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153 Cards in this Set

  • Front
  • Back
What antibacterial were discovered in 1910?
-salvarsan, an arsenic derivative effective against syphilis
-by Erlich
What antimicrobial drugs were discovered in the 1930's
-sulfoamides by Domagk
What antimicrobial was discovered in 1928?
-first antibiotic discovered by Fleming
What was discovered in 1940?
1st clinical trials of penicillin by Florey, Chain
How can selective toxicities be realized?
-attacking targets unique to the pathogen cell that are not present in the host
-attacking targets in the pathogen cell that are similar but not identical to those in the host
-attacking targets in the pathogen cell that are shared by the host, but that vary in importance between pathogen and host
Who found the 1st microbe?
-Hook-dutch scientist, made first microscope
What is selective toxicity?
-microbes are inhibited selectivity without damage to the host cell
-ideally no patient harm and lethal to antimicroorganism
What are bactericidal effects of the antibiotics?
-will kill microorganisms without help from host's immune system
What are bacterialstatic effects of the antibiotics?
-inhibit bacterial cellular replication but will not kill
-must have healthy immune system to kill microbe
What are antibiotics?
-chemicals produced by microorganisms
-have capacity to kill or inhibit the growth of microrganisms
What are 3 factors that prevent infection?
-environmental factors
-vaccination
-education
What are antimicrobial drugs classification based on?
-mechanism of action
-chemical structure
-specturm of activity
Whata re the various mechanisms of actions for antimicrobial drugs?
-cell wall synthesis
-cell membrane function
-nucleic acid synthesis and replication
-protein sysntheis
-synthesis of central metabolites
What are the various chemical structures of antimicrobial drugs?
-B-lactam (penicillins, cephalosporins, carbapenems, and monobactams)
-flouroquinolones (ciprofloxacin)
-sulfoamides (sulfadiazine)
-aminoglycosides (gentamicine)
-macrolides (erythromycin)
Whata re various spectrum of activities for antimicrobial drugs?
-gram-positive cocci
-gram-negatives
-anaerobes
-pseudomonas
-fungi
-viruses
-parasites
What are the main characteristsics of preservatives?
-used to prevent the overgrowth of bacteria and fungi in pharmaceutical products, laboratory asera and reagents, cosmetic products, and contact lenses
-should not be irritant or toxic to tissues to which they will be applied
-must be effective
-must have sufficent solubility and stability
What are the various biological properties of antimicrobial drugs?
-antibiotic-produced by microorganism
-semi-synthetic drugs-derrivatives of AB-slightly modified
-synthetic drugs- organic chemicals, nearly all antiviral drugs
What are commonly used preservative agents?
-benzoic acid and salts
-parabens
-sorbic acid and salts
-benzyl alcohol
Why are benzoic acid and salts considered preservative agents?
-has good solubility
-occur naturally in many plant and animal speciues
-slightly soluble in water but more soluble in alcohol and otger polar organic solvents
-used in preservative in food, drugs, and personal products
-sodium benzoate is used preferably as one of the principal preservatives in foods and beverages (but in limited concentration)
How are parabens considered a preservative agent?
-commonly used in cosmetics
-alkyl esters of p-hydroxybenzoic acid
-common names are methylparaben, ethylparaben, propylparaben, and butylparaben
-used as antifungal preservatives
-mimic estrogen activity in human body
-drive breast cancer in deoderant
How is sorbic acid and salts considered a preservative?
-salt preferred over acid due to solubility
-poisioning can occur if too high of a concnetration
-used as an antifungal preservative
How is benzyl alcohol considered a preservative?
-prohibited in children since 1982 and allergy patients
-very toxic (can casue hypotension and vasodilation with major adverse effects
-knowna s phenylcarbinol and pheynl methanol
-used as a bacteriostatic preservatifve in parenteral medications
What are the two types of germicides?
-disinfectants
-antiseptics
What are disinfectants?
- for non-living tissues--> surfaces
-strong chemical agents that inhibit or kill microorganisms
-prevent infection by reducing the number of potentially infective organisms by killing,removing, or diluting them
What are antiseptics?
