Exam 2 Drugs Flashcards
Entecavir (NRTI)
A nucleoside analog with selective and potent activity against Hep B, including Lamivudine-resistant HBV. Most POTENT inhibitor. Slows progression of HBV, and improves liver inflammation and fibrosis that occurs.
SE: diarrhea, headache, fatigue, vomiting, anorexia, chills, upset stomach
Tenofovir PMPA (NtRTI)
Acyclic nucleoside phosphonate Diester analog
-available as an ester prodrug
Inhibits viral reverse transcriptase and acts as a DNA chain terminator
*Inhibits both HIV and HBV Replication
-Acts against Lamivudine-resistant HBV
Adefovir (NtRTI)
A nucleoTide analog used for the tx of HBV infections.
Adefovir diphosphate replaces deoxyadenosine monophosphate in HBV DNA, resulting in DNA chain termination and thus inhibition of DNA replication.
-Slows the progression and improves liver function
-Acts against Lamivudine-resistant HBV
Interferon alfa-2a, Pegylated interferon alfa-2a or alfa-2b
Interferon alfa-2a or 2b acts similarly to endogenous IFN-a
-leads to antiviral, antiproliferative, and immunomodulatory effects
Inhibits viral replication and cleaves ssRNA
AE: flu-like sx, hepatotoxicity, increased risk of infections, and exacerbation of psychiatric conditions
PEGylation: addition of poly(ethylene glycol) increases resistance to proteolytic degradation, increases water solubility, and reduces their antigenicity
True Bacteria
Staph. Aureus
E. Coli
Filamentous Bacteria
Mycobacterium Tuberculosis
M. Leprae
Spirochete
Treponema Pallidum (Syphilis)
Mycoplasma
Mycoplasma Pneumonia
Rickettsia
Rickettsia Prowazekii (Typhus)
Chlamydia
Chlamydia trachomatis (can cause many forms of diseases: sepsis) (blindness)
Colonization
The presence of bacteria that are NOT causing disease
Siderophores
Iron Receptors (bacteria must have iron to multiply)
Can bacterial proliferation rates surpass the protective response?
Yes
Exotoxins
Enzymes released during growth causing specific responses.
Immunogenic (anti-toxin production)
Endotoxins
Lipopolysaccharides contained in the cell walls of Gram (-) organisms.
Pyrogenic Effects
Bacteremia or Septicemia
Presence of bacteria in the blood due to a failure of the body’s defense mechanisms
Usually caused by gram (-) organisms
Bacterial Sepsis
Associated w/ ARDS, DIC, Hemodynamics effects, and renal failure
Gram (+) Bacterial Sepsis
Staphylococcus Aureus
Streptococcus Pneumoniae
S. Aureus is associated w/ an overall mortality rate ranging b/ 10-30%
Gram (-) Bacterial Sepsis
E. Coli
Klebsiella species
Pseudomonas Aeruginosa
-Proeus species, P. Aeruginosa and Acinetobacter species are associated w/ prior antibiotic exposure
Respiratory Infections: Pneumonia
-Community Acquired
Pneumococcal pneumonia (streptococcus pneumonia) Mycoplasma pneumonia in the young
Respiratory Infections: Pneumonia
-Nosocomial Infections (ICU, Ventilators)
Staph. Aureus, Klebsiella pneumonia, P. Aeruginosa
Respiratory Infections: Pneumonia
-Immunocompromised patients
P. Jiroveci
Respiratory Infections: Pneumonia
-Portal Of Entry
Aspiration of oropharyngeal secretions
Inhalation of aerosols
From blood bacteremia
Hepatitis
Inflammation of the liver
Acute Viral Hepatitis
Inflammation of the liver that begins suddenly and lasts a few weeks
Chronic Viral Hepatitis
Inflammation of the liver that lasts at least 6 months
Cirrhosis
Irreversible inflammatory disease of the liver, a leading cause of death
Acute Infection Sequence of Viral Hepatitis
Incubation Period
Prodromal (pre-icteric) Phase: wt loss, fatigue, anorexia, vomiting, and low grade fever
Icteric (Jaundice) Phase: Lasts 2-6 weeks
