Drug Metabolism And Excretion NURS 1060 PDF

Drug Metabolism And Excretion NURS 1060: Exam 2 1 OUTCOME  Discuss critical thinking and clinical reasoning to provide quality patient care 2 COMPETENCY  Discuss critical thinking and clini...

Drug Metabolism And Excretion NURS 1060: Exam 2 1 OUTCOME  Discuss critical thinking and clinical reasoning to provide quality patient care 2 COMPETENCY  Discuss critical thinking and clinical judgment used to provide accurate and safe medication administration 3 CONCEPT  Clinical Decision Making: A process used to examine and determine the best actions to meet desired goals; requires anticipating, recognizing and organizing patient problems to respond with urgency and/or importance in a preferential order to avoid or minimize adverse changes in a patient’s condition.  Acid-Base Balance: The physiological mechanisms that maintain blood pH critical to homeostasis and optimal cell function. 4 Unit Outcomes  Discuss drug metabolism in the liver.  Explain the therapeutic outcome of drug metabolism.  Identify factors that can influence drug metabolism.  Discuss concepts related to drug excretion.  Define peak and trough concentration 5  Defined as the enzymatic alteration of drug structure Drug Also known as biotransformation Metabolism Most often takes place in the liver 6  Induction or Inhibition of drug- metabolizing enzymes Consideration First-pass effect s in Drug Metabolism Enterohepatic Recirculation Therapeutic Consequences 7  Most drug metabolism that takes place in the liver is performed by the hepatic microsomal enzyme system, also known as the P450 Hepatic system. Drug- Metabolizin g Enzymes Each of the P450 cytochrome that metabolize drugs only metabolizes certain drugs. 8  A substrate is any drug Cytochrome metabolized by CYP 450 enzymes P 450 Drugs that cause CYP450 drug System interactions are referred to as either inhibitors or inducers. (CYP450) Can cause adverse reaction or therapeutic and failure Interactions Not every drug inhibits or induces the liver enzymes 9 P 450 Cytochrome System Drug Interactions Inducers Inhibitors  Drugs that increase the  Drugs that inhibit P450 and rate of drug metabolism decrease drug through synthesis of metabolism. cytochrome P450 enzymes.  Inhibitor drug administered  Inducer drug administered  Drug metabolized by those  Drug metabolized by those enzymes is also enzymes is also administered administered  Increased metabolism-  Decreased metabolism- plasma drug levels plasma drug levels increase decrease Induction of Drug-Metabolizing Enzymes Example Phenobarbital (barbiturate, seizure management)  Inducer- causes the liver to synthesize drug metabolizing enzymes  Results in faster metabolism of Phenobarbital and other medications/waste products metabolized by the same enzymes Clinical Implications:  Drug-Drug Interaction: May need increased drug dosages to maintain therapeutic concentration  Therapeutic Use: induce liver enzymes to decrease bilirubin levels 11 Inhibition of Drug-Metabolizing Enzymes Example Grapefruit juice  Inhibitor- One or more flavonoids found in grapefruit juice inhibit CYP enzymes  Decreased hepatic metabolism can increase serum concentrations of certain drugs 12 Grapefruit Juice Example  nifedipine (treats high blood pressure) usually metabolized by enzymes that grapefruit juice inhibits  What could happen to the patient who takes grapefruit juice with nifedipine? 13 Case Study  Julia is a 56-year-old patient admitted to the cardiology unit with new-onset atrial fibrillation. She has been prescribed amiodarone for her irregular heartbeat and is set to receive her first dose with her morning breakfast tray. When you arrive in the room, you notice that she has grapefruit juice on her breakfast meal tray.  Is this a concern? Why? What is the nurse’s next action? 14  Rapid hepatic inactivation of certain oral drugs All drugs absorbed from sites along the GI First-Pass tract—stomach and intestine must go through the liver, via the hepatic portal vein, Effect on their way toward the heart and the general circulation. For some drugs, passage is uneventful. Others undergo extensive metabolism or First-Pass Effect. 