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VM722 Pharm > Pharm Final > Flashcards

Pharm Final Flashcards

1
Q

Adjuvant

A

tx when there is no measurable dz to suppress secondary tumor formation. Generally a treatment after surgical resection

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2
Q

Neoadjuvant

A

treatment to shrink or pre-treat tumor prior to sx

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3
Q

different goals for cancer tx

A

Cure, Remission, Palliation (reduce pain, improve fx),

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4
Q

Multi drug chemo protocols

A

standard for curative intent, or intense tx

Ideally drug combos have complimentary activity and don’t have overlapping toxicity

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5
Q

MTD (max tolerated dose)

A

dose that allows for the highest exposure (aka max pharm response/efficiacy) w/ acceptable toxicity

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6
Q

DLT (dose limiting toxicity)

A

MTD is determined by highest dose level at which no more than 1/6 patients develop a DLT

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7
Q

CR (complete remission) measurement response

A

complete disappearance of tumor and symptoms of dz

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8
Q

PR (partial remission) measurement response

A

decreased volume by > or = 50% or max diam > or = to 30%

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9
Q

SD (stable disease) measurement response

A

no increase of decrease (or increased <20% in diam)

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10
Q

PD (progressive dz) measurement response

A

increase volume >25%, increase diam >20% new lesions

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11
Q

Methods of resistance to chemo drugs

A
  • decrease drug uptake
  • decrease biotransformation/activation
  • increase inactivation
  • Multidrug resistance: ABCB-1 gene & p glycoprotein transporter
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12
Q

Glucocorticoids MOA

A

alter gene transcription

direct lytic effect on malignant cells in lymphoid malignancies, leukemia, myeloma

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13
Q

Antimetabolites MOA

A

block purine/pyrimidine biosynth (so no DNA made)

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14
Q

Methotrexate

A

folate analog

rarely used in vet med b/c enterohepatic recycling + GI accum = toxicity before therapeutic effect

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15
Q

5-Fluorouracil

A

treat epithelial tumors

Contraindicated in cats - deficient in DPD to metabolize this drug –> drug accum = toxicity

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16
Q

Cytosine Arabinoside, Ara-C, Cytarabine

A

Used for dz w/ CNS involvement because can cross BBB

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17
Q

Alkylating agents MOA

A

Interfere w/ replication
Cross link DNA by covalently binding macromolecs - no longer separatable for replication
or cause non-repairable DNA lesion

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18
Q

Common side effects from alkylating agents

A

BAG: bone marrow suppression, alopecia, GI

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19
Q

Cyclophosphamide

A
  • must be metabolized in the liver to be active (drug alone won’t kill tumors) - PRO drug
  • Causes SHC (sterile hemorrhagic cystitis), neutropenia, thrombocytopenia, GI side effects in cats
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20
Q

Chlorambucil

A
  • use if Cyclophosphamide causes SHC or for certain chronic tumors
  • delayed onset, may cause cerebellar toxicity
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21
Q

Chemo drugs able to cross BBB

A

Cytidine analogs

CCNU

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22
Q

Decrease occurrence of SHC

A

Caused by acrolein metabolite - damage bladder tissue
Mesna - neutralizes acrolein in bladder
Furosemide - diuretic dilutes & increases acrolein clearance
Also, switch to Chlorambucil

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23
Q

Anti-tubulin agents MOA

A

Interfere w/ spindle fiber formation, thus chrom separation during mitosis
stop replicating cells in M phase –> then they die

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24
Q

Vinca Alkaloids

A

inhibit microtubule assembly

  • Vinchristine = peripheral neuropathy but minimal myelosuppression, for lymphoma
  • Vinblastine - BAG, less neurotoxicity, for mast cell tumors
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25
Q

Anti-tumor antibiotics MOA

A

form complexes w/ DNA, inhibit DNA/RNA synth

BAG side effects

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26
Q

Single most broadly used chemotherapeutic active agent used in veterinary oncology

A

Doxorubicin. very efficaious!!