-can be used on liviing tissue
-disinfecting agents with low toxicity fro host cells
-can be used directly on the skin, mucous membranes or wounds
What are 3 classes of disinfectants?
high level (more powerful, destroy microbacterial, fungi, other bacteria, but not spores)
-intermerdiate level (most viruses and fungi never spores)
-low level (no mycobacteri, wiull kill enveloped virues such as HIV)
What is antisepsis?
-application of an agent to living tissue for the purpose of preventing infection
What is decontamination?
-destruction or marked reduction in number or activity of microorganisms
What is sanitation?
-reduction of microbial load on an inanimate surface to a level considered acceptable for oublic health pruposes
What is sterlization?
-a process intended to kill or remove all types of microroganisms, including spores, and usually including viruses with an acceptable low porbability of survival
What is pasteruization?
-a process that kills nonsporulating microorganisms byt hot water or steam at 65-100 degrees C
What are commonly used anti-infective agents?
-alcohol and related compounds
-phenols and their derivative
-peroxygen agents (hydrogen peroxide)
-halogen containign compounds
-cationic surfactants
How is alcohol and related compounds a commonly used anti-infective agent? related compounds? disadvantages?
-ethanol and isopropanol are most frequently used
-killing vegetative bacteria, mycobacterium tuberculosis, fungi, and inactivating lipophilic viruses
-bactericidal at 60-80% concentration
-related compounds are formaldehyde and glutaraldehyde
-expensive
-evaporate quickly
-needs time to work
-causes irritation
How are phenols and their derivatives common used anti-infective agents?
-not effective for spores or non-envelope viruses
-phenol itself is no longer uses becuase of corrosive effect on tissue, it;s toxicity when absorbed is carcinogenic
-mixtures of phenolic deriuvatvives are often used
-bactericidal and fungicidal, disrupt cell walls and membrane, and inactivates enzymes
-used for hard surface decontamination in hopsitals and laboratories
How is hydrogen peroxide a commonly used anti-infective agent?
-have high killing activity against bacteria, sporesm viruses, and fungi
-not toxic and do not injure environment
-cheap and very effective
-fast working and not very stable
What halogen containign compounds are commonly used anti-infective agents?
-iodine
-iodophors
-chlorine
How is iodine a commonly used anti-infective agent?
-oldest and quickest
-most active antiseptic for intact skin
-used in various solutions: 2%-5%
How are iodophors a commonly used anti-infective agent?
-complex of iodine with polyvinyl pyrolidone
-kill vegetative bacteria, mycobacteria, fungi, and lipid-containing viruses
-used as antiseptics adn disinfectants
How is chlorine a commonly used anti-infective agent?
-universal disinfectant
-very cheap adn fast acting
-5.25% sodium hypochlorite is rtypical formulation for household bleach
-forms hypochlorous acid in water
-chlorine dioxide and chloramine T are alternative compounds
What are considered cationic surfactants for anti-infecting agents?
--soluble in water and exhibit surface active properties
-each molecule has a hydrophilic head and hydrophilic tail
-disrupt microorganisms cell processes and used as a germicide and sanitizer
-include dyes, mercury compounds, and nitrofuran derivatives
What is the gram stain?
-fast and accurate process
-frequently used
-the different stains are ther result of differences in the cell walls of gram-positive and gram negative bacteria
What are common sites of invasion for gram-positive bacteria?
-skin (wounds, surgical sites, indwelling catheters), throat, lungs (pneumonia and adult bacterial meningitis)
Whata re common sites of invasion for gram-negative bacteria?
-urinary tract, lungs (pneumonia), CNS (meningitis), sexually transmitted diseases (gonorrhea)
What are gram positive bacteria?
-have 2 layers:
--inner cytoiplasmic membrane
--outer thick peptidoglycan layer (60-100%)
-low lipid content
-no porin channel
-vulnerable to lysozyme and penicillin attack
-has endotoxins
-peptidoglycan doesn't block the diffusion fo small molcules such as antibiotics
Whata re gram negative bacteria?
-has 3 layers:
--inner cytoplasmic membrane
--thin peptidoglycan layer (5-10%)
--outer membrane with lipopolysaccharide
-high lipid content
-porin channel
-resistant to lysozyme and penicillin attack
What are mycobacteria?
