Infectious Disease & Pharmacology Worksheet PDF

Units 3 and 4: Infectious Disease and Ocular and Dermatologic Pharmacology Worksheet - SAID IN CLASS WHEN WOULD YOU USE ONE VS THE OTHER C&S. DON\'T OVER PRESCRIBE ANTIBIOTICS. PAY ATTENTION IF ITS IS VIRAL X1 DAY. - PAY ATTENTION TO SPECIFIC MENTIONS AND FILL OUT THE BULLETS. IE CLIND...

Units 3 and 4: Infectious Disease and Ocular and Dermatologic Pharmacology Worksheet - SAID IN CLASS WHEN WOULD YOU USE ONE VS THE OTHER C&S. DON\'T OVER PRESCRIBE ANTIBIOTICS. PAY ATTENTION IF ITS IS VIRAL X1 DAY. - PAY ATTENTION TO SPECIFIC MENTIONS AND FILL OUT THE BULLETS. IE CLINDA MYACIN AND CDIFF, QUINOLONES AND TENDON RUPTURE, PT EDUCATION LIKE TAKING WITH FOOD OR PHOTOSENSITIVITY 1. Rules of antibiotic stewardship CDC WEBSITE - When to prescribe broad vs C&S. URI x1 day no fever green snot say no and tell them to come back because it is probably viral 2. Antibiotic selection including different types of antimicrobial therapy. 3. Diagnostic tests associated with antibiotic stewardship and drug monitoring - Cultures, Vanco trough, renal function, liver function. - HOW DO YOU MONITOR ANTIBIOTICS. CULTURES, RENAL FUNCTIONS, LIVER FUNCTION, TROUGH **Infectious Agents** 1. **Tetracyclines** - **[Common Meds:]** Demeclocycline, tetracycline, minocycline, and doxycycline are available in US for systemic use. - **[MOA:]** Tetracyclines inhibit bacterial protein synthesis by binding to the 30S bacterial ribosome. - This binding prevents the access of aminoacyl tRNA (replication) to the acceptor site on the mRNA-ribosome complex. - Tetracyclines are a series of derivatives of basic 4 ring structure. - **[Uses:]** - Broad spectrum bacteriostatic & generally 2nd line drugs of choice. - Generally, NOT used for Staph/Strep infections. Is active against MSSA and MRSA. - Tetracyclines are typically bacteriostatic and have a broad spectrum of activity. - More active against gram-positive than gram-negative microorganisms. - Doxycycline: Atypical Community-Acquired Pneumonia, Malaria prophylaxis, Bacillus anthracis, alternative indication for Syphilis caused by Treponema pallidum. - Minocycline: Acne. - More tolerated thant the other tetracyclines, less GI SE - Glycylcyclines: Tigecycline (Tygacil) - generally active against organisms that have acquired resistance to tetracycline. Effective against Enterobacteriaceae, Acinetobacter, and B. fragilis. - Activity varies against different pathogens, and resistance has been observed. - Resp tract infections: Good activity against S. pneumoniae, H. influenzae, mycoplasma and chlamydophilia pneumonia - STIs: Doxy no longer recommended for gonococcal infections because of resistance. Can be used to treat chlamydia. Epididymitis: One dose of rocephin + doxycycline x10 days. - **[Duration:]** - **[SE:]** Adv Rxns: GI distress, photosensitivity, hepatic toxicity, renal toxicity, leukocytosis, tooth discoloration in peds and fetal bone retardation - **[Black Box:]** Tetracyclines readily bind to calcium deposited in newly formed bone or teeth in young children, as well as to fetal teeth during pregnancy. This can result in discoloration and enamel dysplasia. - Retardation of fetal bone growth - Tetracyclines can also be deposited in bone, resulting in deformity &/or growth inhibition. As a result, tetracyclines are generally avoided in pregnancy. If the drug is given for long periods to children less than 8 years old, similar side effects can occur (Deck & Winston, 2015). - Renal toxicity -- elevation of BUN - **[PT Education:]** Potentiates warfarin (impairs vit. K production in intestinal flora) - Do not give until child is 8 years old - Photosensitivity - Rare: hepatotoxicity - Pregnancy category D \\ - Tetracyclines distribute widely in the body, including urine, prostate, and various tissues. - Calcium (milk or dairy products), antacids & minerals form chelates with tetracyclines & interfere with absorption - Elimination pathways and need for dose adjustment vary among different tetracyclines. - Susceptible bacteria include: Streptococcal pneumoniae, Bacillus anthracis (Anthrax), Clostridium tetani, Brucella (brucellosis), Helicobacter pylori, Actinomyces, Rickettsia (Rocky Mountain Spotted Fever), **Chlamydial diseases, syphilis, Lyme disease,** and Mycoplasma. 