Routes of Administration in Pharmacology

Study Notes

Enteral administration involves placing the drug into any part of the gastrointestinal tract.
Oral (p.o.) administration:
- Absorption occurs from the stomach and small intestine (primary site for all drugs).
- Rate of absorption depends on rate of dissolution of tablet/capsule, pKa of the drug, and the chemical nature of the drug (acidic, basic, neutral).
Sublingual (under the tongue) administration:
- Absorption occurs via passive diffusion.
- Drugs enter general circulation before passing through the liver.
- Commonly used for nitroglycerin.
Rectal administration:
- Absorption occurs via passive diffusion.
- Drugs enter general circulation before passing through the liver.
- Good for unconscious or vomiting patients.

Subcutaneous (s.c.) administration:
- Absorption occurs by passive diffusion through capillary membranes.
- Lipid-soluble drugs are absorbed more easily.
- Rate of absorption depends on blood flow to injection site.
Intramuscular (i.m.) administration:
- Generally same characteristics as s.c. route.
- Can use larger volumes than s.c. route; more irritating drugs.
- Good for orally labile drugs (e.g. insulin).
- Depot preparations.
Intravenous (i.v.) administration:
- No absorption involved, drugs placed directly into the blood.
- Rapid onset of action; known amount of drug delivered.
- Drug cannot be withdrawn or absorption retarded.
- Good for emergency situations or hospitalized patients.
Intraarterial (i.a.) administration:
- Achieve high concentration of drug into one body site (e.g. liver).
- Used for cancer treatment.
Inhalation administration:
- Primarily used for anesthetic/analgesic gases.
- Absorption occurs via passive diffusion.
Intrathecal administration:
- Injection into spinal subarachnoid space.
- Used in spinal anesthesia and central nervous system (CNS) chemotherapy.

Factors influencing drug distribution:
- Physicochemical properties.
- Nature of biological membranes encountered.
- Protein binding and storage.
- Blood perfusing a given tissue.
- Disease states.
Capillary endothelial membrane:
- First barrier to distribution.
- Same processes for drugs leaving.
- Special capillaries:
  - Kidney.
  - Liver.
Blood-brain and blood-CSF barrier:
- Drugs cross blood-brain barrier mainly via passive diffusion.
- Blood-brain barrier (BBB) has tight junctions between brain capillary endothelial cells.
- Drugs enter CSF via passive diffusion at ventricles or via active bidirectional transport systems in the choroid plexus.
- Active transport primarily out of CSF and into blood.
Fetal barrier - the placenta:
- Similar characteristics as capillary beds.
- Most drugs enter the fetus.
Other tissues:
- Prostate: prostatic fluid pH=6.4.
  - Ion trapping of basic drugs.
  - Blood supply.

Generally occurs in liver, but may also occur in kidney, lung, nerve tissue, plasma, or gastrointestinal tract.
Results of biotransformation:
- Activate an inactive drug.
- Inactivate an active drug.
- Convert active drug to active metabolite.
- Convert active drug or metabolite to toxic metabolite.
- Metabolites are generally more polar, more water soluble, and excreted faster than the parent drug.
General classes of chemical transformation:
- Phase I: oxidation, reduction, hydrolysis.
- Phase II: conjugation, etc.