-hepatomegaly, dark urine, clay colored stools, itching, jaundice as bilirubin builds up in the blood
Recovery Phase: resolution of jaundice
Fulminant HBV
Results from impairment or necrosis of hepatocytes
Hepatitis B Virus
DNA Hepadnaviridae HBsAG - Diagnosis Severe and Chronic Transmission: sexual, Injection-drug use, Perinatal Incubation: 60-180d PX: Hygiene, Vaccine Chronicity: YES Liver Cancer: YES
Hepatitis C Virus
RNA
Flaviviridae Family
Anti-HCV= diagnosis
Mild to severe
Transmission = injection-drug use, Sexual
Incubation: 35-60 days
Hygiene, Blood screen, IFN-a : prophylaxis
Chronicity: YES Liver Cancer: YES
HEP B VIRUS
dsDNA
Chronic HBV carriers- worldwide reservoir of infection
Cirrhosis and Hepatocellular Carcinoma = Complications
Vaccine is based on Australian Antigen
HBV can cause fulminant hepatitis, and irreversible tissue necrosis which requires a liver transplant
Has infected 1/3 of population
360 million chronic carriers
HEP C VIRUS
ssRNA
Complications = Chronic infection, Cirrhosis, and Carcinoma
Hep B/C Complications
Cirrhosis: scarring of the liver marked increase in fibrous connective tissue, resulting in a firm, modular, distorted liver
Decompensated Cirrhosis: increase in portal HTN, Ascites (fluid accumulation in peritoneum), splenomegaly, encephalopathy, Jaundice
Respiratory Infections: TB or Mycobacterium Avium Complex (MAC)
TB has the highest death toll of any infectious pathogen
POE: airborne transmission
TB Detection: Tubercle formation, Caseous necrosis, (+) skin test
Respiratory Infections: Acute Bronchitis
Acute infection or inflammation of the airways or bronchi
Commonly viral pathogen (can become bacterial)
Causes similar sx to pneumonia but does NOT demonstrate pulmonary consolidation and chest infiltrates
Respiratory Infections: Acute Epiglottitis
More common in Children
Severe, rapidly progressive, life-threatening infection of the epiglottis and surrounding area
-usually caused by Haemophilus influenzae type B
Manifestations: high fever, sore throat, inspiratory stridor, and severe respiratory distress
Tx: Emergency airway and antibiotics
UTI
Inflammation of the urinary epithelium following invasion and colonization by some pathogen within the urinary tract
- complicated
- uncomplicated
- persistent
UTI Pathogens
E. Coli
Staphylococcus Saprophyticus
Enterobacter spp
Cystitis
Inflammation of the bladder
Manifestations: frequency, dysuria, urgency, and lower abdominal and/or Supra pubic pain
TX: antimicrobial therapy, increased fluid intake, avoidance of bladder irritants, and urinary analgesics
GI Infection: Shigellosis
Seen with dysentery
-Causes shigellosis: binds epithelium of GI tract and causes it to die off. Can cause a severe form of diarrhea. (Fecal-oral transmission)
GI Infection: Campylobacter Enteritis
By C. Jejuni (Fungus)
-Vibrio cholera: will lose close to 1L/ hour of fluid
E. Coli (O107): makes an exotoxin
Bacterial STD: Campylobacter Jejuni
Disease: Campulobacter enteritis
Bacterial STD: Chlamydia trachomatis
Disease: Urogenital infections
Bacterial STD: Neiserria Gonorrhoeae
Disease: Gonorrhea
Bacterial STD: Shigella
Disease: Shigellosis
Bacterial STD: Treponema pallidum
Disease: Syphilis
Gonorrhea
Caused by microorganisms of the species Neisseria Gonorrheae (aerobic, non-spore-forming, gram -, diplococcus (round))
-presence of pili helps the microorganisms attach themselves to the epithelial cells of mucous membrane
Infections can result in: disseminated gonococcal infection (CGI) and Perihepatits, as well as ophthalmia neonatorum.
