Anti-Infectives

Front 1

Microbes can be ___,____or____.

Back 1

bacteria, fungi, or viral.

Front 2

Defined as the invasion of pathogens OR the reaction of tissues to pathogen invasion.

Back 2

Define Infection

Front 3

Name three factors that determine the infection from a pathogen. TQ.

Back 3

Virulence of pathogen, number, and/or host resistence.

Front 4

The ability of a pathogen to be immune to anti-infective (either natural or reSquired).

Back 4

Resistance

Front 5

The range of activity of a drug (can be narrow, intermediate, or broad).

Back 5

Spectrum

Front 6

A combination of two drugs produces more effect than would be expected if their individual effects would be added.

Back 6

Synergism

Front 7

A combinatino of two drugs produces less effect than either drug alone.

Back 7

Antagonism

Front 8

What are the six components that one must consider when determining patient-drug-pathogen interaction.

Back 8

Pharmokinetics (patient-drug), pharmodynamics (drug on patient), immunity (patient on pathogen), sepsis (pathogen on patient), resisance (pathogen on drug), selective toxicity (drug on pathogen).

Front 9

Absorption, metabolism and excretion are all part of what?

Back 9

Pharmokinetics (what the patient does to the drug)

Front 10

What determines enzyme metabolism of a drug?

Back 10

Chemical structure.

Front 11

What diminishes the usefulness of drugs?

Back 11

Toxic metabolites.

Front 12

Useful anti-infectives must have what?

Back 12

selective toxicity and favorable pharmacokinetics.

Front 13

What is the ideal pharmodynamic (drug on patient) response of an anti-infective?

Back 13

No response. "kill microbes, keep patient safe"

Front 14

What is the target of anti-infective drugs.

Back 14

The microbial cell, NOT the host.

Front 15

True or False, antibacterial drugs are usually safe, but can become toxic from inapproriate use (e.g. dose, allergy).

Back 15

True

Front 16

Name three resistance mechanisms (pathogen on drug).

Back 16

mutation, adaption, and gene transfer.

Front 17

Defined as drug that exhibits toxicity toward microbe while having little or no effect on host.

Back 17

Selective toxicity (drug on pathogen)

Front 18

What two mechanisms determine selective toxicity?

Back 18

1. blocking pathways essential for growth or survival.
2. Blocking a reaction vital for both host and microbe, but due to the difference in components (or affinity) involved, effect is exerted predominately on the microbe.

Front 19

Static vs Cidal

Back 19

Static is inhibition of growth or replication. (inhibitory)
Cidal is death of organism (lethal)

Front 20

Defined as the appearance of a new infection during treatment of the primary infection-as a result of treatment.

Back 20

Superinfection

Front 21

What is the role of PBP in cell wall synthesis?

Back 21

Penicillin binding proteins (a protein innate to many microbes) assists in the assemby, maintenance and regulation of bacterial cell walls.

Front 22

How do beta-lactam drugs (penicillin) work?

Back 22

They bind to the penicillin binding protein (pbp) membrane which results in inhibition of enzymes that form crosslinks in cell wall. This action weakens the cell wall so it can't withstand osmotic pressure=cell lysis and death (bacteriocidal). "beta-lactam cock block PBP"

Front 23

How many groups of penicilllin are there? What group is penicillinase resistant?

Back 23

Four groups. Group 2 (anti-staphylococcal) are penicillinase resistant. Group 2 is used to treat strep and staphloycocci, but not MRSA.

Front 24

What is penicillinase?

Back 24

An enzyme made by bacteria to degrade the beta-lactam ring of antibiotics making them useless.

Front 25

What group of penicllin is used to treate systemic infections?

Back 25

Group 4 or extended spectrum penicillins

Front 26

Describe the spectrum covereage of cephalosporins?

Back 26

1st generation (more gram postive; used to treat skin infections/prophylaxis)-2nd (same)-3rd more negative & hospital infections-4th mostly negative, pseudomonas and anerobic infections, tx meningitis and crosses the BBB.

Front 27

What drugs could be used to treat meningitis?