-weakly gram-positive by acid fast stain (tuberculosis and leprosy)
Whata re bacterial cell wall inhibitors?
-two important classes of antibiotics in this group are the B-lactams and glycopeptides
-prevent bacterial cell wall synthesis or repair of cell wall
-bacterialcidal
have selective toxicity
What is the mechanisms of action of bacterial cell wall inhibitors?
-alanine added to CHO-tripeptide--> "T" shapped cell wall precursor (D-cycloserine)
-precursor transported across plasma membrane by carrier (vancomycin)
-carrier recycled back into cell to carry other precursors (bacitracin)
-precursor linked to existing cell wall by transpeptidase (penicillins, cephalosporins)
What are B-lactams of cell wall inhibitors?
-include penicillins, cephalosporins, the monobactams, and the carbapenems
-all B-lactams have a beta-lactam ring (key to inhibition process)
What are the penicillins of cell wall inhibition?
-to be effective the beta-lactams must penetrate the cell layers, keep its beta-lactam ring intact, bind to the transpeptidase
-antibiotic resistance is major problem in the treatment of the bacterial infections (B-lactamase activity, mutations, impaired penetration of drug, efflux)
-can casue anaphylactic reaction (loos of ability to maintain blood pressure)
-include penicillin G, penicillin V, methicillin, nafcillin, and isoxazolyl penicllins (oxacillin, cloxacillin, an dcicloxacillin), ampicillin, amoxicillin, carbencillin, piperacillin, ticaracillin, a nd mezlocillin
What is penicillin G?
-given by IM or IV
-sensitive to beta lactamase
What is peniciilin V?
-oral form of penicillin
-acid stable
-still used in pneumonia caused by streptococcus pneumoniae
What is methicillin, nafcillin, and isoxazolyl penicillins (oxacillin, cloxacillin, and dicloxicillin)?
-semi-synthetic, p[enicillinase-resistant penicillins
-used for gram-positive bacteria
-methicilin, nafcillin, and oxacillin given by IV
-cloxacillin, adn dicloxacillin is given oral
What is ampicillin and amoxicillin?
-haeva broad spectrum of action but are B-lactamase sensitive
-use "amp-gent" combo which is IV ampicillin and aminoglycosides (gentamicin)
What are carbencillin, piperacillin, ticarcillin, and mezlocillin?
-sensitive to penicillinases
What are cephalosporins?
-5-10% of patients with allergy to penicillin also ahve reaction to cephalosporin
-more resitant to beta-lactamases than penicllins
-MRSA is resistant to all cephalosporins
-include dirst and second generation
Whata re first generation cephalosporins?
-cefazolin, cephalexin, cefadroxil, cepharadine, cephapirin, and cephalothin
-excellant gram-positive coverage
-excellant for skin infection
-beta-lactamase sensitive
What are second generation cephalosporins?
-cefuroxime, cefotetan, cefoxitin, cefamandole, cefaclor, cefmetazole, cefonicin, cefprozil, loracarbef, and cefdinir
-have broader gram-negative coverage
-generalyl more resistant to B-lactamase
What are the third generation cephalosporins and characteristics?
-ceftazidine, ceftriazone, ceftizoxime, cefotaxime, cefixime, cefoperazone, cefpodozine, and ceftibuten
-have expanded gram-negative coverage
-used to treat a wide variety of serious infections when other drugs fail
-ceftriaxone is an excellant choice for meningitis (penetrates into cerebralspinal fluid)
What is the fourth generation of cephalosporins?
-cefepime
-more resistant to B-lactamases
-clinical role is similar to that of third-generation
What is Aztreonam as an antibacterial?
-monobactam
-for gram-negative bacteria only
-minimal cross-reactivity with penicillins
-crosses blood-brain barrier, joints
-B-lactamase resistant
-good combo with vancomycin and clindamycin for braod-spectrum coverage
What is imipenem and meropenem as antibacterials?
-carbapenems
-haev the broadest spectrum in coverage
-B-lactamaase resistant, including ESBL's (extended spectrum beta lactamases)
-MRSA is resistant to carbapenems
-given with Cilastatin (kidney dihydropeptidase inhibitor)
What is vancomycin as an antibacterial?
