Pharm Final Part Three

Front 1

What are the Worm drugs that interfere w/ muscular activity?

Back 1

niclosamide
praziquantal
albendazole
mebendazole
thiabendazole
diethylcarbamazine

Front 2

Niclosamide MOA?

Back 2

Uncouples oxidative metabolism

Tapeworm scolex releases from the intestinal wall

Front 3

Praziquantal MOA?

Back 3

opens calcium channels to cause muscular tetany
-- spastic paralysis
-- causes tegmental damage which activates the host immune system

Front 4

Albendazole, Mebendazole MOA?

Back 4

inhibits microtubules needed for glucose intake --> ↓ [glycogen] and [ATP] --> death

Front 5

Thiabendazole MOA?

Back 5

inhibits mitochondrial fumurate reductase

Front 6

Diethylcarbamazine MOA?

Back 6

Immobilizes microfilariae via decreased muscular activity
-- also alters surface membranes to make organism more susceptible to host immune defenses

Front 7

Worm drugs which interfere w/ synaptic transmission?

Back 7

pyrantel pamoate
levamisole
piperazine
ivermectin

Front 8

Pyrantel pamoate, levamisole MOA?

Back 8

ganglionic nicotinic cholinergic agonists = muscular tetany

Front 9

Piperazine MOA?

Back 9

a GABA agonist at chloride channel in NM jxn
-- flaccid muscle paralysis

Front 10

Ivermectin MOA?

Back 10

releases GABA and ↑ GABA binding --> facilitate opening of chloride channels in NM junction
-- flaccid muscle paralysis in helminths, insects and ectoparasites
-- may also cause tonic paralysis of musculature of nematodes via glutamate-gated Cl- channels found only in invertebrates

Used a lot in the cow industry

Front 11

What are the WORM drugs?

Back 11

Cestodes (tapeworms) – NICLOSAMIDE is DOC on exams

PRAZIQUANTAL is DOC in real world

Third drug – MEBENDAZOLE

Front 12

Treatment of roundworms?

Back 12

Ascaris lumbricoides

Albendazole
Mebendazole
Pyrantel pamoate
Piperazine

Front 13

Treatment of pinworms?

Back 13

Enterobius vermicularis

Mebendazole (a safety pin has a bend in it)
Pyrantel pamoate

Front 14

Treatment of hookworms?

Back 14

Necator americanus

Albendazole
Mebendazole

Front 15

Treatment of whipworms?

Back 15

Truchuris Trichuria

Albendazole
Mebendazole

Front 16

Treatment of threadworms?

Back 16

Strongyloides stercoralis

Ivermectin is the DOC
Albendazole
Thiabendazole

Front 17

Treatment of trichinosis?

Back 17

Trichinella spiralis

Albendazole
Mebendazole

Front 18

Treatment of filariasis?

Back 18

Wucheria bancrofti
-- diethylcarbamazine

Onchocerca volvulus
-- Ivermectin is the DOC

Front 19

Other uses of ivermectin?

Back 19

Tx of onchocerciasis and strongyloidasis (threadworm), ectoparasites

Front 20

Treatment of trematodes?

Back 20

(flukes) Schistosoma

Praziquantal is the DOC

Front 21

CLINICAL: Patient passes tape worm segments (proglottids) - most likely Taenia saginata (beef tapeworm) or a patient who likes to eat sushi passes tapeworm segments - most likely to be Diphyllobothrium latum (fish tapeworm) - treat with?

Back 21

Niclosamide or Praziquantal

Fish tapeworm causes megaloblastic anemia because the worm takes up all the vitamin B12 in the gut

Always worry that patient may have Taenia solium, pork tapeworm, which may produce cysticercosis (larval cysts) in the brain, orbit, muscles, liver and lungs.
Tx cysticercosis w albendazole

Praziqunatel is DOC if identity of the type of tapeworm is uncertain

Front 22

CLINICAL: Baby w anal itching (pruritis) and a postive “cellophane tape” test?

Back 22

Pinworm infestation

Tx w/ mebendazole or pyrantel pamoate

Front 23

CLINICAL: Patient w mixed infestation = cestode (tapeworm) + trematode (fluke). Tx?

