Study Doc Finals PDF

Final Exam hints Penicillins: > 3, treatment of gonorrhea, syphilis, meningitis, side effects, prophylactic drug of drugs for surgery and dental procedures -​ Treatment of gonorrhea: procaine penicillin G with probenecid to prolong its action. Not in use anymore due to resistance, c...

Final Exam hints Penicillins: > 3, treatment of gonorrhea, syphilis, meningitis, side effects, prophylactic drug of drugs for surgery and dental procedures -​ Treatment of gonorrhea: procaine penicillin G with probenecid to prolong its action. Not in use anymore due to resistance, currently a 3rd gen. Cephalosporin ceftriaxone is used. -​ Treatment of syphilis ( Treponema pallium): Benzathine Penicillin G (3 wk, 1 inj.) -​ Treatment of meningitis: penicillin G (benzylpenicillin) Side effects: ​ Allergic reaction ( rash, angioedema, anaphylaxis). Steven Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) - blistering and peeling of the skin, full contradiction. ​ GI: diarrhea, Pseudomembranous colitis from clostridioides difficile may occur with penicillin use, esp. Ampicillin. ​ Nephritis: acute interstitial nephritis- particularly. Methicillin ​ Neurotoxicity: seizures if injected intrathecally, GABAergic inhibition ​ Hematologic toxicities: decrease coagulation (high doses piperacillin, nafcillin, pen. G) > 2wks therapy, nafcillin (neutropenia). Prophylactic drugs for surgery and dental procedures: ​ Amoxicillin is used prophylactically in dental procedures at high risk for bacterial endocarditis. ​ ampicillin-sulbactam (Unasyn) and cefazolin (a related beta-lactam- 1st gen. cephalosporin, post surgical) used in surgery (not sure about this one) 3. Cephalosporins: 4: mechanisms, classes, uses, side effects Mechanism: binds to PBP and inhibits bacterial cell walls synthesis, hence bactericidal. Less susceptible to penicillinases due to difference in structure for staph but many other bacteria produce other beta-lactamases. Other mechanism:↓ permeability or change in PBP. MRSA is also resistant. Classes and uses: 1st generation: cefazolin (parenteral) and cephalexin (oral). Active against gram positive cocci, including staph and common streptococci. Many strains of E. coli and K. pneumoniae are sensitive. Minimal active against gram negative cocci, enterococci, MRSA and most gram-negative rods. Uses : Most common use cellulitis and surgical prophylaxis. 2nd generation: cefaclor, cefuroxime and cefprozil. Slightly less gram positive activity with extended gram-negative activity. Marked difference in members against different organisms. Uses: ​ infection caused by anaerobe Bacteroides fragilis (cefotetan, cefoxitin) ​ sinus and ear and respiratory infection caused by H. influenzae or M. catarrhalis (cefuroxime Cefacolor) 3rd generation: Main feature is ↑ gram negative activity and good BBB penetration (eg. Ceftazidime, cefotaxime). Most are active against Providencia, Serratia marcescens and beta lactamase-producing strains of H. influenzae and Neisseria. Less effective vs Enterobacter which produces extended spectrum beta-lactamases. Uses: ​ The most active vs penicillin-resistant pneumococci = ceftriaxone and cefotaxime. ​ ceftazidime vs pseudomonas and ceftizoxime vs bacillus fragilis. ​ Drug of choice for N. gonorrhea = ceftriaxone (parenteral) and cefixime (oral). A single injection of ceftriaxone is = to 10 days course of amoxicillin in acute otitis media. 4th generation: cefepime , ceftaroline. Cefepime combines gram positive activity of 1st generation agents + the gram negative activity of the 3rd generation agents. It is resistant to beta-lactamases produced by gram-negatives, including Enterobacter, Haemophilus, Neisseria and some penicillin resistant pneumococci. Uses: Ceftaroline also works against MRSA only beta-lactam with this feature. Side effects: Allergy: skin rashes to anaphylactic shock. Incidence is less compared to penicillin. Cross-reactivity between penicillin and cephalosporins is incomplete (5-10%), hence some cases can still use cephalosporins implicated, except for anaphylaxis. Other adverse effects: Pain at IM injection site and phlebitis after IV administration. Increased nephrotoxicity when combined with aminoglycosides. Drugs containing a methylthiotetrazole group (e.g cefoperazone , cefotetan) may cause hypoprothrobinemia and disulfiram-like reaction to ethanol. 