-glycopeptides
-does not contain a B-lactam ring (therefore B-lactamase resistant)
-binds to cell wall precursor (pentapeptide, at a step earlier than penicillin) and prevents transfer across plasma membrane
-bactericidal (cell wall inhibitor)
-covers all gram-posivtive bacteria, even MRSA
-is not absorbed orally
What are drugs that work inside the cells?
-targets protein synthesis, genetic code, bacterial ribosomes, bacterial RNA polymerase, DNA gyrase, and folic acid metabolism
-can damaage eukaryotic DNA therefore sometimes carcinogenic
What antibiotics inhibit bacterial protein synthesis?
-most of these drugs are bacteriostatic
-animoglycosides are bactericidal
-prokaryotic 70S ribosome consists of a 30S and a 50S subunit
-each composed of rRNA and numerous protein
What antimicrobial drugs target the 30S rubosome subunit?
-tetracyclines
-aminoglycosides
What are tetracyclines?
-antimicrobial drug that targets the 30S subunit
-do not give during pregnancy
-cross placenta and excreted in milk
-binds to calcium (cone) causing major deformities
-differences in clinical efficacy are minor: pharmacokinetics of absorpotion, distribution, and excretion
-binds to 30S subunit and inhibit protein synthesis
-bacteriostatic
-high selectivity derives froma ctive accumulation of drugs of bacteria but not in mammalian cells
-has drug interaction with foods high in calcium (binds to bones an causes developmental abnomalies for 65+)
What are tetracyclines classified as and examples?
-short acting: Chlortetracycline, tetracycline, and oxytetracycline
-intermediate-acting: demeclocycline and methacycline
-long-lasting: doxycycline andf minocycline
-doxycycline chelates cations poorly, so is better absorbed with food
What are aminoglycosides as antibacterials? Examples?
-include streptomycin, neomycin, kanamycin, amikacin, gentamicin, tobramycin, sisomicin, netilmicin
-used to treat infections casued by gram-negative bacteria
-binds to 30S subunit and inhibit protein synthesis
-bactericidal, have concentration-depending killing
-act synergistically with antibiotics, such as beta-lactams
What are streptomycin as an aminoglycoside? gentamicin? amikacin? neomycin? netilmicin?
-streptomycin is the oldest one in the family
-gentamicin is most commonly used: effective against both gram-positive and gram-negative organisms; used in sever infections (sepsis and pneumonia)
-amikacin has the broadest spectrum and is good for hospital infections
-neomycin is used only topically (broad spectrum but very toxic)
-netilmicin is given orally before GI surgery
What are anitmicrobial drugs that target the 50S subunit of ribosomes?
-macrolides
-antimetabolites
What are macrolides? Examples of drugs?
-named for their large lactone rings to which deoxy sugars are attached
-include erythromycin, azithromycin, and Clarithromycin
-bind to 50S subunit and inhibit protein synthesis
-commonly used as second line drugs for skina dn soft tissue infection (broad spectrum)
-frequently used for upper respiratory tract infections
-safest antibiotics
What are antimetabolites? How does it work as an antibacterial? Examples?
-inhibit synthesis of nucleotides (purine and pyrimidiine) which are the building blocks of DNA and RNA
-good rugs for urinary tract infections
-adverse effects are rare in persons without AIDS
-bacteria need folate, when inhibited, kills bacterial cells
-sulfonamides
-trimethoprim
What are sulfonamides as an antimetabolite?
-sulfamethoxazole
-looks like PABA inhibits PABA--> DHFR process
-bacteriostatic
-resistance can occur as a result of decreased permeability to the antibacterial drug; increased PABA production
-sulfonamides are perhaps the most allergenic of antibiotics
What is trimethoprim as an antimetabolite?
-inhibits bacterial dihydrofolic acid reductase (DHFR)
-bacteriostatic
-useful in the treatment if chronic bacterial prostatitis
What is Bactrim as ana ntimetabolite?
-trimethoprim and sulfamethoxazole act synergistically to kill many gram-positive and gram-negative bacteria
-don;t give while patient is on warfarin (dangerous)
What are antibiotics that inhibit bacterial DNA synthesis?