Back 23

Mixed infestations treat w/ praziquantal

Front 24

What are the antiprotozoal drugs?

Back 24

Metronidazole

Pentamidine isethionate

Front 25

Metronidazole MOA?

Back 25

Reduced to active nitroderivative that inhibits DNA replication

Active against anaerobic protozoa and bacteria

Front 26

Metronidazole is the DOC for?

Back 26

Giardia lamblia
-- beaver fever
-- camper’s fever

Trichomonas
-- trichomoniasis

C Diff infections

Front 27

Metronidazole can also treat…?

Back 27

Entamoiba histolytica (amebiasis)

Obligate anaerobic bacteria
-- Bacteroides
-- Clostridium difficile

Front 28

S/E’s of Metronidazole?

Back 28

disulfiram-like rxn w/ EtOH headache, n/v, flushing

teratogenic

Front 29

MOA of Pentamidine isethionate?

Back 29

Unknown

Front 30

Therapeutic use of Pentamidine isethionate?

Back 30

Second-line drug for PCP (Trim-sulfa is first)
-- use if pt can’t take sulfonamides

Front 31

What are the antimalarial drugs?

Back 31

Primaquine
Chloroquine
Mefloquine
Sulfadoxine-Pyrimethamine

Front 32

Primaquine S/E’s?

Back 32

Can cause acute hemolysis in pt w/ malaria in pts w/
-- glucose-6-phosphate dehydrogenase deficiency

Front 33

Chloroquine S/E’s?

Back 33

Principal drawback is the wide-spread occurrence of resistance strains

tinnitus, headache

Front 34

Mefloquine is DOC for…?

Back 34

prophylaxis for areas w/ chloroquine-resistant strains

Front 35

Sulfadoxine-pyramethamine is DOC for…?

Back 35

treatment of chloroquine-resistant malaria b/c it has a different MOA than chloroquine

Front 36

Sulfadoxine MOA?

Back 36

inhibits dihydropteroate synthase

Front 37

Pyrimethamine MOA?

Back 37

inhibits DHF reductase
-- can cause megaloblastic anemia

Front 38

What are the antiviral drugs?

Back 38

Acyclovir

Ganciclovir

Idoxuridine

Amantadine

Zanamivir

Zidovudine

Saquinavir

Interferons

Front 39

Acyclovir MOA?

Back 39

Converted to acyclovir-monophosphate by thymidine kinase.

Other enzymes convert it to acyclovir-triphosphate (acyclo-GTP)

Inhibits viral DNA polymerase.

Front 40

Why isn’t acyclovir toxic to the host cells?

Back 40

Mammalian cells phosphorylate acyclovir at 1/30-1/00 the rate of the HSV

Acyclo-GTP is 1/10-1/30 less active in inhibiting mammalian DNA polymerase

Front 41

Acyclovir is for treatment of…?

Back 41

HSV

Front 42

What causes HSV resistance to acyclovir?

Back 42

a mutation which causes a deficiency of thymidine kinase

Front 43

CASE: Immunocompromised patient w mucocutaneous HSV infection. Treatment?

Back 43

Acyclovir

Front 44

CASE: Patient w HSV encephalitis. Treatment?

Back 44

Acyclovir

Front 45

CASE: Patient w genital HSV infection. Treatment?

Back 45

Acyclovir

Front 46

Keratoconjunctivitus caused by HSV is treated with…?

Back 46

Trifluridine (trifluorothymidine)

Front 47

Ganciclovir MOA?

Back 47

Phosphorylated to a triphosphate which inhibits DNA polymerase
-- triphosphate is a competitive substrate w deoxyguanosine triphosphate for incorporation into DNA

Stops DNA chain elongation to inhibit DNA synthesis

Front 48

Ganciclovir is used to treat…?

Back 48

Cytomegalovirus (CMV)

Front 49

CASE: Immunocompromised patient w/ CMV infection. Treatment?

Back 49

Ganciclovir

Front 50

Idoxuridine MOA?

Back 50

triphosphate inhibits viral DNA polymerase(resembles thymidine)

Front 51

When HSV becomes resistant to idoxuridine, it will also be resistant to…?

