Cancer - Patho #4 PDF

Cancer Compare and contrast benign and malignant tumors Benign Tumors: ○ Not cancerous. ○ Movable! ○ Encapsulated ○ Grow slowly and don’t spread to other parts of the body. ○ Cells look more like normal cells. ○ EX: Lipoma, Leiomyoma Malignant Tu...

Cancer Compare and contrast benign and malignant tumors Benign Tumors: ○ Not cancerous. ○ Movable! ○ Encapsulated ○ Grow slowly and don’t spread to other parts of the body. ○ Cells look more like normal cells. ○ EX: Lipoma, Leiomyoma Malignant Tumors (Cancerous): ○ Grow quickly and invade nearby tissues. ○ Fixed! Will not move ○ Can spread (metastasize) to distant body parts. ○ Cells often look abnormal and poorly organized. ○ EX: Carcinoma, Adenocarcinoma, Sarcoma, Lymphoma, Leukemia Carcinoma in Situ: Early-stage cancer that hasn’t invaded deeper tissues. ○ May stay unchanged, progress to invasive cancer, or disappear. Describe metastasis and the different metastasis sites for selected cancers. Cancer Spread (Metastasis) ○ Invasion: Cancer cells grow into nearby areas. ○ Metastasis: Cancer cells travel through blood or lymph to other parts of the body and form new tumors. SPREADS! ○ Skin Melanoma → Brain Metastases ○ Breast Cancer → Lung, Liver, Bone & Brain Metastases ○ Lung Cancer → Bone, Adrenal Gland, & Brain Metastases ○ Ovarian Cancer→ Pleura & Liver Metastases ○ Colorectal Cancer → Liver Metastases ○ Pancreatic Cancer → Lung & Liver Metastases Describe environmental-lifestyle factors that contribute to the development of cancers. Tobacco Use ○ Impact: Cigarette smoking is the leading preventable cause of cancer and is considered highly carcinogenic. ○ Cancers Linked: Lung, mouth, throat (pharynx and larynx), esophagus, pancreas, kidney, bladder, liver, cervix, colon, rectum, and acute leukemia. ○ Secondhand Smoke: Exposure to environmental tobacco smoke (ETS) also increases the risk of lung cancer. Diet and Nutrition ○ Carcinogenic Foods: Diets high in red and processed meats are linked to an increased risk of colorectal cancer. ○ Protective Foods: Fruits, vegetables, and whole grains contain antioxidants and fiber, which can lower cancer risk.  ○ Food Contaminants: Toxic chemicals and mutagenic agents in food, such as certain preservatives or charred meats, contribute to cancer risk. Obesity ○ Mechanism: Excess body fat can lead to increased levels of insulin and hormones like estrogen, which promote cancer cell growth. ○ Cancers Linked: Endometrial, colorectal, kidney, esophageal, breast (postmenopausal), and pancreatic cancers. ○ Outcome: Obesity correlates with poorer cancer prognoses and higher recurrence rates. Alcohol Consumption ○ Classification: Alcohol is a human carcinogen. ○ Risk Synergy: The combination of alcohol and tobacco greatly increases the risk of cancers in the upper digestive and respiratory tracts. ○ Cancers Linked: Oral cavity, pharynx, larynx, esophagus, liver, colorectal, and breast cancer. Physical Inactivity ○ Mechanism: Regular exercise helps regulate hormones, maintain a healthy weight, and support immune function, which lowers cancer risk. ○ Link: Physical inactivity contributes to increased risks of breast, colorectal, and endometrial cancers. Infections ○ Viruses and Bacteria: Human Papillomavirus (HPV): Strongly linked to cervical, anal, oropharyngeal, and other genital cancers. Hepatitis B and C: Associated with liver cancer. Helicobacter pylori (H. pylori): Linked to stomach cancer. Epstein-Barr Virus (EBV): Associated with nasopharyngeal cancer and certain lymphomas. ○ Parasitic Infections: Some parasites are associated with cancer risk in specific regions (e.g., schistosomiasis linked to bladder cancer). Ultraviolet (UV) Radiation ○ Source: The sun is the main source, with UV-A and UV-B rays contributing to skin damage. ○ Cancers Linked: Skin cancers, including basal cell carcinoma, squamous cell carcinoma, and melanoma. ○ Prevention: Protective measures like sunscreen and clothing can reduce UV exposure and skin cancer risk. Ionizing Radiation ○ Sources: X-rays, CT scans, radioactive substances. ○ Cancers Linked: Leukemias and increased risk for thyroid, breast, lung, stomach, colon, and other cancers. ○ Exposure: Occupational or accidental exposure, as seen in nuclear plant workers or radiological accidents, increases cancer risk. Air Pollution ○ Outdoor Pollution: Smog and particulate matter linked to lung cancer.  ○ Indoor Pollution: More harmful than outdoor pollution, often due to tobacco smoke, radon gas, and pollutants from household products. ○ Effect: Particulate pollution causes oxidative stress and DNA damage, leading to cancer development. Chemical and Occupational Exposure ○ Occupational Carcinogens: Include asbestos (linked to mesothelioma and lung cancer), benzene (linked to leukemia), and heavy metals. ○ Industries at Risk: Workers in chemical manufacturing, dye production, rubber industry, and mining face higher cancer risks due to prolonged exposure to carcinogens. Socioeconomic and Demographic Factors ○ Access to Healthcare: Impacts early detection and treatment availability. ○ Geographic Location: Influences exposure to environmental carcinogens and access to resources. ○ Lifestyle Choices: Differ based on cultural practices, which may affect diet, exercise, and exposure to risk factors. Cancer Diagnosis Initial Steps for Cancer Diagnosis ○ Screening Tests: Routine tests used to detect cancer early, before symptoms appear (e.g., mammograms for breast cancer, Pap smears for cervical cancer, colonoscopies for colorectal cancer) ○ Physical Exams: Doctors check for lumps, abnormalities, or changes in the body that may indicate cancer. Diagnostic Imaging ○ X-rays: Basic imaging to find tumors or masses. ○ CT Scans (Computed Tomography): Provides detailed cross-sectional images of the body to locate and assess tumors. ○ MRI (Magnetic Resonance Imaging): Uses magnets and radio waves to create detailed images, particularly helpful for brain, spine, and joint assessments. ○ PET-CT Scan (Positron Emission Tomography): Involves the injection of a radioactive glucose tracer. Cancer cells, which use more glucose than normal cells, appear brighter on the scan. Biopsy Procedures ○ Purpose: Obtaining a tissue sample to confirm the presence of cancer and determine its type and aggressiveness. ○ Types of Biopsies: Incisional Biopsy: Removes a portion of a lesion (e.g., muscle mass biopsy). Core Needle Biopsy: Extracts tissue with a hollow needle, often guided by ultrasound or CT (e.g., for prostate or liver masses). Fine Needle Aspiration: Collects cells for cytology but does not preserve tissue structure (e.g., for thyroid nodules). Exfoliative Cytology: Collects cells shed from the surface of tissues (e.g., Pap smear for