Exam 2 Drugs Table PDF

INFECTIOUS DRUGS Tetracyclines Sulfonamides Beta-Lactam Antibiotics Nucleoside Analogues (Bacteriostatic protein synthe...

INFECTIOUS DRUGS Tetracyclines Sulfonamides Beta-Lactam Antibiotics Nucleoside Analogues (Bacteriostatic protein synthesis inhibitors that (DNA Disruptors - inhibition of folic acid (cell membrane/wall inhibitors) (Anti Herpes/Antiviral Agents) target ribosomes) synthesis) 1.​ Penicillins 2.​ Cephalosporins Derivatives of a basic 4-ring structure. ​Derivatives of para-minobenzenesulfonamide and congeners of Common meds: PCN, cephalosporins, carbapenems, and Common meds: acyclovir (zovirax), valacyclovir (valtrex), para-aminobenzoic acid (PABA). monobactams which share a common structure (β-lactam ring) famciclovir (famvir), penciclovir, ganciclovir & valganciclovir Common meds: “-cycline” ​ Sulfur must attach directly to the benzene ring. Demeclocycline, tetracycline, minocycline, and doxycycline ​ Inhibits folic acid synthesis in susceptible Used for: broad spectrum (gram +/-) , potent antibacterial killing MOA: inhibit viral DNA synthesis & replication; must block entry bacteria. into cells or be active inside hot cells to be effective MOA: Inhibits bacterial protein synthesis by binding to the 30S ​ Bacteriostatic MOA: Inhibit the last step in peptidoglycan synthesis by acylating the bacterial ribosome subunit. ​ Highly protein-bound (albumin) transpeptidase via cleavage of the β-lactam ring. Used/Duraton: ​ Prevents aminoacyl tRNA from binding to the ​ Transpeptidase targets collectively termed ​ HSV (initial outbreak & suppression therapy), mRNA-ribosome complex. Common meds: “sulfas” or Trimethoprim-Sulfamethoxazole penicillin-binding proteins (PBPs). ​ Herpes zoster (shingles), ​ Bacteriostatic (Bactrim) ○​ Lethality involves lytic and nonlytic ​ Varicella (chickenpox) mechanisms. ​ Bell’s palsy Used for: Broad spectrum bacteriostatic & generally 2nd line MOA: competitively inhibits dihydropteroate synthase, blocking ​ Natural PCNs are active against aerobic, gram (+) drugs of choice. folic acid synthesis organisms. ​ Acyclovir (zovirax): HSV-1, HSV-2, VZV, EBV, CMV, ​ More against gram (+) than gram (-) ​ Active against some gram +/- bacteria and HSV-6 ​ NOT used for Staph/Strep infections. Is active against parasites. Considerations: allergy testing ​ Valacyclovir (Valtrex): Converted to acyclovir; more MSSA and MRSA. ​ Effective against Haemophilus ducreyi, Nocardia, effective against VZV ​ Doxycycline: Atypical community-acquired Klebsiella Penicillins ​ Famciclovir (Famvir): HSV-1, HSV-2, VZV, EBV, pneumonia, malaria prophylaxis, Bacillus anthracis, ​ Many strains of E.coli are resistant. ​ Wide distribution in the body, high concentrations in Hepatitis B alternative for syphilis (Treponema pallidum). ​ Metabolized in the liver and absorbed in small tissues and fluids. ​ Penciclovir: Topical treatment fro HSV & VZV ​ Minocycline: Acne (less GI side effects). intestine ​ Rapid renal elimination, short half-lives. infections ​ Glycylcyclines (Tigecycline): Effective against ​ Limited penetration into CSF, enhanced in inflammation. ​ Ganciclovir & Valganciclovir: Active against CMV & Enterobacteriaceae, Acinetobacter, and B. fragilis, ​ Resistance mechanisms affect pharmacokinetics. all herpes virus (used for CMV retinitis) including some tetracycline-resistant bacteria. Used for: ​ Respiratory: S. pneumoniae, H. influenzae, ​ UTI (sulfonamides not first choice; TMP-SMX is Uses: Prophylactic use - Considerations: mycoplasma, chlamydophila pneumoniae preferred) ​ Spleen patients (PCN V) ​ Safe during pregnancy (acyclovir, valacyclovir, & ​ STIs: chlamydia (doxycycline), epididymitis ​ Nocardiosis ​ Rheumatic fever famciclovir) (ceftriaxone + doxycycline for 10 days), gonorrhea ​ Toxoplasmosis ​ Lifetime - may be considered ​ Acyclovir - excreted in breastmilk; safest choice for (doxycycline no longer recommended due to children resistance) Duration: Rapid GI absorption (70%-100% of PO dose) Adverse Effects: IgE mediated reactions (Maculopapular rash, ​ H. pylori: tetracycline + bismuth + metronidazole ​ In urine within 30 mins urticarial rash, fever, bronchospasm, vasculitis, serum sickness, Adverse Effects: ​ Peak levels in 2-6 hours exfoliative dermatitis, SJS, angioedema and anaphylaxis) ​ Acyclovir/Valacyclovir: N/V/D, HA, neurotoxicity & ​ Post treatment completion symptoms can persist 1-2 wks nephrotoxicity (rare) Contraindications: Avoid in pregnancy - disruption in folic acid after ​ Valacyclovir: risk of thombocytopenic purpura & ​ Effective against: streptococcus pneumoniae, bacillus synthesis (neural tube defects) ​ Cross-hypersensitivity with cephalosporins hemolytic uremic syndrome in anthracis, clostridium tetani, brucella, helicobacter ​ Full body rash