Analgesic Drugs Overview

Analgesic Drugs

• Analgesic drugs, opium is a Greek word meaning "juice".
• Three main receptor families: μ (mu, MOR), κ (kappa, KOR), δ (delta, DOR).
• Opioid agonist: MORPHINE, a prototype opioid from the opium poppy.
• Mechanism of action: mimics endogenous opioid peptides, mainly at mu receptors.
• Therapeutic uses: acute pain from AMI and cancer, cough suppression, dyspnea relief from pulmonary edema, preoperative anxiety relief.
• Adverse effects: orthostatic hypotension, miosis, urinary retention, constipation, emesis, respiratory depression, drowsiness, dysphoria, neurotoxicity, tolerance and physical dependence, withdrawal syndrome.
• Contraindications and cautions: allergy to narcotic agonists, toxic poisons, respiratory dysfunction.
• Drug interactions: CNS depressants, anticholinergic drugs, hypotensive drugs, monoamine oxidase inhibitors.
• Agonist-antagonist Opioids: lower potential for abuse, less respiratory depression.
• Nalbuphine: agonist at kappa receptors and antagonist at mu receptors, with dosage-dependent ceiling effect.

Fentanyl

• A potent opioid analgesic (100x morphine potency).
• Formulations: parenteral, transdermal, transmucosal, intranasal.
• Transdermal fentanyl patches: reservoir in skin, delayed onset, prolonged offset, for chronic severe pain management, requires prior daily opioid use.
• Transmucosal fentanyl: lozenges, buccal tablets, sublingual spray, sublingual tablets, for breakthrough cancer pain in opioid-tolerant patients.
• Ionsys: patient-activated system for on-demand delivery of fentanyl (iontophoresis-based), for acute postoperative pain.
• Contraindications: heat application over a patch, history of respiratory depression, and shock.

Butorphanol

• Agonist at kappa receptors and antagonist at mu receptors.
• Analgesic effects are less potent than morphine.
• Used for moderate to moderately severe pain.

Naloxone

• Opioid antagonist (antidote).
• Blocks opioid receptors, reversing respiratory depression, sedation, and psychotomimetic effects.
• Indications: opioid overdose and postoperative opioid depression.

Non-steroidal anti-inflammatory drugs (NSAIDs)

• Ketorolac: short-term pain management, often equal or superior to opioids in analgesic efficacy.

Benzodiazepines

• Common sedative-hypnotics and anxiolytics.
• Indications: anxiety, insomnia, seizure disorders, muscle spasms, alcohol withdrawal.
• Adverse effects: CNS depression, anterograde amnesia, sleep-driving/related behaviors, paradoxical effects, respiratory depression.
• Interactions with CNS depressants.

Hydantoins (Phenytoin)

• Anticonvulsant, effective in treating tonic-clonic and partial seizures.
• Adverse effects include gingival hyperplasia, dermatologic effects, pregnancy effects, cardiovascular effects, and potential drug interactions.

Chemotherapy

• Aims to eliminate cancerous cells.
• Principles: target DNA/metabolism, affect replication of all proliferating cells.
• Treatment strategies: curative goals, control of disease, symptomatic relief, use as adjuvant or neoadjuvant/maintenance therapy.
• Tumor susceptibility: rapidly dividing cells are more susceptible to treatment.
• Combination chemotherapy: higher response rates, overlapping host toxicities, improved cell-killing effectiveness.
• Resistance: intrinsic or acquired, multidrug resistance, step-wise selection of amplification of drug efflux genes (e.g., P-glycoprotein).
• Toxicity: bone marrow suppression (myelosuppression), extravasation (leakage into surrounding tissues), fertility reduction, related to killing rapidly dividing cells in other tissues.

Anti-metabolites

• Structurally similar to normal compounds that exist within cells.
• Interfere with synthesis of purine or pyrimidine nucleotides, inhibiting synthesis or competing in DNA/RNA synthesis.
• Methotrexate (MTX), pemetrexed, and pralatrexate.
• Purine antagonists: cladribine, fludarabine, mercaptopurine, pentostatin, and thioguanine.
• Pyrimidine antagonists: capecitabine, cytarabine, floxuridine, fluorouracil, and gemcitabine.
• Adverse effects: varied and potential for serious complications.

Mitotic Inhibitors

• Natural products or semisynthetic drugs from plants.
• Bind to tubulin, preventing assembly of microtubules critical to mitosis, inhibiting cell division.
• Vinca alkaloids (vinblastine, vincristine, and vinorelbine).
• Taxanes (paclitaxel).

Topoisomerase Inhibitors

• Topotecan and irinotecan.
• Inhibit DNA-topoisomerase I actions, resulting in DNA strand breaks.
• Treatment for ovarian and colorectal cancer and small cell lung cancer.
• Important interactions exist between different agents.

Hormonal Agents

• Used in breast and prostate cancer treatment.
• Breast cancer: antiestrogens (tamoxifen, toremifene), aromatase inhibitors (anastrozole).
• Prostate cancer: androgen deprivation therapy (ADT) agents like leuprolide, goserelin, and histrelin.
• Mechanism: blocking or suppressing endogenous hormones impacting tumor growth.
• Potential adverse effects: diverse, reflecting hormone disruption.

Targeted Anticancer Drugs

• Designed to bind specific targets within or on cancer cells, suppressing tumor growth, with reduced impact on healthy cells.
• EGFR tyrosine kinase inhibitors (e.g., cetuximab): block EGFR receptors, used in colorectal, head, and neck cancers.
• Side effects can be severe if not managed properly.

Eye Medications

• Miotics: contract pupils, increasing aqueous outflow for glaucoma.
• Mydriatics: dilate pupils for eye exams, procedures.
• Anti-infectives/anti-microbials: treat eye infections.
• Lubricants: relieve dry eye symptoms.
• Osmotics: manage elevated intraocular pressure.

Ear Medications

• Antibiotics for ear infections.
• Analgesics for pain relief.
• Anti-inflammatory drugs.
• Anti-viral drugs.
• Ceruminolytics to aid in impaction removal.

Vestibular Disorders

• Symptoms: dizziness, unsteadiness, vertigo, nausea.
• Underlying causes: Meniere's disease, labyrinthitis, inner ear infections.