cervical cells). Tumor Markers  ○ Definition: Substances produced by cancer cells found in the blood, urine, or tissues. ○ Examples: CA-125: Indicator for ovarian cancer. PSA (Prostate-Specific Antigen): Used for prostate cancer. CEA (Carcinoembryonic Antigen): Associated with GI, pancreas, and lung cancers. ○ Uses: Aid in diagnosing cancer, determining treatment response, and monitoring recurrence. Describe the World Health Organization’s TNM system for tumor staging. T - Tumor (Primary Tumor): Describes the size and extent of the main (primary) tumor. ○ T0: No evidence of a primary tumor. ○ T1-T4: Increasing size and/or local spread of the primary tumor. T1: Tumor ≤2 cm in size. T2: Tumor 2–5 cm in size. T3: Tumor extends into surrounding tissues like skin or chest wall. T4: Tumor has spread to nearby structures or tissues. N (Nodes): Indicates whether cancer has spread to nearby lymph nodes, and the extent of node involvement. ○ N0: No lymph node involvement. ○ N1-N2: Increasing number and fixation of involved nodes. N1: Limited lymph node involvement, typically mobile nodes. N2: Greater number of lymph nodes involved or nodes fixed to surrounding tissues. M (Metastasis): Shows whether cancer has spread to other parts of the body (distant organs), confirmed BY PET SCAN ○ M0: No distant spread. ○ M1: Demonstrable Metastases ○ M2: Suspected Metastases Example of Staging: cT2N1M0 indicates a clinical finding of a tumor larger than 2 cm but less than 5 cm, with some mobile lymph node involvement, but no distant spread. p = pathologic c = clinical staging Compare and contrast stage 1, stage 2, stage 3, and stage 4 tumors. Aspect Stage 1 Stage 2 Stage 3 Stage 4 Typically small and Larger than stage 1 May vary in size Size varies, but the localized. and may have but shows defining feature is Tumor Size grown into nearby significant growth spread beyond the structures. into nearby primary site. tissues or structures.  No lymph node Minimal or no lymph Clear involvement Can involve extensive Lymph Node involvement (N0). node involvement of regional lymph regional lymph nodes Involvement (may be N1). nodes (N1, N2). and distant sites (N3). No distant No distant No distant Presence of distant Metastasis metastasis (M0). metastasis (M0). metastasis (M0), metastasis (M1). but local or regional spread. Confined to its May have begun Advanced local Spread to distant Spread/Extent organ of origin with spreading to nearby spread to nearby organs such as lungs, no invasion of tissues but remains tissues or regional liver, bones, or brain. nearby tissues. in the same area. lymph nodes. Generally Good prognosis, but More complex Poor prognosis due to favorable with high survival rates are prognosis due to extensive spread; Prognosis survival rates. lower than stage 1 regional spread; treatment focuses on due to larger size or survival rates managing disease deeper invasion. decrease. rather than curing. Often treated Surgery may be Requires Often involves systemic effectively with combined with multimodal treatment Treatment surgery alone. radiation or treatment (e.g., (chemotherapy, Approach chemotherapy to surgery, radiation, targeted therapy, or address the risk of and/or immunotherapy) to spread. chemotherapy) to control disease and manage regional alleviate symptoms. spread. Typically small and Larger than stage 1 May vary in size Size varies, but the localized. and may have but shows defining feature is Tumor Size grown into nearby significant growth spread beyond the structures. into nearby primary site. tissues or structures. Describe the gene products of proto-oncogenes, oncogenes, and tumor-suppressor genes Tumor Suppressor Aspect Proto-oncogenes Oncogenes Genes (p53) Mutated or overactive Genes that control cell Normal genes regulate Definition forms of growth and repair cell growth and division. proto-oncogenes. damaged DNA. Promote controlled cell Act as brakes on cell N/A (oncogenes are only Role in Normal Cells growth, division, and cycle; initiate DNA repair found in mutated states). survival. or apoptosis. Role in Cancer Can transform into Drive uncontrolled cell Loss of function leads to  oncogenes if mutated or growth, contributing to unregulated cell growth overexpressed. cancer. and genomic instability. Gain-of-function Produce proteins that Loss-of-function mutations mutations that enhance Mechanism of Action help cells grow and impair cell cycle arrest, cell proliferation and divide properly. repair, and apoptosis. survival. Activated by mutation, Result from the mutation Inactivated by mutations, Activation/Inactivation amplification, or or activation of deletions, or loss of chromosomal changes. proto-oncogenes. heterozygosity. Support normal Promote continuous, Halt the cell cycle for mpact on Cell Cycle progression through cell unchecked cell cycle repair or induce cell death cycle phases. progression. if damage is irreparable. Tumor Suppressors: BRCA 1, BRCA 2, RB1 - BRCA 1: Most dangerous when affected, affect women mostly. - Breast, ovarian, pancreas and prostate cancers - BRCA 2: Affects mostly men. - RB1: Causes retinoblastoma in children Compare and contrast the modalities for cancer treatment: surgery, radiation, and chemotherapy (adjuvant vs neoadjuvant). Surgery ○ What It Is: Physically removes the tumor from the body. ○ Purpose: Best for early-stage cancer that hasn’t spread. It aims to remove the entire tumor. ○ Benefits: Can be curative if all cancer is removed. ○ Risks: Infection, pain, recovery time, and possible recurrence. ○ Role: Often the first treatment, followed by other therapies if needed. Radiation Therapy ○ What It Is: Uses high-energy rays to kill cancer cells. ○ Purpose: Targets specific areas to shrink or destroy tumors. ○ Benefits: Effective for localized cancer; can prevent recurrence or be palliative to relieve symptoms. ○ Risks: Fatigue, skin changes, and possible damage to nearby tissues. ○ Role: Can be used alone or after surgery to ensure any remaining cancer cells are destroyed. Chemotherapy ○ What It Is: Uses drugs to kill or stop cancer cells from growing. ○ Types: Adjuvant Chemotherapy: Given after surgery to kill leftover cancer cells and reduce recurrence. Neoadjuvant Chemotherapy: Given before surgery to shrink tumors and make them easier to remove.  ○ Benefits: Treats cancer that may have spread throughout the body. ○ Risks: Affects healthy cells too, causing side effects like nausea, hair loss, and fatigue. ○ Role: Often part of a broader treatment plan with surgery or radiation. Comparison ○ Surgery removes cancer directly but is best for localized cases. ○ Radiation targets cancer cells precisely and can be used before or after surgery. ○ Chemotherapy treats widespread cancer but has more systemic side effects and can be used before (neoadjuvant) or after (adjuvant) surgery. Discuss major toxicities of chemotherapeutic (anti-cancer) drugs and strategies that can be taken to minimize drug-induced harm. Bone Marrow Suppression (Myelosuppression) ○ Description: Chemotherapy can reduce the production of blood cells, leading to neutropenia (low white blood cells), thrombocytopenia (low platelets), and anemia (low red blood cells). ○ Consequences: Neutropenia: Increased risk of infection; the lowest count (nadir) typically occurs 10-14 days after treatment. Thrombocytopenia: Higher risk of bleeding and bruising. Anemia: Causes fatigue and weakness. ○ Management Strategies: Use of colony-stimulating factors (e.g., filgrastim) to stimulate white blood cell production. Platelet transfusions or erythropoietin (e.g., epoetin alfa) for severe thrombocytopenia and anemia. Good hygiene and neutropenic precautions to prevent infection. Digestive Tract Injury ○ Description: The lining of the gastrointestinal (GI) tract is highly sensitive to cytotoxic drugs, leading to side effects like stomatitis (oral inflammation) and diarrhea. ○ Consequences: Stomatitis: Can cause painful mouth sores, making eating and speaking difficult. Diarrhea: Results from damage to the intestinal lining, affecting nutrient and fluid absorption. ○ Management Strategies: Preventative oral care (soft toothbrushes, sodium bicarbonate rinses). Use of mouthwashes with topical anesthetics for mild stomatitis; systemic opioids for severe cases. Anti-diarrheal medications (e.g., loperamide) to manage diarrhea. Nausea and Vomiting ○ Description: Chemotherapy drugs can trigger the chemoreceptor trigger zone, causing significant nausea and vomiting. ○ Management Strategies: Premedication with antiemetic drugs (e.g., ondansetron, dexamethasone, aprepitant). Combining different classes of antiemetics for better effectiveness.  Alopecia (Hair Loss) ○ Description: Damage to hair follicles causes temporary hair loss, usually beginning 7-10 days after treatment. ○ Management Strategies: Scalp cooling caps can help reduce blood flow to hair follicles, lessening the degree of hair loss. Choosing wigs or hairpieces before treatment begins for preparation. Explain the growth fraction and how tissue growth fraction affects the response to chemotherapy. Growth Fraction: The growth fraction is the ratio of actively dividing (proliferating) cells to resting (G0 phase) cells in a tissue. ○ High GF: A tissue with a large number of dividing cells and few resting cells ○ Low GF: A tissue with mostly resting cells and fewer cells undergoing division Target: Most chemotherapeutic drugs are more effective against actively dividing cells. They disrupt processes like DNA synthesis and mitosis, which only proliferating cells carry out. ○ HIGH GF: Response: Respond better to chemotherapy because a larger percentage of their cells are in the cell cycle, making them more susceptible to the drugs. Examples: Cancers such as lymphocytic leukemia, Hodgkin's disease, certain testicular cancers, and small cell lung cancer have high growth fractions and are generally more responsive to chemO. ○ LOW GF Response: These cancers, such as solid tumors of the breast, lung, prostate, colon, and rectum, have a lower growth fraction and respond poorly to chemotherapy. The higher number of cells in the G0 phase makes them less affected by the drugs. NORMAL TISSUES ○ Normal Tissues with high GF are affected by chemo Bone marrow: Leads to myelosuppression (reduced blood cell production). Gastrointestinal tract: Causes mucositis and other GI issues. Hair follicles: Results in hair loss. Describe the benefits and challenges of intermittent and combination therapy. Intermittent Therapy: Chemotherapy given in cycles with breaks in between ○ Good for letting healthy cells recover but risks cancer cell regrowth.. ○ BENEFITS Allows time for normal cells to heal, reducing side effects. Prevents severe damage to organs and tissues. Patients feel better during rest periods. ○ CHALLENGES Tumor cells may grow back during breaks. Requires careful scheduling to ensure effectiveness. Must watch patients to know when to restart treatment. Combination Therapy: Using two or more drugs at the same time.  ○ More effective against cancer but increases side effects and complexity. ○ BENEFITS Targets cancer in different ways, increasing cell kill. Harder for cancer to become resistant to multiple drugs Hits cancer cells in different growth stages ○ CHALLENGES Each drug adds its own side effects, increasing overall impact. Must carefully plan doses and schedules. Managing combined side effects can be difficult. Describe the major toxicities and other important toxicities of chemotherapeutic drugs. MAIN TOXICITIES Myelosuppression: Reduces the number of circulating blood cells. ○ CONSEQUENCES Infection: Due to loss of neutrophils (neutropenia). Bleeding: From decreased platelets (thrombocytopenia). Anemia: Due to reduced red blood cells. ○ Management: May involve colony-stimulating factors to boost cell production, transfusions, and infection precautions. Neutropenia: Neutrophil count may drop to its lowest level (nadir) between days 10-14 post-treatment. ○ Risk: Increased risk of severe infections, with fever as an early warning sign. ○ Management: Isolation, avoiding high-risk foods (e.g., unpasteurized dairy, raw meat), and potentially using antibiotics. Thrombocytopenia: Low platelet count increases bleeding risk. ○ Precautions: Avoiding aspirin, using soft toothbrushes, and limiting invasive procedures. ○ Management: Platelet transfusions if count is very low Anemia: Low Iron ○ Impact: Can cause significant fatigue and weakness. ○ Management: Transfusions and erythropoietin use, although the latter is limited in curative cases due to potential tumor growth stimulation. OTHER TOXICITIES Digestive Tract Injury ○ Stomatitis: Painful mouth inflammation that can progress to ulceration, lasting for weeks. ○ Diarrhea: Results from epithelial damage in the GI tract, manageable with loperamide. Nausea and Vomiting ○ Cause: Stimulation of the chemoreceptor trigger zone. ○ Prevention: Using antiemetics like ondansetron and combinations of other supportive drugs. Alopecia ○ Hair loss begins about 7-10 days after starting treatment and peaks in 1-2 months. ○ Outcome: Hair typically regrows after treatment stops. Reproductive Toxicity  ○ Effect: Potential harm to developing embryos, permanent or temporary infertility. ○ Management: Fertility preservation methods before treatment. Cardiotoxicity ○ Drugs: Some like anthracyclines can cause cumulative heart damage. ○ Monitoring: Regular heart function tests during treatment. Peripheral Neuropathy ○ Drugs: Taxanes, such as paclitaxel, can cause tingling, numbness, or pain. ○ Management: Adjusting dosages if necessary. Describe tumor lysis syndrome, its clinical manifestations, and medical and nursing management Tumor Lysis Syndrome (TLS): Medical emergency that happens when cancer treatment quickly destroys many tumor cells. This release of cell contents into the blood causes serious chemical imbalances. ○ Common in: Cancers with fast-growing tumors, like leukemia and lymphoma. ○ S/S Nervous System: Fatigue, muscle cramps, tingling, and seizures. Heart: High blood pressure and irregular heartbeats. Digestive System: Nausea, vomiting, stomach pain, and diarrhea. Kidneys: Flank pain, low or no urine output, and risk of kidney failure. Other: Itching and symptoms of gout. ○ Labs High Levels: Potassium (hyperkalemia): Can affect the heart. Phosphate (hyperphosphatemia): Can lead to low calcium. Uric Acid (hyperuricemia): Can damage the kidneys. Low Levels: Calcium (hypocalcemia): Can cause muscle and nerve issues. Tests: Blood tests for electrolytes, EKGs for heart activity, and urine tests for kidney function. ○ Prevention Hydration: Give lots of fluids before and after treatment to flush out toxins. Medications: Allopurinol to prevent uric acid buildup. Rasburicase for fast reduction of uric acid. ○ Nursing Management Monitoring: Check vital signs and lab results regularly. Watch for signs of heart or nerve problems. Track fluid intake and output closely. Teach patients to notice symptoms early, like muscle problems or changes in urination. Keep patients well-hydrated and prepare for possible treatments like dialysis if needed. HIV Define a retrovirus in terms of the transcription of information between viral deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). Also, compare the sequence of the basic events in retroviruses with what typically goes into a host cell. Retrovirus: Type of virus that has RNA as its genetic material. Unlike typical viruses, retroviruses use an enzyme called reverse transcriptase to transcribe their RNA into DNA once inside a host cell. ○ Transcription Process: The viral RNA is reverse-transcribed into complementary DNA (cDNA). This cDNA integrates into the host cell’s genome, becoming a permanent part of the host's DNA. The integrated viral DNA (provirus) is then used by the host's cellular machinery to produce viral RNA and proteins, leading to the creation of new virus particles. ○ Retrovirus Lifecycle Entry: The virus binds to the host cell and enters it. Reverse Transcription: The viral RNA is converted to DNA using reverse transcriptase. Integration: The viral DNA integrates into the host cell's DNA with the help of integrase. Transcription and Translation: The host cell transcribes and translates the viral DNA as if it were its own, producing viral proteins and RNA. Assembly and Release: New virus particles are assembled and released from the host cell to infect more cells. Recognize that helper T-lymphocyte (CD4) cells are the main target of HIV. Also, explain what CD4 cells do to/for HIV, why they are important to the host, and how these facts relate to the opportunistic infections that accompany AIDS Primary Role: CD4 cells serve as the main target for HIV, which uses these cells as entry points. ○ Immune Coordination: CD4 cells are central to activating and regulating other immune responses They stimulate B-lymphocytes to produce antibodies. They also activate cytotoxic T cells that destroy infected cells HIV’s Mechanism of Infection: ○ HIV binds to CD4 receptors to gain entry into cells. ○ The virus hijacks the cell machinery to replicate, reducing the overall CD4 cell count. ○ A decreased CD4 count weakens the host’s immune system. HIV to AIDS ○ A lower CD4 count results in an impaired immune response. ○ Once CD4 cells drop below a critical level, the body becomes susceptible to opportunistic infections (e.g., pneumonia, tuberculosis). ○ The progression of HIV to AIDS is marked by severe immune compromise and frequent opportunistic infections​ Describe the 3 phases of HIV infection and the likely levels of CD4 cells and HIV in each. Also, explain why the CD4 cells and HIV levels change as they do. Acute (Primary) HIV Infection: ○ Duration: Typically 2-4 weeks after initial exposure. ○ CD4 Cell Levels: Rapid decline shortly after infection due to active viral replication. ○ HIV Levels: Spike to very high levels (high viral load) during this period, as the virus spreads throughout the body. ○ Explanation: This phase is marked by high levels of viral replication as HIV targets CD4 cells. The immune system responds but cannot immediately control the virus, leading to an initial sharp decline in CD4 cells. Chronic (Clinical Latency) Phase ○ Duration: Can last several years (10 years or more without treatment). ○ CD4 Cell Levels: Generally stable but may slowly decline over time. ○ HIV Levels: Moderate viral load; lower than the acute phase but ongoing replication persists. ○ Explanation: HIV continues to replicate at a lower level. The immune system manages to partially suppress the virus, maintaining relative stability in CD4 count. However, the persistent replication leads to gradual immune system weakening. AIDS ○ Duration: Final stage of HIV infection; timeline varies based on treatment status. ○ CD4 Cell Levels: Drop below 200 cells/mm³, signaling severe immune suppression. ○ HIV Levels: High viral load due to immune system collapse and inability to control replication. ○ Explanation: The virus overwhelms the immune system, depleting CD4 cells. This severe immunosuppression leads to susceptibility to opportunistic infections and cancers, defining the progression to AIDS​ In simple terms, explain what the main classes of antiretroviral drugs do to impair viral replication or function biochemically. Be familiar with their associated adverse effects and drug interactions. Nucleoside Reverse Transcriptase Inhibitors (NRTIs) ○ Function: Mimic natural nucleotides and incorporate into viral DNA during replication, causing chain termination. ○ Key Adverse Effects: Lactic acidosis, hepatomegaly, and bone marrow suppression. ○ Drug Interactions: May interact with other drugs affecting bone marrow or those metabolized by the liver. Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) ○ Function: Bind directly to reverse transcriptase enzyme, blocking its activity and preventing viral DNA synthesis. ○ Key Adverse Effects: Rash, hepatotoxicity, and central nervous system symptoms. ○ Drug Interactions: Can induce or inhibit liver enzymes, affecting levels of other drugs like anticonvulsants or antimicrobials. Protease Inhibitors (PIs) ○ Function: Block HIV protease enzyme, preventing cleavage of viral proteins needed for assembly of infectious particles.  ○ Key Adverse Effects: Hyperglycemia, lipid abnormalities, gastrointestinal distress. ○ Drug Interactions: Significant potential due to inhibition of cytochrome P450 enzymes; interactions with statins, sedatives, etc. HIV Integrase Strand Transfer Inhibitors (INSTIs) ○ Function: Inhibit integration of viral DNA into the host genome, a critical step in HIV replication. ○ Key Adverse Effects: Insomnia, headache, and potential allergic reactions. ○ Drug Interactions: Can interact with antacids and other medications affecting the absorption of INSTIs. Fusion Inhibitors (e.g., Enfuvirtide) ○ Function: Prevent fusion of HIV with host cell membrane, blocking entry into the cell. ○ Key Adverse Effects: Injection site reactions, increased risk of bacterial pneumonia. ○ Drug Interactions: Minimal drug interactions. CCR5 Antagonists (e.g., Maraviroc) ○ Function: Block CCR5 co-receptor on host cells, preventing viral entry. ○ Key Adverse Effects: Hepatotoxicity, upper respiratory symptoms. ○ Drug Interactions: May interact with other drugs processed by CYP3A4 enzymes​ Give a reasonable explanation of why HIV infection does not kill people directly, pointing out that infected individuals die of the consequences of other events that develop when the infection turns into AIDS HIV doesn’t kill directly; instead, it weakens the immune system by destroying CD4 cells, which help the body fight infections. Immune System Failure: As CD4 cells decrease, the immune system can't protect the body as well. ○ When CD4 cells drop very low, the condition becomes AIDS, leaving the person defenseless. Opportunistic Infections: With a weakened immune system, people get serious infections and certain cancers that a healthy body could normally fight off. ○ These infections and complications are what actually cause death, not HIV itself. GI Understand the following diseases (i.e. presenting signs/symptoms, treatment options, emergency interventions if relevant, ongoing management) Peptic Ulcer Disease (PUD) Signs/Symptoms: Break in the protective mucosal lining, often in the stomach or duodenum. Symptoms include epigastric pain, which may improve with food/antacids (for duodenal ulcers). Treatment: Focuses on reducing acid secretion, antibiotics for Helicobacter pylori infection, and lifestyle modifications. Emergency Interventions: Surgery for bleeding/perforated ulcers. Ongoing Management: Avoid NSAIDs, stress reduction, dietary adjustments. Liver disease Signs/Symptoms: Jaundice, ascites, portal hypertension, hepatic encephalopathy, varices. Treatment: Addressing the underlying cause (e.g., alcohol, hepatitis); use of diuretics for fluid control; low-protein diets for encephalopathy. Emergency Interventions: Paracentesis for severe ascites; bleeding varices require endoscopic or surgical intervention. Ongoing Management: Monitoring liver function; lifestyle changes (e.g., abstinence from alcohol). Hepatitis A Transmission: Fecal-oral route (e.g., contaminated food/water). Signs/Symptoms: Often acute with fever, fatigue, jaundice, nausea, abdominal discomfort, and dark urine. Treatment: Supportive care, as it usually resolves on its own. Prevention: Vaccination, improved hygiene, and sanitation practices. Hepatitis B Transmission: Contact with infected blood, bodily fluids; perinatal transmission possible. Signs/Symptoms: Can be acute or chronic; jaundice, fatigue, abdominal pain, joint pain, dark urine. Treatment: Antivirals (e.g., tenofovir), interferon therapy for chronic cases. Prevention: Vaccination, safe sex practices, blood screening. Hepatitis C Transmission: Primarily through blood (e.g., IV drug use, contaminated needles). Signs/Symptoms: Often asymptomatic initially; chronic infection can lead to cirrhosis, liver cancer. Treatment: Direct-acting antivirals (DAAs) can cure most cases. Prevention: No vaccine; avoid sharing needles, screen blood products. Hepatitis D Transmission: Blood-to-blood contact; occurs only with hepatitis B (requires HBV for replication). Signs/Symptoms: Can worsen HBV infection, leading to more severe liver disease. Treatment: Pegylated interferon; managing HBV reduces HDV risk. Prevention: HBV vaccination prevents HDV co-infection.  Hepatitis E Transmission: Fecal-oral route, especially in areas with poor sanitation. Signs/Symptoms: Similar to HAV, often self-limiting; can be severe in pregnant women. Treatment: Supportive care; resolves spontaneously in most cases. Prevention: Improved water sanitation, hygiene measures. Pancreatitis Signs/Symptoms: Severe abdominal pain, nausea, vomiting, fever, jaundice. Treatment: Bowel rest (NPO), pain management, fluids, treatment of underlying causes (e.g., gallstones, alcohol). Emergency Interventions: Management of shock; surgery if complications (e.g., necrosis) arise. Ongoing Management: Dietary modifications, avoiding alcohol, treating chronic pancreatitis risk factors. Appendicitis Signs/Symptoms: Epigastric/periumbilical pain shifting to the right lower quadrant (RLQ), rebound tenderness, fever. Treatment: Appendectomy, antibiotics. Emergency Interventions: Immediate surgery if rupture is suspected. Ongoing Management: Post-surgical recovery and infection monitoring. Bowel obstruction Signs/Symptoms: Abdominal distension, colicky pain, vomiting, inability to pass stool. Treatment: NG tube decompression, fluid replacement, surgery for complete or prolonged obstruction. Emergency Interventions: Prompt surgical intervention for ischemia/perforation. Ongoing Management: Diet modifications, addressing underlying causes. Cholecystitis/Cholelithiasis Signs/Symptoms: RUQ pain, fever, nausea; can radiate to shoulder/back. Treatment: Pain management, antibiotics; cholecystectomy for recurrent cases. Emergency Interventions: Surgery for severe inflammation or gallstone-related obstruction. Ongoing Management: Diet adjustments to prevent stone formation. Diverticulitis Signs/Symptoms: Pain in lower abdomen (often left side), fever, changes in bowel habits. Treatment: Antibiotics, bowel rest. Emergency Interventions: Surgery for abscess, perforation, or obstruction. Ongoing Management: High-fiber diet, weight management​ Pharmacological Management of GI problems Proton pump inhibitors (PPIs) Examples: Omeprazole, Lansoprazole, Pantoprazole MOA: Irreversibly inhibits the H+/K+ ATPase pump in gastric parietal cells, significantly reducing acid secretion. Considerations  ○ Administer 30 minutes before meals for optimal absorption. ○ Used for GERD, ulcers, and H. pylori treatment (in combination with antibiotics). ADRs ○ Headache, nausea, diarrhea, and abdominal pain. ○ Long-term use: Risk of osteoporosis, hypomagnesemia, and vitamin B12 deficiency. H2 receptors Examples: Ranitidine, Famotidine MOA: Blocks histamine at H2 receptors in the gastric parietal cells, reducing acid secretion. Considerations: ○ Take at bedtime for better nocturnal acid suppression. ○ Avoid in severe renal impairment without dosage adjustment. ADRs ○ Rare: CNS effects like confusion in the elderly. ○ Ranitidine concerns regarding potential carcinogenic impurities (specific to recalls). Antiemetics Examples ○ Dopamine antagonists (Metoclopramide): Promotes gastric emptying and blocks dopamine receptors in the chemoreceptor trigger zone (CTZ). ○ Serotonin antagonists (Ondansetron): Blocks serotonin receptors in the CTZ and vagal nerve endings. ○ Antihistamines (Meclizine): Blocks histamine receptors. ○ Anticholinergics (Scopolamine): Blocks muscarinic receptors, reducing vestibular input. Considerations ○ Tailor the choice of antiemetic to the underlying cause (e.g., chemotherapy-induced vs. motion sickness). ADRs ○ Dopamine antagonists: Extrapyramidal symptoms, sedation. ○ Serotonin antagonists: Constipation, headache, QT prolongation. ○ Antihistamines and anticholinergics: Drowsiness, dry mouth. Bowel regimens (laxatives, stool softeners, Lactulose, etc.) Examples & MOAs ○ Bulk-forming laxatives (Psyllium): Absorbs water into the stool, increasing bulk. ○ Osmotic laxatives (Lactulose, Magnesium citrate): Draws water into the colon. ○ Stimulant laxatives (Bisacodyl): Stimulates peristalsis by irritating the intestinal lining. ○ Stool softeners (Docusate): Lowers stool surface tension, allowing water penetration. Considerations ○ Ensure hydration with bulk-forming laxatives.  ○ Avoid stimulants in cases of suspected bowel obstruction. ADRs ○ Bulk-forming: Bloating, gas. ○ Osmotic: Electrolyte imbalances, dehydration. ○ Stimulant: Cramping, dependency risk. Antibiotics (such as Amoxicillin, Clarithromycin, Metronidazole, etc.) Examples: Amoxicillin, Clarithromycin, Metronidazole MOA: ○ Amoxicillin: Inhibits bacterial cell wall synthesis. ○ Clarithromycin: Inhibits bacterial protein synthesis by binding to the 50S ribosomal subunit. ○ Metronidazole: Causes DNA strand breaks in anaerobic bacteria. Considerations ○ Always used in combination therapy (e.g., triple or quadruple therapy) with PPIs to prevent resistance. ○ Avoid alcohol with metronidazole (disulfiram-like reaction). ADRs ○ Amoxicillin: Diarrhea, hypersensitivity reactions. ○ Clarithromycin: Metallic taste, GI upset, QT prolongation. ○ Metronidazole: Nausea, peripheral neuropathy. Sucralfate Class: Cytoprotective agent MOA: Forms a protective barrier over ulcers by binding to exposed proteins in the ulcer base. Considerations ○ Administer on an empty stomach. ○ Avoid co-administration with antacids or other medications within 2 hours. ADRs ○ Constipation, dry mouth. Misoprostol Class: Prostaglandin analog MOA: Increases mucosal defense by promoting bicarbonate and mucus secretion; also reduces gastric acid secretion. Considerations: ○ Used for NSAID-induced ulcer prevention. ○ Contraindicated in pregnancy (induces uterine contractions). ADRs ○ Abdominal cramping, diarrhea. Antacids Examples: Calcium carbonate, Magnesium hydroxide, Aluminum hydroxide MOA: Neutralize gastric acid, increasing gastric pH. Considerations: ○ Separate from other meds by at least 2 hours (can interfere with absorption). ○ Monitor for acid rebound with prolonged use.  ADRs ○ Calcium carbonate: Hypercalcemia, constipation. ○ Magnesium hydroxide: Diarrhea. ○ Aluminum hydroxide: Constipation, hypophosphatemia. Pain Describe the effect of endorphins on the transmission of pain impulses. Endorphins: endogenous opioid that modulate pain by binding to opioid receptors in the nervous system. ○ Inhibition of Pain Impulses: Inhibit the transmission of pain signals at the spinal cord level by blocking the release of pain-inducing neurotransmitters such as substance P and glutamate. ○ Activation of Descending Pain Modulation Pathways: stimulate descending inhibitory pathways in the brainstem, which suppress pain transmission in the spinal cord. ○ Endorphins contribute to a sense of well-being and euphoria, which can indirectly reduce the perception of pain. Differentiate between acute and chronic pain. Acute Pain: serves as a protective mechanism, signaling actual or potential tissue damage. It is typically sudden in onset and has a clear cause. A-Delta Fibers: pain is sharp & well localized C-Fibers: Dull, aching, poorly localized ○ Duration: Short-term, usually lasting less than 3-6 months or until the underlying cause resolves. ○ Clinical Characteristics Associated with autonomic responses such as increased heart rate, blood pressure, and respiratory rate. Often sharp or intense in nature. Responds to Opioids Well Defined SNS response ○ Examples: Surgical pain, trauma, or burns. ○ Treatment Goal: Identify and treat the underlying cause, and provide adequate pain relief. Chronic Pain: Pain that persists beyond the expected healing time or occurs in the absence of an identifiable acute injury. It is considered a disease in its own right. ○ Duration: Long-term, lasting more than 3-6 months. ○ Clinical Characteristics: Less linked to autonomic responses but often associated with psychological factors such as depression, anxiety, and sleep disturbances. Can be dull, aching, or diffuse in nature. May not have a single cause May not respond to opioids Difficult to pinpoint Responses other than SNS ○ Examples: Arthritis, neuropathy, or fibromyalgia. ○ Treatment Goal: Focuses on managing pain, improving function, and enhancing quality of life rather than achieving complete pain relief.  Differentiate between somatic pain, visceral pain, referred pain, neuropathic pain, peripheral pain, and central pain and the various treatments associated with each type of pain Pain Type Definition Characteristics Examples First-Line Severe Cases Somatic Pain Pain from skin, Localized, sharp, Bone NSAIDs, Opioids, local muscles, bones, or dull and fractures, acetaminophen. anesthetics. or connective aching. arthritis. tissue. Visceral Pain Pain from Diffuse, deep, Gallstones, Antispasmodics Opioids, internal organs. cramping, or pancreatitis. (e.g., antiemetics. aching; dicyclomine). autonomic symptoms. Referred Pain Pain perceived Diffuse and Heart attack Treat Analgesics. at a location poorly localized. (pain in underlying different from the arm/jaw). cause. source. Neuropathic Pain from nerve Burning, Diabetic Anticonvulsants Antidepressants, Pain damage or shooting, neuropathy, (e.g., lidocaine dysfunction. tingling; phantom gabapentin). patches, opioids. hyperalgesia, limb pain. allodynia. Peripheral Pain from Localized or Peripheral Anticonvulsants Topical agents, Pain peripheral nerve radiating; neuropathy , physical therapy. injury or burning or (e.g., antidepressants dysfunction. stabbing quality. diabetes).. Central Pain Pain from CNS Constant, Post-stroke Antidepressants NMDA injury or burning, or pain, spinal (e.g., antagonists, dysfunction. abnormal cord injury. amitriptyline). cannabinoids. sensations. Discuss the various routes of medications for pain management and any associated effects on dosing, onset of relief, etc Route Description Onset of Relief Considerations Tablets, capsules, - Convenient and cost-effective. or liquid - Slow onset; not ideal for acute Oral (PO) formulations 30-60 minutes severe pain. swallowed. - Absorption affected by GI function (e.g., food, motility). Medication - Rapid absorption bypassing the GI dissolves under tract.  