How to Study Pharmacology PDF

Chapter 2: Notes ​ Pharmacokinetics: ○​ Mechanism and effects of medication within the body ( what meds do in the body and how they do it) ○​ ADME (Absorption, Distribution, Metabolism, Excretion). ​ Pharmacodynamics: How drugs work at the receptor level. Basic Principl...

Chapter 2: Notes ​ Pharmacokinetics: ○​ Mechanism and effects of medication within the body ( what meds do in the body and how they do it) ○​ ADME (Absorption, Distribution, Metabolism, Excretion). ​ Pharmacodynamics: How drugs work at the receptor level. Basic Principles Related to Drug Therapy: Drug Responses 1.​ Drug Responses in the Body: ○​ Drugs do not create new effects; they alter existing body functions. ○​ They typically work by forming chemical bonds with receptors in the body. 2.​ Receptors and Drug Interaction: ○​ Receptors are specific sites in the body that drugs target. ○​ The drug must have a similar shape and chemical affinity to the receptor to bind effectively (like a key fitting into a lock). 3.​ Pharmacodynamics: ○​ This is the study of drug-receptor interactions and the events that lead to a pharmacologic response. ○​ Pharmacodynamics: How drugs work at the receptor level. ○​ 4.​ Types of Drug-Receptor Interactions: ○​ Agonists: Drugs that bind to receptors and stimulate a response (e.g., a drug that activates a receptor to lower blood pressure). ○​ Antagonists: Drugs that bind to receptors but do not stimulate a response; they block the effect of other substances (e.g., a drug that blocks pain receptors). ○​ Partial Agonists: Drugs that stimulate a response but only partially (they provide a weaker effect compared to full agonists). 5.​ Factors Influencing Drug Response: ○​ The intensity of the drug response depends on: ​ Fit: How well the drug fits the receptor. ( dose of medication) ​ Number of receptors occupied: The more receptors a drug binds to, the stronger the effect. (efficacy)  ​ Potency 1.​ Determines the amount of medication needed to elicit an effect. a.​ Medications with high potency produce effect at a lower dosage b.​ Medication with low potency produce effect at a higher dosage 2.​ 6.​ Dose Response Curve ○​ 3 phases: ​ Phase 1: the curve is more or less flat: thats because the dose of medication is too low- so not enough receptors bind to the medication to cause a significant response ​ Phase 2: as the dose increases, more receptors are occupied by the medication until enough is present to produce an effect. (Minimum effective concentration (MEC)) - as dose increases so does the response ​ Phase 3: all receptors are occupied and the curve starts to flatten out. Maximum efficacy of medication is achieved - increased dosage will not produce a response. ○​ How the safety of medication is measured: ​ Compare the effective in 50% of the population for a particular medication, referred to as effective dose or ED50 ​ Compared with the dose that toxic side effects occur in 50% of the population called toxic dose or TD50 ​ The ratio of TD50/ED50 is called the therapeutic index (TI) which is a measure of the medications safety. 1.​ The closer ratio is to 1: the greater the danger of toxicity. a.​ medications with a large or wide therapeutic index is safer , since their toxic dose is much higher than their effective dose. b.​ Medications with small or narrow therapeutic index are more dangerous, since their toxic and effective doses are close to each other. (DOSE MUST FALL W/IN THERAPEUTIC RANGE)  i.​ Medications: Lithium (mood stabilizer), warfarin (anticoagulant), Digoxin (cardiac medication), and Theophylline (bronchodilator) 2.​ Onset, Peak, and Duration Onset, Peak, and Duration: ​ Onset: Time it takes for the medication to reach its minimum effective concentration and start working. ○​ Rapid onset → use bolus/loading dose (large initial dose). ​ Peak: Time when medication reaches its maximum effectiveness/concentration. ○​ Indicates how fast the drug is absorbed. ○​ Example: ​ Oral meds: Peak in 2-3 hours. ​ IV meds: Peak in 30-60 minutes. ​ Duration: How long the medication stays effective (therapeutic concentration). ○​ Depends on distribution and elimination. Safe Medication Administration: 1.​ Understand receptor interactions: ○​ Medications interact with body receptors → therapeutic effects + side effects. ○​ Example: ​ Bethanechol (cholinergic agonist): ​ Therapeutic: Increases bladder emptying. ​ Side effects: ↓ Heart rate, ↓ Blood pressure, abdominal cramping. 