15 First-Pass Effect Outcomes During first-pass of orally ingested drugs, a highly metabolized drug will lose much of its active dose. Very little of the active drug is left in general circulation 16 First-Pass Outcomes NO ACTIVE DRUG REMAINING FOR DRUGS THAT UNDERGO A MEANS NO THERAPEUTIC SIGNIFICANT FIRST-PASS, THEY EFFECTS CAN BE GIVEN PARENTERAL 17 Bypassing the First-Pass Effect  Bypass the path of absorption in GI tract to the liver --- therapeutic concentration  Sublingual – under the tongue is absorbed directly into circulation and bypasses First-Pass Effect  Example: route used it to give nitroglycerine and avoid complete metabolism of the drug by the liver 18 Fig. 4-8. Movement of drugs following GI absorption. All drugs absorbed from sites along the GI tract—stomach, small intestine, and large intestine (but not the oral mucosa or distal rectum)—must go through the liver, via the portal vein, on their way toward the heart and the general circulation. For some drugs, passage is uneventful. First-pass effect drugs undergo extensive metabolism. 19   Repeating cycle in which SOME drugs participate. The drugs are transported:  From the liver into the Enterohepati duodenum (via bile duct) c  Then back to the liver via the portal blood Recirculation  Limited to drugs that have undergone glucuronidation  Glucuronidation = conjugation of glucuronic acid and the drug 20   Some drugs undergo excretion into the bile, after which they re-enter the small intestine (via Enterohepati the bile duct), intestinal enzymes release free c drug, then the drug Recirculation undergoes reabsorption into the portal blood, thereby creating a cycle known as enterohepatic recirculation 21 Fig. 4-8. Movement of drugs following GI absorption. All drugs absorbed from sites along the GI tract—stomach, small intestine, and large intestine (but not the oral mucosa or distal rectum)—must go through the liver, via the portal vein, on their way toward the heart and the general circulation. For some drugs, passage is uneventful. Others undergo extensive metabolism. Still others undergo excretion into the bile, after which they re- enter the small intestine (via the bile duct), and then either (1) undergo reabsorption into the portal blood, thereby creating a cycle known as enterohepatic recirculation, or (2) exit the body in the stool (not shown). 22  What is the MOST important outcome of The Major drug metabolism? Consequen ce of Drug Metabolism prepares Metabolism the drug for excretion Often more water-soluble forms 23 Excretion 24  Defined as the removal of drugs from the body Drugs and their metabolites exit the body Excretion Urine produced by the kidneys is the most common method for excretion of drugs Patients experiencing Renal Failure have a risk to develop what? 25   Glomerular filtration Parts of Renal  Passive tubular Drug reabsorption Excretion  Active tubular secretion 26 Renal Drug Excretion Glomerular Filtration Filtration moves lipid and water-soluble drugs from the blood to urine Protein-bound drugs are not filtered – why? 27 28 Renal Drug Excretion Passive Tubular Reabsorption Lipid-soluble drugs return to Ionized, water the blood soluble drugs because they can remain in the pass through the urine capillary membrane 29 30 Renal Drug Excretion Active Tubular Secretion Requires ATP to be pumped from blood to urine Renal tubule cells contain P-glycoprotein which pumps drugs from the renal tubule cells into the urine Example: PCN (penicillin) 31 32  Enterohepatic Non-renal recirculation (as Routes of discussed earlier) Drug Bile excreted into Excretion small intestine and if (minimal method) remains in GI is excreted as stool 33 Factors that modify renal drug excretion  pH-dependent ionization  Competition for active tubular transport  Age 34  When a drug is administered repeatedly, its plasma concentration will fluctuate between doses as it is metabolized and excreted. The highest level of drug concentration is called the peak concentration Peak and Trough The lowest level of drug concentration is called the trough concentration. The goal is to keep the peak below the toxic level and the trough above the MEC – always in the therapeutic concentration 35 Peak and Trough 36 Case Study  Sara is a nurse working on the medical-surgical floor. She is reviewing her patient’s chart and notes her patient has a 0600 vancomycin infusion; however, the trough level is not available. The nurse phones the lab, and they state they will not be available to draw the trough level for an hour. What actions should the nurse take? 37