04 Antimicrobials

• Metro: metronidazole
• Mr Fragilis stabbed in the abdomen: coverage of polymicrobial anaerobic infections (e.g. intra-abdominal infections)
• Broken helix: free radical metabolites disrupt bacterial DNA (bactericidal)

• Do not enter: activity against Entamoeba histolytica
• Colonel Giardia with the protozoan shield: activity against Giardia
• Mr. Trichomonas with the strawberry: treats vaginitis and cervicitis caused by Trichomonas
• Mrs. Trichomonas: treat both patient and partner
• Ms. Gardner with the venus fly trap: treats bacterial vaginosis caused by Gardnerella
• Helicopter: substitute for amoxicillin in the triple therapy for Helicobacter pylori infection in penecillin-allergic patients
• Mlle. Clostridium with the gas mask: activity against anaerobic bacteria (e.g. Bacteroides, Prevotella, Fusobacterium, Clostridium
• Chocolate fondu fountain: treats pseudomembraneous colitis caused by Clostridium difficile

• No drinking: Concurrent ingestion of alcohol results in a disulfiram-like reaction (flushing, tachycardia, palpitations, nausea, vomiting

Antifungals

• amphotericin, flucytosine
• azoles
• griseofulvin, terbinafine, echinocandins

Amphotericin

• Amphibian: amphotericin (anti-fungal)
• Non sterol: fungal cell membrane composed of ergosterol, not your usual cholesterol
• Holes in amphibian tank: amphotericin and nystatin bind ergosterol to form holes in the fungal cell membrane, leading to electrolyte loss and cell death. Down regulation of erosterol leads to resistance

• Ivy: IV administration of amphotericin
• Fat bubble: liposomal formulations of amphotericin prevent binding to human cholesterol membranes (decreased toxicity)
• Organ systems model: amphotericin treats severe systemic fungal infections

• infusion related immediate reactions and slow accumulated toxicities

• Amphibian binding cholesterol necktie: amphotericin toxicity results from non-selective binding to mammalian cholesterol membranes
• Fainting and holding head: hypotension and headache are immediate infusion-related toxicities of amphotericin
• Shake and bake: fevers and chills are immediate infusion-related toxicities of amphotericin
• Tongue on brain: intrathecal administration of amphotericin to treat fungal CNS infections
• Shaking brain: intrathecal administration of amphotericin can cause seizure and other CNS side effects
• Blue veiny pattern: thrombophlebitis at injection site is an immediate infusion-related toxicity of amphotericin

• 1 shaped acid tube: renal tubular acidosis (RTA) type 1 is cumulative toxicity of amphotericin
• Depleted potassium banana peel: RTA type 1 is associated with hypokalemia
• Magnet falling into sink: amphotericin can cause hypomagnesemia (due to renal magnesium wasting)
• Emergency saline wash: volume expansion with IV normal saline before amphotericin administration prevents kidney damage
• Cracked and drained kidney: amphotericin induced damage to renal tubular cells can cause anemia (decreased erythropoietin production)

Nyastatin

• Nyce: nystatin (same mechanism of action as amphotericin)
• Canada: nystatin is treats Candida infections (candidiasis)
• Snow on crotch: topical nystatin treats mucocutaneous candidiasis (e.g. vaginal candidiasis)
• Swish and swallow drinking fountain: oral nystatin rinse treats oropharyngeal candidiasis

Flucytosine

• Flute: flucytosine (anti-fungal)
• Meningitis helmet: flucytosine and amphotericin combo treats cryptococcal meningitis
• "Crypt": flucytosine and amphotericin combo treats Cryptococcus infections (e.g. cryptococcal meningitis)

• C turned into U: cytosine deaminase in fungal cells converts flucytosine (a fluorinated cytosine) into 5-fluorouracil (5-FU)
• Smeared double helix and single strand: flucytosine halts fungal DNA and RNA/protein synthesis

Azoles

• Pine cones: cone-azole antifungals (e.g. voriconazole, fluconazole, itraconazole, clotrimazole, miconazole, ketoconazole)