Back 27

4th generation cephalopsporin,

Front 28

What is the greatest danger associated with penicillin use?

Back 28

Allergic reaction

Front 29

Name four ways in which bacteria can become beta-lactam resistance?

Back 29

1. inactivation of beta-lactam ring, 2. alteration of PBPs (MRSA), 3. reduction of antibiotic access to PBP's (gram -) and 4. elaboration of efflux mechanisms (gram -).

Front 30

What are two ways to fight bacterial resistance to beta-lactam?

Back 30

1. Group 2 penicillin and some cephalosporins are resistant to beta-lactamases. 2. Use a beta-lactamse inhibitor like (clavulconic acid) with the abx, e.g. Augmentin

Front 31

Name four drugs that are cell metabolism inhibitors (protein synthesis)?

Back 31

M-TAC: macrolides, tetracycline, aminoglycosides, clinidamycin.

Front 32

How do macrolides and clindamycin work?

Back 32

50s inhibitors (ribosome): interferes with protein synthesis by inhibiting the enzyme peptidyl transferase: bacteroSTATIC.

Front 33

How does tetracyclin work?

Back 33

30s inhibitor: interfere with synthesis of bacterial proteins by binding to bacteria directly: bacteroSTATIC.

Front 34

How do aminoglycosides work?

Back 34

They are cell metabolism inhibitors. Specifically, they inhibit 30s (a ribosome subunit) and therefore disrupt initiation of protein synthesis: bacteroCIDAL.

Front 35

These cell metabolism inhibitor is stored in dentine and enamel of unerupted teeth.

Back 35

Tetracylcine

Front 36

Can clindamycin be used for meningitis?

Back 36

No, can't get into CSF

Front 37

What cell metabolism inhibitor is most toxic?

Back 37

Aminioglycoside, limits their use. Toxic to CN 8=auditory and vestibular disturbances.

Front 38

This cell metabolism inhibitor interferes with other abx actrion, decreases effectivenes of PO BC, and increases serum levels of drugs metabolized in the liver.

Back 38

Macrolides.

Front 39

Tetracyclin can not be given with what drugs because it decreases the antibiotics absorption?

Back 39

Calcium supplements and vitamins.

Front 40

Name two cell metabolism inhibitors that do so by inhibiting Folic Acid?

Back 40

Sulfonamides and trimethoprim

Front 41

How do sulfonamides and trimethorprim inhibit cell metabolism?

Back 41

These are antibacterial agents that inhibit folic acid synthesis via competitive inhibition=bacterioSTATIC. Of note, bacteria can't use preformed folic acid, humans can.

Front 42

True or False: trimethoprim can cross into CSF during times of inflammation?

Back 42

True

Front 43

This antibiotic in high concentrations can cause crystal formation leading to kidney obstruction.

Back 43

Sulfonamides

Front 44

This antibiotic competes for sites that bind bilirubin. In newborns, unbound bilirubin is deposited into the basal ganglia which can cause kernicterus (toxic encephalopathy).

Back 44

Sulfonamide

Front 45

This drug interferes with folic acid and use in pregnancy may affect the fetus.

Back 45

Trimethoprim

Front 46

Name three cell replication inhibitors.

Back 46

Quinolone, fluoroquinolones, and nitrofurans (not really a cell inhibitor).

Front 47

This drug class inhibits cell replication by inhibiting DNA gyrase actitivy thereby preventing DNA unwinding.

Back 47

Quinolones

Front 48

This drug class inhibits cell replication by targeting topoisomerase IV (an enzyme responsible for seperating daughter cells after division.

Back 48

Fluoroquinolones

Front 49

True or False, DNA gyrase and topoisomerase are specific for micro-organisms.

Back 49

True

Front 50

True or False quinolones and fluoroquinolones are bacteriostatic but can become bacteriocidal when concentration increased.

Back 50

True

Front 51

True or False: Metal ions reduce absorption of quinolones.

Back 51

True

Front 52

What is the unique mechanism of Nitrofurans?

Back 52

Metabolites (the active part of drug) of nitrofurans effect DNA/RNA synthesis and protein synthesis of bacteria. Selectively toxic. And important: bacteriostatic and bacteriocidal depending on dose.