Back 51

trifluridine

B/C both drugs are thymidine derivatives which inhibit DNA polymerase

Front 52

Amantadine MOA?

Back 52

Inhibits the membrane coat ion channel that allows the acid-mediated dissociation of ribonucleoprotein complex early in replication.
-- This inhibition of uncoating prevents the transfer of viral RNA into the cytoplasm of the mammalian cell

Front 53

Amantadine use?

Back 53

Inhibits coating of influenza A and rubella viruses

Used prophylactically to prevent infection w/ influenza A

Front 54

Zanamivir MOA?

Back 54

Inhibition of viral neuraminidase

Front 55

Zanamivir therapeutic use?

Back 55

Treatment of flu

Front 56

Zidovudine MOA?

Back 56

Converted to an active triphosphate which either
1. inhibits viral DNA polymerase (reverse transcriptase) OR
2. is incorporated into DNA in the place of thymidine to stop DNA chain elongation.

Front 57

Zidovudine therapeutic use?

Back 57

AZT – HIV treatment

Front 58

Zidovudine S/E’s?

Back 58

bone marrow depression

anemia

Front 59

Saquinavir?

Back 59

HIV protease inhibitor

Inhibit HIV aspartic protease which converts polyproteins into functional core proteins and viral enzymes

Front 60

Interferon MOA?

Back 60

causes protein synthesis

1. 2,5 adenine synthetase
-- makes adenylate oligomers which activate RNAase to degrade viral RNA

2. protein kinase phosphorylates elongation factor 2 to prevent peptide viral chain initiation

3. PDEase degrades terminal nucleotide of t-RNA to inhibit viral peptide chain elongation

NET EFFECTS
interferes w viral penetration, uncoating, assembly and release
-- interferes w the synthesis of viral mRNA
-- inhibition of the translation of viral mRNA

Front 61

What are the antifungal drugs?

Back 61

Ampho B

Ketoconazole

Flucytosine

Trim Sulfa

Griseofulvin

Front 62

Ampho B MOA?

Back 62

Binds to ergosterol in fungal membranes to form pores
-- increases the permeability of the fungal membrane
-- cells lose ions and macromolecules
-- enhances penetration of other antifungal drugs such as flucytosine

Front 63

Ampho B resistance?

Back 63

Decreased membrane ergosterol or altered structure of ergosterol

Front 64

Ampho B therapeutic use?

Back 64

DOC for
-- Coccidiodes immitis
-- Aspergillis infections

Also effective against Candida

Front 65

Ampho B S/E’s?

Back 65

Clinical usefulness is limited by its nephrotoxicity
-- histological damage to renal tubules w cell necrosis
-- renal tubular acidosis (a defect of renal function that produces systemic acidosis because bicarbonate ion cannot be reabsorbed in the PT or DT).
-- hyperchloremic metabolic acidosis

Renal toxicity can be avoided by giving mannitol to induce a high rate of urinary flow

Front 66

Ketoconazole MOA?

Back 66

Inhibits fungal CYP450 which prevents the demethylation of lanosterol to ergosterol
-- so blocks cell wall synthesis

All –konazoles have same MOA

Front 67

Therapeutic use of Ketoconazole?

Back 67

Candida infections

Also effective against Coccidiodes immitis

Front 68

CLINICAL: Why is ketoconazole contraindicated in a patient receiving tx w amphoterecin B?

Back 68

Because ketoconazole will BLOCK the antifungal actions of amphoterecin B

Front 69

Ketoconazole and drug interactions?

Back 69

Inhibits CYP450 to ↑ the plasma conc of other drugs
-- esp. cyclosporine in transplant patients (can damage kidneys)
-- fluconazole also ↑ [cyclosporine] by MOA is unknown

Inhibits adrenal 17 & scc CYP450’s
-- adrenal insufficiency
-- ↓ [testosterone]
-- ↓ [estradiol] = gynecomastia
-- ↓ libido & potency in males
-- menstrual irregularities in females

Front 70

Flucytosine MOA?