-quinolones and flouroquinolones
-quinolones are synthetic antibiotics based on a nucleus of two fused six-membered rings
-ythe addition of a flourine atom at position six of the quinolone antibiotics known as flouroquinolones
-have become important as the penicillins and cephalosporins: based on safeness, oral absorption and penetration into tissues
-act by inhibiting prokaryotic type II topoisomerases--DNA gyase (in gram - mostly)
-flouroquinolones appear safe in pregnancy
What are first generation quinolones/flouroquinolones? seond generation? thrid? fourth? respiratory?
-first: Nalidixic acid
-second: norfloxacin, ciprofloxacin, enoxacin, lomefloxacin, and ofloxacin (poor gram + coverage)
-third: Gatifloxacin and levofloxacin (have greater affinity against gram-positive and atypical bacteria)
-fourth: trovafloxacin, moxifloxacin, and gemifloxacin
-respiratory: levofloxacin, gatifloxacin, gemifloxacin, and moxifloxacin (mostly used ffor gram negative)
What is isoniazid as a drug used to treat tubercuosis?
-synthetic
-will penetrate macrophage to deal with bacteria inside
-prodrug actiuvated by catalase-peroxidase
-bactrerial-cidal in dividing mycobacteria
-bacterial-static when resting
-inhbitis synthesis of mycolic acids once drug is activated
-widely distributed to all tissues and fluids within the body
-associated with hepatitis peripheral neuropathy
-give with vitamin 6
What is rifampin as a drug to treat tuberculosis?
-semi-synthetic
-wide spectrum antibiotic, most notably against gram-positive bacteria and TB
-bacterialcidal
-inhibits RNA synthesis
-adverse reactions: induces cytochrome P450, anticoagulant, can't use oral contraceptives, and anticonvulsants are less effective
What is rifabutin as a drug used for treatment of tuberculosis?
-very similar to rifampin ins tructure, antibacterial activity, metabolism, and adverse reactions
-induces cytochrome P450 less than rifampin
What is pyrazinamide as a drug used for treatment of tuberculosis?
-synthetic
-mechanism of action is unknown
-given for no more than 2 months (liver toxicity)
-avoid during pregnancy
What is ethambutol as a drug used for treatment of tuberculosis?
-used for oral administration
-synthetic
-active only against dividing bacteria
-crosses the BBB only if the menines are inflamed (meningitis)
-higher dose is recommended for treatment of tuberculous meningitis
-can cause ocular toxicity: not used for young children
What are fixed-dose combinations of drugs used in the treatment of tuberculosis?
-Rifamate= Isoniazed and Rifampin
-Rifater= isoniazed and rifampin and pyrazinamide
How do you treat active tuberculosis?
-usually a 2 month intensive phase with isoniazed, rifampin, ethambutol and pyrazinamide, followed by 4 months of isoniazed and rifampin
-patients with TB meninitis, bone infections, or TB arthritis, treat for 12 months
How do you conduct treatment of PPD reactors?
-isoniazed is usually given for 9 months
What is mycobacterium leprae (leprosy)?
-chronic disease
-rare in US/Canada
-highest prevalence in India, Brazil, Burma, Indonesia, Madagascar, and Nepal (600 new cases per year)
-grows beter in cooler body temperatures closer to skin surface
-maninly contracted via inhalatiuon
-impossible to grow ona rtificial media
-intracellular pathogen
-slow-growing: needs 20-30 days of generation time
What drugs are used for the treatment of leprosy?
-Dapsone
-rifampin
-clofazimine
How is dapsone used as adrug in treatment of leprosy?
-same mechansism of action as sulfonamides
-blocks PHF suynthesis and inhibits folate synthesis
-well-tolerated
-well-absorbed
How is rifampin used as a drug in treatment of leprosy?
-highly effective in combination with dapsone or others
How is clofazimine used as a drug in treatment of leprosy?
-mechanism of action is unknown (binds DNA)
-resistance developes slowly
How do you treat severe cases of leprosy?
-Rifampin, Dapsone, and Clofazimine used for a mininum of 2 years
How do you treat less severe cases of leprosy?
-Rifampin and dapsone for 6 months
What is the biology of fungi?
