Lecture 4 - Pharmacokinetics Part 1

‭Generic vs. Brand Names‬ ‭●‬ ‭Generic medication must be “bioequivalent” to its brand-name counterpart‬ ‭○‬ ‭Allowed a 20% variation in the‬‭active ingredients‬‭from that original formula‬ ‭○‬ ‭Companies are not required to show two versions are therapeutically equivalent‬ ‭○‬ ‭The active ingredient must be bioequivalent, but inactive ingredients may differ‬ ‭Pharmacokinetics vs. Pharmacodynamics‬ ‭●‬ ‭Pharmacokinetics: Pharmaco (drug or substance) + kinetics (motion)‬ ‭●‬ ‭Pharmacodynamics: Pharmaco (drug) + dynamics (power)‬ ‭Pharmacokinetics and Nursing Practice‬ ‭●‬ ‭Maximize beneficial effects and minimize harm‬ ‭●‬ ‭Knowledge is essential to building confidence in our practice‬ ‭●‬ ‭Pharmacokinetics knowledge + confidence =‬ ‭○‬ ‭Increased patient safety‬ ‭○‬ ‭Decreased stress‬ ‭○‬ ‭Increased job satisfaction‬ ‭●‬ ‭Nurse role as a patient advocate‬ ‭Four Pharmacokinetic Processes‬ ‭●‬ ‭All determine the concentration of the drug at‬ ‭the site of action‬ ‭●‬ ‭Absorption:‬‭How the drug gets to the‬ ‭systemic circulation from admin site‬ ‭●‬ ‭Distribution:‬‭Movement throughout body‬ ‭●‬ ‭Metabolism/Biotransformation:‬‭How the‬ ‭drug is altered to become active or inactive‬ ‭●‬ ‭Excretion:‬‭How the body gets rid of the drug‬ ‭Structure of the Cell Membrane‬ ‭Three Ways to Cross a Cell Membrane‬ ‭●‬ ‭Channels and pores‬ ‭●‬ ‭Transport systems‬ ‭●‬ ‭Direct penetration‬ ‭Channels and Pores‬ ‭●‬ ‭Non-lipid soluble drugs‬ ‭●‬ ‭Drug compound must be very‬‭small‬ ‭●‬ ‭No energy‬‭required‬ ‭Transport Systems‬ ‭●‬ ‭May require energy (ATP)‬ ‭●‬ ‭Selective‬ ‭●‬ ‭Ex. P-Glycoproteins (‬‭PGP‬‭)‬ ‭○‬ ‭“‭E ‬ xporter‬‭” and “Protector”‬ ‭○‬ ‭Located in many key elimination sites:‬ ‭■‬ ‭Liver‬ ‭■‬ ‭Kidneys‬ ‭■‬ ‭Placenta‬ ‭■‬ ‭Intestines‬ ‭■‬ ‭Brain capillaries‬ ‭Direct Penetration‬ ‭●‬ ‭Lipid-soluble‬‭, “like dissolves like”‬ ‭●‬ ‭Synonyms: Nonpolar, lipophilic, hydrophobic‬ ‭●‬ ‭Many drugs are lipid-soluble but not all‬ ‭Non-Lipid Soluble Drugs‬ ‭●‬ ‭Polar molecules‬ ‭○‬ ‭Uneven electrical charge but‬ ‭does not have a‬‭net charge‬ ‭○‬ ‭Cannot pass through cell‬ ‭membrane‬ ‭○‬ ‭Parenteral administration‬ ‭○‬ ‭Ex. water, gentamicin‬ ‭●‬ ‭Ions‬ ‭○‬ ‭Unable to cross cell membranes‬ ‭due to net charge‬ ‭●‬ ‭Quaternary ammonium compounds‬ ‭○‬ ‭Always carry a‬‭positive charge from nitrogen‬ ‭●‬ ‭pH-dependent ionization‬ ‭○‬ ‭Weak acids or bases that can exist in charged/uncharged forms‬ ‭○‬ ‭Charge is dependent on pH of surrounding medium‬ ‭○‬ ‭Acids tend to ionize (give up a proton) in basic (alkaline) environments,‬ ‭becoming negatively charged‬ ‭○‬ ‭Bases tend to ionize (accept a proton) in acidic environments, becoming‬ ‭positively charged‬ ‭○‬ ‭Ex. aspirin (acidic)‬ ‭Factors Affecting Drug Absorption‬ ‭●‬ ‭Rate → onset‬ ‭●‬ ‭Amount → intensity‬ ‭●‬ ‭Route of administration‬ ‭●‬ ‭Rate of dissolution → onset‬ ‭●‬ ‭Surface area‬ ‭○‬ ‭Larger → faster absorption‬ ‭●‬ ‭Blood flow‬ ‭○‬ ‭Higher → faster absorption‬ ‭●‬ ‭Lipid solubility‬ ‭●‬ ‭Food-drug interaction‬ ‭Absorption‬ ‭Absorption in Common Routes of Administration‬ ‭●‬ ‭Intravenous (IV)‬ ‭○‬ ‭Barriers: None (straight to bloodstream)‬ ‭○‬ ‭Absorption patterns: Quick,‬‭all is absorbed‬ ‭‬ A ○ ‭ dvantages: Quick (emergency), predictable, permits use of large fluid volumes‬ ‭○‬ ‭Disadvantages: Irreversible; inconvenient; expensive; drug must