• Emerald perimeter: ergosterol comprises the fungal cell membrane
• Crushed emerald builder: azole antifungals inhibit the synthesis of ergosterol
• Lane closed: azole antifungals inhibit the conversion of lanosterol to ergosterol
• Broken chrome bumper: azole antifungals inhibit fungal cytochrome P-450 responsible for the conversion. Also SE because CYP 450

• Car crushing vortex: voriconazole inhibits mammalian cytochrome P-450, dose reduction of other medication needed (cyclosporin, statin, tacrolimus)
• Blurry flashes: voriconazole may cause blurry vision of flashes of light
• Sepia tone: voriconazole may cause changes in color vision
• Aspirating scarecrow with lung hyphae: voriconazole treats invasive aspergillosis (caused by Aspergillus fumigates)
• Canada: voriconazole treats Candida infections (e.g. esophageal candidiasis)

• Flying monkey: fluconazole
• Canada: fluconazole treats Candida infections (e.g. mucocutaneous candidiasis)
• Snow on crotch: one-time oral dose of fluconazole treats vaginal candidiasis
• Snow in gutter: systemic fluconazole treats esophageal candidiasis
• Crypt: fluconazole treats Cryptococcus infections (e.g. cryptococcal meningitis), lifelong therapy
• Meningitis mohawk helmets: fluconazole has high levels of CNS penetration (treats cryptococcal meningitis)

• Good witch: itraconazole (azole antifungal)
• Dimorphic butterfly: itraconazole treats systemic infections with dimorphic fungi (e.g. histoplasmosis, blastomycosis, coccidioidomycosis, sporothrix))
• Tarnished ruby slippers: itraconazole treats onychomycosis and dermatophytosis
• Tin man: dermatophytes (tinea)

• Close trim: topical clotrimazole treats tinea infections (e.g. dermatophytosis)
• My cone: topical miconazole treats tinea infections (e.g. dermatophytosis)
• Snow on crotch: clotrimazole and miconazole treat vaginal candidiasis

• treats onychomycosis and cutaneous dermatophytes
• Adrenal lock: ketoconazole inhibits 17,20-desmolase (the first step of steroid hormone synthesis from cholesterol)
• Male and female symbols: ketoconazole inhibits production of androgens and estrogens
• Moon face: ketoconazole inhibits overproduction of cortisol (treats the symptoms of cushing's disease)
• Ketoconazole can cause anti-androgenic side effects (e.g. gynecomastia)

Griseofulvin, Terbinafine, Echinocandins

• Broken spindle vines: griseofulvin binds fungal cell microtubules, halting mitosis
• Rusty tin man: dermatophytes (e.g. tinea corporis, tinea pedis, and tinea cruris)
• Grease: griseofulvin antifungal agent, stay in keratin tissues thus best for capitis and skin
• Tin man hat: oral griseofulvin and terbinafine are first line therapy for tinea capitis in children

• SE: GI distress, headache, rash; heptatotoxicity, granulocytopenia
• Greased up chrome bumper: griseofulvin activates cytochrome P-450

• Turban: terbinafine (anti-fungal agent)
• Non sterol: fungal cell membrane composed of ergosterol (not your usual cholesterol)
• Squealing pig pen: terbinafine inhibits fungal squalene epoxidase causing accumulation of squalene

• Little tin man: topical terbinafine is used to treat tinea infections (e.g. dermatophytosis)
• Biting nails: oral terbinafine treats onychomycosis
• Tin man hat: oral griseofulvin and terbinafine are first line therapy for tinea capitis in children

• Mud puddles: terbinfine can cause GI side effects
• Liver spot: terbinafine can cause hepatotoxicity

• Echino-Canadian fur cap: echinocandins (e.g. caspofungin, micafungin, anidulafungin)
• Crumbling brick wall: echinocandins act at the fungal cell wall
• Polysaccharide shaped wall: echinocandins inhibit the synthesis of beta-1-3-glucan (polysaccharide, not ergosterol) in the fungal cell wall, not cell membrane

