also being distributed, metabolized, or excreted).

Absorption: what it is and what influences it

Absorption is the entry of drugs into the body from the administration site, described as the passage through cell membranes.

Key determinants of absorption

Liposolubility (fat solubility)
Degree of ionization
Characteristics of the pharmaceutical preparation
Site of absorption
Presystemic elimination, especially first hepatic passage (the drug may be destroyed before reaching systemic circulation)

General rule stated

Liposoluble, low-molecular-weight, and non-ionized drugs cross biological membranes more easily.

Mechanisms by which drugs cross membranes

Passive diffusion (most drugs use this)
- The drug crosses the membrane by dissolving in the lipid bilayer
- Movement is down a concentration gradient
- Occurs without energy expenditure
- Rate depends on drug concentration
  - faster when concentration is higher on one side
  - continues until concentrations equalize across the membrane
- Follows first-order kinetics and is governed by Fick’s (FIC’s) law (as stated)
Ionization concept (important for passive diffusion)

Many drugs are weak acids or bases and exist as:

  - **Ionized fraction**: **water-soluble**
  - **Non-ionized fraction**: **lipid-soluble** (crosses membranes more easily)

The amount ionized/non-ionized depends on:

  - the drug’s **acidic/basic nature**
  - the **pH of the medium**
  - the drug’s **pK**
  - the pH at which **50%** of the drug is ionized

The Henderson–Hasselbalch equation (Henderson-Geselbag as stated) links pH and pK to determine ionized vs unionized fractions.

Changing pH can therefore change membrane crossing:

  - can **accelerate elimination via urine**
  - can **block absorption** using substances that alter pH

Diffusion through pores / filtration
- Passage through aqueous channels in the membrane
- For substances with:
  - low molecular weight
  - negative charge
- Positively charged substances are said to cross via active transport.
Active transport / carrier-mediated transport (transport by carriers)

Protein-like carriers:

  - capture the drug on one side of the membrane
  - transport it to the other side

Can occur as:

  - **Facilitated transport** (passive; **no energy expenditure**)
  - **Active transport** (energy expenditure)

Compared with passive diffusion, carrier-mediated transport can:

  - become **saturated**
  - after saturation, the rate **stops increasing**
  - show **competition** if other substances use the same carrier

Kinetics are described as mixed-order kinetics, governed by the Michaelis–Menten equation (referred to as Michelis-Enter in the subtitles).

Locations where this is important include:

  - **blood-brain barrier**
  - **digestive tract**
  - **renal tubule**
  - **bile ducts**
  - **placenta**

Endocytosis and exocytosis (for macromolecules/particles)

Involve rupture/opening of the cell membrane.

  - **Endocytosis**
      - membrane forms an **invagination**
      - invagination closes to form a **vacuole**
      - vacuole is released into the **cytoplasm**
      - described as a proposed method for **selectively releasing drugs inside cells**
  - **Exocytosis**
      - opposite process
      - membrane opens to allow **exit** of cellular components
      - described as a mechanism for release of many **neurotransmitters and hormones**

Other systems
- Ionomorphs
- Liposomes

These are stated to be less quantitatively important than the mechanisms above.

Factors that alter absorption

Physiological factors

age
pregnancy
presence of food

Pathological factors

diseases involving diarrhea
vomiting
absorption disorders

Iatrogenic factors

drug interactions
incorrect administration of the preparations

Bioavailability and related concepts

Bioavailability = the amount of drug that enters systemic circulation and can therefore produce the effect.
Bioavailability is described as more clinically important than absorption.
A common simplification noted: people often say “absorption” when they actually mean bioavailability.

Bioavailability depends on blood concentration, but not on the time it takes to reach it.

To include time, the term bioequivalence is used:

two drugs are bioequivalent if they reach the same blood concentration in the same time (or within a close interval)

Plasma concentration, MEC/MTC, and therapeutic margin

Drug effects correlate with plasma levels.

Two key concentrations:

MEC (Minimum Effective Concentration): needed to produce effect
MTC (Minimum Toxic Concentration): if exceeded, causes toxic effects

The difference between effective and toxic concentrations is the therapeutic margin.

Narrow therapeutic index drugs: small difference between MEC and MTC

Plasma level curve and administration route

Plasma drug levels vary over time, producing a plasma concentration vs time curve.
For oral administration, the curve has the general shape referenced in the video.
Parameters mentioned:
- CMT: Minimum toxic concentration
- CME: Minimum effective concentration
- Therapeutic interval (therapeutic range between CME and CMT, as implied)
- Cmax: maximum plasma concentration

Relationship to effects

effects are expected to be more intense near Cmax

Latency period (delay to reach efficacy)

Latency period = time from first administration until reaching MEC
To reduce latency:
- administer drug intravenously, directly at effective concentration

AUC (area under the plasma curve)

AUC reflects bioavailability

Speakers / sources featured

nurseprescription.com (source/channel named in the subtitles)

Tema 2. FARMACOCINÉTICA; Absorción.

Key takeaways