2. **Sulfonamides** - **[Common Meds:]** Trimethoprim-Sulfamethoxazole (Bactrim/DS) SEE BELOW - **[MOA:]** Competitive inhibitors of dihydropteroate synthase, blocking the **synthesis of folic acid.** - **Antimicrobial a**ctivity against Gram + and Gram -- bacteria, and parasites limits its use - Haemophilus ducreyi, Nocardia, Klebsiella still responsive - Many strains of E.coli are resistant. - **Derivatives** of para-aminobenzenesulfonamide and congeners of para-aminobenzoic acid (PABA). - Sulfur must be directly linked to the benzene ring. - Sensitive microorganisms are those that must synthesize their own folic acid. - Bacteriostatic - Highly protein-bound (albumin) - **[Uses: ]** - UTI-Because a significant percentage of UTIs are caused by sulfonamide-resistant microorganisms, sulfonamides are no longer a therapy of first choice; TMP-SMX is preferred - Nocardiosis - Toxoplasmosis - E.coli, S. pyogenese, S.pneumoniae, H. influenza, and some protozoa - **[Duration:]** - this class of drugs is absorbed rapidly from the gastrointestinal (GI) tract. Typically, 70% to 100% of an oral dose is absorbed and can be found in the urine within 30 min of ingestion. Peak plasma levels are achieved in 2 to 6 h, depending on the drug. Peak plasma drug concentrations achievable in vivo are about 100 to 200 μg/mL. The small intestine is the major site of absorption, but some of the drug is absorbed from the stomach - **[SE:]** - Adverse Reactions: may take a week to manifest unless previously sensitized. Primarily derm hypersensitivity reactions. - Common: **Rash, fever, GI SE** - Uncommon: **Crystalluria- encourage 1200ml urine output daily to prevent.** - Severe: Steven-Johnson's syndrome, Vasculitis, Hemolytic anemia in patients with **G6PD deficiency** (KNOW THIS) - **[Black box:]** - **[PT Education:]** - **Drug Interactions** - anticoagulants, sulfonylurea hypoglycemic agents, and hydantoin anticonvulsants - Avoid use in pregnancy: Because you are blocking the folic acid and increasing risk for defects - Target bacteria that have to use folic acid in order to reproduce and metabolize. A Lot of resistance and allergies. So most are not used but we still use Bactrim in high volume. Trimethoprim-Sulfamethoxazole - **[Common Meds:]** - **[MOA:]** - Trimethoprim (TMP) exerts a synergistic effect with sulfonamides; TMP inhibits bacterial dihydrofolate reductase (DHFR) - The antimicrobial activity of the combination of TMP-SMX results from actions on sequential steps of the enzymatic pathway for the synthesis of tetrahydrofolic acid. - Coadministration of a sulfonamide and TMP (TMP-SMX) introduces sequential blocks in the biosynthetic pathway for tetrahydrofolate; the combination is much more effective than either agent alone - bacteriostatic/bactericidal activity - Figure 57--2 Steps in folate metabolism blocked by sulfonamides and trimethoprim. Coadministration of a sulfonamide and trimethoprim introduces sequential blocks in the biosynthetic pathway for tetrahydrofolate; the combination is much more effective than either agent alone. - **[Uses: ]** - UTI- effective for susceptible bacteria, but should avoid empiric use when local resistance \>20% - Treatment options: BID x3 days for uncomplicated or 10-14 days in complicated or pyelonephritis - **Chronic Bronchitis** - **Acute OM in children and AC Maxillary Sinusitis in adults** - GI infections (Shigella); no longer recommended for traveler's diarrhea - Pneumocystis jiroveci in HIV patients - **MRSA** - Nocardia - Can also be used to treat bacterial prostatitis. - **[Duration:]** - **[SE:]** - **[Black box:]** - **[PT Education:]** - DI: potentiates effects of warfarin, phenytoin, hypoglycemic agents, and methotrexate - Contraindicated in CCr is \ - Amplifies affect of sulfa drug. High resistance pseudomonas 