• Ivy: echinocandins are delivered IV for systemic Candida infections (e.g. candidemia)
• Canada: echinocandins have excellent activity against Candida infections (e.g. mucocutaneous candidiasis)
• Exhaust pipe with snow: echinocandins treat esophageal candidiasis
• Scarecrow with lung hyphae: echinocandins treat invasive aspergillosis (caused by Aspergillus fumigatus)

HIV Antivirals

NRTI

• Knights of the Round Table: NRTIs
• Reverso transcriptum: reverse transcriptase
• Nucleoside-shaped mace: NRTIs are nucleotides or nucleosides (sugar on base)
• Broken double helix bookmark: NRTIs incorporate into growing viral DNA strand. Competitive inhibitor
• Broken spike: NRTIs lack a hydroxyl group at the 3' end (no phosphodiester bond formation > chain termination)
• Page 3' to 5': NRTIs inhibit 3' to 5' phosphodiester bond formation
• Activating "P" scroll: nucleosides need phosphorylation by cellular enzymes in order to be activated

• Feast: -dine suffix of NRTIS (e.g. lamivudine, stavudine, zidovudine)
• Sir Lancelot: Lamivudine (nucleoSIDE RTI)
• Sir Tristan: tenofovir (nucleoTIDE RTI)
• Princess Izolde and dove sigil: Zidovudine (nucleoSIDE RTI)
• Sir Steve: stavudine (nucleotide RTI)
• Sir Dan: didanosine (nucleoSIDE RTI)
• Abracadabra: abacavir (nucleoSIDE RTI)
• Excalibur: emtricitabine (nucleoSIDE RTI)

• Woodgrain cisternae: NRTIs can cause mitochondrial toxicity
• Sour milk: NRTIs can cause lactic acidosis
• Stockings and gloves: lamivudine, stavudine, and didanosine can cause peripheral neuropathy

• Sir Lancelot: Lamivudine (nucleoSIDE RTI)
• Hippie Hippo sigil: lamivudine and tenofovir treat hepatitis B infection
• Woodgrain cisternae: NRTIs can cause mitochondrial toxicity
• Sour milk: NRTIs can cause lactic acidosis
• Stockings and gloves: lamivudine, stavudine, and didanosine can cause peripheral neuropathy

• Sir Tristan: tenofovir (nucleoTIDE RTI)
• Actively sailing the tide: tenofovir is a nucleotide and does not need activation by phosphorylation
• Hippie Hippo sigil: lamivudine and tenofovir treat hepatitis B infection

• Princess Izolde and dove sigil: Zidovudine (nucleoSIDE RTI)
• Pregnant Izolde: Zidovudine is used during pregnancy and breastfeeding to reduce vertical transmission of HIV
• Devoured marrow: zidovudine may cause myelosuppression
• Pale white dress: zidovudine can cause megaloblastic anemia
• Multi-lobed sand timer: zidovudine can cause agranulocytosis
• Centrally fat horse: zidovudine and stavudine can cause lipodystrophy (redistribution of fat from extremities to trunk)

• Sir Steve: stavudine (nucleotide RTI)
• Centrally fat horse: zidovudine and stavudine can cause lipodystrophy (redistribution of fat from extremities to trunk)
• Woodgrain cisternae: NRTIs can cause mitochondrial toxicity
• Sour milk: NRTIs can cause lactic acidosis
• Stockings and gloves: lamivudine, stavudine, and didanosine can cause peripheral neuropathy

• Sir Dan: didanosine (nucleoSIDE RTI)
• Squeezed sponge: didanosine can cause pancreatitis
• Woodgrain cisternae: NRTIs can cause mitochondrial toxicity
• Sour milk: NRTIs can cause lactic acidosis
• Stockings and gloves: lamivudine, stavudine, and didanosine can cause peripheral neuropathy

• Abracadabra: abacavir (nucleoSIDE RTI)
• HLA-B spell: Abacavir hypersensitivity is associated with the HLA-B 57:01 allele
• Delayed reaction to rash: abacavir may cause a delayed type 4 hypersensitivity reaction

• Excalibur: emtricitabine (nucleoSIDE RTI)
• Dark gloves: emtricitabine can cause hyperpigmentation of palms and soles