-free-living organisms: yeasts, molds, and dimorphic fungi
-eukaryotic, heterotrophic organisms (need aerobic environment)
-have ergosterol: essential sterol for fungi and target of anti-fungal drugs
What is the pathophysiology of fungal infections?
-results from mycotoxin production, allergenicity, and tissue invasion
What are superficial fungal infections? treatment?
-tinea nigra (asymptomatic)
-pigment change of the skin
-treat with shampoo containing selenium sulfide and imidazoles (tyopically)
What are cutaenous fungal infections of the skin, hair and nails? treatments?
-dermatophytosis and candidiasis
-matophytic (live on dead layer)
-fungi secrete keratinase which digetss keratin
-casues scaling oif the skin, loss of hair, and crumbling of nails
-treat dermatophytosis with Griseofulvin (for severe infections) and terbinafin
-treat candidiasis with nystatin and clotrimazole in the mouth and miconazole for vaginitis
What are subcutaneous fungal infections? treatment?
-following trauma to the skin, will enter body and remain localized
-treat with itraconazole and local excision
What are symptomatic fungal infections? How it is like TB? Unlike?
-systemic mycosis
-caused by 3 dimorphic fungus (histoplasma, blasmycesma and coccidioides)
-like TB: can be inhaled, primary infectuions in the lung
-aymptomatic, mild, severe, or chronic lung infections
-can disseminate hematogenously to distant site (meningitis)
-unlike TB: no person-to-person transmission
-fungi with spores
-not acid-fast bacteria
What are polyenes that are anti-fungal?
-amphotericin B
What is amphotericin B as an anti-fungal drug?
-1st line of drugs used to treat
-produced by soil actinomycetes
-used for severe fungal infection
-no oral absorption, only by IV (doesn;t cross BBB)
-punches holes in ergosterol and increases membrane permeability--> causes death
-causes renal toxicity, acute febrile reaction (fever), anemia, and inflammation of the vein
-lipid formulation of drug tolerated better
What is flucytosine as an anti-fungal drug?
-synthetic
-anti-metabolite
-used in combination with amphotericin B to treat systemic mycoses (to avoid resistance)
-large volume of distribution
-inhibits DNA synthesis and cell division
-causes bone marrow depression, nausea, vomiting, and diarrhea
What are the azoles that treat fungi infections?
-synthetic compounds
-imidazoles: ketoconazole, miconazole, anmd clotrimazole
-Triazoles: fluconazole, itraconazole, and voriconazole
-micoanazole and clotrimazole are used for topical fungal infections
-rest used for systemic fungal infections
-block enzyme in ergosterol synthesis (leads to cell wall permeability)
What is ketoconazole as an anti-fungal drug?
-has broad spectrum of activity
-largely replaced by the newer, more effective, lexx toxic triazoles
What is fluconazole as an anti-fungal drug?
-most heavily used becasue less toxic with a very borad spectrum
-kills candida infections as well
What is itraconazole as a anti-fungal drug?
-azole choice of treatment for dimorphic fungi
-has poor oral absorption
What is voriconazole as an anti-fungal drug?
-newest triazole
-has broad activity
-has excellant activity against fluconazole resistant Candidia species
What are posaconazole and Ravuconazole as anti-fungal drugs?
-D. Glucan syntheis inhibitors
What are Caspofungin and micafungin as anti-fungal drugs?
-good candida drugs for IV administration
-inhibit 1,3 D-glucan synthase--> inhibits fungal cell wall synthesis
What is terbinafine as an anti-fungal drug?
-blocks eergosterol synthesis-->inhibits fungal cell wall synthesis
-accumulates in nails
-little potential for drug-drug interactions
What is griseofulvin as an anti-fungal drug?
-isolated froma number of molds of the genus penicillium
-inactive against bacteria, yeast, and fungi that cause systemio disease
-static rather than cidal; inhibits fungal mitosis
-works very slowly
-should be avoided in pregnancy
What is nystatin as an anti-fungal drug?
-used in the treatment of oral abd vaginal candidiasis
-same mechanisms of action as amphotericin B
-too toxic: used only topically
What is viral morphology for RNA viruses?