3. **Beta-lactam antibiotics** - β-Lactams - Includes PCN, cephalosporins, carbapenems, and monobactams which share a common structure (β-lactam ring) - Widely used due to broad spectrum, potent antibacterial killing, and favorable tolerability. - **MOA:** Inhibit the last step in peptidoglycan synthesis by acylating the transpeptidase via cleavage of the β-lactam ring. - Transpeptidase targets collectively termed penicillin-binding proteins (PBPs). - Lethality involves lytic and nonlytic mechanisms. - Broad Spectrum: Gram +/- - Natural PCNs are active against aerobic, gram (+) organisms. - Aminopenicillins have greater activity against Gram(-) bacteria (Ex: Ampicillin, Amoxicillin, Augmentin) - [Mechanisms to Resistance: ] - Alterations in PBP target, reduction of concentration at the target site, and enzymatic degradation of β-lactam. (e.g., the resistance of Pseudomonas aeruginosa - Resistance mechanisms include mutations, acquisition of low-affinity PBPs, and enzymatic inactivation. (e.g., penicillin resistance in pneumococci) - Gram-positive bacteria more prone to alterations in the PBP target. - [Resistance due to Concentration Reduction and Enzymatic Degradation:] - Reduced penetration in gram-negative bacteria due to outer membrane barrier. - Active efflux pumps as a mechanism of resistance. - Enzymatic inactivation via β-lactamases produced by bacteria. - Beta-lactam antibiotics are one of the most commonly prescribed drug classes with numerous clinical indications. From a biochemical point of view, these drugs have a common feature, which is the 3-carbon and 1-nitrogen ring (beta-lactam ring) that is highly reactive. PCNs, cephalosporins, Carbapenems. - The targets for the actions of beta-lactam antibiotics are known as penicillin-binding proteins (PBPs). This binding, in turn, interrupts the terminal transpeptidation process and induces loss of viability and lysis, also through autolytic processes within the bacterial cell. - Bacteria often develop resistance to β-lactam antibiotics by synthesizing a β-lactamase, an enzyme that attacks the β-lactam ring. To overcome this resistance, β-lactam antibiotics are often given with β-lactamase inhibitors such as clavulanic acid. - β-Lactamase Inhibitors - An increasing number of β-lactams are co-formulated with molecules whose role is to "protect" the β-lactam from the β-lactamase. - These β-lactamase inhibitors bind to β-lactamases and prevent the enzymes from hydrolyzing β-lactam agents in the vicinity. - Clavulanic acid has poor intrinsic antimicrobial activity but is an irreversible mechanism-based inhibitor that binds β-lactamases produced by a wide range of gram-positive and gram-negative microorganisms - Sulbactam is similar in structure to clavulanic acid. It is available for IV/IM use combined with ampicillin. - possesses intrinsic activity against Acinetobacter spp. and has been used in high dosages to treat multidrug-resistant Acinetobacter infections. - Tazobactam has good activity against many of the plasmid-mediated β-lactamases, including some of the extended-spectrum class. - It is available as a combination product with piperacillin and ceftolozane. - Avibactam and relebactam are structurally similar non--β-lactam β-lactamase inhibitors that provide inhibition against both narrow- and extended-spectrum β-lactamase (ESBL)-type, chromosomal AmpC, and KPC-type β-lactamases - Avibactam is co-formulated with ceftazidime, - relebactam is co-formulated with imipenem/cilastatin - Vaborbactam is a boronic acid--based non--β-lactam β-lactamase inhibitor that provides broad inhibition of β-lactamases like avibactam and relebactam. - Vaborbactam is co-formulated with meropenem 4. **Penicillin's** - **[Common Meds:]** - Agents with extended antimicrobial activity against Pseudomonas, E.coli, Klebsiella and other gram - (piperacillin (ureidopenicillin) and piperacillin/tazobactam; Ticarcillin (carboxypenicillin)-Pseudomonas - Are commonly combined with beta-lactamase inhibitors (tazobactam). - Pipracillin/tazobactam has the broadest spectrum