The Route of a Pill (pharma)
Ever wondered what happens when you swallow a pill?
1. Ingestion: Swallowing the Pill
The pill is taken with water and travels down the esophagus into the stomach.
Pills can be coated to resist stomach acid (enteric coated) or designed to dissolve quickly or slowly (extended release, immediate release, etc.).
2. Stomach: Initial Breakdown Begins
In the stomach, acids and enzymes (especially pepsin and hydrochloric acid) begin breaking down the pill's outer shell.
However, many active ingredients are not absorbed in the stomach because:
~ The stomach is acidic (pH \~1.5–3.5).
~ It’s a temporary holding place; most absorption happens later.
3. Small Intestine: Major Site of Absorption
The broken-down pill moves into the small intestine.
The small intestine is the main site of drug absorption due to:
~Large surface area (villi and microvilli).
~Neutral pH.
~Presence of digestive enzymes and bile from the liver/pancreas.
~ The active ingredients of the pill pass through the intestinal wall into the bloodstream.
4. Liver (First Pass Metabolism): Processing the Drug
Blood from the intestines goes to the liver via the portal vein.
In the liver, drugs are metabolized (chemically altered) by enzymes. This is called first pass metabolism. Some drugs are greatly reduced in potency here, which is why dosing accounts for this loss.
5. Systemic Circulation: Drug Acts on Target Areas
After the liver, the remaining active drug enters the general circulation.
It’s transported to target tissues/organs (e.g., brain, muscles, lungs), depending on the drug’s purpose. The drug binds to specific receptors or enzymes to produce its therapeutic effect.
6. Metabolism and Deactivation
Over time, the body continues to metabolize the drug to inactive or water-soluble forms (mainly in the liver). This is part of detoxification.
7. Excretion: Leaving the Body
Metabolized drug components are eliminated by:
~ Kidneys (most common route — via urine).
~ Liver/bile → intestines → feces.
~Less commonly: lungs (exhalation), sweat, or saliva.
Since drugs go everywhere, they can cause side effects in tissues they’re not meant to act on and some drugs are naturally drawn to (or stored in) certain tissues.
Common Tissues Where Drugs Are Stored
1. Fat (Adipose Tissue)
Most common storage site for lipophilic (fat loving) drugs. These drugs dissolve into fat and accumulate over time. Can be slowly released back into the bloodstream — prolonging drug effects.
Examples:
~THC (cannabis)
~Diazepam (Valium)
~Certain anesthetics (like propofol)
~Some antidepressants and antipsychotics
->In people with higher body fat, these drugs may stay in the body longer.
2. Bone
Some drugs bind tightly to calcium or integrate into the mineral matrix.
They can accumulate over long periods, sometimes years.
Examples:
~Lead and other heavy metals (not drugs, but toxicants)
~Tetracycline antibiotics (can discolor teeth and bones)
~Bisphosphonates (osteoporosis drugs)
->Drug stored in bone is released very slowly and can even affect developing teeth in children or fetuses.
3. Brain and Nervous Tissue
The blood brain barrier (BBB) limits entry, but drugs that are small and fat soluble can cross and accumulate. The brain is rich in lipids, making it a natural reservoir for lipophilic drugs.
Examples:
~Antidepressants
~Antipsychotics
~Anesthetics
~Benzodiazepines
->This is why central nervous system (CNS) drugs often have lingering effects or withdrawal symptoms.
4. Muscle
Some drugs bind to proteins or accumulate in muscle tissue.
Less common than fat or bone storage, but still relevant.
Examples:
~Digoxin (used in heart failure) can accumulate in skeletal and cardiac muscle.
~Some antibiotics and antimalarials.
->In individuals with high muscle mass, distribution volume may be altered.
5. Liver and Kidneys
These organs process and excrete drugs — but some drugs also build up in them. Especially true if the drug is toxic to these organs or is not metabolized easily.
Examples:
~ Amiodarone (antiarrhythmic)
~Certain chemotherapies
~Some herbal alkaloids
->Storage here may lead to organ toxicity over time.
Why Tissue Storage Matters
Effect of Storage Explanation
Prolonged half-life: Drug is released slowly back into circulation
Delayed toxicity: Can cause damage later even after stopping the drug
Drug interactions: Stored drug can be displaced by another substance
Withdrawal effects: Slow release from tissues can prolong withdrawal
Redistribution Effect
Some drugs (especially anesthetics) go rapidly to the brain (high blood flow), then redistribute to fat/muscle, which:
Causes the effect to wear off even though the drug is still in the body.
Example: Thiopental — rapid anesthesia but wears off quickly due to redistribution to fat.
Have you taken any of these in the past?