Front 53

True or False resistance is almost never seen in nitrofurans?

Back 53

True

Front 54

Why does nitrofuran have a fast onset of action?

Back 54

Because it has rapid metabolism.

Front 55

Can pregnant women take nitrofan? Why?

Back 55

No-b/c interferes with RBC enzyme systems in babies

Front 56

This is a anti-tuberculosis drug that only works on dividing cells.

Back 56

Isoniazid

Front 57

What is the MOA of isoniazid?

Back 57

Blocks mycobacterium cell wall. When used alone can develop resistance.

Front 58

What is the MOA of rifampin?

Back 58

Blocks RNA synthesis and does not target mammalian polymerases. It is active against several bacteria and some viruses.

Front 59

Why are isoniazd and rifampin used together? Whats the risk?

Back 59

Alone can lead to resistance of TB strands. Increased risk for hepatitis.

Front 60

Define mycoses.

Back 60

The infection and resulting disease caused by fungi

Front 61

Allergic disease, mushroom poisoning, and mycotoxins are all examples of what?

Back 61

Adverse affects of fungi

Front 62

What are the two clinical groupings of fungi?

Back 62

Skin and deep mycoses

Front 63

True or False: dimorphic systemic mycoses can happen to anyone.

Back 63

True. Fungi can overcome physiological defenses by changing morphological form. Usually occurs in lungs.

Front 64

Human mycoses is generally related to what two things?

Back 64

Immunological status and environmental exposure.

Front 65

Name two causes for increased human mycoses

Back 65

More travel, greater age, disease, sicker pts=greater immunocompromise.

Front 66

What is the main difference between animal and fungal cell membrane?

Back 66

Animalls cell made of cholesterol, Fungi cell membrane made from ergosterol.

Front 67

Name the four structural classes of anti-fungals.

Back 67

Membrane disrupting agents, ergosterol synthesis inhibitors, glucan synthesis inhibitors, and antimetabolites and misc.

Front 68

Name a class of antifungals that disrupt the membrane.

Back 68

Polyenes (amphotericin B and Nystatin)

Front 69

How do polyenes work? What type of microbe do they attack? Name two.

Back 69

Bind to sterols (preferably ergosterol, but not exclusively) and disrupt the osmotic intergrity of the cell membrane (ions leak from inside to outside of cell)-FungiCIDAL. Amphotericin B and Nystatin.

Front 70

This drug can be used to treat meningits but must be given intrathecally.

Back 70

Amphotericin B a polyene

Front 71

This drug has poor oral absorption but is often used to treat oral canidiasis.

Back 71

Amphotericin B

Front 72

What is the major limitation to Amphotericin B

Back 72

Neprhotoxicity, b/c it also binds to cholesterol in human cells and killing them

Front 73

What drugs increases the risk of neprhotoxicity?

Back 73

Cyclosporine and aminoglycoside

Front 74

The use of Amphotericin B will increase the accummulation of renaly cleared drugs, name two.

Back 74

Flucytosine and fluconazole.

Front 75

Azoles and Allylamines both do what?

Back 75

Both are ergosterol synthesis pathway inhibitors but address it in two different ways making them fungistatic or fungicidal

Front 76

Name two broad classes of azoles.

Back 76

Imidazoles (older) and triazoles (newer)

Front 77

What is the main difference between imidazoles and triazoles?

Back 77

Metabolized more slowly and have less effect on human sterol synthesis.

Front 78

Explain the MOA of azoles.

Back 78

Inhibit Lanosterol demethylase (a CYP 450) and impair the synthesis of ergosterol=fungiSTATIC

Front 79

This antifungal (an azole) can be used to treat meningitis

Back 79

Fluconazole

Front 80

True or False: Because azoles are bacterostatic, resistance can develop

Back 80

True

Front 81

True or False Azoles have numerous and dangerous interactions.

Back 81

True: any other drug that uses the cyp 450 can cause major interactions.