post ampicillin → think MONO immunocompromised patients pylori, actinomyces, rickettsia (RMSF), chlamydia, Drug interactions: Anticoagulants, sulfonylurea hypoglycemic ​ Chronic acyclovir suppression has been safely syphilis (treponema pallidum), lyme disease, agents, and hydantoin anticonvulsants Considerations: PCN G injection, monitor for 15 mins for rx used for up to 10 years. mycoplasma ​ Toxic effects - bone marrow depression, granulocytopenia, Remdesivir SE: may take a week unless previously sensitized. Primarily and hepatitis MOA: A nucleotide analog,acts by inhibiting RNA-dependent derm hypersensitivity reactions. RNA polymerase (RdRp) Duration: Varies. Doxycycline and minocycline have longer ​ Common: Rash, fever, GI symptoms half-lives (~16-18 hours). ​ Uncommon: Crystalluria - encourage 1200ml urine Adverse Effects: decreased glomerular filtration rate, output daily to prevent. - drink lots of water! hemoglobin, and lymphocyte count; respiratory failure; pyrexia; Contraindications:Pregnancy (Category D) – Can bind to fetal hyperglycemia; and increased glucose. bone and teeth, leading to retardation of bone growth and tooth Black Box: Severe: SJS, Vasculitis, Hemolytic anemia (G6PD discoloration. deficiency) Used for global pandemics: EBOLA, MERS, SARS, & COVID ​ Do NOT use in children < 8YO ​ Avoid in pregnancy Patient education: Encourage water intake. ​ Photosensitivity - use sunscreen ​ Monitor renal & hepatic function Trimethoprim-Sulfamethoxazole (Bactrim) Drug Interactions: ​ MOA: Trimethoprim (TMP) synergizes with ​ Chelate formation with calcium, antacids, and minerals sulfonamides by inhibiting bacterial dihydrofolate will ↓ absorption. reductase (DHFR), blocking sequential steps in ​ Bacteriostatic effects may reduce the activity of PCNs. tetrahydrofolic acid synthesis. ​ ↓ effectives in COCs ​ Potentiates warfarin (impairs Vit K- producing gut flora) ​ Bacteriostatic/bactericidal 1  Cephalosporins SE: GI distress, photosensitivity (use sunscreen), hepatic toxicity, ​ Resistance: pseudomonas aeruginosa, Common meds: “CEF-” renal toxicity, leukocytosis, tooth discoloration in peds and fetal bacteroides fragilis, enterococci, e. Coli cephalosporin P, N, & C bone retardation ( 12 YO ​ CAUTIOUS with renal/psychiatric patients - retains & buildup in system Contraindications: MOA: Selective binding to parasite GABA-A and ​ CYP3A4-metabolized drugs that prolong QT interval (e.g., glutamate-gated chloride ion channels, vital for invertebrate Black Box: Tendonitis/tendon rupture (esp. >60YO, astemizole) nerve and muscle function runners,corticosteroid usage, and solid-organ transplant recipients) ​ Drug hypersensitivity ​ Different binding activity than ivermectin for GABA-gated Cl-channels Patient education: Sun protection, can cause CDIFF, SE: SE: Mazzotti Reaction ​ hepatic toxicity (rare) ​ Antiandrogenic effects (lowered testosterone levels) Praziquantel Used for: schistosomiasis (Schistosoma species) Black Box: Potent CYP3A4 inhibitor; cardiac arrhythmias & death due ​ Also can treat, liver flukes, intestinal flukes, and to QT prolongation lung flukes ​ Approved for children > 4YO Itraconazole (Sporanox) Uses: broad-spectrum antifungal for immunocompromised and MOA: increase muscular activity of worms, causes Ca²⁺ influx, non-immunocompromised patients contraction, and spastic paralysis, and leads to tegumental ​ Blastomycosis (pulmonary & extrapulmonary) damage. ​ Histoplasmosis & aspergillosis ​ Onychomycosis (tinea unguium) of toenails/fingernails SE: abdominal discomfort and drowsiness ​ ↑ eosinophils due to parasite killing and antigen Contraindications: release ​ Coadministration with QT-prolonging drugs (e.g., Definitions: astemizole, cisapride) → risk of ventricular tachycardia, Onchocerciasis (river blindness) torsades de pointes, sudden death ​ caused by onchocerca volvulus ​ symptoms: severe itching, skin nodules, blindness Black Box: ​ 2nd most common infectious cause of blindness ​ Congestive heart failure Lymphatic Filariasis (neglected tropical disease - NTD) ​ Potent CYP3A4 inhibitor ​ Caused by thread-like worms ○​ Increases drug concentrations metabolized ​ Adult worms live in human lymphatic system by CYP3A4 ​ Disrupts fluid balance, causes infections 3  ○​ Serious cardiac arrhythmias & death with Strongyloidiasis: caused by strongyloides stercoralis concurrent QT-prolonging drugs (roundworm) Ascariasis: caused ascaris lumbricoides (“large roundworm”)l can grow up to 35 cm long Enterobiasis (Pinworm infection) ​ Highly contagious, common in children ​ Transmitted via ingestion or inhalation of eggs ​ Main symptom: severe rectal itching Influenza Treatments Antiprotozoal Medications Nitroimidazoles Urinary Anti-Infectives Common meds: Oseltamivir (Tamiflu), Zanamirvir (Relenza), Protozoa & Common meds: Common meds: Metronidazole (Flagyl) & Tinidazole (Tindamax), Complicated symptoms: fever, pelvic/flank pain, pyuria Peramivir (Rapivab), Baloxavir (Xofluza), Amantadine and ​ Amebiasis: poverty, crowded, & poor sanitation Nifurtimox and Benznidazole Uncomplicated symptoms: dysuria and frequency Rimantadine ○​ Metronidazole or Tinidazole Urine culture taken without dysuria, frequency, and with a small ○​ Paromomycin & Iodoquinol - amebic Metronidazole (Flagyl) & Tinidazole (Tindamax) to moderate amount of WBC in the UA has asymptomatic MOA: inhibits virus by blocking a viral enzyme called neuraminidase colitis or liver abscess develops, bacteriuria. DOES NOT NEED ABXs → blocks spread of viral particles luminal agent needed Used for/Dosages: ​ Giardiasis: intestinal protozoa; fecally ​ Trichomoniasis: single dose, 2g PO Common meds: Methenamine (Hiprex), Nitrofurantoin Used for: Flu A & B; treatment or chemo-prophylaxis contaminated food/H2O; children, institutionalized ○​ Parasites still present, consider repeated (Macrobid), and Fosfomycin (Monural) persons, MSM; 3 syndromes: asymp, acute self partner transmission Duration: limited diarrhea, chronic diarrhea with steatorrhea ​ Amebiasis: first-line agent Other drugs discussed: TMP-SMX, ​ Oseltamivir (Tamiflu) - 5 day & wt loss ○​ 500 - 700 mg PO TID for 7-10 day trimethoprim-sulfamethoxazole, quinolones (ciprofloxacin) ​ Zanamivir (Relenza) - 5 day ○​ Metronidazole (5-7 days, $4) ​ Giardiasis: Tinidazole = 1st line treatment ○​ Tinidazole (1 dose, $36-$61) ○​ 2 gm Methenamine (Hiprex) Recommended for: ○​ Paromomycin - pregnant women Used for: suppressive therapy for chronic cystitis ​ Oseltamivir: 3 mo > (for chemo-prophylaxis) ($362) MOA: Metronidazole is essentially a prodrug. The nitro group is MOA: acidification of the urine by forming formaldehyde ​ Zanamivir: 7 yrs > (treatment); 5 yrs > ○​ Nitazoxamide - kids < 12 YO (no reduced in anaerobic bacteria, microaerophilic bacteria, and protozoans ​ Activity against uropathogens except proteus and (chemo-prophylaxis) available on market; $$$$) to produce the active form. enterobacter ​ Peramivir: 2 yrs > (treatment) ​ Trichomoniasis: flagellated protozoan ​ Nitro group reduction produces reactive compounds that ​ Baloxavir: 12 yrs > (treatment); approved for 12 yrs Trichonmonas vaginalis; in GU tract → vaginitis & interact with DNA, leading to structural damage and Contraindications: renal insufficiency with post exposure (chemo-prophylaxis) urethritis; increased risk of HIV inhibition of replication SE: GI upset with higher doses ○​ Metronidazole or Tinidazole Contraindications: ​ Babesiosis: Babesia microti or B. divergens SE: N/V, abd pain, dizziness, HA, metallic taste, peripheral neuropathy Patient education: $30+ ​ Zanamivir - respiratory comorbidities (tick-borne zoonosis); resembles malaria (withdraw if numbness/paresthesias occurs) ○​ Clindamycin & Quinine or Nitrofurantoin (Macrobid) Adverse Effects: Azithromycin & Atovaquone Drug Interactions: Warfarin (↑ anticoagulant effect) Used for: prevention & treatment of uncomplicated UTIs ​ Oseltamivir: N/V, HA, serious skin reactions and ​ Disulfiram-like reaction with ETOH (N/V, skin flushing, ​ Not for complicated or severe UTIs, bacteremia, sporadic, transient neuropsychiatric events tachypnea, dyspnea) pyelonephritis ​ Zanamivir: bronchospasm, sinusitis, and dizziness. ○​ Avoid ETOH 48 hrs before, during, and 72 ​ Gram +/- ​ Peramivir: Diarrhea, serious skin reactions and hrs post treatment ​ Effective: E. coli and enterococci sporadic, transient neuropsychiatric events ​ Resistant to proteus and pseudomonas Black Box: Metronidazole has been shown to be CARCINOGENIC in Amantadine/Rimantadine mice and rats. MOA: bacteriostatic; activated by enzymatic reduction, damages MOA: inhibit early steps in viral replication by targeting the M2 bacterial DNA protein in influenza A virus; prevent viral uncoating and replication Nifurtimox and Benznidazole ​ Resistance due to mutations in the RNA sequence MOA: Trypanocidal effects through mitochondrial nitroreductase SE: orange/brown urine encoding the M2 protein; widespread resistance limits activation;trypanocidal activity derived from the development of nitro ​ Acute pneumonitis & pulmonary fibrosis can occur clinical use free radicals in the mitochondria and damaging cellular DNA and should be discontinued ​ Serious SE: Used for: ○​ Liver injury, peripheral neuropathy ​ American Trypanosomiasis (Chagas Disease) ○​ Long term use > 6 mo → interstitial pneumonitis with progressive fibrosis Considerations: ○​ Hemolytic anemia with G6PD ​ Benznidazole: FDA-approved for children (2-12 YO) deficiency ​ Nifurtimox: Not FDA-approved Dosing: QID with meals; 1x/day for prevention SE: N/V, myalgia Contraindications: pregnancy, impaired renal function, G6PD, Toxicity: Benznidazole - specific and pediatrics (< 1mo) ​ Urticarial dermatitis - may require treatment discontinuation Fosfomycin (Monural) ​ Bone marrow suppression - monitor CBC every 2-3 weeks Used for: prevention & treatment of UTI due to early-onset suppression ​ Gram +/- activity ​ Effective: uropathogens (E.coli & Enterococcus) 4  ADME: ​ Resistant to pseudomonas & acinetobacter ​ Nifurtimox MOA: inhibits MurA which impairs bacterial cell wall synthesis ○​ Well absorbed; rapid biotransformation. ​ Benznidazole SE: GI distress vaginitis, HA, dizziness ○​ Rapidly absorption ○​ Terminal elimination half-life: 12 hours. Administration: Powder form, dissolves in water than taken orally Aminoglycosides Lincosamides Atypical Antifungals Hep C Medications (irreversible inhibition of protein synthesis 30s) Common meds: ”-mycin” Common meds: Clindamycin/Lincomycin Common meds: Amphotercin B (Fungizone), Echinocandin, Common meds: interferon-cytokine, Sofosbuvir-Velpatasvir Gentamicin, tobramycin, amikacin, streptomycin, paromomycin, and Griseofulvin (Gris-PEG,Grifulvin V), Terbinafine (Lamisil), Ciclopirox (Epclusa), Sofosbuvir (Sovaldi), Glecaprevir-Pibrentasvir neomycin MOA: Binds to the 50S ribosomal subunit to suppress bacterial Olamine (Penlac), & Nystatin (Mycostatin) (Mavyret) protein synthesis MOA: ​ Antimicrobial activity: gram (+) aerobes & Amphotericin B (Fungizone) Interferons ​ Bactericidal inhibitors of protein synthesis; disrupts anaerobes, some parasitic infections. MOA: Binds to ergosterol in fungal cell membranes, forming Drug Class: Cytokine initiation complexes → misreading mRNA. ​ Anaerobes: pores/channels; increases membrane permeability, leading to cytosolic MOA: antiproliferative effects against tumor cells, inhibits viral ​ Concentration-dependent killing (peak/MIC ratio ○​ Gram (+) - pepostreptococci, leakage and loss of integrity replication, and modulates host immune response critical) clostridium perfringens, actinomyces ​ Amphipathic or amphoteric polyene macrolide molecule ​ Postantibiotic effect allows for extended-interval dosing ○​ Gram (-) - prevotella species, with the broadest spectrum of activity of any of the Used for: chronic Hep B & C and Hep B & C infections, hairy cell bacteroides fragilis, fusobacteria currently available antifungal drugs leukemia, AIDS-related Kaposi’s sarcoma Used for: ​ Gram (+) cocci: staphylococci & streptococci ​ Aerobic gram (-) bacteria ​ Toxin production inhibition: group A streptococci & Used for: SE: cardiovascular (hypotension, arrhythmia, tachycardia, ​ Streptomycin, amikacin used for mycobacterial MRSA ​ Invasive mucormycosis cardiomyopathy), thyroid dysfunctions, FLS, hepatotoxicity, infections ​ Cryptococcal meningitis: use in combo with 5-flucytosine photosensitivity, bone marrow suppression (high doses) ​ Paromomycin treats intestinal amebiasis Resistance to Lincosamides: is the gold standard treatment ​ Tobramycin is preferred for Pseudomonas aeruginosa ​ Macrolides resistance may lead to clindamycin ​ Histoplasmosis, blastomycosis, coccidioidomycosis, Pharmacokinetics: ​ Severe infections: sepsis, healthcare-associated resistance. penicilliosis (talaromycosis) ​ IM or SC pneumonia (MDR gram-negatives) ​ Not a substrate to macrolide efflux pumps. ​ LEISHMANIASIS: parasitic disease (Leishmania ​ Kidney is the main site of metabolism ​ Bacterial Endocarditis: combo use and enhances ADME: parasites) spread by sand flies ​ Elimination half-life: ~2 hrs clinical response in gram (+) cases ​ Metabolized to N-demethylclindamycin & ​ Skin sores (cutaneous leishmaniasis); ​ UTI: reserved for resistant cases; Gentamicin for lower clindamycin sulfoxide affects spleen, liver, bone marrow (visceral Sofosbuvir-Velpatasvir (Epclusa) UTI ​ Excreted in urine & bile leishmaniasis) MOA: ​ Meningitis: rarely used (3rd-gen cephalosporins ​ Prodrug based on a uridine analog preferred), except for resistant gram (-) & listeria Black Box: PSEUDOMEMBRANOUS COLITIS Adverse Effects: fever, chills tachypnea, stridor, hypotension ​ Metabolized in cells to an active form ​ Mild to life-threatening (infusion-related rx) ​ Competes with uridine triphosphate for Special treatments for: ​ Consider CDIFF infection ​ Treat with meperidine to shorten reaction incorporation into HCV RNA by NS5B polymerase ​ Tularemia & plague: streptomycin/gentamicin ​ Avoid in non-bacterial infections, such as most ​ Decrease reactions with tylenol, ibuprofen, or IV ​ Mycobacterial infections: amikacin & streptomycin (2nd upper respiratory tract infections hydrocortisone Used for: Fixed-dose combination (Sofosbuvir-Velpatasvir line for TB) ​ Alters normal gut flora, allowing CDIFF ​ Hematologic toxicity: hypochromic, normocytic anemia 400mg/100mg) FDA