4. Monobactams and carbapenems- 2: uses and side effects Monobactams Prototype is aztreonam. MOA: inhibits bacteria cell wall synthesis by preferentially binding to a specific penicillin-binding protein (PBP3) and is synergistic with aminoglycosides. Uses: It has no activity against gram positive organisms or anaerobes. It is resistant to beta-lactamases produced by certain gram negative rods, including Klebsiella, pseudomonas, and Serratia. Side effects: GI upset, vertigo, headache, and rarely hepatotoxicity. Possible superinfection. Skin rash. No cross allergenicity with penicillin. Carbapenems Carbapenems: chemically different from penicillin but have the beta-lactam ring w/ low susceptibility to beta-lactams. The sulphur atom of the thiazolidine ring has been externalized and replaced by a carbon atom. Example: Imipenem, meropenem, doripenem, and ertapenem. MOA: inhibit cell wall synthesis Uses: active against beta-lactamase-producing gram positive and gram-negative organisms, anaerobes and pseudomonas aeruginosa. Unlike other carbapenems, ertapenem lacks coverage against. P. aeruginosa, enterococcus species, and acetobacter species. Side effects: ​ N,V,D. Eosinophilia and neutropenia are less common compared to other beta-lactams. ​ High level imipenem may provoke seizure. ​ Cross- reactivity is less than 1% with penicillin. Carbapenems/ beta-lactamase inhibitors combinations: ​ Meropenem vaborbactam for complicated UTI, ​ imipenem-cilastin-relebactam for hospital and ventilator acquired pneumonia. 5. Tetracyclines: 5: uses, side effects Uses ​ Primary use: Treatment of mycoplasma pneumonia (adults), chlamydia, rickettsia, vibrio, and some spirochetes. ​ Doxycycline: is the alternative to macrolides in the initial treatment of community-acquired pneumonia (CAP). Treatment of choice in Lyme disease (10  days early and 2 to 4 wks for disseminated infection). Malaria and treatment of amebiasis. Doxycycline is an alternative for syphilis, leptospirosis, and acne. ​ Tetracycline: Helicobacter pylori and meningococcal carrier state (minocycline). ​ Tigecycline is a derivative of minocycline and the only member of this class. It is indicated for complicated skin and soft tissue infections, complicated intra-abdominal infection and community-acquired pneumonia Side effects (Tetracyclines) Adverse effects: gastric irritation, esophagitis, teeth discoloration, hypoplasia of teeth and temporary stunting of growth, rare hepatotoxicity, severe sunburn, benign intracranial hypertension (pseudotumor cerebri). Contraindicated in pregnant and breastfeeding women and children less than 8 years of age. (Glycylcyclines - Tigecycline) Adverse effects: nausea, vomiting, acute pancreatitis, elevated LFT’s and Cr may occur, photosensitivity, pseudotumor cerebri, discoloration of permanent teeth. It decreases clearance of warfarin. 6. Fluoroquinolones: 5: Uses, mechanism of action, side effects Mechanism of action: Inhibits bacterial DNA gyrase (topoisomerase II) & topoisomerase IV (gram +ve organisms), which in turn inhibits DNA replication & transcription, DNA repair, recombination & transposicion causing bacterial cell death. Uses by generations: Fluoroquinolones are classified by “generations” based on their antimicrobial spectrum of activity. ​ 1st generation: Nalidixic acid: has spectrum for common uropathogens (PECKS) ​ 2nd generation: Ciprofloxacin , ofloxacin, norfloxacin (not in use) have active against aerobic gram-negative, pseudomonas, atypical pneumonia pathogens: H. influenzae, Moxarella catarrhalis. ​ 3rd generation: Levofloxacin, gatifloxacin less active against gram negative but have > activity against gram +ve cocci, including streptococcus pneumoniae & various strains of enterococci. (Respiratory quinolones) ​ 4th generation: Moxifloxacin , gemifloxacin, delafloxacin & trovafloxacin: MRSA and enhance activity against anaerobes. Do not use moxifloxacin for UTI.  