NNRTI

• Outside camelot: not Knights of the Round Table - NNRTIs
• Fleeing "P"d signal: NNRTIs are not phosphorylated by intracellular enzymes
• Arrow in Reverso Transcriptum: direct binding and allosteric inhibition of HIV reverse transcriptase
• Broken double helix bookmark: halted DNA polymerase activity

• Elven pine forest: eevirapine
• Queen Elfavirenz: efavirenz
• Princess Delavir: delavirdine

• Jaundiced yellow glow and liver spot: liver failure can occur within 6 weeks of starting therapy
• Dark moon: side effect of insomnia and nightmares
• Mesmerized by hallucinations: side effect of CNS symptoms (e.g. dizziness, drowsiness, headache, psychosis)
• Tarantula: teratogenic. Avoid both efavirenz and delavirdine in pregnancy
• Chrome bumper: varying effects on the cytochrome P-450 system
• Sloughed off mask: side effect of Stevens-Johnson syndrome (SJS-TEN). Association with skin rash

Protease Inhibitors

• Guinevere: -navir suffix of protease inhibitors
• Fleeing "P" signal: protease inhibitors are not phosphorylated by intracellular enzymes
• Sword in the stone: protease inhibitor
• immature knight: virion remains immature. HIV must cleave long proteins into smaller ones. Inhibit polyprotein cleavage

• Paul's Smithy: POL gene codes for production of HIV enzymes (e.g. protease)

• Indigo princess: indinavir
• Right on!: ritonovir has greatest cytochrome P-450 inhibitory effect and boosts concentration of other protease inhibitors

• Elevated candy jar: side effect of hyperglycemia due to insulin resistance
• Elevated butter: side effect of dyslipidemia
• Central adiposity: side effect of lipodystrophy
• Broken chrome bumper: inhibition of cytochrome P-450

• Indigo princess: indinavir
• Stones in kidney fountain: indinavir may cause nephrolithiasis
• Adequate hydration helps to prevent nephrolithiasis
• Elevated candy jar: side effect of hyperglycemia due to insulin resistance
• Elevated butter: side effect of dyslipidemia
• Central adiposity: side effect of lipodystrophy
• Broken chrome bumper: inhibition of cytochrome P-450

• Right on!: ritonovir has greatest cytochrome P-450 inhibitory effect and boosts concentration of other protease inhibitors
• Elevated candy jar: side effect of hyperglycemia due to insulin resistance
• Elevated butter: side effect of dyslipidemia
• Central adiposity: side effect of lipodystrophy
• Broken chrome bumper: inhibition of cytochrome P-450

• Speeding rifle: rifampin activates cytochrome P-450 and decreases the concentration of protease inhibitors (rifabutin is better)

Misc Inhibitors

• Invading ship: budding virion invades next cell
• 120 battering ram: surface glycoprotein gp120 allows HIV to gain entry
• 41 grappling hook: surface glycoprotein gp41 facilitates HIV fusion, if made it then:
• Reverso transcriptum spell: reverse transcriptase
• Double helix staircase behind keyhole: integrase allows viral DNA to integrate with host cell DNA

• Gagged prisoners in the core of the ship: gag structural gene codes for virion core proteins (e.g. p24, p7) (24 hours, 7 days)
• 24 hour sundial: gag structural gene codes for virion core proteins (e.g. p24, p7)

• Envoy coming ashore: env structural gene encodes viral envelope proteins for infiltration (e.g. gp41, gp120)
• 120 battering ram: surface glycoprotein gp120 allows HIV to gain entry
• Helper squire and CCR5 banner: gp120 binds to the host cell CD4 molecule and chemokine receptor (CXCR4 or CCR5)
• 41 grappling hook: surface glycoprotein gp41 facilitates HIV fusion

In the HIV replication cycle, polyprotein precursors are encoded by structural genes (gag, pol, and env). Only the polyprotein product of the env gene is glycosylated to become gp160. The gp160 is then proteolytically cleaved within the endoplasmic reticulum and Golgi apparatus to form gp120 and gp41. gp120 mediates viral attachment by binding to the CD4 receptor of susceptible cells. Transmembrane gp41 anchors gp120 through noncovalent interactions, thereby mediating the fusion process between viruses and target cells. A few antiretroviral medications interact with these glycoproteins.

