Pharmacology: Key Concepts PAT201 Fall 2024 Week 2 PDF

Pharmacology: Key Concepts PAT201 Fall 2024 Week 2 1  Pharmacokinetics *What the body does to a drug & Pharmacodynamics *What the drug does to the body 2 2 Pharmacokinetics What the...

Pharmacology: Key Concepts PAT201 Fall 2024 Week 2 1  Pharmacokinetics *What the body does to a drug & Pharmacodynamics *What the drug does to the body 2 2 Pharmacokinetics What the body does to a drug Movement of a drug through the body (ADME) as drug enters blood (Absorption) as drug moves to target tissues (Distribution) as drug is metabolized (Metabolism) and as drug is removed from body (Excretion/Elimination) 3  Pharmacokinetics (ADME) Four Processes of Pharmacokinetics Absorption How drug reaches the circulation Distribution How drug reaches target tissue Metabolism How drug is altered by body Excretion How drug is removed from body 4 Figure 3.2, Adams et al., 2025, p. 21 Pharmacokinetics Drug must reach target tissue at high enough concentration to produce a desired/therapeutic effect Nurse must be aware of the many factors impacting amount of drug reaching target tissue 5 ABSORPTION 6 Absorption Movement of drug from site of administration, across membranes, to circulation absorption affected by drug route physical form of drug size of drug molecule degree of ionization lipid water solubility body area of absorptive surface, vascularity, blood flow to site of drug administration, functional integrity of surface digestive motility, pH, presence of other substances, exposure to digestive enzymes co-morbidities, diseases 7  _____ Coated tablets Factors Affecting Absorption: Drug _____ Capsules Form _____ Tablets Number these oral _____ Enteric-coated tablets preparations with 1 being the fastest to absorb and 7 _____ Liquids (elixirs, syrups) being the slowest to absorb _____ Powders _____ Suspension solutions 8 Bioavailability Amount of drug absorbed into systemic circulation Physiologically available to reach target cells ⭢ produce effect Percentage of drug delivered to circulation from 0% to 100% Bioavailability is conditional on many factors! 9 Factors Affecting Absorption: Routes of Administration Routes of administration enteral parenteral What are some examples? topical WHY is it important to know this? 10 Oral Route Explain this diagram focusing on the role of the liver 11 Figure 3.1, Adams et al., 2025, p. 20 First-Pass Effect/Metabolism Clinical judge ment: What does a nurse need to cons ider when a drug route is changed from PO to IV? What abo ut from IV to PO? WHY? 12 Figure 3.6, Adams et al., 2025, p. 27 0% 33% 75% IV drugs are considered to be bioavailable by what percent? Why? 60% 50% 15% 93% 100% 13 Factors Affecting Absorption: Drug Ionization Influenced by pH of surrounding fluid acids are absorbed in acids i.e. stomach bases are absorbed in bases i.e. small intestine 14 Factors Affecting Absorption: Drug Solubility Lipid-soluble drugs not limited by barriers that stop water-soluble drugs More completely distributed to body tissues due to lipid bilayers Lipophilic drugs cross membranes more easily than hydrophilic drugs Lipid solubility determines how quickly a drug is absorbed mixes within the bloodstream crosses membranes becomes localized in body tissues 15 Some Other Factors Affecting Absorption Blood flow and surface area increase blood flow = increase rate of absorption increase surface area = increase rate impact of temperature on blood flow GI tract environment presence of food may decrease absorption presence of certain foods and drugs may alter rate of absorption motility – influences time during which absorption can occur 16 DISTRIBUTION 17 Distribution Transportation of drugs throughout body after absorbed or injected to target tissue Several factors affect drug distribution blood flow drug solubility drug-protein complexes ability to pass through membranes 18  Blood flow to target tissue increased blood flow = more drug reaching target tissue Factors Drug solubility Affecting hydrophilic drugs transported in solution lipophilic drugs Drug portion of drug is in solution (free drug) & portion is bound to plasma proteins (i.e. albumin) Distribution Drug-protein complexes plasma protein binding Drug being able to pass through membranes 19  Lipophilic drugs in equilibrium between being in solution (free drug) and being bound to plasma proteins Factors Affecting Drug Only portion of drug in solution (free drug) is available to diffuse to target Distribution: tissue Drug-Protein Binding Properties of drug allow some lipophilics to bind better to plasma proteins than others –competition for binding sites on plasma proteins can create drug interactions 20 Effect of Protein Binding Explain this diagram! Figure 3.5, Adams et al., 2025, p. 25 21 Factors Affecting Drug Distribution: Passage of Drugs Through Plasma Membranes Drugs must cross membranes to produce effects Properties of drugs affect movement across plasma membranes concentration gradient *Diffusion simple diffusion facilitated diffusion *Active Transport Osmosis 22 Factors Affecting Drug Distribution: Special Barriers Drug must move from circulation to target tissues to create response Blood–brain barrier (BBB) Fetal–placental barrier (FPB) 23 METABOLISM 24 Metabolism Process by which structure (and function) of drugs, nutrients, vitamins, and minerals is altered Also called biotransformation Liver is primary site for metabolism Metabolism usually makes drug more water soluble and excretable (hydrophilic) 25  Factors Affecting Drug Metabolism Ability of client to metabolize drugs changes across life span Infants? older adults? Ability of client to metabolize drugs influenced by many factors decreased metabolism with liver disease genetic variations of CYP enzymes 26  Microsomal enzymes in liver carry out most metabolic activities cytochrome P450 (CYP) Factors Affecting Drug enzyme that metabolizes many drugs many isoenzyme systems within CYP Metabolism: P450 (CP450) Determine speed at which drug is metabolized metabolizes drugs normally metabolizes drugs more quickly metabolizes drugs more slowly 27 EXCRETION 28  Removal/elimination of drug from body kidney is primary site for excretion pulmonary, glandular, fecal/bile excretion rate of excretion influences concentration of drug in blood Excretion Renal excretion most drugs (not attached to albumin) are filtered into nephron pH of urine can influence reabsorption of drug from nephron BUT…drug bound to plasma protein (albumin) is not filtered. WHY? 29  30 Figure 52.1, Adams et al., 2025, p. 851 Factors Affecting Drug Excretion: Renal Damage Damage to kidney usually reduces excretion of drug Clinical Judgement: What would the nurse consider for a client with acute kidney injury or chronic kidney disease? WHY? 31 Factors Affecting Drug Excretion: Enterohepatic Recirculation Lipid soluble drugs can be reabsorbed with bile via enterohepatic recirculation → decreases rate of excretion Why is this concept important to understand? 32  Enterohepatic Recirculation Figure 3.7, Adams et al., 2025, p. 29 33 Drug Plasma Concentration and Therapeutic Response Minimum effective concentration Toxic concentration Therapeutic index Therapeutic range Define each of these terms Drug half-life Loading doses Maintenance doses 34  Single-Dose Administration Figure 3.8, Adams et al., 2025, p. 30 35  Goal of Nurse Maintain drug at a concentration Maintaining plasma concentration within (therapeutic range) in blood that therapeutic range requires careful produces therapeutic response dosing plasma drug levels rise as drug must consider magnitude and absorbed and decrease as drug frequency of dose and drug half-life excreted more than 90% of a drug is excreted if plasma levels exceed therapeutic after four half-lives range, drug is more likely to produce more adverse effects (toxic range) therapeutic range can be very narrow! 36  Time it takes for plasma concentration of drug to be reduced by 50% Provides estimate of duration of action Drug Half-Life Drugs with short half-lives given more frequently to maintain drug in therapeutic range. But, there are exceptions! Drugs with long half-lives given less frequently 37 Loading versus Maintenance Doses Loading dose when important for drug to reach therapeutic range quickly larger dose leads to more rapid absorption and shorter onset of action Maintenance doses to maintain drug within therapeutic range repeated dosing required to maintain steady plasma concentration of drug next dose given before plasma concentration dips out of therapeutic range 38  Multiple-Dose Administration Figure 3.9, Adams et al., 2025, p. 32 39  What the drug does to the body to create a response related to Pharmacodynamics the mechanism of action of a drug how a drug interacts with a target tissue altering activity of a cell through interactions with receptor altering activity of an enzyme 40 Pharmacodynamics: Receptors Most drugs influence biological response through interactions with cellular receptors Receptor cellular molecule to which drug binds to produce effects intrinsic activity – ability of drug to bind to receptor and produce an effect affinity – degree of attraction most drugs enhance or inhibit