2.​ Know onset, peak, and duration: ○​ Example: ​ Insulin aspart (rapid-acting insulin): ​ Onset: 5-15 minutes → Ensure food is ready to avoid hypoglycemia. 3.​ Monitor medications with narrow therapeutic index: ○​ Example: ​ Gentamicin (aminoglycoside): ​ Monitor trough level (lowest drug level before next dose) → Prevent toxicity (neurotoxic/nephrotoxic). Pharmacodynamics: ​ Definition: What medications do to the body and how they work. ○​ Medications bind to receptors to create effects: ​ Agonist: Enhances receptor activity. ​ Partial agonist: Moderate activity. ​ Antagonist: Blocks receptor activity. ​ Dose-response curve: Shows the relationship between dose and effect. ​ Therapeutic index: Safety margin of a drug. ○​ Wide therapeutic index = safer. ○​ Narrow therapeutic index = requires close monitoring. 7.​ Assessing Drug Effectiveness:  ○​ The effectiveness of a drug is measured by its ability to achieve the desired physiologic change (e.g., lowering blood pressure for antihypertensive drugs). ○​ A baseline assessment is needed before starting therapy to track changes. ○​ Regular assessments should be compared with the baseline to evaluate how well the drug is working. 8.​ Nursing Role: ○​ Nurses should perform a thorough assessment to gather baseline data and track changes over time. ○​ Regular comparisons help healthcare providers evaluate drug effectiveness. Routes of Drug Administration Simplified ​ Enteral Route: ○​ Administers drugs directly into the GI tract. ○​ Methods: ​ Oral (swallowed). ​ Rectal (via the rectum). ​ Nasogastric (through a tube into the stomach). ​ Parenteral Route: ○​ Bypasses the GI tract. ○​ Methods: ​ Subcutaneous (subcut): Injected under the skin. ​ Intramuscular (IM): Injected into a muscle. ​ Intravenous (IV): Injected into a vein. ​ Percutaneous Route: ○​ Absorbs drugs through skin or mucous membranes. ○​ Methods: ​ Inhalation: Breathed in (e.g., inhalers). ​ Sublingual: Placed under the tongue. ​ Topical: Applied on the skin. Drug States After Administration 1.​ Liberation Simplified ​ Definition: ○​ Liberation is when the drug is released from its dosage form and dissolved in body fluids before absorption. ​ Process: ○​ Dosage form (e.g., tablet, capsule) disintegrates. ○​ Active drugs dissolve in body fluids (e.g., GI fluids). ○​ Drug crosses the stomach or intestinal lining into the bloodstream. ​ Influencing Factors: ○​ Dosage form: ​ Example: Solution, suspension, capsule, tablet (with coatings). ○​ Food/Water: ​ Taking the drug with or without food or water affects liberation. ​ Purpose: ○​ Converts the drug into a form that can trigger a response in the body. 2.​ Absorption ​ Definition: ○​ The process where a drug moves from its entry site into the bloodstream or lymph for distribution. ​ Factors Affecting Absorption: ○​ Route of Administration: Determines the rate of absorption (e.g., IV is fastest, subcutaneous is slowest). ○​ Blood Flow: Poor circulation can impair absorption, especially for injections. ○​ Drug Solubility: Solubility in body fluids is essential for absorption. ​ Key Practices for Better Absorption: ○​ Oral Drugs: Take with a large glass of water (8 ounces). ○​ Parenteral Drugs: Administer correctly in the appropriate tissue. ○​ Reconstitution: Use only the recommended diluent for injections. ​ Route-Specific Details: ○​ Subcutaneous (Subcut): Slowest absorption, especially with impaired circulation. ○​ Intramuscular (IM): Faster due to better blood flow in muscles. ○​ Intravenous (IV): Immediate absorption; once in bloodstream, cannot be retrieved. ○​ Topical: Influenced by: ​ Drug concentration. ​ Length of contact. ​ Skin thickness and hydration. ○​ Inhaled Drugs: Affected by: ​ Depth of breathing. ​ Droplet size. ​ Surface area and blood supply of mucous membranes. ​ Special Considerations: ○​ Heat or Massage: Speeds up absorption. ○​ Cold: Slows absorption. ○​ Newborns and Infants: Increased absorption due to thinner, more hydrated skin. 3.​ Distribution 1.​ Definition: ○​ Drug distribution refers to how a drug spreads throughout the body via blood and lymphatic systems, reaching receptor sites or areas of action. 2.​ Factors Affecting Distribution: ○​ Blood Supply: Organs with rich blood supply (e.g., heart, liver, kidneys, brain) get the drug quickly. ○​ Tissue Types: Organs with less blood supply (e.g., muscles, skin, fat) receive the drug more slowly. 