• Mare with CCR5 banner: the entry inhibitor maraviroc allosterically binds CCR5, not CXCR4
• Fusion hook deflector: fusion inhibitor enfuvirtide binds gp41

• Endoplasmic reef: env encoded surface proteins are first sent to the host cell endoplasmic reticulum

• Reverso transcriptum spell: reverse transcriptase
• Doubling army: reverse transcriptase transcribes viral RNA into double stranded DNA
• King arthur and elf queen elfavir: NRTIs and NNRTIs inhibit reverse transcriptase. Resistance from mutated pol gene

• Paul the blacksmith producing swords, spell books, and keys: pol gene encodes for protease, reverse transcriptase, and integrase

• Double helix staircase behind keyhole: integrase allows viral DNA to integrate with host cell DNA
• Key deflector blocking route: the integrase inhibitor raltegravir/dolutegravir binds viral integrase
• Crispy chicken with bite: integrase inhibitors may cause rhabdomyolysis

Anti Heptatitis

Interferons

• Infected manager releasing cyto-coins: interferons are immunomodulatory cytokines released from virus infected cells that activate immune response (modulate T cells, activate macrophages, buff up antiviral cell response)
• Luke: interleukins upregulate interferon synthesis in infected cells

• Pac man: Interferon alpha
• yellow Hippo: interferon alpha treats hepatitis B and C infections
• Melanotic ghost: interferon alpha treats malignant melanoma
• Hairy creature: interferon alpha treats hairy cell leukemia
• Posies: interferon alpha treats Kaposi sarcoma caused by HHV8
• Accumulated tokens: interferon alpha treats condyloma accuminata caused by HPV
• Plush cancer crab in kidney machine: interferon alpha treats renal cell carcinoma

• Interferon alpha may cause a flu like syndrome, or more severe symptoms including profound fatigue, tinnitus, retinopathy, confusion; occurs within a few hours.
• Devoured marrow: interferon alpha may cause myelosuppression
• Plush wolf: interferon alpha may cause drug induced lupus

• beta invaders: Interferon beta
• Combat Lesions through Time and space: Interferon beta treats multiple sclerosis (MS). MS lesions in different time and space

• gamma ga: Interferon gamma
• Destroyed granulomatous asteroids: interferon gamma treats chronic granulomatous disease (CGD). Activate macrophages

Hep C Treatment

• Sea Hippo: hepatitis C
• Identify the HCV genotype to select treatment regimen
• Stony liver under microscope: liver fibrosis is assessed before beginning treatment
• Photographic evidence: all patients with virologic evidence of chronic HCV infection should be considered for treatment
• Sustained search for 6 months: sustained virologic response (SVR) - HCV RNA not detected by PCR for 6 months after stopping treatment

• Alpha shaped antenna: once weekly pegylated-interferon alpha is the traditional standard treatment (with daily ribavirin)
• Ribs: daily ribavirin is the traditional standard treatment (with once weekly pegylated interferon alpha

• Purine G shaped stakes: ribavirin is a guanosine nucleoside analog
• 3 pepper shakers: ribavirin is phosphorylated three times by intracellular enzymes into its active nucleotide form
• Disrupted RNA rope: the activated nucleotide form of ribavirin inhibits RNA production

• Bursting fruits: ribavirin causes dose dependant hemolytic anemia
• Tarantula: ribavirin is teratogenic

• Sofa with nucleoside pattern: sofosbuvir - a nucleoside analog
• Disrupted RNA rope: sofosbuvir inhibits NS5B RNA production
• Fatigued explorer: side effects of sofosbuvir include fatigue and nausea

• Stuck machete: NS3/4A protease inhibitor
• Simmering: simeprevir (a protease)
• Flash photo: seide effects of simeprevir include photosensitivity and rash
• Broken chrome bumper: simeprevir inhibits cytochrome P450
• North Sea under investigation: new investigational drugs include second generation NS3/NS4A protease inhibitors and NS5A inhibitors