of all PCNs including MRSA, H.influenza, B. fragilis, and most E.coli and Klebsiella. - **[MOA:]**  - PCN consists of a thiazolidine ring connected to a β-lactam ring attached to a side chain. - Classified according to their spectra of antimicrobial activity - **[Uses: ]** - PCN G/PCN V- active against sensitive strains of gram + cocci, but ineffective against most strains of S. aureus. - Penicillinase-resistant PCN (nafcillin, dicloxacillin, oxacillin)- preferred agents for penicillinase-producing S. Aureus and Staphylococcus epidermis that are not methicillin resistant (methicillin-susceptible staphylococci (MSSA); Isoxazolyl Penicillins: Oxacillin, Cloxacillin, Dicloxacillin for resistant strains. - Aminopenicillins (Ampicillin, amoxicillin)- broad spectrum; cover gram +/-; can be compounded with clavulanate or sulbactam to prevent hydrolysis by A β-lactamases; Effective for respiratory infections, urinary tract infections, enterococcal infections. - Antibacterial prophylaxis with penicillin V for asplenic patients. - Penicillin for rheumatic fever prophylaxis. - Lifetime prophylaxis may be considered. - PCN Adverse Reactions - Hypersensitivity reactions are the most common adverse effect noted and the most common cause of drug allergy. Most are IgE mediated. (TYPE I) - **[Duration:]** - Rapid renal elimination, short half-lives. - **[SE:]** - Maculopapular rash, urticarial rash, fever, bronchospasm, vasculitis, serum sickness, exfoliative dermatitis, Stevens-Johnson syndrome, angioedema and anaphylaxis. (PCN G/B highest risk) - Can occur with any formulation. - Symptoms can persist for 1-2 weeks after therapy has stopped. - Cross-hypersensitivity reactions possible to cephalosporins. - Rashes (like full body) following administration on ampicillin can be a result of concurrent mononucleosis. - Other adverse reactions include bone marrow depression, hepatitis, and CNS dysfunction. - [Considerations]: - Evaluate patient history for allergic reactions. - Conduct skin testing for allergy risk. Penicillin skin testing has a high negative predictive value. - **Desensitization for true penicillin-allergic patients in a controlled setting** - **[Black box:]** - **[PT Education:]** - Toxic effects include bone marrow depression, granulocytopenia, and hepatitis. - Requires renal adjustment in renal dysfunction. 5. **Beta-lactam antibiotics cephalosporins** - **[Common Meds:]** Ceftriaxone (Rocephin), Ceftolozane/tazobactam (zosyn) - **[MOA:]** - Inhibit bacterial cell wall synthesis, similar to penicillin. - Different PBP binding profiles from penicillins. - Lack of binding to essential PBPs in Enterococcus spp. (ineffective) - **[Uses: ]** - Commonly used for sinusitis, otitis media, gonorrhea, bronchitis, and skin infections - Does penetrate CSF so can be used in meningitis - Therapeutic Uses: - **First-generation for skin and soft-tissue infections.** - **Cefazolin as prophylaxis for surgical procedures.** - **Third-generation for serious infections like meningitis. (CEFTRIAXONE/ROCEPHIN)** - **Antipseudomonal cephalosporins for nosocomial infections.** - [1st generation]: used for skin and soft tissue infections: Primarily against gram positive bacteria, S.aureus and S. epidermis - Gram (+); modest activity against E.coli, Klebsiella, and Proteus - Cefadroxil (Duricef) - Cephalexin (Keflex) - [2nd generation]: same as 1st generation, plus Klebsiella, proteus, E.coli, H. influenzae, M. catarrhalis. - Gram (+) and Gram (-) - Cefuroxime (Ceftin) - Cefaclor (Ceclor) - [3rd generation:] broader indications, more active against gram negative bacterial; less active against gram + cocci - Weak Gram (+), Gram (-), Beta lactamase - Ceftibuten (Cedax) - Cefixime (Suprax) - [Extended 3rd gen:] Gram (+), Gram (-), Beta lactamase - Ceftriaxone (Rocephin)- Excellent antistreptococcal activity and gonorrhea; Used for empiric treatment of meningitis in nonimmunocompromised adults and children. - Cefdinir (Omnicef) - Cefditoren (Spectracef) - [4th generation] : resistant to beta-lactamase, primarily active against