approved for chronic Hepatitis C (HCV) ​ Parasitic infections: paromomycin for intestinal overgrowth, Black Box: ONLY USE IN LIFE THREATENING FUNGAL genotypes 1-6: protozoa INFECTIONS ​ Without cirrhosis or with compensated cirrhosis ​ Cystitis fibrosis: aminoglycosides for acute Adverse Effects: ​ NOT for noninvasive infections (e.g., oral thrush, (Child-Pugh A): 12 weeks of Sofosbuvir-Velpatasvir exacerbations ​ GI: diarrhea (high risk CDIFF superinfection) esophageal or vaginal candidiasis in immunocompetent ​ Decompensated cirrhosis (Child-Pugh B/C): 12 ​ Neomycin: skin/mucosal infections ​ Skin: rashes, exudative erythema multiforme patients with normal neutrophil counts) weeks of Sofosbuvir-Velpatasvir + Ribavirin ​ Oral neomycin: bowel prep, selective digestive (blistering,sloughing) ​ Do not OVERDOSE → fatal cardiac/cardiopulmonary decontamination ​ Liver: reversible elevation of liver enzymes arrest Sofosbuvir (Sovaldi) ​ Hem: granulocytopenia, thrombocytopenia MOA: A nucleotide analog inhibitor of hepatitis C virus NS5B SE: ​ Neuromuscular - potentiates blocking agents polymerase—the key enzyme mediating HCV RNA replication. ​ Ototoxicity: 1st sign - high-pitched tinnitus; may persist for up to 2 weeks post-therapy Echinocandins Used for: against ALL HCV genotypes ​ Vestibular toxicity: HA (1-2 days), N/S, vertigo (1-2 ​ Caspofungin (Cancidas): water-soluble; used for invasive wks); ~12-18 mo recovery period candidiasis, aspergillosis Adverse Effects: seen with combo usage with Ribavirin: fatigue ​ Nephrotoxicity: accumulates in proximal tubules → ​ Micafungin (Mycamine): water-soluble; linear and HA mild proteinuria, hyaline & granular cases in UA, ↓ pharmacokinetics, approved for invasive candidiasis & GFR, prolonged half-life (20-40x) in renal impairment prophylaxis Glecaprevir-Pibrentasvir (Mavyret) ​ Neuromuscular blockade: may occur after ​ Anidulafungin (Eraxis): 1st pangenotypic NS3.4A protease inhibitor-NS5A inhibitor intrapleural/intraperitoneal use; revered with IV calcium combination, ribavirin-free option for most chronic HCV patients; salts MOA: potential 8-week tx for non-cirrhotic patients with renal disease or ○​ Inhibits ACh release at neuromuscular ​ Inhibits fungal cell wall synthesis → blocks β (1-3)-glucan HIV coinfection, NOT for decompensated cirrhosis patients junction production → cell wall disruption & fungal death ​ Fungicidal against candida spp., fungistatic against MOA: 5 Considerations/Clinical Application:: aspergillus spp. ​ Glecaprevir (GLE): NS3/4A protease inhibitor ​ caution in pregnancy, neonates, pediatrics is preventing HCV polyprotein cleavage controversial Resistance: develops due to mutations in FKS1 & FKS2 (glucan ​ Pibrentasvir (PIB): Next generation NS5A inhibitor ​ Resistance patterns - vary by bacterial strain synthase regions) with pangenotypic antiviral activity in vitro ​ TDM: optimizes efficacy, minimizes toxicity ​ Major toxicities: nephrotoxicity & ototoxicity Administration & AE: Used for: Treatment-naive, noncirrhotic HCV genotypes 1-6 - 8 ​ Combination therapy: used with cell wall-active agents ​ IV ONLY wk course (e.g., β-lactams, vancomycin) for synergy ​ Histamine-like effects with rapid infusion ○​ Helps expands antimicrobial spectrum, ​ Contraindicated in pregnancy Adverse Effects: HA and fatigue enhances bacterial killing (synergy), and reduces resistance development Griseofulvin (Gris-PEG,Grifulvin V) Black Box: avoid in pregnant → fetal hearing loss MOA: binds to fungi microtubular proteins during metaphase, where it inhibits the assembly of complete microtubules. Resistance: ​ Enzymatic inactivation, poor intracellular penetration, Used for: dermatophyte infections of skin, hair, and nails low ribosomal affinity ​ Microsporum, epidermophyton, trichophyton ​ Spread by plasmid-mediated resistance genes ​ Tinea capitis: for children (1 month tx) ​ Amikacin & plazomicin effective against resistant ​ Ringworm (tinea corporis) strains - broader activity ​ Tinea cruris (Jock itch) ​ Tinea pedis (athlete’s foot) ADME: poor oral, rapid IM; limited tissue penetration due to polarity; ​ Onychomycosis (finger/toenails) renal (glomerular filtration); accumulates in kidneys & inner ear → ○​ Fingernails: 6-9 mo tx toxicity ○​ Toenails: 1 yr tx ○​ Itraconazole and terbinafine more effective for onychomycosis SE: Hypoplastic heart failure, conjoined twins, abortion, cleft palate - NOT RECOMMENDED FOR PREGNANT (Cat. C) ​ HA, GI upset, neuro effects, hepatotoxicity - prolonged use, leukopenia, neutropenia, albuminuria ADME: variable absorption; deposited in keratin precursor cells Terbinafine (Lamisil) Drug Class: Allylamine (Non-azole inhibitor of ergosterol biosynthesis) MOA: inhibits squalene epoxidase, an enzyme in sterol synthesis. Inhibition of this