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Pharmacology > Fall '13 Quiz 2 > Flashcards

Fall '13 Quiz 2 Flashcards

1
Q

What is the suffix for fluoroquinolones drugs?

A

“-floxacins”

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2
Q

What was the first veterinary fluoroquinolone?

A

Enrofloxacin

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3
Q

What does Enrofloxacin turn into after hepatic metabolism?

A

Ciprofloxacin

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4
Q

What was the first quinolone drug that fluoroquinolones are based on?

A

Nalidixic acid

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5
Q

What are regular fluoroquinolones’ method of action?

A

Inhibit DNA gyrase

relaxes supercoiled DNA

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6
Q

Inhibition of DNA gyrase effects which type of bacteria?

A

Gram negative coliforms

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7
Q

What are advanced fluoroquinolones’ method of action?

A

Inhibit Topoisomerase IV

separates replicated DNA during cell division

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8
Q

Inhibition of Topoisomerase IV effects which type of bacteria?

A

Gram positive

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9
Q

Are fluoroquinolones -cidal or -static?

A

-cidal

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10
Q

What happens when fluoroquinolones inhibit these enzymes?

A

Stabilizes the enzyme-DNA complex
= breaks DNA
= triggers apoptosis

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11
Q

What is a first generation fluoroquinolone? What is it effective against?

A

Nalidixic acid (no F- atom)
Gram negative bacteria
Urinary tract only

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12
Q

What is a second generation fluoroquinolone? What is it effective against?

A

Enrofloxacin
Mostly Gram negative bacteria
Some Gram positive bacteria

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13
Q

What is a third generation fluoroquinolone? What is it effective against?

A

Pradofloxacin
Gram negative bacteria
More Gram positive bacteria

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14
Q

What generation of fluoroquinolones has the broadest spectrum of activity?

A

Third

Pradofloxacin

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15
Q

What type of bacteria are resistant to fluoroquinolones?

A

Obligate anaerobes

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16
Q

Are fluoroquinolones effective against Pseudomonas?

A

Yes!

but only some drugs

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17
Q

Are fluoroquinolones effective against Mycobacteria?

A

Yes!

if it is rapidly growing

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18
Q

What is special about the the drug category fluoroquinolones?

A

They are the most advanced drugs we have today

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19
Q

How likely is it that bacteria will become resistant to fluoroquinolones?

A

Very likely!

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20
Q

What bacterial resistance mechanism leads to a LARGE increase in the MIC value for fluoroquinolones?

A

Mutations in the drug binding sites

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21
Q

What bacterial resistance mechanism leads to a SMALLER increase in the MIC value for fluoroquinolones?

A

Increased expression of drug efflux transporters

& decreased drug uptake

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22
Q

What is an amphoteric substance?

A

It has both an acidic group and a basic amine group

fluoroquinolones are amphoteric

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23
Q

What species have good oral bioavailability and which one have poor?

A 
Good = monogastrics
Poor = ruminants
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24
Q

What is the only fluoroquinolone that has poor bioavailability in monogastrics?

A

Ciprofloxacin

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25
Q

How well do fluoroquinolones penetrate restricted sites?

A

Well!

BBB, prostate, bone

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26
Q

What cell type accumulates fluoroquinolone drug?

A

Phagocytes

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27
Q

Do fluoroquinolones have a short or long half-life?

A

Long

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28
Q

How quickly can fluoroquinolones kill bacteria at the Cmax?

A

20 minutes!

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29
Q

Do fluoroquinolones produce at post-antibiotic effect? If so how for how long?

A

Yes

4-8 hrs after elimination

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30
Q

When would you reach for a fluoroquinolone antibiotic?

A

As a second or third drug after others have failed

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31
Q

Are fluoroquinolones effective against intracellular pathogens?

A

Yes!

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32
Q

What fluoroquinolone drug is approved for use in cattle? What disease is it used to treat?

A

Enrofloxacin (& Danofloxacin)
Bovine respiratory disease (BRD)
(only in beef cattle)

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33
Q

What fluoroquinolone drug is approved for use in swine? What disease is it used to treat?

A

Enrofloxacin

Swine respiratory disease (SRD)

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34
Q

What are some of the major adverse effects of fluoroquinolones?

A
  1. GI effects
  2. Canine toxic shock syndrome
  3. Arthropathy
  4. Potentiates seizures
  5. Retinal degeneration in cats
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35
Q

What happens in Canine toxic shock syndrome?

A

Associate with Enrofloxacin monotherapy

Superantigen from killed Streptococci

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36
Q

Why can fluoroquinolones cause blindness in cats?

A

Genetic polymorphisms in a drug efflux pump
Drug accumulates in retina and generates free radicals
High doses of enrofloxacin

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37
Q

What are two “Nitro-“ antibacterial drugs?