Clinical uses of fluoroquinolones: GI and GU infections: gram negative organisms- N. gonorrhea, E. coli, Klebsiella pneumoniae, C. jujuni, Enterobacter, P. aeruginosa, Salmonella & Shigella species. Ofloxacin eradicates Chlamydia trachomatis with a 7- day course. Cipro is the simple UTI specialist, due to ↑ negative coverage. Cipro can be used for traveler's diarrhea, typhoid fever, anthrax, pseudomonas, Moxifloxacin for mild-moderate intra-abdominal infections. Respiratory: Levaquin is the standard respiratory quinolone for CAP including for (chlamydiae, mycoplasma, legionella). It has enhanced activity vs Streptococcus pneumoniae. Moxifloxacin can be use as a second line, for TB, not not for CAP due to poor coverage for pseudomonas aeruginosa. Gemifloxacin used for community acquired pneumonia(CAP). Skin/ skin structure: Delafloxacin has improved activity vs gram +ve cocci, including MRSA & enterococcus species, hence it can be used for ABSSSI & CAP. Moxifloxacin have been used in meningococcal carrier state, TB treatment and prophylactic management of neutropenic patients. Avoid fluoroquinolones in gonorrhea due to increased resistance. Continued When treating Staphylococcal infection- fluoroquinolones typically are combined with a 2nd active agent- such as rifampin. Do not use it for enterococcus infection due to ↓ sensitivity. Because of toxicity when systemically administered, gatifloxacin is available as an ophthalmic solution. Ciprofloxacin (CiproR) is a drug of choice for prophylaxis & treatment of anthrax. Levofloxacin (LevaquinR) & ofloxacin(FloxinR) = alternative for urethritis & cervicitis. Can be used in children–example pseudomonal infections in patients w/ cystic fibrosis. Quinolones are rarely associated with aortic dissection or rupture! Side effects: ​ GI distress (N/V/D- most common) ​ tendinitis and tendon rupture. ​ Do not use it for pregnant + patients under 18 years old!! May damage growing cartilage & cause arthropathy. ​ Others- skin rashes. HA, dizziness, insomnia, abnormal liver function, phototoxicity, neurotoxicity. Opportunistic infections caused by C. albicans & strep may occur.  ​ 3rd generation may cause QTc prolongation. 7. Sulphonamides: 3: uses, mechanism of action, and side effects Mechanism of action: Antimetabolites (inhibitors of folic acid synthesis). As antimetabolites of PABA, they are competitive inhibitors of dihydropteroate synthetase. Uses: Trimethoprim-Sulfamethoxazole (TMP-SMZ)- is the drug of choice for pneumocystis pneumonia (Pneumocystis jirovecii). It is used for MSSA skin and skin structure infections- cellulitis and abscesses. Sinus, ear and respiratory infections caused by Haemophilus influenzae & Moraxella catarrhalis. It is drug of choice for nocardiosis (a highly fatal gram +ve infection, most common in immunocompromised patients), & toxoplasmosis. It is a possible backup for cholera, typhoid fever and shigellosis and MRSA and listeria monocytogenes. Sulfadiazine + pyrimethamine is 1st line therapy for acute toxoplasmosis. Sulfadoxine + pyrimethamine (FansidarR) is the 2nd line for malaria. Sulfasalazine is used in the treatment of inflammatory bowel disease Sodium sulfacetamide ophthalmic solution or ointment is used for bacterial conjunctivitis. Silver sulfadiazine is used for prevention of infection of burn wounds. Side effects: ​ paradoxically increases activity of rickettsiae. ​ Most common- fever, skin rashes, exfoliative dermatitis, photosensitivity, urticaria, nausea, vomiting, diarrhea. Stevens-Johnson syndrome occurs < 1%. Crystalluria, hemolytic or aplastic anemia, granulocytopenia, thrombocytopenia or leukemoid reactions. ​ Sulfonamides may provoke hemolytic reactions in patients w/ G6PD deficiency. If taken near the end of pregnancy ↑ the risk of kernicterus in newborns. 