Liberation
The medication enters the body and “liberates” the active ingredient that has been administered. Excipients or vehicles used to deliver the medication releases the active ingredient. There may be three steps: disintegration, disaggregation, and dissolution.
- Cell membranes are relatively impermeable to ionized molecules.
- Excipient formulation is also important in medical bioequivalence, with different vehicles resulting in different plasma concentrations and therapeutic effects.
Absorption
The movement of the drug into the bloodstream after administration. Most medications are taken by mouth (enteral).
- Diffusion: passive transport where a solute moves across cell membranes from higher to lower concentrations.
- Facilitated Diffusion: active transport where a solute is moved against a concentration gradient with energy by a carrier e.g. an enzyme or protein.
- Pinocytosis: cells carry drugs across their membranes by engulfing the drug particles in a vesicle.
- Factors Affecting Absorption:
- Drug Solubility: water-soluble drugs require enzymes or proteins to be absorbed. Fat-soluble drugs are easily passed through the GI membrane.
- Local Condition at the Site of Absorption: weak acids are less ionized in the stomach, readily passing through the small intestine.
- Pain, Stress, Solid Food, Fatty/Hot Food all slow down gastric emptying, which consequently slows down drug absorption.
Distribution
The process by which the drug becomes available to body fluids and tissues; the movement of the drug from circulation to body tissues.
- Factors Affecting Distribution:
- Size of the targeted organ/tissue
- Blood flow (to target)
- Solubility: fat-soluble drugs may enter other areas of the body more easily e.g. crossing the Blood-Brain Barrier
Metabolism (Biotransformation)
The process by which the body chemically changes drugs into a form that can be excreted. This is primarily done by the liver, but is also contributed to by the plasma, kidneys, and intestinal membranes.
- First-Pass Effect/Metabolism: In the GI Tract, some drugs are metabolized by the liver, converting a portion of the absorbed drug to its inactive form which is then excreted. This is taken into account for dosage.
- Cytochrome P450 System (CYP450 Enzymes): the main system of the liver against xenobiotics; these convert drugs to their metabolites (possible their bioavailable form)
Medication for Patients with Liver Dysfunction
An important aspect of medication for patients with liver dysfunction is the decreased rate of metabolism and the decreased effect of first-pass metabolism, which may cause toxicity for normally therapeutic dosages and frequencies.
Drug Half-Life
Drug halflives (T½) determine the amount of time needed for a drug’s plasma concentration to be halved. This can be used to determine the frequency of dosages to maintain the therapeutic concentration of the drug in the body e.g. q4 or q8 for short T½ and BID or OD for longer T½.
- Factors Affecting Metabolism
- Genetics: others simply metabolize drugs faster or slower.
- Physiologic
- Liver Disease
- Infants have slower metabolism.
- Older Patients have slower metabolism, blood flow, and enzyme production.
- Environment: stress, second-hand smoke, etc. may also affect drug metabolism as a primary or secondary effect.
Excretion (Elimination)
The removal of the drug from the body. The main route for excretion are the kidneys through the urine. Drugs are also
- Factors Affecting Excretion:
- Free, unbound, and water-soluble drugs are filtered in the kidney.
- Urine pH also influences drug excretion.
- Acidic urine promotes the elimination of weak base drugs and vice versa.
- Pre-renal, Intrarenal, Postrenal, or Kidney Disease in general slow down the elimination of drugs, which should be reflected in the dosages given for the patient.