Front 82

What drug changes the pH of stomach and inhibits absorption of azoles

Back 82

H2 antagonists/PPI; need an acidic environment for absorption

Front 83

Explain the MOA of Allylamines.

Back 83

Inhibit squalene epoxidase which blocks the entire pathway of ergosterol synthesis=fungiCIDAL. Note: ergosterol is needed for synthesis of the cell membrane in fungi.

Front 84

What is the difference of azoles and allylamines if the both block the ergosterol pathway?

Back 84

Azoles blocks Lanosterol Demethylase (later in pathway of ergosterol synthesis) and allaylamines block Squalene Epoxidase at the beginning of pathway.

Front 85

Terbunafine (lamictal) is what?

Back 85

An allylamine used to treat dermatophytosis

Front 86

Explain the MOA of echinocandins: glucan synthase inhibitors.

Back 86

Echinocandins block glucan syntase, an enzyme that is important in cell wall synthesis.

Front 87

Echinocandis are often used in what type of therapy?

Back 87

Salvage therapy for invasive aspergillus when nothing else works.

Front 88

Explain the MOA of antimetabolites (a structural class of antifungals)

Back 88

Can either block fungal DNA and protein synthesis ( as in flucytosine) or block fungal mitosis (as in griseofulvin)

Front 89

What is an important complication of animetabolite use?

Back 89

bone marrow suppression

Front 90

This antimetaboite can be used to treat fungal meningits in AIDs patients, >50% absorped into CSF

Back 90

Flucytosine

Front 91

This antimetabolite is deposited in keratin precuror cells where it persists, providing prolonged fungal resistance.

Back 91

Griseofulvin

Front 92

Outline the different virus types.

Back 92

DNA or RNA, enveloped or non-enveloped, double strand or single strand.

Front 93

Name the four paths of viral entry.

Back 93

1. translocation (naked). 2. Injection of genetic material (naked). 3. Receptor mediated endocytosis (naked and enveloped). 4. Membrane fusion (enveloped).

Front 94

What form of viral entry uses a cage?

Back 94

Receptor mediated

Front 95

The drugs to treat herpes do so by what mechanism?

Back 95

Inhibition of viral DNA polymerase.

Front 96

Drugs to treat influenza do so by what mechanism?

Back 96

Inhibit M2 protein which is the protein needed to take the virus out of its protective cage so that it can get into the nucleus.

Front 97

Enfuviritide (T-20) is what type of drug?

Back 97

A fusion or entry inhibitor. Used as an antiretroviral drug that inhibits entry of virus into CD4 cells.

Front 98

What is enfuviritide (T-20) made from? It is used in what type of patients?

Back 98

HIV envelope. Multi-drug resistant HIV

Front 99

Explain the MOA of enfuviritide.

Back 99

Docks to receptor site where the HIV particle would normally dock and therefore inhibits entry.

Front 100

What is important to remember about enfuviritide (t-20)

Back 100

Does not work on already affected cells.

Front 101

Name three adverse affects of enfuviritide (t-20)

Back 101

1. nodule or cyst development
2. Hardening of skin
3. peripheral neuropathy

Front 102

Name two drugs that are specific for treatment of influenza A

Back 102

Amatidine and Rimatidine

Front 103

Name the complications of amantidine and rimantidine

Back 103

no to pregnancy of lactation. high doses may produce cardiac arrythmias, HALLUCINATIONS, and suicidal ideation

Front 104

What two drugs decrease rimantidine plasma levels?

Back 104

Aspirin and acetaminophen

Front 105

What is the MOA of anit-herpetic drugs?

Back 105

DNA synthesis inhibitors by inhibiting DNA polymerase and DNA replication

Front 106

How do antiherpetic drugs tx herpes?

Back 106

Dont cure, but decrease shedding, decrease pain (except in shingles), increase speed of healing.

Front 107

Acyclovir and Valcyclovir (prodrug) MOA is what?

Back 107

Affinity for viral thymidine kinase which converts antiherpetic drugs to acyclovir monophosphatase which gets incorporated in to virus and inhibits virus replication.

Front 108

What are the two ways that acyclovir (valcycloir) inhibit virus replciation?