Sublingual / the tongue or in 5-15 minutes - Useful for breakthrough pain or Buccal the cheek pouch patients unable to swallow. (e.g., fentanyl lozenges). Suppositories - Alternative for patients who can't inserted into the take oral meds. Rectal (PR) rectum (e.g., 30-60 minutes - Absorption can be inconsistent. morphine, - Useful for nausea or vomiting. acetaminophen). Medication - Ideal for severe acute pain (e.g., delivered directly postoperative). Intravenous into the Immediate - Requires monitoring for rapid onset (IV) bloodstream of side effects (e.g., respiratory (e.g., morphine, depression). fentanyl). Injection into - Less reliable absorption compared to Intramuscular muscle tissue IV. (IM) (e.g., ketorolac, 15-30 minutes - Painful at the injection site. morphine). - Risk of tissue injury with repeated use. Injection under - Slower absorption compared to IV Subcutaneous the skin (e.g., 15-30 minutes but less invasive. (SubQ) hydromorphone). - Preferred for patients needing intermittent or continuous administration (e.g., PCA pumps). Medication - Provides continuous pain control for Transdermal delivered through Delayed (hours); chronic pain. the skin via a steady-state: ~12-24 - Risk of delayed removal in overdose patch (e.g., hours situations. fentanyl, - Not suitable for acute pain. lidocaine) Gaseous or nebulized agents - Rapid onset and short duration. Inhalation (e.g., nitrous Seconds to minutes - Requires specialized equipment. oxide for labor pain). Direct injection - Highly effective for localized pain Epidural / into the epidural (e.g., labor or postoperative pain). Intrathecal or spinal space Immediate - Requires close monitoring for (e.g., morphine, complications like hypotension or bupivacaine). infection. Application on the - Best for localized pain. Topical skin (e.g., Minutes to hours - Minimal systemic absorption, capsaicin cream, reducing systemic side effects.  diclofenac gel). Absorption - Quick onset; bypasses GI tract. through nasal - May cause local irritation. Nasal mucosa (e.g., 10-20 minutes fentanyl nasal spray) Dosing Adjustments: Routes like IV require lower doses due to 100% bioavailability, whereas oral routes often need higher doses to account for first-pass metabolism. Onset of Action: IV is fastest for acute severe pain, while transdermal and oral routes are more suitable for chronic, steady pain control. Convenience vs. Precision: Oral medications are easier for long-term use, but routes like epidural or IV provide precise and rapid control for acute or severe scenarios. Distinguish among pure opioid agonists, agonist-antagonists, and antagonists in terms of their mechanism of action; also, place various named drugs (discussed in class) in the appropriate category. Pure Opioid Agonist ○ MOA: Bind strongly to mu opioid receptors (and sometimes kappa receptors) and activate them fully. This produces the full range of opioid effects, including analgesia, sedation, euphoria, respiratory depression, and constipation. ○ Examples: Strong Agonists: Morphine, Fentanyl, Hydromorphone Moderate Agonists: Oxycodone, Codeine Weak Agonists: Tramadol (also inhibits serotonin and norepinephrine reuptake). ○ Clinical Use: Used for moderate-to-severe pain (e.g., postoperative pain, cancer pain). Morphine and fentanyl are often used for acute severe pain or as part of anesthesia. Codeine is frequently combined with acetaminophen for mild-to-moderate pain and is also used as a cough suppressant. ○ ADRs Respiratory depression, sedation, constipation, nausea, vomiting, and potential for abuse or dependence. Agonist-Antagonist ○ MOA: These drugs act as agonists at some opioid receptors (usually kappa receptors) and as antagonists at others (typically mu receptors). They provide pain relief but with a ceiling effect on analgesia and respiratory depression, reducing the risk of overdose. ○ Examples Buprenorphine: Partial agonist at mu receptors and antagonist at kappa receptors. Pentazocine: Kappa agonist and weak mu antagonist. Nalbuphine: Kappa agonist and mu antagonist. ○ Clinical Use:  Used for mild-to-moderate pain and, in the case of buprenorphine, for opioid dependence treatment (e.g., Suboxone, a combination of buprenorphine and naloxone). These drugs are particularly useful when the goal is to minimize the risks of respiratory depression or dependence. ○ ADRs Can cause dysphoria due to kappa receptor activation. May precipitate withdrawal symptoms in patients already dependent on pure opioid agonists. Antagonists ○ MOA: Bind to opioid receptors but do not activate them. They block the effects of opioid agonists and can displace opioids already bound to the receptors. ○ Examples: Naloxone (Narcan): Short-acting antagonist used to rapidly reverse opioid overdoses. Naltrexone: Longer-acting antagonist used for managing opioid and alcohol dependence. Methylnaltrexone: Peripheral antagonist used to treat opioid-induced constipation without affecting central analgesia. ○ Clinical Use: Naloxone is the drug of choice for acute opioid overdose, effectively reversing respiratory depression. Naltrexone is used in maintenance therapy for patients recovering from opioid or alcohol addiction to prevent relapse. Methylnaltrexone targets GI side effects without crossing the blood-brain barrier, allowing continued pain relief. ○ ADRs Naloxone may cause withdrawal symptoms in opioid-dependent individuals. Naltrexone can cause gastrointestinal upset and liver toxicity with long-term use Discuss the therapeutic uses for opioid agonists, agonist-antagonists, and antagonists. Opioid Agonists: ○ Acute Pain: Postoperative pain, trauma, acute severe pain (i.e morphine, fentanyl, hydromorphone) ○ Chronic Pain: Cancer pain, end-of-life care (i.e long-acting oxycodone, morphine) ○ Moderate Pain: Codeine / hydrocodone combined with non-opioid analgesics for milder cases ○ Anesthesia Adjunct: Can be used as part of the anesthesia mix during surgery (i.e fentanyl) ○ Cough Suppression: Codeine / hydrocodone can be