Back 70

converted to fluorouracil
-- inhibits thymidylate synthesis
-- thus inhibits DNA synthesis

Front 71

Fungal resistance to Flucytosine?

Back 71

Develops rapidly and limits its clinical effectiveness, so amphoterecin B is used to treat systemic fungal infections, or flucytosine and amphoterecin B are given together

Ampho B enhances penetration of flucytosine: synergistic antifungal activity

Front 72

Flucytosine S/E’s?

Back 72

bone marrow depression
-- limits clinical usefulness

Front 73

CLINICAL: Which drug is selectively toxic to fungi because mammalian cells are unable to catalyze its deamination?

Back 73

Flucytosine

Front 74

Trim-sulfa is the DOC for…?

Back 74

PCP (+ silver stain)

Secondary drug is pentamidine (espec if sulfa allergy)

Front 75

Griseofulvin MOA?

Back 75

Disrupts mitotic spindle by interacting w polymerized microtubules
-- fungal mitosis is inhibited

Inhibits fungal CYP450 to block synth of ergosterol

Front 76

Griseofulvin therapeutic use?

Back 76

used to tx dermatophytes w hypae
-- Trichophyton
-- Microsporum
-- Epidermophyton.

Can also tx athlete’s foot w miconazole

DOC for ringworm on USMLE (in real world –conazole)

Front 77

PCN MOA?

Back 77

interact w penicillin-binding proteins to inhibit transpeptidation and peptidoglycan synthesis
-- cell wall synthesis is inhibited

Front 78

PCN elimination?

Back 78

Eliminated by renal tubular secretion.

-- Probenecid increases the half-life by inhibiting renal secretion (clearance).

-- The [PCN] in serum ↑ whereas the [PCN] in the urine ↓

Front 79

What can inhibit penicillinases (beta-lactamases)?

Back 79

Clavulinate

Sulbactam

Tazobactam

Front 80

Which PCNs are resistant to beta-lactamases?

Back 80

Acid labile
-- methcillin
-- nafcillin

Acid stabile
-- oxacillin
-- cloxacillin
-- dicloxacillin

Front 81

What is the primary beta-lactamase producing bacteria?

Back 81

S. aureus

Front 82

What else is resistant to beta-lactamases?

Back 82

Imipenem/Cilastatin
-- resistant to beta-lactamase
-- metabolized by renal tubular dihydropeptidases
-- Cilastatin inhibits the renal peptidases to decrease renal clearance of imipenem to increase the half-life

MOA
-- block transpeptidase-dependent cross-linkage of peptidoglycan

Front 83

PCN S/E’s?

Back 83

HSN rxns are common to all the PCNs

Front 84

Cephalosporin MOA?

Back 84

cef—

Have the same MOA as the PCNs

1st generation – very good MSSA and Strep coverage, OK community GNR

2nd generation – better Strep coverage, but worse Staph coverage
-- better community GNR
-- better anaerobic coverage

3rd generation
-- G(+) coverage varies by drug
-- all have improved GNR coverage
-- some cover nosocomial GNR
-- ALL penetrate CNS better than 1st or 2nd generation, and thus are preferred for meningitis

Front 85

CLINICAL: Patient w gonorrhea

Back 85

Tx w penicillin for 8 weeks

Front 86

CLINICAL: Patient returns with similar symptoms but no diplococci in urine (no longer has gonorrhea)

Back 86

patient has Chlamydia infection

Tx w tetracycline unless patient is a PG female--then tx w erythromycin

Front 87

CLINICAL: Patient has Streptococcus infection and is allergic to PCNs. Tx?

Back 87

Erythromycin (macrolide)

These others are better b/c they don’t cause diarrhea:
-- Clarithromycin has better extracellular concentration
-- Azithromycin

Front 88

Vancomycin MOA?

Back 88

Bactericidal

Binds to 30S subunit
-- interfere w/ initiation complex of peptide formation
-- causes misreading of mRNA and break polysomes into non-functional monosomes.

Front 89

Vancomycin therapeutic use?

Back 89

given i.v. for bacterial infections b/c not absorbed when given p.o

-- Serious life-threatening MRSA in the hospital
-- If MSSA, can use any PCN
-- outpatient, treat w/ trim-sulfa or clindamycin or doxycycline

Front 90

If C.diff occurs w/ i.v. vancomycin…?