8. Antifungal: 4: mechanism of action, uses 1. Polyenes (Amphotericin B, Nystatin) MOA: Binds ergosterol, forming pores in the fungal membrane → leakage of K⁺ → fungicidal. Uses: Amphotericin B: Severe systemic infections (Candida, Cryptococcus, Histoplasma, Mucormycosis). Nystatin: Topical use for Candida infections (oral thrush, vaginal candidiasis, cutaneous candidiasis). 2. Antimetabolite (Flucytosine) MOA: Converted to 5-FU inside fungal cells, inhibits DNA & RNA synthesis → fungistatic. Uses: With Amphotericin B for Cryptococcal Meningitis. With Itraconazole for Chromoblastomycosis. 3. Azoles (Fluconazole, Itraconazole, Voriconazole, Posaconazole, Isavuconazole, ketoconazole) MOA: Inhibits 14α-demethylase, blocking ergosterol synthesis → disrupts fungal membrane → fungistatic. Uses: Fluconazole: Candidiasis, Cryptococcus, Coccidioides. Itraconazole: Blastomycosis, Histoplasmosis, Sporothrix, Onychomycosis. Voriconazole: Invasive Aspergillosis. Posaconazole: Broad-spectrum (Candida, Aspergillus, Mucormycosis), prophylaxis in cancer patients. Isavuconazole: Similar to Posaconazole but better tolerated. 4. Echinocandins (Caspofungin, Micafungin, Anidulafungin) MOA: Inhibits β-(1,3)-glucan synthase, blocking fungal cell wall synthesis → fungicidal. Uses: Invasive & esophageal Candidiasis. Empiric antifungal for critically ill patients. Micafungin for prophylaxis in bone marrow transplant patients. 5. Allylamines (Terbinafine, Naftifine, Butenafine) MOA: Inhibits squalene epoxidase, blocking ergosterol synthesis → fungicidal. Uses: Terbinafine: Onychomycosis (nail fungus) especially in diabetics, Tinea infections. 6. Other Antifungals Griseofulvin: Inhibits microtubules & mitosis → fungistatic (used for tinea capitis, skin infections). Ciclopirox: Inhibits fungal DNA, RNA, and protein synthesis (used for seborrheic dermatitis, tinea, onychomycosis). Tolnaftate: Distorts fungal hyphae growth (used for tinea pedis, tinea cruris, ringworm). 9. Anti-TB drugs: 3: uses, side effects First Line anti-TB drugs: 1. Isoniazid (INH) ​ Uses: ○​ Treatment of active TB (in combination therapy). ○​ Latent TB infection (as monotherapy). ​ Side Effects: ○​ Hepatotoxicity: Elevated liver enzymes; risk increases with age. ○​ Peripheral Neuropathy: Due to pyridoxine (vitamin B6) deficiency; prevented by co-administration of pyridoxine. ○​ CNS Effects: Seizures, irritability, and dysphoria. ○​ Lupus-like Syndrome: Rare occurrence. 2. Rifampin (RIF) ​ Uses: ○​ Treatment of active TB (in combination therapy). ○​ Alternative for latent TB in INH-resistant cases. ​ Side Effects:  ○​ Hepatotoxicity: Monitor liver function tests. ○​ Orange Discoloration: Of bodily fluids (urine, sweat, tears); Gastrointestinal Disturbances: Nausea, vomiting. ○​ Flu-like Symptoms: Fever, chills, myalgia. ○​ Drug Interactions: Potent inducer of cytochrome P450 enzymes, reducing efficacy of other drugs (e.g., oral contraceptives, anticoagulants). 3. Pyrazinamide (PZA) ​ Uses: ○​ Part of initial combination therapy for active TB. ​ Side Effects: ○​ Hepatotoxicity: Dose-related; monitor liver function. ○​ Hyperuricemia: Can precipitate gout attacks. ○​ Arthralgia: Joint pain without swelling. ○​ Gastrointestinal Upset: Nausea, vomiting. 4. Ethambutol (EMB) ​ Uses: ○​ Included in combination therapy for active TB to prevent resistance. ​ Side Effects: ○​ Optic Neuritis: Dose-dependent; results in decreased visual acuity and red-green color blindness; reversible upon discontinuation. ○​ Hyperuricemia: May exacerbate gout. ○​ Peripheral Neuropathy: Rare. Second-Line Anti-TB Drugs These are used when first-line drugs are ineffective due to resistance or intolerance. 1. Streptomycin ​ Uses: ○​ Severe TB cases, including meningitis and disseminated disease. ​ Side Effects: ○​ Ototoxicity: Hearing loss, vertigo; monitor auditory function. ○​ Nephrotoxicity: Renal impairment; monitor kidney function. ○​ Neuromuscular Blockade: Rare; can exacerbate conditions like myasthenia gravis. 