gram positive bacteria. - Antipseudomonal cephalosporins: - Ceftolozane/tazobactam (zosyn) - [5th generation:] Anti-MRSA have structural modifications allowing for binding to and inactivation of the altered PBPs expressed by MRSA, MRSE, and penicillin resistant S. pneumoniae. Ceftaroline FDA approved April 2020 - None are reliable against atypical bacteria - Antipseudomonal Cephalosporins: - - - - - - - - **[Duration:]** - **[SE:]** - Hypersensitivity reactions, similar to penicillins. - Maculopapular rash, anaphylaxis, and Coombs reaction. - Rare instances of bone marrow depression and diarrhea. - **[Black box:]** - **[PT Education:]** - Renally excreted so should be reduced in renal insufficiency 6. Nucleoside analogues - **[Common Meds:]** - **[MOA:]** - Inhibit viral DNA synthesis and replication. - Antiviral drugs must either block entry into the cells or be active inside host cells to be effective. - **[Uses: ]** - **Acyclovir (Zovirax):** active against HSV-1 and HSV-2; varicella-zoster virus (VZV); Epstein-Barr virus (EBV), cytomegalovirus (CMV), and herpes virus 6 (HSV-6). - **Valacyclovir (Valtrex)** is converted to acyclovir after oral administration; more effective against VZV - **Famciclovir (Famvir):** active against HSV-1 and HSV-2, VZV, EBV, and hepatitis B virus - **Penciclovir:** Topical tx for HSV or VZV infections - **Ganciclovir & valganciclovir:** active against CMV and all herpes viruses. Indicated for CMV retinitis - Clinical use: - Herpes simplex virus: both initial outbreak and suppression therapy - Herpes zoster (shingles): start within 3 days of the outbreak - Varicella (chickenpox): start within 24 hrs of the outbreak - Bell's palsy - Acyclovir, valacyclovir and famciclovir - may use during pregnancy - Acyclovir excreted in breastmilk; safest choice in children - **[Duration:]** - Chronic acyclovir suppression has been used safely for up to 10yrs. - **[SE:]** - Acyclovir/valacyclovir: N/V/D, HA, neuro/nephrotoxicity (rare) - Valacyclovir may cause thrombocytopenia purpura, a hemolytic uremic syndrome in immunocompromised patients - **[Black box:]** - **[PT Education:]** - Antiherpes Agents: Nucleoside Analogues - Pay attention to history and frequency of outbreak! More than once, suppressive therapy - Rational drug selection: Choice based on cost and convenience 7. **Fluoroquinolones** - **[Common Meds:]** - [2nd generation:] Weak gram (+), Gram (-), Pseudomonas - Ciprofloxacin (Cipro) primary and acute - Ofloxacin (Floxin) - [3rd generation:] Gram (+), Gram (-), Atypicals, Beta lactamase, DRSP, MRSA, +/- Pseudomonas, +/- Anaerobes - Levofloxacin (Levaquin) primary and acute - [4th generation]: Gram (+), weak gram (-), Atypicals, Beta lactamase, DRSP, MRSA, +/- Pseudomonas - Moxifloxacin (Avelox) - Gemifloxacin (Factive) - Delafloxacin (Baxdela)-new\* - **[MOA:]** - Target bacterial DNA gyrase and topiosomerase IV, which are enzymes essential for DNA replication; Gyrase introduces negative supercoils into DNA, inhibiting bacterial growth. - **[Uses:]** **[(NOT used in cellulitis)]** - UTIs, prostatitis, sexually transmitted diseases (when all else fails), GI and abdominal infections, respiratory tract infections, bone and joint infections, other infections. - Duration and dosage recommendations for specific conditions. - [UTI]: Cipro- reserve for complicated UTI or pyelonephritis. 3 days uncomplicated; 5-7 in complicated - Prostatitis: Norfloxacin, cipro, ofloxacin, levofloxacin; Administer for 4-6 wks if patient unresponsive to Bactrim - STDs: Chlamydia: 7 days ofloxacin or Levofloxacin and Haemophilus ducreyi (chanroid)- 3 days cipro - GI: Traveler\'s diarrhea 1-3 days with any fluroquinolone, Cipro can be prophylactic. - Resp: Levo, moxi, and gemi have high activity against S. pneumoniae, H. influenzae, and atypical pathogens. Used in CAP, unresponsive sinusitis, CF - Osteomyelitis: weeks to months of treatment - **[Duration:]** - **[SE:]** - Cipro: potent CYP450 inhibitor may increase the effect of other meds (i.e. warfarin, propranolol) - Neuro: Rare: hallucinations, delirium, seizures, peripheral neuropathy, and possibly optic neuritis - Due to the risk of prolonged QT/Torsade\'s-use cautiously with other meds that prolong QT (amiodarone, quinidine) - **Hypo/hyperglycemic events possible** when given with insulin/antidiabetic agents - Common: n/v, diarrhea, dizziness, **confusion, HA** - Rashes and photosensitivity: encourage sunscreen - Can not be used in **pregnancy, breastfeeding, or children under 16** - **Due to lack of studies but also risks of damage to kids** - **[Black box:]** - Risk of tendonitis, tendon rupture (especially in patients \60): Black box warning - Tendon rupture more prevalent in \>60, taking corticosteroids, and solid-organ transplant recipients - **[PT Education:]** - [Resistance]: MRSA, gonorrhea, Pseudomonas, staphylococci. E.coli, Campylobacter, Salmonella, and S. pneumoniae are increasingly resistant - [ADME] (Absorption, Distribution, Metabolism, Excretion): - **Well-absorbed orally, high volume of distribution.** - Concentrations in various tissues higher than serum levels. - Renal clearance, dosage adjustment needed for renal failure. 8. **Glycopeptides** - **[Common Meds:]** (Vancomycin, Teicoplanin, Telavancin, Dalbavancin, Oritavancin) - Teicoplanin is similar to vancomycin. - Telavancin and oritavancin have additional membrane-disrupting mechanisms. - **[MOA:]** bactericidal. Inhibit bacterial cell wall synthesis in gram-positive bacteria. - **[Uses: ]** - Oral-provides concentrations sufficient to treat Clostridium difficile colitis - Skin/soft tissue and Bone/joint infections - Respiratory tract infections - CNS infections (bacterial meningitis) - Endocarditis and Vascular Catheter infections - Active against the majority of gram+ bacteria, including MRSA, PCN-resistant strep, and ampicillin-resistant enterococci. - Essentially all species of gram-negative bacteria and mycobacteria are **resistant** to glycopeptides. - Vancomycin is effective against MRSA, streptococci, and enterococci. - Vancomycin is used for skin/soft-tissue, bone/joint, respiratory tract, CNS infections, endocarditis, and vascular catheter infections. - **[Duration:]** - **[SE:]** - [Side Effects:] - Phlebosclerotic (vancomycin is irritating to tissue) - Nephrotoxicity: rare - Ototoxicity (rare) (increased risk if given with aminoglycosides) - Hypotension & "Red Man Syndrome" (flushing due to histamine release) if given IV in less than 1 hour - **Allergy history must be assessed because it is a very high law suit and malpractice issue.** - **[Black box:]** - **[PT Education: ]** - new guidelines recommend targeting an area under the curve between 400 and 600 mg\*h/L for serious MRSA infections (Rybak et al., 2020). Area under the curve can be estimated through sampling one or more levels during a dosing interval and applying standard population-based or Bayesian procedures. Instead of previous Vanc Troughs 9. **Azole antifungals** - **[Common Meds:]** Fluconazole (Diflucan) Miconazole (Monistat) Ketoconazole (Nizoral): - Azole antifungals categorized into imidazoles and triazoles - Available Azole Agents: - Ketoconazole: Replaced by itraconazole, mainly used topically. - Itraconazole: Triazole with a broad spectrum, especially active against Aspergillus spp. - Fluconazole: Effective against Candida and Cryptococcus, with various therapeutic uses. - Voriconazole: Superior efficacy against invasive aspergillosis, approved for candidemia and esophageal candidiasis. - Posaconazole: Broad-spectrum, including activity against mucormycosis, approved for prophylaxis and treatment. - **Fluconazole (Diflucan)** - Indications: - a broad spectrum "azole of choice" in the treatment and secondary prophylaxis of cryptococcal meningitis. - It is the agent most commonly used for treating mucocutaneous candidiasis. - Thrush and yeast infections - Contraindications: - drug hypersensitivity - Side Effects: - minor GI upset (most common) - Rare cases of serious hepatic toxicity, including fatalities - **Miconazole (Monistat-Derm, Oravig (buccal