Back 108

competively inhibit incorporation of dGTP and act as a chain terminator because it lacks 3 prime hydroxy.

Front 109

True or False: Acyclovir is specific for viral cells b/c is has an affinity of thymidine kinase (only found in virus).

Back 109

True

Front 110

Why is acyclovir given as prodrug?

Back 110

Valcylovir is the prodrug for acylclovir and is completely converted to acyclovir by first-pass metabolism. Bioavailability is 3-5 times higher.

Front 111

Penciclovir/famciclovir are what? What is their MOA?

Back 111

Anti-herpatics. Competitive inhibitor of viral DNA polymerase via specifity to viral TK. Tx HSV and VSV infected cells

Front 112

Ganciclovir and Valganciclovir (prodrug) are what?

Back 112

Anti-herpetic. MOA: competitive inhibitor of viral DNA polymerase. Unique in that is treats ALL herpetic; especially CMV

Front 113

Ganiciclovir/Valganciclovir are used to treat what?

Back 113

Treatment of CMV retinitis in immunocompromised pts and prophylactic use.

Front 114

This antiviral has a specificity for viral TK and ihibits viral DNA polymerase AND cellular DNA polymerase making it more toxic.

Back 114

Trifluridine

Front 115

Trifluridine is administered how and used to treat what?

Back 115

Topical to tx ocular herpes

Front 116

Cidofir

Back 116

A nucleotide analog that does not require viral TK or other viral kinases; its activated by HOST cell kinases. Used against MUTANT viruses.

Front 117

Foscarnet

Back 117

Not a purine or pyrimidine analog. Inhibits viral DNA and RNA polymerases (tx. hiv, hsv, and cmv) Used for tx of viruses resistant to nucelosides/nucleotide analogs.

Front 118

Nucleoside and nucelotide transcriptase inhibitors (NRTI) specificity is what?

Back 118

Blocks HIV replication and the infection of new cells, but they have little effect on cells that are already infected. ``

Front 119

Nucleoside and nucelotide transcriptase inhibitors (NRTI) MOA is what?

Back 119

competitive inhibitor of reverse transcriptase.

Front 120

Nucleoside and nucleotide transcriptase inhibitors (NRTI) can do what?

Back 120

All can produce potentially fatal syndrome called lactic acidosis and severe hepatomegaly.

Front 121

Nonnuceosdide inhibitors (NNRTIs) MOA?

Back 121

Inhibit viral reverse transcriptase by inducing a conformational change in enzyme that causes enzyme inactivation.

Front 122

Efavirenz

Back 122

A non-nucleoside reverse transcriptase inhibitor (NNRTI); can't give in pregnancy

Front 123

Nevirapine

Back 123

NNRTI; adults and children but monitor hepatotoxicity

Front 124

Delavirdine

Back 124

NNRTI; adults and adolescents over 16

Front 125

What drugs do you need to be wary of when giving NNRTI?

Back 125

Other drugs that are metabolized for CYP 450

Front 126

What is the MOA of protease inhibitors?

Back 126

Inhibit HIV protease activity (which is required for production of mature infectious virus).

Front 127

Who should you avoid using protease inhibitors in?

Back 127

Can cause increase bleeding in hemophiliacs.

Front 128

What is HAART therapy?

Back 128

Highly active anti-retroviral therapy.

Front 129

What consists of combo therapy in the treatment of HIV

Back 129

RT + protease inhibitors. more effecious at lower doses and reduced toxicity.

Front 130

Neuraminidase Inhibitors work on viruses?

Back 130

Block viral release (influenza)

Front 131

Zanamivir & Oseltamivir

Back 131

Both are neuraminidase inhibitors, reduce influenza by 1-2 days

Front 132

Zanamivir (relenza) works on what type of influenza? What can it do to lungs?

Back 132

This drug is a neuraminidase inhibitor (blocks viral release). Used to tx Influenza A & B , poor PO bioavailability so given in inhaler form, may cause bronchospasms

Front 133

True or False: Osteltamivir (tamiflu) oral bioavailability: 70%; GI distress. Used for prophylactic uses.

Back 133

True