2. Ethionamide ​ Uses: ○​ Multi-drug resistant TB (MDR-TB). ​ Side Effects: ○​ Gastrointestinal Distress: Nausea, vomiting, diarrhea. ○​ Hepatotoxicity: Monitor liver enzymes. ○​ Neurotoxicity: Peripheral neuropathy; pyridoxine supplementation recommended. ○​ Endocrine Effects: Gynecomastia, menstrual irregularities. 3. Capreomycin ​ Uses: ○​ MDR-TB, especially when resistance to aminoglycosides is present. ​ Side Effects: ○​ Nephrotoxicity: Monitor renal function. ○​ Ototoxicity: Hearing loss; audiometric monitoring advised. ○​ Injection Site Reactions: Pain, abscess formation. 10. Antimalarials: 3: Uses Main Uses of Anti-Malarial Drugs: 1.​ Treatment of Active Malaria: ○​ Plasmodium falciparum (the most severe form of malaria) and other Plasmodium species can be treated using various anti-malarial agents such as: ​ Chloroquine: Often used for uncomplicated cases of malaria. ​ Artemisinin-based combination therapies (ACTs): First-line treatment for drug-resistant P. falciparum malaria. ​ Quinine: Used in severe malaria, especially in combination with other drugs like doxycycline or clindamycin. ​ Mefloquine: Used for both treatment and prevention, particularly in areas where resistance to chloroquine is prevalent. 2.​ Prevention (Prophylaxis) of Malaria: ○​ Anti-malarial drugs are also prescribed to individuals traveling to regions where malaria is endemic, to prevent the onset of the disease: ​ Chloroquine: For prevention, although resistance in some areas limits its use. ​ Mefloquine and Atovaquone-proguanil: Common prophylactic drugs in areas with resistant malaria strains. ​ Doxycycline: Another option for prevention, used especially in travelers. 3.​ Other Uses: ○​ Autoimmune Disorders: Some anti-malarial drugs, especially hydroxychloroquine and chloroquine, are used to treat autoimmune conditions like rheumatoid arthritis and lupus due to their immunomodulatory effects.  ○​ Secondary Infections or Co-Infections: Anti-malarials can be used as adjunctive therapy in treating co-infections that occur alongside malaria, particularly in immunocompromised individuals. 11. Antivirals: 2: uses, Hep B, influenzae and HIV Antiviral Drugs for Hepatitis B: ​ Nucleoside Reverse Transcriptase Inhibitors (NRTIs): ○​ Tenofovir (TDF, TAF): A first-line therapy, effective at reducing viral load. ○​ Entecavir: Another NRTI with strong antiviral activity against hepatitis B. ○​ Lamivudine: Used, but less commonly due to resistance issues. Uses: ​ Chronic Hepatitis B in patients with high viral load or evidence of liver damage. ​ Long-term suppression of the virus to prevent progression to cirrhosis or hepatocellular carcinoma (liver cancer) Antiviral Drugs for Influenza: ​ Neuraminidase Inhibitors: ○​ Oseltamivir (Tamiflu): Commonly prescribed for the treatment of influenza A and B, especially if given within the first 48 hours of symptom onset. ○​ Zanamivir: Another neuraminidase inhibitor used for treating influenza. ​ Baloxavir marboxil: A newer antiviral that works by inhibiting the cap-dependent endonuclease activity of the viral polymerase. ​ Amantadine and Rimantadine (though rarely used now due to resistance): Target the viral M2 protein, preventing viral uncoating. Antiviral Drugs for HIV:  ​ Nucleoside Reverse Transcriptase Inhibitors (NRTIs): ○​ Zidovudine (AZT), Lamivudine, Emtricitabine: These drugs inhibit the reverse transcriptase enzyme and prevent viral replication. ​ Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs): ○​ Efavirenz, Etravirine, Nevirapine: Inhibit the reverse transcriptase enzyme at a different site than NRTIs. ​ Protease Inhibitors (PIs): ○​ Ritonavir, Atazanavir, Darunavir: These inhibit the HIV protease enzyme, preventing the maturation of new viral particles. ​ Integrase Inhibitors:- use for HIV positive naive patients ○​ Raltegravir, Dolutegravir: Block the HIV integrase enzyme, preventing the integration of viral DNA into the host genome. ​ Entry Inhibitors: ○​ Maraviroc: Inhibits the CCR5 receptor on CD4 cells, preventing the virus from entering cells. Uses: ​ First-line ART regimens typically combine NRTIs with either NNRTIs or PIs or integrase inhibitors to achieve viral suppression and prevent resistance. ​ ART reduces the viral load to undetectable levels, improving the immune system's function and preventing opportunistic infections. ​ Prophylactic use (PrEP) with drugs like emtricitabine/tenofovir (Truvada) can reduce the risk of HIV transmission in high-risk individuals. 