tablets), Monistat Vaginal Cream)** - Indications: - local treatment of oropharyngeal candidiasis (Oravig ®) - athelete\'s foot (tinea pedis), tinea crurus & tinea corporis caused by Trichophyton spp & Epidermophyton floccosum , cutaneous candidiasis, tinea versicolor (Monistat - Derm ®) - vaginal yeast infections (Monistat Vaginal Cream) - One day vs 7 day. One day dosage is very high so a lot more SE and issues vs 7 day cream almost like a chemical burn - Imidazoles: - clotrimazole, miconazole, ketoconazole, econazole, butoconazole, oxiconazole, sertaconazole, sulconazole, tioconazole, and luliconazole - Triazoles: - efinaconazole, terconazole, itraconazole, fluconazole, voriconazole, posaconazole, and isavuconazole. - **Ketoconazole (Nizoral):** - Indications: - Use of systemic ketoconazole has fallen out of clinical use in the USA. However, it is currently used as a topical antifungal in creams for treating dermatophytosis & candidiasis, and as a shampoo for the treatment of seborrheic dermatitis. - Contraindications: - Coadministration drugs that are metabolized by CYP3A4 and which prolong the QT interval (e.g. astemizole) with ketoconazole tablets is contraindicated. Drug hypersensitivity. - Side Effects: - When used orally, ketoconazole has been associated with hepatic toxicity, including some rare fatalities. - **Antiandrogenic (lowered testosterone levels) have been reported when taken orally.** - Black Box Warnings: POTENT CYP3A4 INHIBITOR. Serious CARDIAC ARRHYTHMIAS & death have been observed that prolong the QT interval (ORAL DOSAGE). - **Itraconazole (Sporanox )** - Indications: - a broad spectrum antifungal indicated for the treatment of the following fungal infections in immunocompromised and non-immunocompromised patients: - Blastomycosis, pulmonary and extrapulmonary - Histoplasmosis, Aspergillosis - Onychomycosis due to dermatophytes (tinea unguium) of the toenail with or without fingernail involvement. - Contraindications: - Coadministration of other drugs that prolong the QT interval (e.g. astemizole or cisapride) with itraconazole is contraindicated. These combinations can produce ventricular tachycardia, torsades de pointes & sudden death,. - **[MOA:]** inhibit 14-α-sterol demethylase. Impairs the biosynthesis of ergosterol, leading to growth arrest. Some azoles increase cellular permeability - **[Uses:]** Antifungal see above meds for specific uses - **[Duration:]** - **[SE:]** - Adverse effects vary among azoles, including hepatotoxicity, QT prolongation, hallucinations, and rash. - Drug interactions play a crucial role in adverse outcomes. - Specific considerations for each azole in terms of safety and tolerability. - **[Black box:]** Black Box Warnings: - CONGESTIVE HEART FAILURE: When itraconazole was given to dogs or healthy human volunteers, negative inotropic effects were observed. If signs of CHF are observed, use of itraconazole should be reassessed. Intraconazole is a POTENT CYP3A4 INHIBITOR & may increase the concentration of other drugs metabolized by this enzyme. Serious CARDIAC ARRHYTHMIAS & death have been observed in patients taking other drugs concomitantly that prolong the QT interval and that are substrates for CYP3A4. - **[PT Education:]** 10. **Nitroimidazoles** - **[Common Meds:]** Metronidazole (Flagyl) and Tinidazole (Tindamax) - **[MOA:]** Metronidazole is essentially a prodrug. The nitro group is reduced in anaerobic bacteria, microaerophilic bacteria, and protozoans to produce the active form. - Activation leads to the formation of reactive compounds interacting with DNA, potentially disrupting its structure and inhibiting replication. - **[Uses: ]** - Amebiasis: Agent of choice, 500-750mg PO TID x7-10 days. - Giardiasis: Tinidazole 2gm is 1st line treatment. - Relatively inexpensive agent with broad-spectrum efficacy against anaerobic bacteria. - Typical doses: 250 to 500 mg twice or three times daily, intravenous or oral routes. - Used in combination with other antimicrobials for polymicrobial infections. - Component of prophylaxis for colorectal