Back 90

P.O. vancomycin will still cure it (but want to limit p.o. use b/c this can cause resistance)

But DOC is metronidazole

Front 91

Aminoglycoside MOA?

Back 91

Bactericidal

Binds to 30S subunit
-- interfere w initiation complex of peptide formation
-- causes misreading of mRNA and break polysomes into non-functional monosomes

Front 92

Aminoglycoside kinetics?

Back 92

Decreased GFR increases the half-life of gentamicin

PCN’s enhance the cellular penetration of aminoglycosides = synergistic effects

Front 93

Aminoglycoside toxicity?

Back 93

1. ototoxic

2. nephrotoxic, more so in elderly patients

3. drug accumulates in cells of PT and causes necrosis so urinary excretion of brush border enzymes increases
-- effect usually reversible since cells of PT can regenerate

4. get defect of renal concentrating mechanism because gent acts on DT and CD to decrease the sensitivity to ADH

5. decreased GFR, mild proteinuria, hyaline and granular casts in urine

NET EFFECT = mild increase in serum creatinine, hypokalemia, hypocalcemia and hypophosphatemia

Front 94

Trim-Sulfa MOA?

Back 94

Bacteristatic

See pg 6 for schematic

Front 95

Trimethoprim – why doesn’t it affect humans?

Back 95

100,000x more active against bacterial enzyme vs. mammalian enzyme

Front 96

Trim-Sulfa therapeutic use?

Back 96

Patient w/ AIDS develop infection w/ PCP – treat w/ trim sulfa

Front 97

Trim-sulfa S/E’s?

Back 97

Sulfonamides can displace bilirubin from plasma protein binding sites

Can cause kernicterus in neonates

Front 98

Tetracycline MOA?

Back 98

Bacteriostatic

Bind to 30S subunit to block aminoacyl t-RNA binding to the acceptor (A) site

Front 99

Tetracycline therapeutic use?

Back 99

Acts against gram (+) and (-) organisms, Rickettsiae, Mycoplasma, Chlamydia and amebas

NOT used for pneumococcal pneumonia
-- tx w/ PCNs, Cephalosporins, or Erythromycin

Front 100

Tetracycline S/E’s?

Back 100

Chelates Ca
-- adverse effect on formation of teeth and bones - fetus and babies
-- bioavailability decreased by milk and food in GI tract

Severe rash w/ sunlight

Front 101

Lincosamide MOA?

Back 101

Lincosamide = Clindamycin

Bacteriostatic

Binds to 50S subunit and blocks aminoacyl translocation of peptide chain

Front 102

Clindamycin therapeutic use?

Back 102

First line for anaerobic coverage above the diaphragm

Second line for skin infections

Good staph, strep coverage

Front 103

CLINICAL: You have treated a pt w/ clindamycin and they develop pseudomembraneous colitis. How do we treat this?

Back 103

Tx w/ oral metronidazole (or oral vancomycin)

Front 104

How do we treat TB?

Back 104

RIPE
Rifampin (induces CYP450)
Isoniazid
Pyrazinamide
Ethambutol

Front 105

Isoniazid S/E?

Back 105

causes hepatic damage

Front 106

Drugs which inhibit DNA gyrase?

Back 106

nalidixic acid

FQ’s
-- ciprofloxacin

forms negative DNA supercoils

Front 107

What are the protein synthesis inhibitors?

Back 107

buy AT 30, CELL at 50

A = aminoglycosides (cidal) + spectinomycin (static) – use for FCN resistant gonorrhea
T = tetracyclines (static)

C = chloramphenicol (static)
E = erythromycin (static)
L = lincomycin (static)
L = cLindomycin (static)

Since chloramphenicol, macrolides and clindamycin work at the same site, do NOT use them together because they will interfere w/ each other

Front 108

What are the bactericidal drugs?

Back 108

PCNs, cephalosporins, aztreonam, imipenem
vancomycin
bacitracin
cycloserine
aminoglycosides (gentimicin, etc)
methenamine
polymixin, colistin
rifampin
isoniazid
FQ’s (norfloxacin, etc)
nalidixic acid

Front 109

What are the bacteristatic drugs?

