Pharmacodynamics and Pharmacokinetics

• Medications are administered to achieve a desired effect, with pharmacodynamics describing how a medication alters bodily functions or processes. All medications have the potential to cause toxic effects.

Medication Administration Process (Pharmacokinetics)

• Absorption describes how the medication enters the body
• Distribution describes how the medication travels around the body
• Biotransformation describes how the medication is chemically changed by the body
• Elimination describes how the medication leaves the body
• Pharmacokinetics refers to the body's action on a medication.

Principles of Pharmacodynamics

• Receptor sites, located in proteins connected to cells, are activated by endogenous chemicals or exogenous chemicals like medications.
• Medication binding to a receptor site can open or close ion channels, activate biochemical messengers, or prevent/begin normal or abnormal cell function.
• Newer medications target specific receptor sites.
• Agonist medications initiate or alter cellular activity.
• Antagonist medications prevent agonist chemicals from reaching receptor sites.

Agonist Medications

• Affinity is a medication's ability to bind to a receptor site.
• They bind with receptor sites to initiate or alter cell action.
• The threshold level is the point at which cellular activity alteration begins, with increasing concentrations leading to increased effects until all receptor sites are occupied and the cell's maximum capacity is reached.
• Potency refers to the concentration of medication needed to start a cellular response; higher potency means a lower concentration or dose is needed.
• Efficacy is the ability to initiate or alter cell activity therapeutically.

Antagonist Medications

• These medications bind with receptor sites to prevent cellular response to agonist chemicals, inhibiting normal cellular activation and treating harmful agonist effects.
• Competitive antagonists temporarily bind with receptor sites, with efficacy depending on concentration near the sites and affinity compared to agonists.
• Noncompetitive antagonists permanently bind, preventing activation by agonists until new receptor sites or cells are created, and cannot be overcome by increased agonist doses.
• Partial agonist chemicals bind to receptor sites but initiate less activity than full agonists, lowering the efficacy of other agonists.

Alternative Mechanisms of Drug Action

• Medications can alter cell function without interacting with receptors, engineered to target microorganisms, lipids, water, or exogenous toxic substances.
• Antimicrobials target specific substances in bacterial or fungal cell walls, including antibiotics and antifungals.
• Chelating agents bind with heavy metals to create compounds that can be eliminated.
• Sodium bicarbonate can also act in this way.

Other Alternative Mechanisms

• Diuretics create osmotic changes, altering fluid and electrolyte distribution.
• Electrolyte-based medications change ion concentration and distribution in cells and fluids.

Factors Affecting Response to Medications

• Choice of medication
• Dose
• Route
• Timing
• Manner of administration
• Monitoring
• Age affects medication response due to differences in body composition.
• Infants require higher weight-based doses of water-soluble medications, while elderly people need higher doses of fat- and lipid-soluble medications.
• Titration is important for pediatric or elderly patients
• Altered metabolism/elimination may prolong effects.
• Extremes of age can lead to paradoxical reactions.
• Weight-based dosing involves multiplying a medication quantity by the patient's weight in kilograms, with the advantage of proportional dosing and pre-calculated factors.
• Limitations of weight-based dosing include needing the patient’s weight, not considering distribution/metabolism/elimination alterations, and basing it on ideal body weight.

Environmental and Other Factors

• Hyperthermia may increase drug metabolism, reducing the amount returned to circulation.
• Hypothermia impairs the effectiveness of medications used in traditional cardiac life support.
• Genetic factors require caution when administering medications to patients with genetic disorders like primary pulmonary hypertension, sickle cell disease, or glucose-6-phosphate dehydrogenase deficiency.
• Factors during pregnancy such as increased cardiac output, intravascular volume, respiratory rate, renal blood flow, and decreased hematocrit and gastrointestinal motility, along with endocrine changes, affect medication absorption, distribution, and elimination, while the effect on the fetus must be considered.
• Psychosocial factors can affect individuals and their reaction to medications and subsequent treatment
• Factors such as pain, anxiety, and discomfort can vary among individual patients.
• Medication administration is complicated by the placebo effect.

Types of Medication Responses

• Therapeutic effects are the desired outcomes based on the patient’s condition, matching the medication's indications.
• Repeated dosing may be needed with medications capable of demonstrating cumulative action.
• Adverse effects are undesired clinical changes causing harm or discomfort, with consideration needed based on the patient's condition.
• Severity can vary
• Side effects can be desirable or harmful, and idiosyncratic reactions can be unexpected.

Therapeutic Index

• Median lethal dose (LD50) is the dose causing death in 50% of animals tested Median toxic dose (TD50): dose at or above which causes toxic effects in 50% of animals tested
• The therapeutic index is the relationship between the median effective dose and median lethal dose, where a large difference indicates safety and a small difference requires monitoring.
• Immune-mediated responses result from initial exposure/sensitization to an allergen in genetically predisposed patients, with medication sensitivity possible after the first exposure.
• Avoid administering medications to patients who have had a serious reaction to the medication.
• Medication tolerance is decreased efficacy with repeated use, resulting from down-regulation, which reduces available cell receptors.
• Cross-tolerance is tolerance to a class of medications from repeated exposure, while tachyphylaxis is rapid tolerance from repeated doses in a short time.
• Stimulants and depressants are prone to misuse and abuse, with repeated exposure causing habituation and prolonged exposure causing dependence.
• Medication interactions, or interference, are undesirable, with incompatibility during administration being a major concern, and medications potentially increasing, decreasing, or altering each other’s effects.

FDA Pregnancy Categories

• Category A: No risk to the fetus in studies of pregnant women.
• Category B: Animal studies show no risk, but no well-controlled studies in pregnant women.
• Category C: Animal studies show potential risk, but benefits may outweigh risks.
• Category D: Positive evidence of human fetal risk, but benefits may justify use in life-threatening situations.
• Category X: Contraindicated in pregnancy; risks clearly outweigh benefits.