3.​ Chemical Properties Influencing Distribution: ○​ Protein Binding: ​ Drugs often bind to plasma proteins (e.g., albumin) for transport.  ​ Bound drug: Inactive, cannot cross cell membranes, cannot act on receptors, cannot be metabolized or excreted. ​ Free (unbound) drug: Active form, can bind to receptors, produce effects, be metabolized and excreted. ○​ The ratio of bound to free drug remains constant in the bloodstream. As free drug is used, more bound drug is released to maintain balance. 4.​ Lipid Solubility: ○​ Lipid-soluble drugs tend to accumulate in fat tissue (adipose tissue) due to low blood flow there. ○​ These drugs stay in the body longer because they are slowly released from fat as blood drug levels decrease. ○​ New equilibrium occurs if more drug is introduced, affecting how it’s distributed, metabolized, and excreted. 5.​ Selective Distribution: ○​ Some drugs cannot pass certain barriers (e.g., blood-brain barrier or placental barrier). ○​ Drugs that can pass these barriers affect specific tissues (e.g., brain, fetus). 6.​ Importance of Distribution: ○​ The amount of drug reaching the receptor sites directly influences its effectiveness. ○​ If insufficient drug reaches the receptors, the pharmacological response is weak or absent. Metabolism Simplified ​ Definition: ○​ The process by which the body inactivates drugs. ​ Primary Site: ○​ Liver: Main organ responsible for drug metabolism. ​ Other Sites (Minor Role): ○​ White blood cells. ○​ GI tract. ○​ Lungs. ​ Factors Affecting Metabolism: ○​ Genetic: Variations in enzyme systems can affect drug metabolism. ○​ Environmental: Exposure to pollutants can impact metabolism.  ○​ Physiologic: Factors like age and concurrent illnesses play a role. ○​ Drug Interactions: Other drugs may enhance or reduce metabolism. ​ Purpose: ○​ Converts drugs into metabolites to prepare for excretion. Excretion Simplified ​ Definition: ○​ The process of eliminating drug metabolites or active drugs from the body. ​ Primary Routes: ○​ GI Tract: Excreted in feces. ○​ Renal Tubules (Kidneys): Excreted in urine. ​ Other Routes: ○​ Skin: Evaporation. ○​ Lungs: Exhalation. ○​ Saliva and Breast Milk: Secretion. ​ Importance of Kidneys: ○​ Kidneys are the main organs for excretion. ○​ Impaired kidney function (e.g., renal failure) can lead to: ​ Prolonged drug action. ​ Increased drug duration. ○​ Monitoring: ​ Review urinalysis and renal function tests to adjust dosage and frequency as needed. Half-Life ​ Definition: ○​ The time required for 50% of a drug to be eliminated from the body. ​ Factors Determining Half-Life: ○​ Metabolism: How efficiently the body processes the drug. ○​ Excretion: How effectively the body eliminates the drug. ​ Practical Use: ○​ Known Half-Lives: Help calculate dosages and frequency of administration. ○​ Long Half-Life Drugs: ​ Example: Digoxin (36 hours). ​ Administered once daily. ○​ Short Half-Life Drugs:  ​ Example: Aspirin (5 hours). ​ Administered every 4–6 hours. ​ Effect of Impaired Function: ○​ Hepatic/Renal Impairment: ​ Longer half-life due to reduced metabolism or excretion. ​ Example: Digoxin’s half-life increases from 36 hours to 105 hours in complete renal failure. ​ Monitoring: ○​ Renal and Hepatic Function Tests: ​ Check for impairments. ​ Notify healthcare provider if abnormalities are detected. Drug Actions ​ Key Phases: ○​ Onset of Action: ​ When the drug concentration becomes sufficient to start a physiologic response. ​ Influenced by: ​ Route of administration. ​ Absorption, distribution, and receptor binding rates. ​ Higher doses may shorten the onset time. ○​ Peak Action: ​ The time when the drug reaches its highest concentration at receptor sites. ​ Produces the maximum pharmacologic response. ○​ Duration of Action: ​ The length of time the drug produces a pharmacologic effect. ​ Time-Response Curve: ○​ Illustrates the relationship between drug administration and response. ○​ Key Points: ​ Minimum Effective Concentration: Drug must reach this level for an effect. ​ Toxicity Threshold: Levels above this cause toxic effects. ​ Therapeutic Range:  ​ Ideal drug concentration falls between the minimum effective response and the toxic threshold. ​ Ensures safety and effectiveness. Drug Blood ​ Definition: ○​ The amount of drug present in the blood, measured by a blood sample. ​ Why It’s Important: ○​ For some drugs (e.g., anticonvulsants, antibiotics), it’s crucial to ensure the drug level is within the therapeutic range for effectiveness and safety. ​ Adjustments Based on Blood Level: ○​ Low Blood Level: ​ Drug may not be effective. ​ Solution: Increase dosage or give the drug more often. ○​ High Blood Level: ​ Risk of toxicity (harmful effects). ​ Solution: Decrease dosage or give the drug less often. Adverse Effects of Drugs ​ Definition: ○​ Drugs can affect more than one body system, causing side effects (mild) or serious adverse effects (can lead to toxicity). ​ Adverse Drug Reaction (ADR): ○​ WHO Definition: Any harmful, unintended effect of a drug used for prevention, diagnosis, or therapy. ○​ Common definition: "Right drug, right dose, right patient, bad effect." ○​ ADR vs. ADE: ​ ADR: Harmful effect of a drug. ​ ADE (Adverse Drug Event): Injury caused by medical intervention with a drug (e.g., mistakes in administration). ​ Statistics: ○​ ADRs are responsible for 100,000+ deaths per year in hospitals (one of the top 6 causes of death in the U.S.). ○​ 6% of hospitalized patients experience a significant ADR. ○​ ADRs contribute to 5%-9% of hospitalization costs. ​ Common ADRs: ○​ Rash, nausea, itching, thrombocytopenia (low platelets), vomiting, hyperglycemia (high blood sugar), diarrhea. ​ Most Affected Drug Classes: ○​ Antibiotics  ○​ Cardiovascular medications ○​ Cancer chemotherapy agents ○​ Analgesics (pain relievers) ○​ Anti-inflammatory agents ​ Predictability and Monitoring: ○​ Most ADRs are predictable based on the drug’s effects. ○​ Patient monitoring is key to adjusting doses for maximum benefits and minimal adverse effects. ​ Medication Safety: ○​ Accurate information on drug-drug interactions is crucial for prescribers to avoid ADRs. ○​ Clinical decision systems help avoid interactions by providing relevant data. ​ Reporting ADRs: ○​ Hospitals have internal systems for reporting suspected ADRs. ○​ Healthcare providers should report ADRs to improve safety. Idiosyncratic Reaction ​ Definition: ○​ An idiosyncratic reaction is an unpredictable and abnormal response when a drug is first taken. ​ Characteristics: ○​ The patient may have a stronger-than-expected response to the drug. ○​ Genetic factor: Often caused by the patient's inability to metabolize the drug due to a genetic deficiency of certain enzymes. ​ Rarity: ○​ Idiosyncratic reactions are rare. ○​ The FDA MedWatch program allows voluntary ADR reporting. Allergic Reaction ​ Definition: ○​ Allergic reactions (also called hypersensitivity reactions) occur when the immune system responds to a drug it has been exposed to before. ​ How it Happens: ○​ After the first exposure, the immune system develops antibodies against the drug. ○​ On reexposure, these antibodies cause a reaction. ​ Common Reaction:  ○​ Hives (raised, irregular patches on the skin) and severe itching (urticaria). ​ Severe Reaction: ○​ In rare cases, a severe, life-threatening reaction called anaphylaxis occurs. ○​ This causes respiratory distress and cardiovascular collapse, which requires immediate medical attention. ​ What to Do: ○​ If a mild allergic reaction occurs, do not take the drug again. ○​ Warning: Future exposure to the drug could cause anaphylaxis. ○​ Inform healthcare providers about the allergic reaction and avoid the drug. ○​ Wear a medical alert bracelet/necklace to indicate the allergy. Drug Interactions ​ Definition: ○​ A drug interaction occurs when the effect of one drug is changed by another drug. ​ Types of Drug Interactions: ○​ Increase the action of one or both drugs. ○​ Decrease the effectiveness of one or both drugs. ​ Beneficial Drug Interactions: ○​ Some interactions can be helpful, e.g., combining caffeine (stimulant) with an antihistamine (depressant). ○​ Caffeine reduces the drowsiness caused by the antihistamine without affecting its primary effect. ​ Mechanisms of Drug Interactions: ○​ Interactions can affect how the drug is absorbed, distributed, metabolized, or excreted. ○​ Interactions can also enhance the pharmacologic effect (the drug's desired Changes in Absorption (Drug Interactions) ​ Location: Most absorption changes happen in the GI tract, especially in the stomach.  ​ Examples: 1.​ Antacids + Ketoconazole: ​ Effect: Antacids increase stomach pH, reducing the dissolution of ketoconazole tablets. ​ Solution: Take the antacid at least 2 hours after ketoconazole. 2.