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27
Q

Doxorubicin MOA

A

inhibits RNA, DNA polymerase, topoisomaerase II

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28
Q

Doxorubicin toxicity

A
  • GI, hematopoietic and cardiac toxicity
  • Cardiac in dogs, renal in cats
  • Cardiac related to total lifetime dose, but can also get acute toxicity, messes w/ heart through multiple mechs
  • Vesicant - bad local tissue damage if leaves vessels
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29
Q

Mitoxantrone

A

synthetic doxorubicin
similar MOA but forms less ROS’s
used in dogs w/ cardiac issues or that have reached lifetime doxo limit

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30
Q

L-Asparaginase MOA

A

depletes asparaginase in blood –> inhibits protein synth in tumor cells

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31
Q

L-Asparaginase

A
  • Exclusively used for lymphoproliferative disorders often in relapse settings (e.g. lymphoma)
  • blocks methotrexate efficacy & toxicity
  • long half life
  • can get anaphylaxis, pancreatitis, DIC
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32
Q

Cisplatin

A

contraindicated in cats - fatal fulminant pulmonary edema

renal toxicity, BAGS, neurotox, ototox,

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33
Q

Carboplatin

A

BAGs, neurotox, rare nephrotoxicity

Dose based on renal fx (GFR) not weight

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34
Q

Molecular target agent vs. Cytotoxic agents

A

MTA’s block signaling pathways for tumor cell proliferation, survival
Mostly targeted toward kinase reactions (used in cell signaling ubiquitously)
Pro - only target tumors, not local tissue (vs. cytotoxic target any dividing cells)

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35
Q

Toceranib

A

TKI
Inhibits c-Kit - expressed by mast cell tumors to block formation in dogs
- resistance to drug happens quickly
- GI toxicity, neutropenia

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36
Q

Chemo agents that cross-link DNA

A

Platinum agents

alkylating agents

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37
Q

only 2 vet-approved chemo drugs

A

Palladia & Tanovea

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38
Q

Drugs to not give to cats

A

5-fluoricil

cisplat

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39
Q

4 ways antimicrobial drugs are classified

A
  1. class of microorganism they show activity against
  2. antibacterial spectrum of activity
  3. bacteriostatic or cidal
  4. time of conc dependent activity
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40
Q

broad spec means it potentially works against:

A

bacteria (G+,G-, aerobic, anaerobic), mycoplasma (no cell wall), rickettsia & chlamydia (intracellular), protozoa (euk)

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41
Q

What antibacterials are always static at all concentrations?

A

Tetracyclines

Sulfonamides

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42
Q

Concentration dependent drugs

A

higher the conc of a drug above MIC = faster rate of killing (steady state not important)
peak of Cmax (max serum conc achieved)
To optimize: give higher doses less frequently
aminoglycosides, metronidazole

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43
Q

Concentration and time dependent drugs

A

AUC (unbound drug at steady state)

fluoroquinolones

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44
Q

Time dependent drugs

A

the longer a drug maintains serums conc’s exceeding MIC, the more efficacious (higher doses don’t improve this)
T>MIC
To optimize: give lower doses more frequently
beta lactams, some macrolides, tetracyclines, TMS, chloramphenicol

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45
Q

MIC (minimum inhibitory conc)

A

lowest concentration of a drug required to inhibit visible growth of bacteria

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46
Q

Breakpoint MIC

A

value where plasma conc unlikely to be achieved, no clinical benefit against bacteria w/ MIC above that breakpoint

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47
Q

4 indications for use of antimicrobial combos

A
  1. antimicrobial synergism
  2. polymicrobial infections
  3. decrease chance of resistant isolates emerging
  4. decrease dose-related toxicity
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48
Q

Fluoroquinolone & Quinolone PK’s

A
  • good oral bioavailability in monogastrics
  • large vol of distribution, even to CNS, eye
  • accum in macrophages, neuts, urine
  • extended half-life, dose every 1-2 days
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49
Q

Enrofloxacin

A

can often metabolize into cirprofloxacin (lower MIC than enro)

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50
Q

Quinolone characteristics

A
  • Extended spec (limited against strep, obligate anaerobes)
  • Good against G-‘s, variable against G+
  • anaerobes mostly resistant
  • efficacy is concentration dependent
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51
Q

Quinolone MOA

A

Inhibit bacterial DNA gyrase and/or topoisomerase IV to inhibit DNA replication

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52
Q

Fluoroquinolone characteristics

A
  • active against bacteria, mycoplasma, rickettsia, chlamydia
  • antibacterial against G+/- aerobes
    Bacteriostatic at MIC, bacteriacidal at higher doses
  • Concentration dependent activity
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53
Q

Fluoroquinolone contraindications

A
  • Don’t give cats enrofloxacin at higher doses = retinal degeneration, photoreactivity
  • Younger animals in rapid growth phases
  • Enrofloxacin has some reported neurotoxic effects (hum, dog, cat)
  • Antagonism if Cipro combined w/ chloramphenicol and rifampin
54
Q

How are bacteria resistant to fluoroquinolones

A
  • DNA gyrase mutation and/or topoisomerase IV mutation
    (exception - Campy highly resistant w/ just gyrase mutation)
  • decreased permeability (porins altered)
  • drug efflux
  • target protection (plasmids)
55
Q