used as antitussives for non-productive coughs ○ Diarrhea: Certain opioids can be used to control diarrhea because they slow GI motility  ○ MI: Morphine is used to relieve pain, reduce anxiety, and decrease myocardial O2 demand. Agonist-Antagonist ○ Moderate Pain Relief: Pentazocine / nalbuphine are used for mild-to-moderate pain in cases where minimizing risk of respiratory depression / dependence is crucial ○ Opioid Dependence Treatment: A partial agonist (buprenorphine) often combined with naloxone to manage opioid use disorders Reduces withdrawal symptoms / cravings while having lower risk for abuse & respiratory ○ Obstetric Analgesic: Nalbuphine can be used in labor to provide pain relief with reduced chances for depression for the fetus. Opioid Antagonist ○ Naloxone (Narcan): Primary drug used to reverse respiratory depression & sedation caused by opioid OD Could be used to reverse excessive sedation or respiratory depression following surgical opioid use (avoids abrupt withdrawal symptoms) ○ Methylnaltrexone: Relieves constipation caused by long-term opioid use w/o compromising analgesia ○ Naltrexone: Maintenance therapy to reduce cravings and prevent relapse in opioid/alcohol dependence Discuss the adverse effects of opioids and both their pharmacologic and non-drug management. ADRs → Opioid Agonists ○ NS Respiratory Depression: The most serious adverse effect, opioids suppress the brainstem’s response to CO₂ levels. Sedation: Common, particularly at the start of therapy. Cognitive Impairment: Confusion, delirium, or dizziness, especially in older adults Miosis: Pupillary constriction, often used as a clinical sign of opioid use. ○ GI Constipation: Universally associated with opioids due to reduced GI motility. Nausea and Vomiting: Often related to stimulation of the chemoreceptor trigger zone (CTZ) ○ GU Urinary Retention: Due to increased sphincter tone and reduced bladder contraction. ○ CV Hypotension: Secondary to histamine release or reduced sympathetic tone. ○ Skin Itching: Frequently due to histamine release, not allergic reactions ○ Dependence & Addiction  Physical Dependence: Normal physiologic response with long-term use, leading to withdrawal symptoms upon abrupt discontinuation. Addiction: A psychological condition characterized by compulsive drug-seeking behavior. Pharmacological Management of ADRs ○ Respiratory Depression: Administer naloxone in severe cases, start opioids at lower doses and titrate slowly ○ Constipation: Use laxatives, consider methylnaltrexone / naloxegol (gut motility stimulators) for opioid-induced constipation ○ Nausea & Vomiting: Use antiemetics, consider switching to alternative opioid if nausea persists ○ Itching: Use antihistamines, reduce dose / change opioid if itching is severe ○ Sedation: Reduce dose / switch opioids, use modafinil (CNS stimulant) in selected cases ○ Addiction: Use buprenorphine + naloxone or methadone, long-term plans include naltrexone (prevents relapse) Non-Pharmacological Management of ADRs ○ Respiratory Depression: Use pulse ox to monitor high-risk pts, especially within first 24hr of opioid initiation, encourage careful & slow titration and opioid rotation when needed ○ Constipation: Increase dietary fiber, encourage adequate hydration + physical activity ○ Nausea & Vomiting: Advise pts to take opioids with food, use non-pharmacological relaxation techniques (acupuncture, pressure, ginger…) ○ Sedation: Optimize sleep hygiene & avoid combining opioids with other CNS depressants (i.e alcohol) ○ Dependency & Addiction: Employ cognitive-behavioral theory or group support programs, use non-opioid alternatives (NSAIDs, acetaminophen, physical therapy) for pain ○ Itching: Apply cool compress / use moisturizers, educate pt to avoid scratching Describe opioid drug–related factors that contribute to the development of physical and psychological dependence. Potency & Receptor Binding ○ High Potency: Strong opioids (i.e fentanyl) bind strongly to mu opioid receptors, producing intense analgesia and euphoria → increases risk of dependence ○ Selective Mu Receptor Activation: Opioids that mainly act in mu receptors are more likely to cause dependance than those acting on kappa or delta receptors Onset of Action ○ Rapid Onset: Drugs like fentanyl (especially in IV / nasal) act quickly, producing almost instant relief. This drives psychological dependance ○ Short Delay: opioids with delayed OA are less reinforcing but can still lead to dependance Duration of Action  ○ Short Half-Life Opioids: Drugs like heroin and immediate-release oxycodone have a short duration of action, leading to a cycle of frequent dosing to avoid withdrawal symptoms ○ Long-Acting Formulations: Extended-release formulations (e.g., OxyContin) are less likely to cause rapid highs but still contribute to physical dependence over time. Route of Administration ○ IV: Provides the fastest drug delivery to the brain, producing a rapid, intense euphoria that strongly reinforces psychological dependence. ○ Inhalation (Smoking): Also produces a quick onset and high, increasing addiction potential. ○ Oral / Transdermal: Slower onset and less intense euphoria, but still pose a risk of dependence with prolonged use. Dose & Frequency ○ Higher Doses: Larger doses of opioids increase receptor activation, enhancing euphoric effects and accelerating tolerance development. ○ Frequent Use: Repeated dosing causes chronic receptor stimulation, leading to physical adaptations like tolerance and dependence. Euphoria-Inducing Effects: ○ Reward System Activation: Opioids stimulate the brain's dopaminergic reward pathways, particularly in the nucleus accumbens. This reinforces drug-seeking behavior and psychological dependence. The intensity of euphoria correlates with addiction potential, making some opioids more prone to misuse. RECEPTORS Mu (μ) Receptors: ○ Provide strong analgesia and are the primary target for most opioids. ○ Cause euphoria, respiratory depression, sedation, constipation, and are highly associated with dependence (e.g., morphine, fentanyl). Kappa (κ) Receptors: ○ Offer moderate pain relief with minimal risk of euphoria or dependence. ○ May cause dysphoria, sedation, and hallucinations (e.g., nalbuphine, pentazocine). Delta (δ) Receptors: ○ Play a minor role in pain relief and help modulate mood (e.g., reduce anxiety). ○ Excessive activation may lead to seizures, and drugs targeting these receptors are mostly experimental. EXTRA NOTES: - Anesthesia: Used for relaxation, not really for pain - Hypotension, Respiratory Depression, Postoperative Nausea/Vomiting - EX. Propofol, Ketamine, Etomidate, Benzodiazepines - PERCEPTION OF PAIN - Sensory/discriminative system - Motivational/affective system - Cognitive/evaluative system