12. Aminoglycosides: 1: Side effect (ototoxicity and nephrotoxicity) This class of drug tends to accumulate in the kidneys. They are taken up by the proximal tubule cells in the kidney, where they can accumulate and cause nephrotoxicity. Patients given these drugs are to be closely monitored. Gentamicin: Has the highest association with nephrotoxicity, especially when used in high doses or for extended periods. Tobramycin: Similar to gentamicin, it also carries a significant risk of kidney toxicity. Amikacin: Although less nephrotoxic than gentamicin and tobramycin, amikacin can still cause kidney damage, particularly with prolonged use. Streptomycin, Neomycin, and Kanamycin: These also carry some risk of nephrotoxicity, though they are less commonly used systemically due to their toxicity profiles. 13. Antiprotozoals: 4: Pharmacokinetics of metronidazole, treatment of filariasis, toxoplasma gondii, tape in worm Pharmacokinetics of Metronidazole: ​ Absorption: ○​ Metronidazole is well absorbed from the gastrointestinal tract, with an oral bioavailability of around 80%. ○​ It can be taken with or without food, but food may slightly delay absorption. ​ Distribution: ○​ Metronidazole is widely distributed throughout the body, including the cerebrospinal fluid, brain, liver, lungs, and other tissues. ○​ It can cross the placenta and is secreted in breast milk, so caution is advised during pregnancy and breastfeeding. ​ Metabolism: ○​ Metronidazole is metabolized in the liver, primarily by cytochrome P450 enzymes (CYP2A6). ○​ It is converted into inactive metabolites, some of which are excreted in urine. ​ Half-life: ○​ The elimination half-life of metronidazole is approximately 8 hours, but this can vary depending on factors such as liver function.  ​ Excretion: ○​ Metronidazole and its metabolites are primarily excreted via the kidneys in the urine. ○​ Less than 20% of the drug is excreted unchanged in the urine. Treatment of Filariasis: ​ Diethylcarbamazine (DEC): The drug of choice for treating lymphatic filariasis. It kills microfilariae and adult worms by disrupting their immune evasion mechanisms and affecting their motility. ​ Ivermectin: Effective against the microfilariae of certain filarial species (e.g., Onchocerca volvulus) but not adult worms. It works by paralyzing the worms. ​ Albendazole: Often used in combination with DEC or ivermectin to enhance efficacy, as it has activity against a wide range of helminths. Drugs used in the treatment of toxoplasmosis: ​ Pyrimethamine (usually in combination with sulfadiazine) is the first-line treatment. Pyrimethamine inhibits folate synthesis in the parasite, while sulfadiazine inhibits the synthesis of the parasite's DNA. ​ Clindamycin can also be used as an alternative to sulfadiazine for those who are allergic to sulfa drugs. ​ For severe cases or for patients with immunosuppression (e.g., HIV/AIDS), spiramycin or atovaquone can be used in combination with other agents. Drugs used in the treatment of tapeworm infections: ​ Praziquantel: The drug of choice for most tapeworm infections, including Taenia solium (pork tapeworm), Taenia saginata (beef tapeworm), and Diphyllobothrium latum (fish tapeworm). Praziquantel works by damaging the tapeworm's outer membrane, leading to its paralysis and eventual death. ​ Niclosamide: An alternative to praziquantel, although less commonly used. It inhibits the tapeworm's ability to absorb glucose, leading to the death of the parasite. ​ Albendazole: Used for treating tapeworms and other helminthic infections. It works by inhibiting the polymerization of microtubules in the worm, preventing its ability to absorb nutrients. 