A
  1. Metronidazole

2. Nitrofurantoin

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38
Q

Are “Nitro-“ antibacterial drugs -cidal or static? What is the mechanism?

A

-cidal

Nitrogens –> free radicals –> breaks DNA or RNA

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39
Q

What bacteria are susceptible to “Nitro-“ antibacterial drugs?

A

Anaerobic bacteria!

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40
Q

What other organisms are susceptible to “Nitro-“ antibacterial drugs?

A

Anaerobic protozoa

  1. Coccidia
  2. Trypanosomes
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41
Q

What is a Nitroimidazole prototype drug?

A

Metronidazole

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42
Q

What are some ADME characteristics about Metronidazole?

A
  1. Lipophilic
  2. Good oral bioavailability in monogastrics
  3. Less oral bioavailability in ruminants
  4. Great tissue penetration to restricted sites
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43
Q

What is Metronidazole’s spectrum of activity?

A

Narrow
Bactericidal
Anaerobes only
Spirochetes & Protozoa

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44
Q

What drug is Metronidazole frequently combine with to kill Gram negative aerobes?

A

Aminoglycoside

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45
Q

What are some indications for using Metronidazole in dogs & cats?

A
  1. GI = empirical treatment of diarrhea
  2. GU
  3. Respiratory
  4. Brain abscesses
  5. protozoal infection
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46
Q

Why is Metronidazole NOT approved for use in food animals?

A

Potential carcinogen!

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47
Q

What are some adverse effects of Metronidazole?

A

Not many
Mild GI disturbances
Hypersalivation in cats
Neurotoxic at high doses

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48
Q

What is the mechanism of action of Rifamycins?

A

Inhibit RNA synthesis

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49
Q

Are Rifamycins time-dependant or concentration dependent?

A

Time-dependant

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50
Q

If the effect of Rifamycins -cidal or -static?

A

-cidal

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51
Q

What is the risk associated with using Rifampin alone?

A

High risk of developing bacterial resistance

commonly use in combinations

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52
Q

Which monogastric has surprisingly poor oral bioavailability?

A

Horses

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53
Q

What important to remember about Rifampin’s metabolism?

A

Potent CYP inducer

Increase its elimination and that of other drugs

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54
Q

What is a shocking but normal side effect of Rifampin?

A

Orange-red color to urine, feces & saliva!

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55
Q

What is Rifampin’s spectrum of activity?

A

Narrow
Good against Gram positive bacteria
(not many Gram negatives!)

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56
Q

How can Rifampin’s risk of bacterial resistance be reduced?

A

Use in combination with bacteriostatic drugs like tetracyclines or macrolides

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57
Q

What are some clinical indication for using Rifampin in horses?

A

Rhodococcus infections in foals

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58
Q

What are some clinical indication for using Rifampin in small animals?

A

Staphylococcal infections

esp. MRSA

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59
Q

What are some clinical indication for using Rifampin in food animals?

A

Illegal!

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60
Q

What is main adverse effect with Rifampin?

A

Hepatotoxicity

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61
Q

What are the three important aminoglycosides in vet medicine?

A
  1. Amikacin
  2. Gentamicin
  3. Neomycin
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62
Q

What is the method of action for aminoglycosides?

A

Bind to 30S bacterial ribosome

Abnormal proteins are made

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63
Q

Are aminoglycosides -cidal or -static?

A

-cidal

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64
Q

Are aminoglycosides time-dependant or concentration-dependant?

A

Concentration-dependant

one large dose binds many ribosomes

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65
Q

Do aminoglycosides have a post-antibiotic effect?

A

Yes!

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66
Q

What is the solubility and transport chemistry of aminoglycosides?

A

Water soluble! (sugar molecules)
Basic drugs
Energy-dependant transport into bacteria

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67
Q

What spectrum of activity do aminoglycosides have?

A

Narrow spectrum

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68
Q

What type of bacteria are most susceptible to aminoglycosides?

A

Gram negative aerobic bacilli

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69
Q

What are some special bacteria that are susceptible to aminoglycosides?

A
  1. Pseudomonas

2. Proteus

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70
Q

Do aminoglycosides work on anaerobes?

A

No!

drug uptake is oxygen dependant

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71
Q

What is the most important drug resistance mechanism in bacteria?

A

Bioinactivation of the drug

11 plasmid enzymes can do this

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72
Q

What is the best route of administration of aminoglycoside drugs?

A

SC or IM

poor oral bioavailability

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73
Q

Why should you not mix aminoglycosides and penicillins?

A

Aminoglycosides are bases
Penicillins are acids
Cannot mix acidic and basic drugs together!

