PHARMACOLOGY Lecture one
Dr. nahlah 9-10-2016Introduction
History of Pharmacology
In 1897, Felix Hoffman, a research chemist employed by the "Farbenfabrikin vorm. Freidr. Bayer and Co." synthesized acetylsalicylic acid. On February 1, 1899, Aspirin was registered as a trademark. On March 6th of the same year, this drug was registered with the Imperial Patent Office in Berlin. Aspirin quickly become popular.DEFINITIONS:
1- Pharmacology: is the science dealing with interactions between chemicals ( drugs ) and living systems. ( pharmakon: Drug or Medicine(Greek ) , Logia: a body of knowledge study (Latin) ).2- Drug: chemical substances that, when introduced into the body, alters the body's function by interactions at the molecular level, thereby producing a biological effect. Drugs can be stimulatory or inhibitory .
3- Prodrug: a chemical that is readily absorbed and distributed and then converted to the active drug by biologic processesinside the body.
4- Medical pharmacology : is the science of materials used to prevent, diagnose, and treat disease.
5- Toxicology : Is that branch of pharmacology that deals with the undesirable effects of chemicals in biological system.
6- Pharmacogenomics (or pharmacogenetics): is the study of the genetic variations that cause individual differences in drug response.
Responses that are not found in the general population, such as general toxic effects, allergies, or side effects, but due to an inherited trait that produces a diminished or enhanced response to a drug.
Differences in Enzyme Activity
Acetylation polymorphism
Butylcholinesterase alterations
Cytochrome P450 aberration
General concept of Phramacology
1-Pharmaceutical Phase: describes the stage during which the medication enters the body in one form and changes into another form to be utilized.
2- Pharmacokinetics: Is what the body does to the drug. The magnitud of the pharmacological effect of a drug depends on its concentration at the site of action.
Absorption
Distribution
Metabolism
Elimination
3- Pharmacodynamics: Is what the drug does to the body. Interaction of drugs with cellular proteins, such as receptors or enzymes, to control changes in physiological function of particular organs.
Drug-Receptor Interactions
Binding
Dose-Response
Effect
Signal Transduction
Mechanism of action, Pathways
4- Pharmacotheraputecices: is the proper selection of an agent whose biological effect is most appropriate to treat particular disease state.
Routes of Administration (Routes of Drug Delivery)
The route of administration is determined primarily by the properties ofthe drug (such as water or lipid solubility, ionization, etc.) and by the therapeutic objectives (for example, the desirability of a rapid onset of action or the need for long-term administration or restriction to a local site).
1- Enteral(GI Route)
Oral-
Sublingual-
Rectal
2- Parenteral route:
Intravascular: Intravenous (IV) injection
Intramuscular (IM):
Subcutaneous (SC):
Note: IM/SC-must rely on vascular system perfusion to site to be absorbed-if poor circulation use cautiously.
Other
Inhalation:
Intranasal:
Intrathecal / lntraventricular:
Topical:
Transdermal
Pharmacokinetics
Drug Absorption
Absorption: is the process by which a drug enters the bloodstream without being chemically altered or the movement of a drug from its site of application into the blood or lymphatic system.
Note: The rate and efficiency of absorption depend on the route of administration. For intravenous delivery, absorption is complete, that is, the total dose of drug reaches the systemic circulation. Drug delivery by other routes may result in only partial absorption and thus lower bioavailability. For example, the oral route requires that a drug dissolve in the gastrointestinal fluid and then penetrate the epithelial cells of the intestinal mucosa; disease states or the presence of food may affect this process.
Mechanisms for drug transport across membranes( Absorption ):
A. Passive (simple) diffusionThe driving force for passive absorption of adrug is the concentration gradient across a membrane separating two body compartments, that is, the drug moves from a region of high concentration to one of lower concentration. Passive diffusion does not involve a carrier, is not saturable, and shows a low structural specificity. The vast majority of drugs gain access to the body by this mechanism. Lipid-soluble drugs readily move across most biological membranes, whereas water-soluble drugs penetrate the cell membrane through aqueous channels.
Notes:
1. Rate of transfer of substances are directly proportional to the concentration gradient on both sides of the membrane
2. Rapid for lipophilic, nonionic, small molecules
3. No energy or carrier required.
B. Pore transport (Aqueous channels)
1. Small hydrophilic drugs (<200 MW) diffuse along concentration gradient by passing through pores (aqueous channels)2. No energy required.
C. Facilitated diffusion
Drugs bind to carrier non covalently.
No energy is required.
Active transport
Identical to facilitated diffusion except that ATP (energy) powers are needed.
Drug transport against concentration gradient
E. Pinocytosis and phagocytosis-
Engulfing of drug for large substances to enter the cells Ex: iron and vitamin B12
each complexes with appropriate binding proteins.