Beta lactam MOA

A

Bacteriacidal for growing cells only
prevent cell wall formation, cause lysis
Time dependent

56
Q

beta lactam “eagle” paradoxical effect

A

given in concentrations above optimal killing zone = reduced bactericidal effect
- bad b/c BL’s have large margin of safety, tend to be overdosed

57
Q

beta lactam characteristics

A

Active against G+, variable G-‘s
Bacteriacidal, can be static if conc too high
Time dependent activity

58
Q

Mech’s of resistance to BL’s

A

make beta lactamase enz’s that break beta lactam ring
G+ make them extracellularly
G- make them in periplasmic space so more resistant to penicillins vs cephalosporins

59
Q

Penicllins

A

poorly absorbed orally, short half life, eliminated rapidly (renal)
Procaine has delayed absorption, exotics susceptible to toxicity
Antistaphylococcal resistant to lactamases from S. aureus
MRSA, MRSP resistant to all BL’s
Antipseudomonals against Pseudomonas

60
Q

Extended spectrum aminopenicillins

A

Amp & amoxicillin
More activity against G-‘s, with slightly less G+
Amoxicillin more bioavailable than ampicllin
Combine w/ beta-lactamase inhibitors = increased efficiacy
Give oral to avoid GI issues
Do not use Ampicillin in small rodents or rabbits (clostridial enteritis)

61
Q

What is Amoxicllin best choice to use for

A

best penicllin to treat UTI’s

drug of choice to treat Lepto

62
Q

Cephalosporins

A

Reistant to beta-lactamases
parenteral, short half life = freq doses, excreted in urine
with generation # increasing, see more G- coverage, less G+
Gen 3 & 4 = can induce very resistant super beta lactamses, last resort for uncomplicated infections

63
Q

Ceftiofur

A

resp dz in cattle, sheep, pig, horse

UTI in dogs

64
Q

Carbapenems

A

widest spectrum of activity, resistant to BLases
last resort drugs - usually for resistant nosocomial infections
pair w/ aminoglycoside for pseudomonas (decrease resistance)

65
Q

Clavulonic Acid

A

Beta lactamase inhibitor

used in combo with beta-lactames to inhibit beta-lactamase hydrolysis –> increases BL efficiacy

66
Q

Protein Synthesis inhibitors MOA

A

Bind to a ribosomal subunit to inhibit polypeptide chain formation –> block protein synth

67
Q

Tetracycline characteristics

A
  • against G+, G-‘s, mycoplasma, some mycobacteria, anaplasma, rickettsia, protoza, filarial parasites
  • bind to 16s RNA of 30s subunit
  • antiinflammatory activity
  • mostly bacteriostatic
  • osteotropic
68
Q

Resistance mechs against tetracyclines

A

efflux out drug

ribosomal protection proteins remove tetracycline from tRNA binding site

69
Q

Contraindications of tetracyclines

A
  1. irritants - see vomiting, local tissue damage at injection site
  2. GI flora imbalance –> enterocolitis
  3. Doxy tablets = esophageal stricture in cats
  4. acute heart toxicity, renal toxicosis, yellow teeth
70
Q

Uses for tetracyclines

A

bov/porcine resp dz complexes
plague, tulaermia, listeriosis
Top choice for rickettsia (SA), Chlamidophila felis in cats

71
Q

Chloramphenicol characteristics

A
  • broad spec against G+, G- aer and anerobes, mod against R. equi, G- eneterics develop resistance
  • bind 50s, inhibit mitochondrial prot synth in mammal bone marrow cells
  • bacteriostatic
  • hepatic metabolism - glucuronidation, eliminated in urine or bile
72
Q

Mech of resistance to chloramphenicol

A

enzymatic inactivation by acetylation of the drug (by CATs)

or efflux drug

73
Q

Chloramphenicol toxicity

A

Inhibits cytochrome P450 enzymes
bone marrow suppression (dose dependent)
Banned from food animals
limit use to ~10 days

74
Q

Chloramphenicol uses

A

SA anerobic infections, MRSP

extreme ocular infections, prostatitis, otitis, salmonellosis

75
Q

Aminoglycoside characteristics

A
  • G-aerobes, enteroccoci, some G+ (often MRSP)
  • Combine w/ BL to increase efficacy against strep
  • bind to 30 s subunit
  • bactericidal, conc dependent
  • drugs not effective against anerobic infections
    (bact actively pump AG’s into cell by oxygen-dependent mech)
76
Q