Transmission: requires contact of epithelial surfaces, Gonorrhea also crosses amniotic membranes. Humans are the only natural hosts
Syphilis: appearance of a chancre (boil)
Can spread through the blood as well as the lymph: Secondary
Cardiovascular syphilis, Neurosyphilis: Tertiary
-Latent syphilis: asymptomatic but potential recurrent infections
-Congenital (from mother to fetus)
Chlamydial Infections
Trachoma-a leading cause of preventable infectious blindness
Nongonococcal or nonspecific urethritis: nonreportable STI, Syndrome caused by most commonly by Chlamydia Trachomatis
-Trichomonas vaginalis, herpes simplex virus, ureaplasma urealyticum and mycoplasma
Staphylococcus Aureus Infections
Commensal bacteria and opportunistic pathogen
Superantigens: enterotoxin and toxic shock syndrome Toxin 1, causes immune overactivation –> toxic shock and food poisoning
Children: impetigo and Staph. Scalded-skin syndrome
Hospital: MRSA is common
Most common cause of food borne outbreaks
Can cause SOFT PAINS: Skin infections, Osteomyelitis, Food poisoning, Toxic shock syndrome, Pneumonia, Acute endocarditis, Infective arthritis, Necrotizing fasciitis, and Sepsis
B-Lactams
Penicillins and B-Lactamase Inhibitors
Cephalosporins & Cephamycins
Carbapenems
Monobactams
** ALL are active against non-B-Lactamase-producing gram - and gram + bacteria
ALL work in the same way/ Time-dependent killing
ALL can cause hypersensitivity reactions or seizures at very high doses
NONE are active against MRSA
B-Lactams: Penicillins
Natural Penicillins (Penicillin G): Short t1/2, tx neurosyphilis Antistaphylococcal Penicillin (Nafcillin): resistant to staphylococcal B-lactamases, Hepatic CL, Tx MSSA Extended-Spectrum Penicillins (Ampicillin): aminopenicillins better than others against gram (-), Antipseudomonal Penicillins
Clavulanic Acid, Sulbactam, & Tazobactam
Inhibit bacterial B-Lactamases
Protect hydrolyzible penicillins from inactivation
Extends the spectrum of the penicillin to strains that would otherwise inactivate it
Predicted on the assumption that the inhibitor is active against the B-lactamase that is produced
Cephalosporin and Cephamycins
More resistant to bacterial B-lactamases than penicillins
First generation: do NOT cross BBB, used in hospitals, good antistaph
Second Generation: Do NOT cross BBB, have extended gram (-) coverage compared to 1st generation, good for anaerobes in upper respiratory infections, community pneumonia, and gonorrhea
Third and Fourth Generations: some cross BBB, expanded gram (-) coverage compared to both 1st and 2nd generations, good for P. Aeruginosa, Enterobacteriacaea, S. aureus, and S. pneumonia
AE: allergy, Methylthiotetrazole containing Cephamycins can cause bleeding and disulfiram-like reactions
Carbapenems: Doripenem, Ertapenem, Imipenem, & Meropenem
Broadest Spectrum ABX
NOT active against Klebsiella Pneumonia Carbapenemase-producing strains
-Imipenem administered w/ an inhibitor of renal dehydropeptidase, Cilastatin (never administered alone)
Good for nosocomial infections and B-lactamase producing GN strains
B-Lactam Monobactam: Aztreonam
Limited to aerobic gram (-) rods (including P. Aeruginosa)
No activity against gram + bacteria or anaerobes
Glycopeptide: Vancomycin
Active ONLY against gram + bacteria
Water soluble and stable. Bind to d-Ala-d-Ala chains on the peptidoglycan wall preventing elongation
**Drug of choice for MRSA
Can cause red man syndrome due to infusion site rxns (Itching)
Cyclic Lipopeptide: Daptomycin
Binds to the cell wall synthesis by inhibiting the synthesis of the cell wall building blocks
**punches holes in the cell wall
Effective against MRSA and VRE
Can cause allergic pneumonitis
Fosfomycin
Inhibits bacterial wall synthesis by inhibiting the synthesis of the cell wall building blocks
Primarily used for uncomplicated UTI
Same applications as Nitrofurantoin
Tetracyclines: Tetracycline, Doxycycline, Tigecycline
Good for Rickettsia, Mycoplasma, Chlamydia, some spirochetes, & Plasmodium
Resistance: impaired influx or increased effluent, Prod of proteins that interfere w/ tetracycline, Enzymatic inactivation
Macrolides: Clarithromycins, Azithromycin, Erthyromycin
Used in outpatient settings for respiratory infections, Mycobacterium Avium, Chlamydia
Needs to be checked for interactions via P450
**resistance: Impaired influx or increased efflux, Prod of esterases that hydrolyze macrolides, lincosamides, and stretogramin, Modification of the ribosomal binding site by mutation or by macrolide-inducible or constitutive methylase
Lincosamides: Clindamycin