14. Opiates: 6: uses, mechanism of action, side effects Mechanism of Action: ​ Opiates act by binding to specific opioid receptors (μ, δ, κ) in the CNS to mimic endogenous peptide neurotransmitters (endorphins, enkephalins, dynorphins). ​ These receptors are G-protein coupled receptors that: ○​ Inhibit adenylyl cyclase, leading to a decrease in cAMP levels. cAMP is like a messenger inside the cell that helps pass signals and activate various processes (like pain perception). When opioid receptors inhibit adenylyl cyclase, less cAMP is produced and neuronal excitability & pain perception are decreased. ○​ Increase postsynaptic potassium efflux → hyperpolarization. Making the inside of the neuron more negatively charged, making it less likely to fire a signal. Opiates increase potassium efflux making the cell more negative. ○​ Reduce presynaptic calcium influx, impeding neurotransmitter release in the spinal dorsal horn. Opiates prevent calcium from entering the presynaptic neuron so no neurotransmitters are released to pass a signal. By inhibiting the release of these neurotransmitters into the spinal dorsal horn, opiates reduce the transmission of pain signals to the brain. CLINICAL USES A. Analgesia: Treatment of relatively constant moderate to severe pain is the major indication. Although oral formulations are most commonly used, buccal and suppository forms of some drugs are available. In the acute setting, strong agonists are usually given parenterally. Prolonged analgesia, with some reduction in adverse effects, can be achieved with epidural administration of certain strong agonist drugs (eg, fentanyl and morphine). Fentanyl has also been used by the transdermal route providing analgesia for up to 72 h. For less severe pain and in the chronic setting, moderate agonists are given by the oral route, sometimes in combinations with acetaminophen or NSAIDs. B. Cough Suppression: Useful oral antitussive drugs include codeine and dextromethorphan. The latter, an over-the-counter drug, has recently been the subject of FDA warnings regarding its abuse potential. Large doses of dextromethorphan may cause hallucinations, confusion, excitation, increased or decreased pupil size, nystagmus, seizures, coma, and decreased breathing. C. Treatment of Diarrhea: Selective antidiarrheal opioids include diphenoxylate and loperamide. They are given orally. D. Management of Acute Pulmonary Edema: Morphine (parenteral) may be useful in acute pulmonary edema because of its hemodynamic actions; its calming effects probably also contribute to relief of the pulmonary symptoms. E. Anesthesia Opioids: are used as preoperative medications and as intraoperative adjunctive agents in balanced anesthesia protocols. High-dose intravenous opioids (eg, morphine, fentanyl) are often the major component of anesthesia for cardiac surgery. 1. Morphine Primary Uses: ​ Moderate to severe pain – including post-surgical, cancer, and trauma pain. ​ Palliative care – for end-of-life pain management and dyspnea (breathlessness). ​ Postoperative pain relief – often administered intravenously or via PCA (Patient-Controlled Analgesia). ​ Myocardial infarction (heart attack) – reduces pain and anxiety while decreasing cardiac workload. ​ Strong μ-opioid receptor agonist. ​ Contraindicated in head injuries (due to increased intracranial pressure). 2. Codeine Primary Uses:  ​ Mild to moderate pain – commonly used in combination with acetaminophen (Tylenol #3). ​ Cough suppression (antitussive) – found in prescription cough syrups. ​ Diarrhea treatment – due to its constipating effect. ​ Prodrug – metabolized by the liver enzyme CYP2D6 into morphine (active form). ​ Genetic variability – some people (ultrarapid metabolizers) convert codeine into morphine too quickly, leading to overdose risk. ​ Not recommended in children