Resistance to aminoglycosides

A

plasmi-mediated enz prevent binding to ribosome
adaptive resistance lasting ~24 hrs if surive first exposure - reduced uptake (High, SId dose is WAY more effective than freq dose or CRI)

77
Q

aminoglycoside toxicity

A

ototoxicity

nephrotoxicity - acute tubular nephrosis from drug accum

78
Q

How to reduce aminoglycoside nephrotoxicity

A

Ca supplement
high prot/Ca diet
give drug SID and higher dose

79
Q

aminoglycoside uses

A

more toxic - topical or oral use against enterobacteriaceae

less toxic drugs - parentally for G- aerobe sepsis, MRSP infec

80
Q

Ondansetron/Zofram

A

5HT3 receptor antagonist (aka anti-emetic)
caution for patients w/ hepatic dysfunction
side effects: constipation, sedation, head shake, arrythmias

81
Q

Maropitant/Cerenia

A

NK1 receptor antagonist (anti-emetic) - dog & cat by blocking substance P from binding
motion sickness in dogs
lower dose w/ hepatic dysfunc
stings

82
Q

Apomorphine

A

D2 agonist used as a canine emetic

Cats don’t have D2 in chemoreceptor trigger zone, not useful

83
Q

What is a more efficacious acid suppressant - Famotidine or Omprazole

A

Omeprazole (proton pump inhibitor) - more efficacious

Famotidine (H2 receptor antagonist)

84
Q

Don’ts when stimulating a cat’s appetite

A

No oral diazepam (–> fulminant hepatic failure)

Cyproheptadine + Mirtazapine together (–> serotonin synd)

85
Q

A Ghrelin agonist will ____ appetite

A

increase

86
Q

Immodium

A

binds to mu opioid receptors –> decreased GI activity –> constipation
(–> megacolon in cats BAD)

87
Q

Drug of choice to move a cats colon

A

Cisapride (5-HT4 serotonineric and ACh agonist)

metaclopramide only stims SI, not colon

88
Q

Erythromycin

A

pro-motility drug, antibiotic
mimics motilin activity - increases upper gI activity like metaclop
Acts on ACh, 5-HT4 receptors

89
Q

Options to treat IBD

A

novel protein, hydrolyzed diet
antibiotics: metronidazole, Tylosin, Budesonide (if intolerant of steroids), Prednisolone!!
Cyclosporine (inhibits cytokines, cell-mediated immunity by targeting T cells)
Probiotics, fecal microbiota transplantation

90
Q

Endectocides are effective against

A

nematodes, arthropods

91
Q

Benzimidazoles are effective against

A

nematodes, some cestodes, protozoans

92
Q

Macrycylic Lactones

A
  • broad spec
  • safe in mammals (can’t cross BBB) except ivermectin
  • paralytics
93
Q

Avermectins

A

lipophilic (fatter animal = longer presence/protection
longer withdrawal in rum - not for milk producers
fasting - better efficacy
Fecal residue issue

94
Q

fecal residues

A

arthropods, annelids don’t want to live there
more toxic to immature (feed directly on organic matter)
poop lasts longer on pasture

95
Q

Benzimidazoles

A

some teratogenic - don’t give during 1st trimester
nematodes
alter metabolic processes - block mitochondrial fx, glu uptake
poorly absorbed, short withdrawal (no residue issues)

96
Q

Tetrahydropyrimidines

A

nematodes
orally
paralytic

97
Q

Pryantel tartate vs. pamoate & morantel

A

tartate: water sol, well absorbed orally, EQ
pamoate: water insol, poor absorbed to act in LI, dog/cat/EQ
morantel: withdrawal time, rum

98
Q

What anthelminitics cause resistance

A

Macrocyclic lactones
Benzimidazoles
Tetrahydropyrimidines
d/t repeated anthelminitic use eliminated susceptible worms

99
Q

Who specifically is resistant

A

Strongyles, Ancylostoma against Benzimidazoles via tubulin resistance & tetrahydropyrimidines

Strongyles, Ascarids, Dirofilaria, Ancylostoma against ML’s

100
Q

Emodepside

A 
new compound class
new MOA - paralytic mech
Cats - Ancylostoma trubaforme, Toxavara cati (topical + prazi)
101
Q

Piperazone

A

very good against ascarids
paralytic
non-toxic to host, gone in 24 hrs

102
Q

Arsenicals

A

alternative to monthly preventatives - not idea b/c arsenic

limited against Dirofilaria

103
Q

Isoquinolones

A

very safe
cestodes, trematodes
MOA - some kind of paralytic
Prazi

104
Q

Praziquantel

A

Taenia, Dupylidium in dogs, cats (but resistance likely)
echinococcus in dogs
anoplocephala in EQ