​ Aluminum-containing Antacids + Tetracycline: ​ Effect: Aluminum salts form an insoluble complex with tetracycline, preventing absorption. ​ Solution: Separate tetracycline and antacid by 3 to 4 hours. ○​ action). Changes in Distribution (Drug Interactions) ​ Binding to Proteins: ○​ Drugs often bind to plasma proteins (e.g., albumin) when absorbed into the blood. ○​ Only unbound drugs are pharmacologically active. ​ Impact of Displacement: ○​ If a drug is highly bound (e.g., >90% bound) to a protein, another drug with a higher affinity can displace it. ○​ Even a small displacement can have a significant impact because it increases the amount of unbound drug available for activity. ​ Example: ○​ Warfarin (anticoagulant) + Furosemide (loop diuretic): ​ Furosemide displaces warfarin from albumin-binding sites. ​ More warfarin becomes unbound, increasing anticoagulant action. ​ Solution: Reduce warfarin dosage to manage the increased effect. Changes in Metabolism (Drug Interactions) ​ Inhibition of Metabolism: ○​ Some drugs slow the metabolism of others by binding to enzymes (e.g., verapamil, ketoconazole, amiodarone, cimetidine, erythromycin). ○​ Effect: Serum drug levels increase, requiring a dosage reduction to avoid toxicity. ○​ Example: ​ Erythromycin inhibits the metabolism of theophylline. ​ Solution: Reduce theophylline dosage based on serum levels and signs of toxicity. ​ After stopping erythromycin, theophylline dosage may need to be increased. ​ Induction of Metabolism:  ○​ Some drugs increase the metabolism of others by stimulating enzymes (e.g., phenobarbital, carbamazepine, rifampin, phenytoin). ○​ Effect: Dosage of drugs with rapid metabolism (e.g., warfarin, doxycycline, metronidazole) needs to be increased to maintain therapeutic levels. ​ Example of Interaction: ○​ Rifampin (enzyme inducer) decreases the effectiveness of oral contraceptives by increasing the metabolism of their components. ○​ Solution: Advise the patient to use additional contraception during rifampin therapy. ​ Discontinuation of Enzyme Inducers: ○​ If an enzyme inducer is stopped, drug metabolism slows down, which can lead to drug accumulation and toxicity if dosage adjustments are not made. Changes in Excretion (Drug Interactions) ​ Alteration of Excretion in the Kidneys: ○​ Drug interactions affecting excretion often occur in the kidney tubules by changing urine pH. ​ Example: Acetazolamide and Quinidine: ○​ Acetazolamide increases urine pH (makes it more alkaline). ○​ Alkaline urine causes quinidine to be reabsorbed in the renal tubules, reducing its excretion. ○​ This can increase both the therapeutic and toxic effects of quinidine. ​ Management: ○​ Regular monitoring of quinidine serum levels and checking for signs of toxicity help guide adjustments to quinidine dosage. Drugs That Enhance the Pharmacologic Effects of Other Drugs ​ Drug Interactions: Occur when one drug enhances the effects of another drug, which can lead to increased physiological effects. ​ Examples: ○​ Alcohol + Sedative-Hypnotics: Both cause sedation, but combined, they can cause significant central nervous system depression. ○​ Aminoglycoside Antibiotics (e.g., Gentamicin, Tobramycin) + Neuromuscular Blocking Agents (e.g., Pancuronium): The antibiotic increases the neuromuscular blockade, prolonging recovery time. ​ Terminology Related to Drug-Drug Interactions: Term Definition Example Additive effect Two drugs with similar actions are Hydrocodone + Acetaminophen combined for a stronger effect. = stronger pain relief. Synergistic The combined effect of two drugs is Aspirin + Codeine = stronger effect greater than the sum of each drug alone. pain relief. Antagonistic One drug reduces or cancels the effect Tetracycline + Antacid = effect of another drug. decreased absorption of tetracycline. Displacement One drug displaces another from Warfarin + Valproic acid = protein-binding sites, increasing the increased anticoagulant effect. active drug’s effect. Interference One drug inhibits the metabolism or Probenecid + Ampicillin = excretion of another drug, increasing its prolonged antibacterial effect of activity. ampicillin. Incompatibility Two drugs are chemically incompatible Ampicillin + Gentamicin = when mixed, leading to deterioration. ampicillin inactivates gentamicin. Nurse's Role: ​ Always check for drug interactions when multiple medications are prescribed. ​ Consult drug resources or pharmacists to ensure patient safety.