enzyme → accumulation of squalane and is toxic to fungal cells. Used for: dermatophyte infections (onychomycosis, candida species, and malassezia furfur Pharmacokinetics: oral & topical formulations. Ciclopirox Olamine (Penlac) Broad-spectrum antifungal activity and inhibits the growth of Malassezia furfur MOA: chelates trivalent metal cations thereby inhibiting metal dependent enzymes required for degradation of peroxides within the fungal cell. ​ Penetrates the dermis, hair follicles, and sebaceous glands. Used for: cutaneous candidiasis and for tinea corporis, cruris, pedis, and versicolor, onychomycosis, seborrheic dermatitis of the scalp Pharmacokinetics: cream, gel, suspension, lotion, and shampoo tinea corporis, cruris, pedis, seborrheic dermatitis, and tinea versicolor 6  ​ Nail lacquer: Onychomycosis Nystatin (Mycostatin) MOA: Binds to ergosterol in the cell membrane of susceptible Candida species with a resultant change in membrane permeability allowing leakage of intracellular components, acidification, and death of the fungus. ​ fungistatic/fungicidal ​ Not effective against bacterial, protzoa, or viruses ​ Not absorbed in the GI, skin, or vagina Uses for: Nystatin oral suspension - candidiasis in oral cavity, vaginal candidiasis & intertriginous candidal infections. Pharmacokinetics: ​ Given topically ​ Moist lesions (diaper rash) - powder preferred, BID or TID ​ Creams/ointments - BID ​ Oral administration has an unpleasant taste HIV Medications 1.​ PrEP (pre-exposure prophylaxis)) 2.​ PEP (post-exposure prophylaxis PrEP 3.​ Apretude (cabotegravir extended-release, IM ​ Prevents HIV transmission through sex or injection injection) drug use. MOA: integrase strand transfer inhibitor (INSTI) ​ Reaches maximum protection for receptive anal sex Dosing: Initial: 600 mg IM, 1 month apart for 2 doses; (bottoming) at about 7 days of daily use. Maintenance: every 2 months ​ Receptive vaginal sex and injection drug use - maximum protection at about 21 days of daily use PEP ​ Combo of 3 drugs: Truvada 1.​ Truvada (emtricitabine/tenofovir disoproxil (emtricitabine/tenofovir disoproxil fumarate) fumarate) and Raltegravir (Isentress) → integrase ​ For all individuals at risk (sex & injection drug use) inhibitor MOA: inhibits HIV-1 reverse transcriptase ○​ Taken once or twice daily for 28 days SE: N/D, HA, fatigue, stomach pain (temporary) ​ Short course of HIV medication taken after a ​ Serious Risks: worsening HBV infection when possible exposure, prevents HIV from establishing discontinued infection Considerations: Must be HIV negative before starting and while ​ Must start within 72 hours of exposure (the taking Truvada for PrEP. sooner, the better, every hour counts) ​ Get tested immediately before and at least every 3 Uses for: EMERGENCY USE ONLY - not for regular HIV months while on it. prevention Special Considerations: 2.​ Descovy (emtricitabine/tenofovir alafenamide) ​ Pregnant women/women at risk of pregnancy → ​ For sexual exposure (except vaginal sex; not studied Raltegravir preferred over Dolutegravir (due to in assigned females at birth) birth defect risk) Used for: at risk adults/adolescents (> 35kg), excluding those at risk ​ Children ( >2 YO) will get the same drugs but from receptive vaginal sex altered dosage Considerations: ​ HIV-negative confirmation before initiation ​ DISCONTINUE who develop lactic acidosis/hepatotoxicity Serious SE: new onset or worsening renal impairment (monitor kidney function), serum phosphorus with CKD patients, lactic acidosis/severe hepatomegaly with steatosis 7  DERM DRUGS Burns Acne - Step Therapy Lice SILVER SULFADIAZINE (SSD) – BINDS TO BACTERIAL DNA TO INHIBIT 1.​ Retinoids REPLICATION 2.​ Isotretinoin 1.​ Permethrin ​ Bactericidal against gram + and gram - 3.​ Azelaic acid ​ MOA: Synthetic pyrethroid that interferes with insect ​ Partial thickness burns or LE stasis ulcers Na+ transport proteins, causing neurotoxicity and “Step therapy: “SA with benzo cream without success”, mild vs. severe, not improving prescribing paralysis. MAFENIDE – TOPICAL SULFONAMIDE – ADJUNCTIVE THERAPY FOR BURNS tetracycline, blood work” - this was stated in class but no where in the notes takes about specific ​ Resistance due to mutations in the transport protein ​ Bacteriostatic against gram + and gram - steps has been increasing. ​ 1% OTC for lice for infants > 2 mo. MOA: inhibits carbonic anhydrase, which plays a role in pH balance and acid-base 1.​ RETINOIDS (tretinoin, adapalene, bexarotene) 2.