Routes of Administration in Pharmacology

Routes of Administration

• 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.

Parenteral Administration

• 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  • Drug cannot be withdrawn or absorption retarded.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.

Topical Administration

• Patches: used for nitroglycerin, nicotine, clonidine, and others.
• Dermatological and ophthalmological applications.
• Intravaginal administration: used for antimicrobials.

Drug Distribution

• 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.

Biotransformation of Drugs

• 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.