105
Q

Benzene sulfonamide

A

Fasciola hepatica (trematod)
inhibits glycolytic pathway
best at 10-12 wks post infection (b/c flukes in bile duct)
liver damage - slaughter issue (also withdrawal)

106
Q

Sulfonamides & Macrolides

A

bacteriostatic broad spec antimicrobials (systemic dz)
inhibit bacteria, protozoa
rarely used along - extensive resistance has developed

107
Q

Sulfonamide MOA

A

outcompetes PAbA to inhibit DHP’s from forming pteroic acid –> no folic acid synth for purine biosynth

108
Q

Who is resistant to Sulfonamides & Macrolides

A

Mycobacterium, mycoplasma, pseudomonas

via changes to PABA or DHP

109
Q

Sulfonamides and urine

A

water insoluble –> form crystals in acidic environ –> lots of UT side effects
metabolized form less soluble but dogs deficieny in this pathway

110
Q

Sulfonamide side effects

A 
UT probs
hematopoetic disorders
derm reactions - toxic epidermal necrolysis
KSC
Idiosyncratic drug reactions
111
Q

Potentiated sufonamides

A

sulfonamide +Trimethoprin (1:5 ratio)

bactericidal synergistic combo

112
Q

Macrolide MOA

A

bind to 50s ribisome –> no protein synth
bacteriostatic, can be cidal at high conc
anti-biofilm
immunomodulatory effects (decrease inflamm rxn)
pro-GI kinetics (motilin receptor agonist)

113
Q

mechs of resistance to Macrolides

A

rRNA methylation (can’t bind to ribosome)
drug efflux
enz inactivation

114
Q

macrolide adverse effects

A

irritants w/ injection
dose related GI disturbances
Tilmicosin - cardiovascular toxicity (not bov, pig)

115
Q

Drug of choice for campy diarrhea or abortion

A

erythromycin

alternate for penicllin sensitivity, treating lepto, rickettsia

116
Q

Lincosamides

A

inhibit prot synth
contraindivated in EQ, rabbits, hamsters, GP’s –> necrotizing enterocoloitis from clostridum overgrowth
Salmonellosis in dogs

117
Q

allyamines

A

block ergosterol formation
fungicidal
synergystic when combined w/ flu, itra, vori

118
Q

Amphotericin B

A 
given IV - systemic treatments
fungicidal - binds and lyses ergosterol
lipid form = less kidney issues
synergistic w/ flucytosine
most toxic antifungal
119
Q

Antifungal azoles

A

bacteristatic - yeast, mycoses, dermatophytes
Flu and vori penetrate CNS
Flu excreted in urine as active drug (rest as bile)
Do not give any for systemic use during pregnancy

120
Q

Ketokonazole

A

better for dogs
may see repro, hepatic, haircoat issues
hepatotoxicity in cats

121
Q

Itraconazole

A

better for cays
dogs get hepatic toxicosis
contraindicated for heart failure

122
Q

Griseofulvin

A

taken orally for dermatophytosis

b/c distributes to keratin precursor cells

123
Q

successful antiviral drug moa’s

A

nucleoside analogues, protease inhibitors

target certain enz of structural target

124
Q

antivirals

A

Idoxuridine - herpesvirus keratitis or skin infec
Acyclovir - herpesvirus family
Ribavirin - small window or toxic

125
Q

neuramidase inhibitors

A

cleave sialic acid residues - viral particles can’t release

influenza A & B

126
Q

Lysine

A

nutritional supp

reduces severity/freq of FHV-1 b/c interferes with arginine absorption

127
Q

CB1 receptors

A 
glutamatergic, ganaergic g prot receptors
mostly in CNS
activated = decreased NT
mostly responsible for cannabis high
relax eat sleep forget
128
Q

CB2 receptors

A

g prot receptors in periphery
activated = decrease cAMP
therapeutic effects of CBD
pain, inflammation modulation

129
Q

potential CBD uses

A 
anti emetic
diabetes mellitus
cancer
antimicrobial
pain, inflammation, immunomodulatory
epilepsy
anxiolytic
130
Q

cannabis toxicity in dogs

A 
high dose, enters CNS b/c lipid soluble
effect in 1 hr, lasts 1-3 days, gone in a week
cB1 receptors dominate toxicity
Ataxia, depression, mydriasis
treat w/ supportive care
131
Q

cannabis vet products

A

all unregulated
dose/bioavailaiblity is variable
no data on dosing
might have regulatory restrictions to comply w/

VM722 Pharm (5 decks)

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