Others

HSV Treatment

• Hermes airline: herpes simplex virus (HSV)

• Recycling bin: acyclovir
• Purine shaped luggage: guanisine nucleoside analog
• Hermes with "P" luggage tag: converted to acyclovir monophosphate via virus encoded thymidine-kinase (occurs selectively in virus/Hermes cells) (only affect infectd cells)
• Herpesvirus-encoded thymidine-kinase is the rate determining activation step
• Bag checkers with "P" tags: converted 2x more to acyclovir triphosphate by cellular kinases

• Branching double helix conveyor belts: viral DNA dependent DNA polymerase
• Baggage jam: acyclovir triphosphate incorporates into replicating viral DNA, halting synthesis

• Closed baggage check: absence of thymidine-kinase confers resistance (CMV/EBV don't have)

• Security officer Cid: Cidofovir
• "P" access badge: cidofovir does not require phosphorylation by the viral kinase "3 active against acyclovir or ganciclovir resistant HSV, CMV, VZV

• Luggage car net: foscarnet is active against acyclovir or ganciclovir resistant HSV, CMV, VZV (no activation at all)

• Conveyor belt stop switch: cidofovir and foscarnet directly inhibit viral DNA polymerase

• Valet parking: valacyclovir
• Daily rate for frequent flyers: daily valacyclovir suppressive therapy for multiple yearly episodes of recurrence
• Open mouth: valacyclovir has improved oral bioavailability

• Recycling bin: acyclovir
• Ivy: IV acyclovir treats serious HSV and VZV infections
• Red winged helmet: IV acyclovir treats HSV encephalitis
• Baby Hermes helmet: IV acyclovir treats neonatal HSV

• Zeus: varicella zoster virus
• Family value: famcyclovir and valacyclovir are preferred treatments for VZV due to superior activity and less frequent dosing
• 3 days: during active shingles infection, valacyclovir and famcyclovir are most effective if given within 3 days of onset of symptoms

• Prepare: HSV prophylaxis
• Cane and organs: HSV prophylaxis important in immunocompromised states and transplant patients
• Pregnant: HSV prophylaxis important in pregnant women with active recurrent genital herpes

• Kidney sharps: IV acyclovir can cause interstitial nephritis or crystalline nephropathy
• Adequate hydration prevents renal side effects
• Uncommon CNS side effects: delirium, confusion, vertigo, hallucinations

CMV

• Mega-Lo Market: cytomegalovirus (CMV)
• 50 items or less: CMV infections are more common with a CD4+ count < 50
• Can recycling: ganciclovir

• G toys: Ganciclovir is guanisine analog
• Market worker with "P" label gun: converted to ganciclovir monophosphate by a CMV encoded kinase (UL97)
• Customers with "P" label guns: converted to ganciclovir triphosphate by cellular kinases
• Branching double helix conveyor belts: viral DNA dependent DNA polymerase
• Grocery jam: ganciclovir triphosphate incorporates into replicating viral DNA, halting synthesis

• Value: valganciclovir
• Open mouth: valganciclovir has better oral bioavailability

• Organs on ice: valganciclovir or ganciclovir is indicated in high-risk solid organ and bone marrow transplant recipients

• Princess Izolde: myelosuppression may be additive in patients receiving zidovudine

• Car net: foscarnet
• Spilled kidney beans: foscarnet may induce renal insufficiency
• Broken milk bottles: foscarnet may cause hypocalcemia
• Falling magnets: foscarnet may cause hypomagnesemia
• Banana peel: foscarnet may cause hypokalemia
• Shaking: foscarnet may induce seizures

• Security officer Cid: Cidofovir
• Broken kidney: cidofovir nephrotoxic, leading to proteinuria, azotemia, and metabolic acidosis
• Probation officer Cid: probenecid blocks the tubular secretion of cidofovir, limiting its toxic effects
• No drugs touching kidney: probenecid prevents excretion and increases plasma concentrations of many different drugs (e.g. penicillins, methotrexate, NSAIDs)