Absorption of Drugs
General definitions in Pharmacology
I. GENERAL DEFINITIONS
- Pharmacology is the study of the interaction of chemicals with living systems.
- Drugs are chemicals that act on living systems at the chemical (molecular) level.
- Medical pharmacology is the study of drugs used for the diagnosis, prevention, and treatment of disease.
- Toxicology is the study of the untoward effects of chemical agents on living systems. It is usually considered an area of pharmacology
- Pharmacodynamic properties of a drug describe the action of the drug on the body, including receptor interactions, dose-response phenomena, and mechanisms of therapeutic and toxic action.
- Pharmacokinetic properties describe the
action of the body on the drug, including absorption, distribution, metabolism,
and excretion. Elimination of a drug may be achieved by metabolism or by
THE NATURE OF DRUGS
A. Size. The great majority of drugs lie in the range from molecular weight 100 to 1,000. Drugs in this range are large enough to allow selectivity of action and small enough to allow adequate movement within the various compartments in the body.
B. Chemistry and reactivity. Drugs may be small, simple molecules (amino acids, simple amines, organic acids, alcohols, esters, ions, etc.), carbohydrates, lipids, or even proteins. Binding of drugs to their receptors. the specific molecules in a biologic system that mediate drug effects, is usually by noncovalent bonds (hydrogen bonds, van de Waals attractions, and ionic bonds), and less commonly by covalent bonds. Weaker, noncovalent bonds require a better fit of the drug to the receptor binding site and, usually, a reversible type of action. Very strong bonding, eg, covalent bonds, usually involves less selectivity and an irreversible interaction.
C. Shape. The overall shape of a drug molecule is important for the fit of the drug to its receptor. Between a quarter and a half of all drugs in use exist as stereoisomers. In most cases the stereoisomers are chiral enantiomers. Enantiomers are mirrored image twin molecules that result from the presence of an asymmetric carbon, or in a few cases, other asymmetric atoms in their structures. Chiral enantiomers often differ in their ability to bind to and alter the function of receptors. They also can differ in their rates of elimination and in their toxicity.
Pharmacokinetics concerns the effects of the body on the administered drug. It can be pictured as the processes of absorption, distribution, and elimination. Elimination includes both metabolism and excretion. All of these processes involve movement of drug molecules through various body compartments and across the barriers separating those compartments.
A. Absorption of Drugs. Drugs usually enter the body at sites remote from the target tissue and are carried by the circulation to the intended site of action. Before a drug can enter the bloodstream, it must be absorbed from its site of administration. The rate and efficiency of absorption differs depending on the route of administration. Common routes of administration of drugs and some of their features include:
Oral (swallowed). Maximum convenience but may be slower and less complete than parenteral (non-oral) routes. Dissolution of solid formulations (eg, tablets) must occur first. The drug must survive exposure to stomach acid. This route of administration is subject to the first pass effect (metabolism of a significant amount of drug in the gut wall and the liver, before it reaches the systemic circulation).
Sublingual (under the tongue). Permits direct absorption into the systemic venous circulation thus avoiding the first pass effect. May be fast or slow depending on the physical formulation of the product. Nitroglycerin is administered by this route in the treatment of angina.
Rectal (suppository). Same advantage as sublingual route; larger amounts are feasible. Useful for patients who cannot take oral medications (eg, because of nausea and vomiting).
Intramuscular. Absorption is sometimes faster and more complete than after oral administration. Large volumes (eg, 5 - 10 mL) may be given. Requires an injection. Generally more painful than subcutaneous injection. Vaccines are usually administered by this route.
Subcutaneous. Slower absorption than intramuscular. Large volumes are not feasible. Requires an injection. Insulin is administered by this route.
Inhalation. For respiratory diseases, this route deposits drug close to the target organ; when used for systemic administration (e.g., nicotine Susan Masters, PhD 63 in cigarettes, inhaled general anesthetics) it provides rapid absorption because of the large surface area available in the lungs.
Topical. Application to the skin or mucous membrane of the nose, throat, airway, or vagina for a local effect. It is important to note that topical drug administration can result in significant absorption of drug into the systemic circulation. Drugs used to treat asthma are usually administered this way.
Transdermal. application to the skin for systemic effect. Transdermal preparations generally are patches that stick to the skin and are worn for a number of hours or even days. To be effective by the transdermal route, drugs need to be quite lipophilic. Nicotine is available as a transdermal patch for those who are trying to stop cigarette smoking.
Intravenous. Instantaneous and complete absorption (by definition, 100%); potentially more dangerous because the systemic circulation is transiently exposed to high drug concentrations.