-positive, negative, or retro (reverse)
-naked: Hepatitis A (cna be + or -)
-enveloped: Hepatitis C (+), influeza (Types A, B, and C; -), mumps (-), rabies (-), and ebola (-)
-complex coat: HIV (I and II)
What is the viral morphology of DNA viruses?
-cannot be trasnlated directly into proteins
-naked: human pailloma
-enveloped: Herpes (I and II), caricell-zoster, and hepatitis B
-complex coat: small pox
What is the step-by-step process of viral replication?
-attachment of the virus to the host cell and entry
-uncoating of viral nucleic acid
-genome replication
-maturation of viral particles
-release from the cell
What are antiviral drugs?
-only virustatic
-viral nucleotide analogs
What is the herpes virus?
-herpes simplex virus type I infects mouth, face, skin, or brain
-herpes simplex virus type II: infects genitals, rectum, skin, and hands
-varicella zoster virus causes chickenpox
-cytomegalovirus casues life-threatening diease (pneumonia) or sight-threatening retinitis in immunocrompromised patients
How is acyclovir used in treating herpes virus?
-highly selective inhbitior of replication
-guanine analogue
-requires three phophorylation steps for activation
-generally well tolerated
-CMV less sensitive to it than HSV and VZV
How is ganciclovir used in treating Herpes virus?
-synthesized derrivative of acyclovir
-not dependent on a virus-specific thymidine kinase for phosphorylation
-was first drug liscenced for use against CMV
-less selective than acyclovir and more toxic
What are retro viruses?
-carry unique enzyme called reverse trasncriptase
-can casue cancer
-example is HIV
-spread by parenteral route, sexual activity, blood product transfusion, IV drug use, and transplacental spread
-forms latent infections in humans
-normal T-cell counts are 1000 cells/uL blood--> HIV infected has 60 cells/mL/year
What are nucleoside reverse trasncirptase inhibitors for use against HIV?
-zidovudine
-didanosine
-zalcitabine
-stavudine
-lamivudine
-emtricitabine
-abacavir
What nucleotide reverse transcriptase inhibitors are used against HIV?
-tenofovir
What non-nucleotide reverse transcriptase inhibitors are used against HIV?
-nevirapine
-delaviradine
-efavirenz
What protease inhibitors are used against HIV?
-sequinavir
-indinavir
-ritonovir
-nelfinavir
-amprenavir
-fosamprenavir
-atazanavir
-tipranavir
-lopinavir
What entry inhibitors are used against HIV?
-enfuvirtide
What are preferred drug regimens used in treatment of HIV?
-zidovudine and laivudine (combivir) and efavirenz
-tenofovir and emtricitabine (truvada) and efavirenz
-combivir and lopinavir
What are the nucleoside reverse transcriptase inhibors of HIV treatment?
-Zidovudine
-lamivudine
-emtricitabine
What is combo thereapy used for?
-prevent resistance
-lower toxicity
-different drugs have different mechanisms of action
-have synergic effect
What is zidovuidne as a nucleoside reverse transcriptase inhibitor for HIV treatment?
-well studied
-prevention of maternal-fetal transmission of HIV
-for HIV-positive pregnant women prenattally + 6 weeks for in fants post natally
-reduces mortality and opportunistic infections (raises t-cell count)
-delays progression to aids
How is lamivudine and emtricitabine used as a nucleoside reverse trasnscriptase inhibotr for HIV treatment?
-newer generation formulation
-well-tolerated
-used to treat patients with HIV/Hepatitis B co-infection
What are the non-nucleoside reverse transcriptase inhibors of HIV infections?
-Nevirapine
How is nevirapine a non-nucleoside reverse transcriptase inhibitor for HIV treatment?
-frequently given to pregnant women
-an inducer of the cytochrome P450 system and metabolized
What are protease inhibitors of HIV treatment?
-saquinavir
How is saquinavir a protease inhibitor for HIV treatment?
-associated with metabolic abnormalites (dyslipidemia, insulin resistance, and lipodystrophy)
-low oral bioavailability
-fortovase is a soft gel formulation of saquinavir with enhanced bioavailability
What is the significance of the drug-drug interations with zidovudine?
-should be used with caution if patient is on other drugs that could cause bone marrow supprsstion or toxicity
-such as doxorubiicin and amphotericin B
What is the hepatitis family virus? What drugs can be used to treat it?