​ Lindane homeostasis ​ Comprise natural & synthetic compounds that exhibit vitamin A- like ​ MOA: organochloride compound that induces neuronal biological activity or bing to nuclear receptors for retinoids hyperstimulation and eventual paralysis of parasites. AE: ​ Used for: 1st line for noninflammatory acne (along or combo) ​ 2nd line due to neurotoxicity in children and adults ​ Metabolic acidosis, esp. Renal failure ​ MOA: they exert their effects on gene expression by activating 2 families weighing < 50 kg and patients with underlying skin ​ Applied to large surface areas of nuclear receptors, retinoic acid receptors (RARs) and retinoid X disorders (atopic dermatitis and psoriasis) ​ pain/burning sensation with application, facial edema, contact receptors (RXRs) - members of the steroid receptor superfamily. ​ Contraindicated: premature infants and seizure dermatitis,hemolytic anemia with G6PD deficiency (rare) ○​ Correct abnormal follicular keratinization disorders ○​ Reduce counts of propionibacterium acnes ​ Boxed warning - must give a Lindance Medication ○​ Reduce inflammation Guide each time lindane lotion or shampoo is ​ Targeted Therapeutic Actions: dispensed ○​ Retinoids target RARs affect cellular differentiation and 3.​ Malathion proliferation ​ Head lice for > 6 YO. ​ Tretinoin, adapalene, & tazarotene: used in ​ Contains ETOH and is flammable acne, psoriasis, and photoaging 4.​ Spinosad ○​ Target RXRs induce apoptosis ​ 0.9% topical suspension for lice for 6 mo > ​ Bexarotene & alitretinoin: use for cutaneous 5.​ Abametapir T-cell lymphoma (CTCL) and Kaposi sarcoma- ​ MOA: exhibits pediculicidal and ovicidal activity induce apoptosis of malignant cells through inhibition of metalloproteinases critical for louse ​ AE: erythema, desquamation, xerosis, burning, and stinging survival and egg development ○​ Decrease over time and lessen with concomitant use of ​ Antiparasitic drug for head lice in 6 mo > emollients ​ 0.74% lotion applied to dry hair and scalp, left in for 10 ○​ Photosensitivity and risk of sunburn min before rinsing ○​ Toxicity: similar to vitamin A intoxication ○​ Only single application is needed ​ SE of SYSTEMIC retinoids: dry skin, nosebleeds, conjunctivitis, reduced ​ AE: skin irritation, eye irritation, pruritus, and hair color night vision, hair loss, alterations in serum lipids & transaminases, change hypothyroidism, IBD flare, musculoskeletal pain, pseudotumor cerebri, and mood alterations. ​ Contraindications: pregnancy ​ Tretinoin ○​ Photolabile - night application for acne & photoaging ○​ Inactivated by benzoyl peroxide (don’t apply together) ​ Adapalene ○​ Same as tretinoin but not inactivated by benzoyl peroxide ○​ Stable in sunlight & less irritating ​ Bexarotene ○​ Approved for early-stage (IA & IB) CTCL ○​ Titrated up from every other day to 2-4 times daily over several weeks to improve tolerance ○​ Concurrent use of insect repellants (DEET) is NOT recommended due to increase absorption ○​ Need one negative pregnancy test prior to starting therapy 2.​ ISOTRETINOIN ​ Used for: recalcitrant and nodular acne vulgaris ○​ Remarkable efficacy in severe acne and may induce prolonged remissions after a single course of therapy ○​ Clinical effects within 1-3 months ○​ ⅓ will relapse, usually within 3 years of stopping therapy ○​ Systemic absorption improved with high-fat meal ​ Contraindications: leukopenia, ETOH, HLD, hypothyroidism, hepatic/renal disease. 8  ○​ Highly teratogenic: PREGNANCY/BREASTFEEDING ○​ 2 negative pregnancy tests on separate occasions are required prior to starting; monthly pregnancy tests for females of childbearing potential 3.​ AZELAIC ACID ​ MOA: inhibits tyrosinase, the initial enzyme in melanin pathway (1.5-2% OTC or 3-4% prescription) ​ Used for: acne Psoriasis Pityriasis Versicolor Tinea Infections (Hyperkeratotic disorder) (Fungal infection) (Dermatophyte infections of the skin) Keratolytic agents reduce hyperkeratosis through myriad mechanisms (e.g., breaking of Drugs used: Drugs: intercellular junctions, increasing stratum corneum water content, increasing ​ Topical ciclopirox or terbinafine cream ​ Topical - allylamines (terbinafine), benzylamines (butefaine), azoles desquamation ○​ ORAL terbinafine does not reach adequate concentrations in the (econazole), ciclopirox 1.​ Topical glucocorticoids superficial stratum corneum ○​ Bacterial superinfection of tinea pedis can occur. ​ MOA: absorption varies among body sites ​ Selenium sulfide, pyrithione zinc, sodium sulfacetamide Antifungal agents such as econazole and ciclopirox can ​ Initial: potent then followed by less potent ​ Oral fluconazole be used for bacterial coverage. ​ Systemic - unresponsive or extensive use terbinafine, fluconazole, 2.​ Acitretin (systemic retinoid) griseofulvin ​ Used for: cutaneous manifestations of psoriasis ○​ Use these if poor response/extensive cutaneous ​ Begin within 4-6 wks, full clinica benefit at 3-6 mo involvement to topical therapy ​ Avoid pregnancy for 3 years AFTER receiving acitretin to ○​ Ketoconazole → risk of severe hepatotoxicity or avoid retinoid-induced embryopathy prolonged QT; not preferred treatment for superficial 3.