Derivative of lincomycin
Good for skin and soft-tissue infections caused by streptococci and staphylococci
Resistance: same as macrolides
Stretogramins: Quinupristin-Dalfopristin 30:70 ratio
Rapidly bactericidal for most susceptible organisms: MSSA, MRSA, and VRE
NOT active against: Enterococcus Faecalis, or Faecium
Resistance: same as macrolides
Oxazolidinones: Linezolid
Inhibits protein synthesis by preventing formation of the ribosome complex
Good for susceptible organisms MSSA, MRSA, VRE, & Enterococcus faecium
AE: myelosuppression or thrombocytopenia
Resistance: Different from the other classes
Aminoglycosides
Irreversible inhibitors of protein synthesis
- blocks the initiation complex
- miscoding of amino acids
- block of translocation on mRNA
Amikacin, Gentamicin, Tobramycin, Streptomycin
Concentration-dependent killing
Synergistic killing w/ cell wall inhibitors in endocarditis
Good for: gram (-) pathogens, Mycobacteria
AE: nephro and Ototoxicity
Resistance: production of an enzyme which inactivates the aminoglycoside
Inhibitors of Folate Synthesis: Trimethoprim/ Sulfonamide
Sulfonamides block dihydropteroate synthase
Trimethoprim (pyrimidine) blocks dihydrofolate reductase
Used as a combo (TMP/SMX): drug of choice for infections such as Pneumocystis Jiroveci, Toxoplasmosis
Good for uncontrolled UTI
AE: hematopoietic disturbances, interacts w/ Warfarin
Inhibitors of DNA synthesis: Fluoroquinolones- Ciprofloxacin, Levofloxacin, Moxifloxacin, and Gemifloxacin
Synthetic fluoridated analogs of nalidixic acid
Blocks bacterial DNA synthesis by inhibiting bacterial topoisomerase II (DNA gyrase) and topoisomerase IV
Broad activity for: UTI, Upper and Lower RTI (levo), bacterial Diarrhea (foodbourne illnesses)
AE: prolonged QTc, Neuropathy, Cartilage degradation, Achilles’ tendon rupture, should be avoided during pregnancy
Resistance: altered targets, active efflux, bacterial proteins which protect DNA gyrase or which inactivated quinolones
Antimycobacterial Drugs: Isoniazid
Inhibits the synthesis of mycolic acids (precursors of mycobacterium cell wall)
Antimycobacterial Drugs: Rifampin
A derivative of Rifamycin inhibits the mycobacterial RNA polymerase
Antimycobacterial Drugs:
Also includes Fluoroquinolones, Macrolides, and Streptomycin
AE: isoniazid-induced hepatitis and peripheral neuropathy
-rifampin colors secretions orange-red (harmless)
Resistance: drug unable to penetrate cell wall, Low pH renders drug inactive, drug exported from cell before it reaches target, mutations in DNA repair genes lead to multiple drug resistance, alteration of target protein structure prevents drug recognition
Fungal Infections
Eukaryotic Cells with rigid walls
Can grow as: molds, yeasts, or both (dimorphic)
Resistance to bacterial wall inhibitors
Pathogenicity: adapts to host environment, Suppresses the immune defenses
Mycoses
Diseases caused by fungi
Dermatophytes
Diseases they produce are called tine as (ringworm)
-tinea capitis, tinea pedis, and tinea cururis (groin infection)
Candida Associated Disease
Most common fungal pathogen
Common in nosocomial infections
Commensal in skin, GI, vagina
Opportunistic Pathogen due to changes in environment
-ABX is can cause oropharyngeal (thrush) and vulvovaginal infections (vaginitis)
-immunocompromised pts (HIV, hematologic cancers) present w/ disseminated infections
-medical devices can lead to invasive candidiasis
Candidemia a major cause of fungal sepsis and septic shock (hypotension, tachycardia, DIC)
Antifungal Drugs: Polyene Antifungal: Amphotericin B
Binds to ergosterol in the fungal cell membrane forming pores
Broad spectrum with good activity against candida, Cryptococcus
AE: infusion-related rxns, Nephrotoxicity
Very poorly absorbed orally
Nucleoside Analog (Antifungal): Flucytosine (5-FC)
Blocks DNA and RNA polymerization (blocks further replication of DNA)
Converted intracellularly first to 5-FU and then to 5-Fluorodeoxyuridine monophophate and fluorouridine triphosphate, which inhibits DNA and RNA synthesis
Cryptococcus associated meningitis
AE: bone marrow toxicity w/ anemia, leukopenia, and thrombocytopenia, as well as lactic acidosis
Imidazole: Ketoconazole
Triazoles: Fluconazole, Itraconazole, Voriconazole, Posaconazole
Azoles block ergosterol synthesis from lanosterol
Broad spectrum w/ good activity against Candida, C. Neoformans, Endemic mycoses
The pharmacology of each of the azoles is unique, some are used topically
Echinocandins: Caspofungin, Micafungin, Andulafungin
