Antimicrobials

bactericidal/fungicidal

• kills sensitive organisms so that number of bacteria/fungus fall quickly after taking the drug

• more rapid response & clinical improvement

bacteriostatic/fungistatic

• inhibits growth of bacteria/fungus but does not kill them

• number of bacteria/fungus remains constant

• requires a functioning immune system to eliminate the microorganisms

narrow-spectrum drugs

active against a single species or limited group

extended-spectrum drugs

intermediate range of activity, usually newer “generations” of a drug that adds more activity than an earlier generation

broad-spectrum drugs

active against a wide range of pathogens, use can drastically alter the body’s normal flora & result in superinfections

minimum inhibitory concentration

lowest concentration of a drug that inhibits microbial growth

empiric therapy

use of antimicrobial drugs before the identification of the infecting microorganism & its drug susceptibility is determined

prophylactic therapy

prevention of infection (ex: sterilization of equipment, disinfectants to reduce pathogens, disinfection of skin & mucous membranes before invasive procedures)

antibiotic

substance produced by a microbe that can inhibit the growth or viability of another microbe

antibacterial

synthetic substance that can inhibit the growth or viability of a microbe

selective toxicity

chemotherapeutics is based on the principle of _______

selective toxicity

bacteria have different features than human cells that are necessary for bacterial survival; antibacterial drugs take advantage of these differences to inhibit or kill the bacteria w/o harming the patient

NRTIs, NNRTIs, protease inhibitors, fusion & entry inhibitors, integrase strand transfer inhibitors, combo regimens

what are the anti-retroviral drugs?

zidovudine, emtricitabine, lamivudine, tenofovir

what are the NRTIs?

efavirenz

what are the NNRTIs?

lopinavir

what are the protease inhibitors?

marviroc, ibalizumab-uiyk, enfuvirtide, fostemsavir

what are the fusion & entry inhibitors?

raltegravir

what are the integrase strand transfer inhibitors?

emtricitabine tenofovir, emtricitabine + tenofovir + efavirenze

what are the combo regimens for HIV?

interferon alfa-2b, peginterferon alfa-2a, peginterferon alfa-2b, lamivudine, tenofovir, ribavirin

what are the anti hep B&C drugs?

oseltamivir, baloxavir, amantadine

what are the anti-influenza drugs?

nirmatrelvir + ritonavir

what are the anti-COVID drugs?

zidovudine

• type: nucleoside-reverse transcriptase inhibitor

• indication: HIV

• MoA: competes w/ endogenous nucleotides → causing DNA chain termination → inhibiting HIV reverse transcriptase

• adverse effects:

  • HA

  • GI disturbances

  • bone marrow suppression

emtricitabine

• type: nucleoside-reverse transcriptase inhibitor

• indication: HIV

• MoA: competes w/ endogenous nucleotides → causing DNA chain termination → inhibiting HIV reverse transcriptase

• adverse effects:

  • HA

  • diarrhea

  • fatigue

  • depression

  • insomnia

lamivudine

• type: nucleoside-reverse transcriptase inhibitor

• indication: HIV, HBV

• MoA: competes w/ endogenous nucleotides → causing DNA chain termination → inhibiting HIV reverse transcriptase or HBV DNA polymerase

• adverse effects:

  • HA

  • dizziness

  • nausea

  • vomiting

  • diarrhea

• more resistance issues

tenofovir

• type: nucleoside-reverse transcriptase inhibitor

• indication: HIV, HBV

• MoA: competes w/ endogenous nucleotides → causing DNA chain termination → inhibiting HIV reverse transcriptase or HBV DNA polymerase

• adverse effects:

  • HA

  • GI disturbances

  • nephrotoxicity

• less resistance

efavirenz

• type: non-nucleoside reverse transcriptase inhibitors

• indication: HIV

• MoA: inhibition of HIV reverse transcriptase, which inhibits HIV DNA synthesis

• adverse effects:

  • dizziness

  • drowsiness

  • nightmares

  • depression

  • mania & psychosis

  • skin rash

lopinavir

• type: protease inhibitor

• indication: HIV

• MoA: inhibits protease which prevents the assembly of mature viral particles after they have been made

• adverse effects:

  • lipodystrophy

  • hyperlipidemia

  • insulin resistance & diabetes

  • hepatotoxicity

  • GI disturbances

• contraindications: can inhibit the metabolism of opioids, TCAs, & other drugs

marviroc

• type: fusion & entry inhibitor

• indication: HIV

• MoA: inhibits chemokine co-receptor 5

• adverse effects:

  • hypotension

ibalizumab-uiyk

• type: fusion & entry inhibitor

• indication: HIV

• MoA: CD4 directed post attachment HIV-1 inhibitor

• adverse effects:

  • diarrhea

  • nausea

  • rash

• immunogenicity is rare

enfuvirtide

• type: fusion & entry inhibitor

• indication: HIV

• MoA: binds HIV glycoprotein 41, blocking fusion

• adverse effects:

  • lymphadenopathy

fostemsavir

• type: fusion & entry inhibitor

• indication: HIV

• MoA: binds glycoprotein 160, blocking fusion

• adverse effects:

  • QT prolongation

raltegravir

• type: integrase strand transfer inhibitors

• indication: HIV

• MoA: prevent DNA strand transfer by binding divalent ions in integrase, inactivating it

• adverse effects:

  • diarrhea

  • nausea

  • rash

large, inert PEG

attachment of interferons to __________slows absorption, decreases clearance, provides higher & more prolonged blood concentration that allows 1x/week dosing

interferon alfa-2b, peginterferon alfa-2a, peginterferon alfa-2b

• type: interferons

• indication: HBV. HCV

• MoA: non-specific anti-viral & immunomodulating effects

• adverse effects:

  • flu-like symptoms

  • bone marrow suppression

  • depression

  • conjunctivitis

  • CNS toxicity (confusion, seizures)

  • retinal ischemia/retinopathy (cotton wool spots, hemorrhages)

  • macular edema

  • retinal vein/artery occlusions

  • CN3 palsy

  • AION

  • disc edema

ribavirin

• indication: HCV

• MoA: unknown

• adverse effects:

  • hemolytic anemia

  • flu-like symptoms

  • bone marrow suppression

  • depression

  • conjunctivitis

  • CNS toxicity (confusion, seizures)

  • retinal ischemia/retinopathy (cotton wool spots, hemorrhages)

  • macular edema

  • retinal vein/artery occlusions

  • CN3 palsy

  • AION

  • disc edema

• used in combo w/ other HCV drugs to boost efficacy

  • not easy to tolerate in combo though

oseltamivir

• indication: influenza A & B

• MoA: inhibit neuraminidase which inhibits the release of the virus from the host cell

• adverse effects:

  • nausea

  • Sevens-Johnson syndrome

  • abnormal behavior/delirium

• must be started w/in 72hrs of sx onset

• reduce sx by ~1day

• doesn’t reduce need for hospitalization or mortality

baloxavir

• indication: influenza A & B

• MoA: inhibits viral RNA polymerase which inhibits viral replication

• adverse effects:

  • nausea

  • abnormal behavior/delirium

• contraindications: dairy products, calcium-fortified beverages, cation-containing laxatives, or oral supplements

• must start w/in 48hr of sx

• reduces sx by ~1day

• more rapidly decreases amount of virus in respiratory secretions

amantadine

• indication: influenza A

• MoA: inhibits M2 protein on influenza A which prevents the uncoating of the viral nucleic acid, stopping the release of viral nucleic acid into the host cell

• adverse effects:

  • mydriasis

  • CV problems

  • nausea

  • hallucinations or psychotic behaviors

  • vivid dreams

• must be started w/in 48hr of sx

• lots of resistance

• not recommended anymore

nirmatrelvir + ritonavir

• type: protease inhibitors

• indication: COVID

• MoA: main drug inhibits Mpro (main protease of virus) & secondary drug slows the metabolism of the main drug

• adverse effects:

  • altered taste

  • diarrhea

  • HTN

  • muscle aches

  • abdominal pain

  • nausea

• reduces risk of hospitalization

• 5-day tx course

• rebound effect

rifampin

• type: anti-mycobacterial

• indication: active or latent TB

• MoA: deactivates RNA polymerase which inhibits microbial transcription

• adverse effects:

  • hepatitis

  • decreased platelets

  • drug-drug interactions

  • orange urine, sweat, tears (CL)

isoniazid

• type: anti-mycobacterial

• indication: active or latent TB

• MoA: inhibits mycolic acid in mycobacteria cell wall synthesis

• adverse effects:

  • hepatitis

  • peripheral neuropathy from vitamin B6 deficiency

  • rare optic neuropathy

pyrazinamide

• type: anti-mycobacterial

• indication: active TB

• MoA: unknown

ethambutol

• type: anti-mycobacterial

• indication: active TB

• MoA: inhibits arabinosyl transferase which inhibits cell wall synthesis

• adverse effects:

  • bilateral retrobulbar optic neuropathy

  • color vision loss

fluconazole, voriconazole, miconazole, clotrimazole, ketoconazole

list the azole anti-fungal drugs

amphotericin B, nystatin

list the polyene anti-fungal drugs

griseofulvin

list the stand alone anti-fungal drugs

miconazole, clotrimazole, ketoconazole

• type: broad-spectrum anti-fungal topicals

• MoA: inhibit ergosterol synthesis → disrupts cell membrane → fungus dies

• adverse effects:

  • well tolerated

fluconazole

• type: broad-spectrum anti-fungals

• MoA: inhibit ergosterol synthesis → disrupts cell membrane → fungus dies

• adverse effects:

  • liver toxicity

• widest therapeutic index

voriconazole

• type: broad-spectrum anti-fungals

• MoA: inhibit ergosterol synthesis → disrupts cell membrane → fungus dies

• adverse effects:

  • photophobia

  • idiopathic intracranial HTN → papilledema

  • color vision changes

  • liver toxicity

amphotericin B

• type: polyene anti-fungal

• indication: life-threatening mycotic infections

• MoA: bind ergosterols in fungal cell membrane → causes pores in cell membrane → fungus dies

• adverse effects:

  • high renal toxicity

  • bone marrow suppression

  • liver toxicity

  • chills

  • fever

  • HA

  • nausea

  • vomiting

• VERY toxic

• IV admin

nystatin

• type: polyene anti-fungal

• indication: candida oral thrush, vaginal yeast infections

• MoA: bind ergosterols in fungal cell membrane → causes pores to form → fungus dies

• adverse effects:

  • well tolerated

• topical

• not used in eye

griseofulvin

• indication: dermatophyte infections

• MoA: binds microtubules → interferes w/ mitosis

• adverse effects:

  • well tolerated

• narrow spectrum

• oral

• requires long tx

• high failure rates

neurocysticercosis

• parasitic worm infects brain, eyes, muscle

• can contract from consuming or handling raw pork

malaria

plasmodium parasite via mosquitos

toxoplasma gondii protozoan parasite

can contract from:

• consuming or handling raw meat containing tissue cysts

• drinking water contaminated with oocysts shed by cats

• congenital from mother to fetus

albendazole

• type: anti-parasitic

• indication: neurocysticercosis

• MoA: binds beta-tubulin → prevents microtubule assembly → cannot absorb glucose → parasite dies

• adverse effects:

  • retinal inflammatory damage caused by the death of the parasite

• must weigh the need for the therapy with the adverse effect of the therapy on the retina

metronidazole

• indication: trichomoniasis STI, intestinal amoebas, parasites, anaerobic bacteria, acne rosacea

• MoA: disrupts microbe DNA synthesis

• adverse effects:

  • dry mouth

  • metallic taste

  • nausea & vomiting if taken w/ alcohol

  • irritation of skin & eyes/tearing

chloroquine, hydroxychloroquine

• indication: malaria

• MoA: builds up heme which is toxic to plasmodium parasite

• adverse effects:

  • whorl keratopathy

  • Bull’s eye maculopathy

  • central VF defects

  • color vision changes

gamma-hexachlorocyclohexane

• indication: head lice & scabies

• MoA: organochloride absorbed through the exoskeleton → insect death

• adverse effects:

  • neurotoxicity

• not used around eyes

• not 1st line recommendation anymore

anti-septics

surface acting agents applied to the body

disinfectants

surface acting agents applied to non-living surfaces

povidone-iodine, chlorhexidine, chlorhexidine gluconate 1% & ethyl alcohol 61%, polyhexamethylene biguanide, hydrogen peroxide, ethanol or isopropyl alcohols 70%, bleach

list the antiseptics/disinfectants