​ Calcipotriene (vitamin analogue) fungal infections. ​ A TOPICAL VITAMIN D ANALOGUE THAT IS APPROVED FOR THE TREATMENT OF PSORIASIS. ​ MOA: exerts its effects through the vitamin D receptor. On ​ 1st line for OTC topical ‘azole’ therapy for tinea corporis (ringworm) binding the vitamin D receptor, the drug-receptor complex or tinea pedis (athlete's foot) associates with the RXR-α and binds to vitamin D response elements on DNA, increasing expression of genes that modulate epidermal differentiation and inflammation, leading to improvement in psoriatic plaques ​ Applied BID to psoriasis on the scalp or body, often in combination with topical corticosteroids. ​ AE: Hypercalcemia and hypercalciuria may develop when the cumulative weekly dose exceeds the recommended 100 g/week limit and resolves within days of discontinuation of calcipotriene. ​ Calcipotriene may be inactivated by concomitant use of acidic topical agents such as salicylic acid or lactic acid. 4.​ Coal tar ​ Distillation product from coal ​ MOA: unknown; known to suppress DNA synthesis ​ Anti-inflammatory, antimicrobial, and antipruritic activity ​ Poorly tolerated - unpleasant odor, messy, and staining of clothes ​ AE: folliculitis or irritant contact dermatitis ​ Tinea capitis (hair) - Griseofulvin, terbinafine ○​ Griseofulvin - antifungal drug to treat dermatophyte 9  infections. ○​ MOA: inhibiting microtubular protein assembly during metaphase. ○​ If treatment fails, may need to increase length of treatment or adjusting dose. ○​ Terbinafine - may be more effective ​ Onychomycosis (nails) - Terbinafine, Itraconazole, Griseofulvin ○​ ○​ Treatment with systemic therapy Other treatment that are topical: cicloirox lacquer efinaconazole, & tavaborole 💅, ​ 48 wks for topical treatment ​ For mild-to-moderate cases, that does not involve nail matrix, & who can’t take systemic therapy ○​ Terbinafine ​ Fingernails: 250 mg daily for 6 wks ​ Toenails: 250 mg daily for 12 wks ​ May have pulsed dosing of 500 mg daily for 1 wk per month for 3 months ○​ Itraconazole - more effective against candida in nails ​ Fingernails: 200 mg daily for 6 wks ​ Pulsed dosing: 400 mg PO daily for 1 wk per month for 2 months ​ Toenals: 200 mg daily for 12 wks ​ Pulsed dosing: 400 mg PO daily for 1 wk per month for 3 months ​ Fungus will persist in the nail 6-9 mo POST treatment is done. ○​ Griseofulvin - less effective & longer course of tx and not preferred ​ inhibiting microtubular protein assembly during metaphase Hordeolum (stye) Glaucoma Herpes Zoster Ophthalmicus HORDEOLUM (STYE) – INFECTION OF THE GLANDS OF THE EYELIDS ​ Glaucoma: progressive loss of retinal nerve fiber layer tissue with corresponding visual HERPES ZOSTER OPHTHALMICUS ○​ Usually Staph field loss ​ REACTIVATION OF VARICELLA ZOSTER IN THE TRIGEMINAL ○​ Topical antibiotics (gel, drops, or ointment) ​ Medications are targeted to decreasing the production of aqueous humor at the ciliary NERVE ○​ Warm compresses body and increasing outflow through the trabecular meshwork & uveoscleral pathway ○​ Systemic acyclovir, valacyclovir, famciclovir – reduce ​ Goal of therapy: reduce intraocular pressure by decreasing production of aqueous severity and complications humor or increase aqueous outflow ​ Prostaglandin analogues (latanoprost, travoprost, etc.) - 1st line therapy; unknown MOA ​ Systemic Therapy for Glaucoma: ○​ Indications: when topical therapy fails to control IOP or prevent optic nerve damage, prior to laser or surgical treatment. Use with a CAI. ○​ CAI: best-tolerated is sustained-release acetazolamide capsules, followed by methazolamide; tablets are least tolerable ○​ Osmotic drugs: glycerin, mannitol, and hypertonic saline. Oral glycerin and IV mannitol are for short-term acute IOP rises ○​ Due to nausea, IV mannitol/acetazolamide may be preferred over oral glycerin ○​ Use cautiously with patients with CHF/renal failure 1.​ Prostaglandin analogues (Latanoprost, Travoprost, Bimatoprost, Tafluprost, & Latanoprostene bunod) ○​ Used for: glaucoma, ocular hypertension 10  ○​ Latanoprost: once daily can cause lash growth; may cause allergic Part of Viral Eye Infections - conjunctival hyperemia, permanent ↑ iris pigmentation, orbital fat atrophy ​ VIRAL KERATITIS 2.​ Nonselective B blockers (Timolol, Levobunolol, & Carteolol) ○​ Etiology: HSV1 or varicella zoster ○​ MOA: bing to both β1 & β2 receptors, decrease ocular blood flow, which ○​ Topical antiviral agents: trifluridine (more toxic to decreases the ultra filtration responsible for aqueous production cornea) and acyclovir/ ganciclovir ​ Autonomic topical drugs targets → ciliary body epithelium ○​ Topical steroids contraindicated in herpetic and BV, reducing aqueous humor production