What are the fundamental principles of pharmacology, including drug nature and sources, routes of administration, drug absorption and bioavailability, and drug distribution?

Fundamental Principles of Pharmacology: Drug Nature, Routes of Administration, Absorption, Bioavailability, and Distribution

Understanding the fundamental principles of pharmacology is essential for healthcare practitioners to effectively administer medications and optimize therapeutic outcomes while minimizing adverse effects.

Drug Nature and Sources

• Drugs can be classified based on their chemical nature (small molecules vs. biologics/biopharmaceuticals) which significantly impacts their pharmacological properties, administration routes, and therapeutic applications 1
• Natural sources of drugs include plants, animals, minerals, and microorganisms, while synthetic drugs are created through chemical processes in laboratories 1
• Biotechnology-derived products follow specific guidelines for preclinical safety evaluation as outlined in ICH guideline S6, which differs from small molecule evaluation protocols 1

Routes of Administration

• The least invasive method of drug administration should be used whenever possible, with oral administration being preferable due to convenience and relatively steady blood concentrations 1
• Different routes of administration include oral, subcutaneous, intravenous, transdermal, sublingual, intrathecal, and rectal, each with specific advantages and limitations 1
• Intravenous administration provides the most rapid onset and shortest duration of action but requires more technical skill and monitoring than oral administration 1
• Subcutaneous and intramuscular injections have disadvantages including wider fluctuations in absorption and more rapid fall-off of action compared to oral administration 1

Drug Absorption and Bioavailability

Fundamentals of Drug Absorption

• Absorption is defined as the movement of drug across the outer mucosal membranes of the GI tract, while bioavailability refers to the availability of drug to the general circulation or site of pharmacological actions 2
• Oral bioavailability specifically refers to the rate and extent to which an active drug substance is absorbed and becomes available to the general circulation 3
• The pharmacokinetics of drugs include absorption, distribution, metabolism, and excretion (ADME), which determine the drug's concentration at the target site over time 1

Factors Influencing Drug Absorption

Physiological Factors

• Sex-related differences significantly impact drug absorption - women generally have lower body weight/size, muscle mass, organ sizes, plasma volume, cardiac output, and organ blood flow compared to men 1
• Age-associated changes affect disposition, metabolism, and responses to medications, particularly in older adults 1
• Gastrointestinal transit time, pH, surface area, blood flow, and presence of food all influence the rate and extent of drug absorption 4

Drug-Related Factors

• Drug solubility, permeability, and the rate of in vivo dissolution are critical determinants of product bioavailability 4
• The Biopharmaceutics Classification System helps predict compounds likely to be associated with bioavailability problems and identifies factors that may alter absorption 4
• Lipophilicity of drugs affects their absorption - lipophilic drugs generally have faster onset, higher volume of distribution, and longer duration of action 1

Formulation Factors

• Pharmaceutical formulations (tablets, capsules, solutions, etc.) significantly impact the rate and extent of drug absorption 4
• Specialized drug delivery systems can be designed to optimize bioavailability based on a drug's physicochemical properties 4
• Administration with high-fat meals can significantly increase oral absorption of certain drugs, potentially exacerbating effects 1

Pharmacokinetic Parameters

• Bioavailability is quantified through parameters such as area under the curve (AUC), peak plasma concentration (Cmax), and time to reach peak concentration (Tmax) 1
• The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) are important parameters for antimicrobial agents that help determine effective dosing 1
• Pharmacodynamics describes the relationship between drug concentration and pharmacologic effect, integrating microbiologic and pharmacokinetic data into clinically relevant relationships 1

Drug Distribution Throughout the Body

• After absorption, drugs are distributed throughout the body via the bloodstream to various tissues and organs 1
• Distribution depends on body composition, plasma volume, organ blood flow, and tissue and plasma protein binding 1
• Volume of distribution (Vd) is a key parameter that relates the amount of drug in the body to the concentration in the blood or plasma 1

Factors Affecting Drug Distribution

• Sex-related differences in body composition affect drug distribution - women have a higher proportion of body fat but lower body weight/size and muscle mass 1
• Lipophilic drugs have larger volumes of distribution in women due to higher body fat percentage, while hydrophilic drugs reach higher peak plasma levels 1
• Protein binding affects drug distribution as only unbound drug can cross cell membranes and exert pharmacological effects 1
• Drug transporters like P-glycoprotein (P-gp) play crucial roles in drug distribution across various barriers in the body 1

Special Considerations

• For patients with continuous pain receiving long-acting medications, breakthrough dosing with fast-onset short-acting drugs may be necessary 1
• When combining drugs, potential pharmacokinetic and pharmacodynamic interactions must be considered, as they may alter absorption, distribution, metabolism, and excretion of one or both drugs 1
• Dosing for most patients requires initiation with low doses followed by careful upward titration, including frequent reassessment for dosage adjustments 1

Common Pitfalls and Caveats

• Administering the same doses to women and men often results in higher drug exposure in women, leading to a higher incidence of adverse drug reactions 1
• Overlapping dose-limiting toxicities may limit escalation of doses to levels required for optimal activity or may affect dose intensity due to dose reductions 1
• Drug-drug interactions may alter the absorption, distribution, metabolism, and excretion of one or both drugs, potentially affecting therapeutic outcomes 1
• Combining drugs with conflicting requirements regarding timing of meals adds challenges to medication administration 1