surgery. - Single-agent treatment for bacterial vaginosis. - Part of regimens for H. pylori infection. - Historical use in nonsevere C. difficile infection, now vancomycin or fidaxomicin preferred. - Intravenous metronidazole in combination with oral vancomycin for fulminant C. difficile infection. - **[Duration:]** - Trichomoniasis generally 2gm PO x1 dose is sufficient. If parasite still present, consider resistance or repeated partner transmission. - **[SE:]** - SE: n/v, abdominal pain, dizziness, HA, metallic taste, Peripheral neuropathy - DI: increases anticoagulant effect of warfarin - Disulfiram-like reaction: Avoid alcohol-48 hours before, during, 72 hours after treatment (N/V, skin flushing, tachycardia, dyspnea) - Should be withdrawn if numbness or paresthesias of the extremities occur. - Reversal of sensory neuropathies may be slow or incomplete. - **[Black box:]** Black Box Warning: Metronidazole has been shown to be CARCINOGENIC in mice and rats. - **[PT Education:]** - Excreted by the kidneys. - Metabolized-liver 11. **Influenza treatments** - **[Common Meds:]** - **[MOA: ]** - inhibit the virus by blocking a viral enzyme called neuraminidase which blocks spread of viral particles. - **[Uses: ]** - [**Duration:** KNOW THE CHART] - **[SE:]** - **[Black box:]** - **[PT Education:]** - Amantadine and Rimantadine: - Inhibit early steps in viral replication, primarily targeting influenza A virus M2 protein. - Resistance arises from mutations in the RNA sequence encoding the M2 protein. - Pharmacokinetic differences between amantadine and rimantadine. - Effective for prophylaxis against influenza A, but limited by resistance. - Asthma/COPD no relenza - How long have they had symptoms and will this really reduce their symptoms? This will not fix it, it may shorten the duration of illness by maybe 24 hours. 12. **Antiprotozoal medications See the highlighted and know them** - [Amebiasis] - most common among individuals living in poverty, crowded conditions, poor sanitation. - Cornerstone of therapy is **metronidazole or tinidazole** - If pt develops amebic colitis or liver abscess-luminal agent needed (paromomycin and iodoquinol) - [Giardiasis] - most commonly reported intestinal protozoal infection in US. - Fecally contaminated food or water. - Common in children, institutionalized individuals, MSM. - 3 Syndromes. - Asymptomatic - Acute self-limited diarrhea - Chronic diarrhea with steatorrhea and wt loss - **5-7 Days of metronidazole (flagyl) usually suscessful (\$4).** - **1 dose of tinidazole (\$36-61).** - **Paromomycin for pregnant women (\$362).** - Nitazoxamide- children \ - Neurocysticercosis: is a preventable parasitic infection of the central nervous system and is caused by the pork tapeworm Taenia solium. Humans become infected after consuming undercooked food, particularly pork, or water contaminated with tapeworm eggs, or through poor hygiene practices. Mexico and South America have high prevalence. - **[Duration:]** - **[SE:]** - Primarily Mild GI symptoms. Monitor liver function if on extended therapy. - Contraindicated in cirrhosis. - **[Black box:]** - **[PT Education:]** - Ivermectin - **MOA**: causing an increase in the permeability of the cell membrane to chloride ions with hyperpolarization of the nerve or muscle cell. Hyperpolarization results in paralysis and death of the parasite either directly or by causing the worms to starve. - **Used** in Onchocerciasis, lymphatic filariasis, strongyloidiasis, enterobiasis, scabies, and head lice. - Scabies: 2 doses should be administered 1-2 weeks apart. Severe cases: 7 doses with food on days 1,2,8,9,12,22,29. - Lice: topical 0.2% lotion. - **SE**: Mazzotti Reaction: fever, headache, dizziness, somnolence, weakness, rash, pruritus, diarrhea, joint pain and muscle spasms, hypotension, tachycardia, lymphadenitis, and peripheral edema-due to death of Onchocerca volvulus (nematode causing river blindness-mostly Africa but can be Mexico, Guatemala, and Venezuela) and not due to ivermectin toxicity. - Not approved for children \