existing physiological or biochemical process receptors are only activated or inhibited by chemicals that bind like lock and key 41  Binding is Usually Reversible Plasma Protein i.e. Receptor Albumin Effect Drug Plasma Compartment Tissue/Organ 42  Agonist drug mimics or enhances action of receptor there is a response! response may be greater than that of endogenous substances Drug Agonists and i.e. morphine has a greater response than endorphins or enkephalins Partial Agonists Partial agonist drug display both agonistic and antagonistic effects produces weaker responses than endogenous substances 43  prevents action inhibitor or blocker by competing with endogenous substance by competing with drug agonist (i.e. morphine) for receptor Drug Antagonists binding sites i.e. naloxone Competitive competes with agonist drug for same receptor site Noncompetitive binds to different receptor site but still inactivates agonist receptor 44 Example: Opioid Receptors Is naloxone a competitiv e or non-comp etitive antagonist ? Explain! 45 Figure 23.4, Adams et al., 2025, p. 337  Synergistic when drugs administered together interact, so combined effects exceed that of each individual drug’s effects diuretics and ACE inhibitors both decrease BP so Synergistic when given together the effects are greater than when given alone versus Additive Additive Responses When drugs used together so that smaller doses of each drug can be given, and toxic effects avoided while adequate drug action is maintained i.e. barbiturate and tranquilizer pre-op i.e. acetylsalicylic acid and codeine for analgesia 46  Drugs can compete for CYP (enzymes used in metabolism of drugs) presence of one drug may alter metabolism of another drug by competing for same enzyme Drug to Drug inhibit CYP enzymes Interactions could reduce metabolism of another drug → toxic levels induce CYP enzymes could increase metabolism of another drug → reduce amount of functional drug compete for binding sites on plasma proteins 47 Other Drug Interactions Food to drug Drug to natural health product Contraindication: caution should be used when certain drugs used together or should be avoided altogether may be harmful E.g., if taking warfarin (anticoagulant), should not take acetylsalicylic acid (antiplatelet) 48 Pharmacotherapy: Drug Classifications and Examples Classification Drug Opioid agonists morphine Opioid antagonists naloxone 49  Indications for use? Mechanisms of action? How would you define… Desired effects? Adverse effects? 50 Opioid Agonists Explain how an agonist drug works! Morphine Indications for use acute and severe chronic pain, acute MI pain, cancer pain Mechanisms of action binds with mu and kappa receptors in brain and dorsal horn of spinal cord mimics endogenous opioids such as endorphins and enkephalins (also stimulate opioid receptors) Desired effects alters perception and emotional response to pain produces profound analgesic and euphoric effects Adverse effects dysphoria (restlessness, depression, anxiety) hallucinations nausea, constipation orthostatic hypotension, dizziness pruritus (itchy sensation) overdose: respiratory depression, cardiac arrest 51  Opioid Antagonists Explain how an antagonist drug works! Naloxone Indications for use acute opioid intoxication, suspected opioid overdose: based on signs of respiratory depression post-operative opioid depression and opioid pruritis Mechanism of action competes with opioids at mµ and kappa opioid receptor sites (competitive antagonist) inhibitory/blocking action Desired effects Be pr epare partial or complete reversal of opioid-induced respiratory depression with d resus c equip itation Important adverse effects (tend to be opposite to effects of opioids) opioi ment d is N (if respo OT rapid loss of analgesia for re n s ible spirat increased BP depre ory ssion ) hyperventilation drowsiness produces withdrawal symptoms in clients physically dependent on opioids 52 What would you anticipate the Doctor will order? Client is in respiratory depression after taking an overdose of an opioid (morphine). Morphine’s ½ life is approx. 3 hrs Naloxone’s ½ life is approx. 1.5 hrs 53  Nurses must recognize there is considerable variation in client response to a particular dose of a drug Need to Use Clinical recognize consequences of giving too much or too little of a drug in terms of therapeutic Judgement! response, risk of adverse effects predict the actions and side effects of administered drugs know when to expect prolonged or exaggerated action of drugs Application of pharmacodynamics is critical for safe and responsible administration of drugs 54