Back 109

spectinomycin
chloramphenicol
macrolides (erythromycin, etc)
lincomycin
clindamycin
tetracyclines
nitrofurans = nitrofurantoin
sulfonamides/trimethoprim

Front 110

How is bacterial resistance usually acquired?

Back 110

Plasmid-mediated resistance is easily transferred by transduction to other species of bacteria

Front 111

What are the β-lactams?

Back 111

PCNs
cephalosporins
monobactans
carbapenems

The transpeptidase enzymes which are inhibited by the β-lactams are called penicillin-binding proteins (PBPs) because they are the target site for these drugs

Front 112

How do G (+) bugs become resistance to β-lactams?

Back 112

1.production of bacterial β-lactamases (penicillinases)

2.altered PBP's with decreased affinity for β-lactams. Synthetic PCN's which are resistant to the β-lactamases may not be effective if if the bug also has altered PBP's

3. MRSA = mutations change the binding sites of the PBP = no β-lactam can bind to the PBP = MRSA is resistanct to all β-lactams (PCN's, cephs, imipenem, aztreonam)

Front 113

How do we treat MRSA?

Back 113

Tx MRSA w clindmycin, trim-sulfa or possibly doxycycline

Front 114

How do G(-) bugs become resistant to β-lactams?

Back 114

1.production of bacterial β-lactamases (penicillinases) which may be inducible

2. reduced permeability --> β-lactams gain access to the periplasmic space (the site of the peptidoglycan wall in gram negative bugs) by passing through channels (called porins) in the outer bacterial membrane.
-- A mutation which decreases the number of porins reduces the entry of the β-lactams to their site of action.
-- Thus a β-lactam could resistant to β-lactamases, and yet not be able to inhibit bacteria growth because it could not reach the PBP's

Front 115

How do bugs become resistant to vancomycin?

Back 115

VRE’s

Vancomycin inhibits cell wall synthesis by binding to the terminal D-ala of the nascent peptidoglycan side chain
-- this action inhibits transglycosylation, so both the elongation and the cross-linking of the peptidoglycan chain are inhibited.

Resistance occurs when a mutation changes the terminal D-ala to a D-lactate
-- vancomycin can no longer bind

Front 116

How do bugs become resistant to FQs?

Back 116

a single point mutation alters the binding of FQ's to the active site of DNA gyrase

Front 117

How do bugs become resistant to aminoglycosides?

Back 117

Aminoglycosides = gentamicin, tobramycin, amikacin

Plasmid-mediated enzymes are transferases which destroy the antibacterial effect of AG's by altering their structure

The altered drug is inactive in inhibiting bacterial protein synthesis.

Enzymatic alterations include acetylation of amine groups and phosphorylation of hydroxyl groups

Front 118

How do bugs become resistant to macrolides?

Back 118

Macrolides = erythromycin, clarithromycin, azithromycin, clindamycin

bacterial enzymes methylate the 23S ribosomal component of the bacterial 50S ribosome

This methylation prevents the binding of erthyromycin and clindamycin to the bacterial ribosome.

Front 119

How do bugs become resistant to tetracyclines?

Back 119

tetracyclines = doxycycline

Pumped into susceptible bugs by an energy-dependent transport system in their cellular membranes.

Plasmids carry resistance genes which decrease the intracellular accumulation and code for efflux pumps which extrude the drug from the cell

Front 120

How do bugs become resistant to folate synthesis inhibitors?

Back 120

folate synthesis inhibitors = trim-sulfa

a plasmid-coded gene synthesizes a form of dihyropteroate synthetase which does not bind sulfonamides even though it still binds PABA

Bacterial folate synthesis continues unabated

Front 121

How do drugs become resistant to rifampin?

Back 121

A mutation causing a single amino acid substitution in the beta-subunit of the DNA-direcdted RNA polymerase reduces the binding of rifampin

Front 122

How do drugs become resistant to chloramphenicol?

Back 122

plasma mediated

Involves the production of acetyltransferases which inactivates the drug