-viruses that primarily infect the liver
-interferon and nucleoside analogs (lamivudine, adefovir, and entacavir) were used for treatment
-interferon and ribaviran were used for hepatitis C
How is lamivudine used as a nucleoside analog for treatment of hepatitis?
-synergistsic with a variety of antiretrovial nucleoside analogs
-inhibits HBV DNA polymerase
-has an excellant safety profile
How is ribavirin used for treatment of hepatitis?
-phophorylated intracellularly by host cell enzymes
-oral bioavailability is about 64%, increases with high-fat meals
What is influenza? What drugs can be used against it?
-classified by their core proteins
-type A infects huymans, other mamals, and birds
-type B and C have only been isolated in humans
adamantanes and neuramnidase are used to treat it
What are adamantanes in treating influenza?
-amatadine and rimantadine (less toxic)
-inhibit uncoated of the viral RNA
-active against influenza A virus only (very anrrow spectrum of action)
-resistance develops in 50% of treated individuals
What are neuraminidases in treating influenza?
-zanamivir and oseltamivir
-inhibit the realease of influenza virus from infected to new host cells
-have activity against both influenza A and influenza B viruses
-do not use zanamivir in patients with asthma or chronic destructive pulmonary disease
What are protozoa?
-free-living, single-celled, eukaryotic
-10000 species are parasitic (trypanosomes and plasmodium)
What is malaria?
-one of the most problematic protozoa disease
-up to 300-500 million cases a year resulting in 1-3 million deaths
-causes periodic episodes of severe chills and high fevers at 48-72 hr intervals
-vector for transmission is the female anopheles mosquito
-chemoprophylaxis: vaccination
How is Chloroquine used to treat malaria?
-drug of choice for both treatment and chemoprophylaxis (vaccination) of malaria
-synthetic 4-aminoquinoline formulated as the phosphate salt for oral use
-mechanism of action remains controversial
-usually very well tolerated, even with prolonged use
-chloroquine-resistant areas: quinidine
-both are safe in all trimesters of pregnancy
What are helminths? How do you treat them?
-problem in tropical areas
-16 types of worms that cause significant infections in humans: 10 roundsworms and 6 flatworms
-mechanism of action: exert an antichilinergic effect on the worms, causing paralysis and expulsion by peristalsis
-includes: albendazole, mebendazole, and thiabendazole
-also ivermectin (doesn't kill adult worm)
What are prions?
-prion diseases are the transmissible spongiform encephalopathies
-leads to dementia, ataxia, myoclonic jerks, and death
-have long incubation time, gradual increase in severity leading to death within months of onset, no host-immune response, non-inflammatory process in the brain (difficult to detect)
-infectious agent consist of only prion proteins (PRNP)
-no curative treatment currently available
How do you identify a microorganism?
-gram stain (+, -, or acid fast)
-immunlogical methods
-location of infection:
-skin--> probably gram-positive-->use nafcillin, dicloxillin
-urinary tract infection-->probably gram-negative--> use trimethoprim or sulfamethoxazole
How do you classify a host's status?
-metabolic and pharmacokinetics consideration: renal function and hepatic function, CNS penetration
-allergy history\
-immune status
-age
-pregnancy
What is drug combination?
-for unknown microbe and unavailable gram stain---> use broad spectrum antibiotics
-to prevent resistance--> may use 2 drugs with different mechanisms of action
-for synergy--> the action of soem drugs make other drugs more effective
How does the development and spread of antimicrobial resistance occur?
-by using antibiotics
-using antibiotics outside the field of medicine
-taking antibiotics for viruses
-using prescibed drugs improperly
What is the mechanism of action of antimicrobial resistance?
-enzyme inhibition (b-lactamases)
-alterations of bacterial membranes
-promotion of antibiotic efflux
-alterations of bacterial protein targets
-bypass of antibiotic inhibition
How do you decrease antibiotic resistance?
-withhold antibiotics
-use narrowest spectrum antimicrobial drug
-base decisions about broadness of empiric coverage on severity of illness
What are the agents of bioterrorism?
-anthrax
-plague
-tularemia
-botulism
-"viral fever"