Inhibits fungal wall synthesis, good for invasive candidiasis
Griseofulvin
Oral fungistatic used for dermatophytosis (invasive-penetrates deeper into the skin)
Terbinafine
Oral and topical fungicidal that blocks ergosterol synthesis at an earlier step than azoles. (Blocks squalene synthesis)
Nystatin
Polyene macrolide much like amphotericin B
It’s too toxic for parenteral administration and is only used topically
Protozoan Infections
Cryptosporidium –> Crytosporidiosis
Giardia Lamblia –> diarrheal syndrome (fecal contam water)
Entamoeba Histolytica –> Amebiasis (fecal contam water)
Plasmodium –> Malaria (mosquito anopheles)- vector borne
Leishmania –> Leishmaniasis (sand flies)
Toxoplasma –> Toxoplasmosis
Malaria
Protist, can produce asexually or sexually
Plasmodium species - through blood can infect liver)
Fever and anemai, splenomegaly RBC get destroyed
evolution of Sickle cell trait
-when have the HbAA/HbAS forms, they are more resistant to Malaria
GI Infections: Giardiasis (protozoan)
Most common causes of waterborne illnesses
Caused by Giardia Lamblia
Amebiasis (GI infections-Protozoan)
GI bleeding and hemorrhage, can also cause liver disease and fatality)
- caused by Entamoeba Histolytica
- most imp parasitic disease
- Dysentery as a result of toxin on colonic epithelium
- can also cause amebic liver disease
Sexually Transmitted Parasitic Infections: Trichomoniasis
Caused by Trichomonas vaginalis
-anaerobic, unicellular, flagellated, parasitic protozoan
Adheres to and damages squamous epithelial cells
-urethra, vagina, and Skene and Bartholin glands
Accounts for 25% of infectious vaginitis cases
Often coexists w/ gonorrhea
Presence confirmed by microscopic examination of vaginal secretions or urine
Antifungal Drugs: antimalarial drugs
Quinolones, Atovaquone, Artemisinins, Doxycyline
-employed prophylactically and as definite therapy
Quinolines: Chloroquine, Mefloquine, Quinine, Primaqine
Oldest and highly effective antimalarial blood schizonticide (quinine from the bark of the cinchona tree)
Primaquine also has gametocide activity for all Plasmodium species and is also used to tx P. Jiroveci
MOA: not clear how they work but they might affect the ability of the parasites to catabolize hemoglobin
AE: hematologic abnormalities, hemolysis, prolonged QTc, hypotension
-quinine can cause cinchonism: tinnitus, headache, nausea, dizziness, flushing, and visual disturbances
Artemisinin: Artesunate
A sesquiterpene lactose endoperoxide
Atovaquone
Used in combo w/ proguanil as quinone-folate antagonist combination for malaria
-also used for mild to moderate P. Jiroveci pneumonia
Amebicides: Metronidazole, Tinidazole
Amebiasis is infection w/ Entamoeba histolytica
Kill trophozoites but not cysts by causing DNA damage
Good for anaerobes including Clostridium
For protests: Amebiasis, Giardiasis, and Trichomoniasis
AE: nausea, dry mouth, metallic taste
Metronidazole: is amebicidal, Bacteriacidal, and Trichomonicidal
Pentamidine
Used in African Trypanosomiasis-sleeping sickness and Leishmaniasis
Also used for pneumocystosis caused by Pneumoscystis Jiroveci
-Highly toxic
Parasitic Infections: Nematodes (roundworms)
Hookworm disease (ancylostoma duodenale or necator americanus)
- -> ascariasis
- -> enterobiasis
- -> filariasis
Parasitic Infections: Flatworms (platyhelminths)
- -> Neuro Cysticercosis (Tania solium)
- -> Schistosomiasis (schistosoma-blood flukes)
Parasitic Infections: Lice
- -> Pediculus humans capitis (head louse)
- -> Pediculus humanus corporis (body louse)
- -> pthirus pubis (“crabs” louse, pubic louse)
Parasitic Infections: Scabies
–> Sarcoptes Scabiei
Helminth Infections
Parasitic worms infect more than 3 billion people worldwide
Skin infections: Scabies
Caused by the adult female itch mite, Sarcoptes Scabiei
Transmission: requires prolonged close skin-to-skin contact
-typically occurs b/ family members or sexual partners
Burrows through the horny layer of the stratum/day
-new larval forms appear in about 10 days
Classic sx is intense pruritus
Antihelminthic Drugs: Albendazole
Inhibits the polymerization of microtubules
Used in: Intestinal Parasites- cysticercosis (T. Solium), ascariasis, enterobiasis (pinworms), Hydatid disease (echinococcus via dogs), Neurocysticercosis
Antihelminth Drugs: Ivermectin
Caused paralysis by intensifying (GABA)-mediated transmission of signals in peripheral nerves
Used in: Onchocerciasis: River blindness (onchocerca volvulus) affects 17-25 million people
-microfilaria
-and ectoparasties such as scabies