be‬‭water-soluble‬‭;‬ ‭risk for infection, fluid overload, and embolism‬ ‭ ‬ ‭Intramuscular (IM)/Subcutaneous (subQ)‬ ● ‭○‬ ‭Barriers:‬‭Capillary‬‭wall (easier to pass)‬ ‭○‬ ‭Absorption patterns: Rapid if water-soluble, slow if poorly soluble‬ ‭○‬ ‭Advantages: Does not have to be water-soluble, allows‬‭depot‬‭/extended release‬ ‭(less doses)‬ ‭○‬ ‭Disadvantages: Discomfort, inconvenient, potential for injury‬ ‭●‬ ‭Enteral/Oral (PO)‬ ‭○‬ ‭Barriers: Epithelium of‬‭GI‬‭tract,‬‭capillary‬‭wall‬ ‭○‬ ‭Absorption patterns: Slow, variable‬ ‭○‬ ‭Advantages: Convenient, inexpensive, reversible, safer‬ ‭○‬ ‭Disadvantages:‬‭Unpredictable‬‭(absorption and pt variability),‬‭can be‬‭inactivated‬ ‭by GI tract, N/V, pt must be conscious/cooperative‬ ‭Absorption in All Routes of Administration‬ ‭●‬ ‭Parenteral (IV, IM, SQ)‬ ‭●‬ ‭Enteral (oral)‬ ‭●‬ ‭Topical‬ ‭○‬ ‭Given on/in the eyes, ears, nose, mouth, rectum, vagina‬ ‭○‬ ‭Barriers are minimal, elicits‬‭local‬‭effects where‬‭given‬ ‭■‬ ‭Less systemic effects‬ ‭●‬ ‭Transdermal‬ ‭○‬ ‭Absorbed‬‭, as opposed to topical‬ ‭○‬ ‭Penetrates the skin to target the site of action‬ ‭○‬ ‭Ex. pain patches‬ ‭●‬ ‭Inhalation‬ ‭○‬ ‭Ex. bronchodilator for asthma‬ ‭○‬ ‭Barriers are minimal, elicits local effects where given‬ ‭■‬ ‭Less systemic effects‬ ‭Question:‬‭Oral or parenteral administration?‬ ‭a.‬ ‭Emergency requiring rapid onset of action‬ ‭i.‬ ‭Parenteral (IV)‬ ‭b.‬ ‭Pt can self-administer drug‬ ‭i.‬ ‭Oral‬ ‭c.‬ ‭When a plasma drug level must be tightly controlled‬ ‭i.‬ ‭Parenteral‬ ‭d.‬ ‭Pt who has dysphagia‬ i‭.‬ ‭Parenteral‬ ‭e.‬ ‭Convenient, affordable option‬ ‭i.‬ ‭Oral‬ ‭ uestion:‬‭The ___ of absorption determines how soon‬‭a drug’s effect will take place, while the‬ Q ‭___ of absorption determines how intense the effects will be.‬ ‭a.‬ ‭Intensity, rate‬ ‭b.‬ ‭Rate, amount‬ ‭c.‬ ‭Amount, rate‬ ‭d.‬ ‭Rate, intensity‬ ‭Distribution‬ ‭Three Determining Factors of Distribution‬ ‭●‬ ‭Blood flow‬‭to tissues‬ ‭●‬ ‭Ability to exit the vasculature‬ ‭●‬ ‭Ability to‬‭enter cells‬ ‭Blood Flow to Tissues‬ ‭●‬ ‭Drugs are carried by the blood to tissues and organs of the body‬ ‭●‬ ‭Blood flow determines the rate of delivery‬ ‭Excretion: Exiting the Vascular System‬ ‭Blood-Brain Barrier (BBB)‬ ‭●‬ ‭Capillary walls of the CNS consist of tight junctions between cells‬ ‭●‬ ‭Drugs must be lipid-soluble or use a transport system to cross the BBB‬ ‭●‬ ‭Membranes of the placenta do not constitute an absolute barrier to the passage of drugs‬ ‭Protein Binding‬ ‭●‬ ‭Plasma contains circulating proteins‬ ‭●‬ ‭Drugs can form‬‭reversible‬‭bonds with these proteins‬ ‭●‬ ‭Only a “‬‭free drug‬‭” is biologically active‬ ‭●‬ ‭Albumin: Protein that is mostly bound to‬ ‭○‬ ‭Low albumin‬‭with a highly protein-bound drug results‬‭in more “free drug,”‬ ‭causing a greater effect‬ ‭■‬ ‭Ex. warfarin and excessive bleeding‬ ‭●‬ ‭Ex. warfarin vs. gentamicin‬ ‭○‬ ‭Protein binding of warfarin: 99%‬ ‭○‬ ‭Protein binding of gentamicin: < 30%‬ ‭Key Points‬ ‭●‬ ‭Understand the difference between chemical, brand, and generic drug names‬ ‭●‬ ‭Drug absorption‬ ‭○‬ ‭How are drugs absorbed from the site of administration?‬ ‭○‬ ‭What can affect absorption?‬ ‭●‬ ‭Drug distribution‬ ‭○‬ ‭What are the three factors that can affect distribution?‬ ‭○‬ ‭What is the impact of protein binding?‬ ‭○‬ ‭What are the unique aspects of the BBB and placenta?‬