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74
Q

What are two newer aminoglycosides? Why do they need to be given slowly?

A
  1. Amikacin & Gentamicin

2. They can paralyze the patient (NMJ blockade)

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75
Q

How well do aminoglycosides penetrate tissues?

A

Not very well

but they can cross placental membranes

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76
Q

What biological fluid inactivates aminoglycosides?

A

Purulent debris

wounds need to be cleaned out

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77
Q

How are aminoglycosides eliminated? What adverse effect is related to the drug’s excretion?

A

Glomerular filtration
Excretion in urine
Risk for nephrotoxicity

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78
Q

In dogs & cats what infections are treated with amikacin or gentamicin?

A
  1. Bacteremia
  2. Skin & soft tissue
  3. Bone & joints
  4. Respiratory
  5. Genitourinary
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79
Q

What infections are treated with aminoglycosides in horses?

A
  1. Bacterial enteritis = neomycin
  2. Uterine infections = gentamicin
  3. General infections = amikacin
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80
Q

Why are aminoglycosides not commonly used in food animals?

A

LONG withdrawal time

months

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81
Q

What aminoglycoside is used to treat bacterial enteritis in food animals?

A

Neomycin

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82
Q

Which aminoglycoside can be used to treat Swine dysentery?

A

Gentamicin

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83
Q

What are the three important adverse effects of aminoglycosides?

A
  1. Nephrotoxicity = acute tubular necrosis
  2. Neuromuscular block = blocks Ca++
  3. Ototoxic effects = high frequency hearing loss
84
Q

What organ can be damaged by aminoglycosides? In what direction does it progress?

A

Organ of Corti

Basal (high greq) to apical (low freq)

85
Q

What do you think of first when you hear tetracycline?

A

Ticks!

arthropod infections

86
Q

What ribosomal subunit are tetracyclines’ site of action?

87
Q

What ribosomal subunit are amphenicols’ site of action?

88
Q

What is the mechanism of action of tetracyclines?

A

Reversibly bind to 30S ribosome

Block tRNAs from binding to the aceptor site

89
Q

Is tetracycline -cidal or -static? Time- or concentration-dependant?

A

-static

Time-dependant

90
Q

Why is tetracycline selective for bacteria?

A

Taken in by bacterial active transport

91
Q

What are two tetracycline derived drugs?

A
  1. Chlortetracycline

2. Doxycycline

92
Q

Which tetracycline derivative is shorter acting and water soluble?

A

Chlortetracycline

93
Q

Which tetracycline derivative is long acting and lipid soluble?

A

Doxycycline

94
Q

What are tetracyclines spectrum of activity?

A

Intermediate to broad spectrum

95
Q

Which tetracycline derivative has some bactericidal activity against a few bacteria?

A

Doxycycline

Time -dependant

96
Q

What organisms are susceptible to tetracycline?

A
  1. Gram negative & positive
  2. Aerobic & anaerobic
  3. Atypicals = think ticks!
  4. Protozoans
97
Q

What bacteria are usually resistant to tetracyclines?

A
  1. Pseudomonas

2. Proteus

98
Q

What type of bacteria carries the most resistance to tetracyclines? The least resistance?

A

Most resistant = enteric bacteria

Least resistance = Intracellular bacteria

99
Q

What is the most important resistance mechanism that affects tetracyclines?

A

Efflux pumps

Decreased penetration of the drug

100
Q

Why is the use of tetracyclines of public health concern?

A

Extensively used in food animals
Many animals harbor resistant enteric bacteria
Esp. Salmonella

101
Q

What type of food limits tetracycline absorption?

A

Foods high in calcium

Esp. milk

102
Q

Why is oral administration of tetracyclines not a good idea in horses or ruminants?

A

Risk for colitis

103
Q

What is unique about tetracycline’s ADME?

A

Can complex with Ca and be deposited in growing teeth and bones

104
Q

Why do tetracyclines tend to persist in the body?

A

Enterohepatic recycling

Little to no metabolism

105
Q

What is the primary route of elimination of tetracyclines?

A

Excreted unchanged

Urine & bile

106
Q

What is important to know about Doxycycline’s elimination?

A

Excretion in the feces

Can be used in patients with renal dysfunction

107
Q

What infections can tetracyclines treat in cats & dogs?

A

Common infections
Tick borne infections
Lyme disease (off label)

108
Q

What infections can tetracyclines treat in horses?

A

Potomac horse fever = neorickettsia

Oxytetracycline

109
Q

Which tetracycline is used most often in food animals?

A

Chlortetracycline

short-acting

110
Q

What type of infections are tetracyclines used to treat in birds?

A

Common bacterial infections

Protozoan infections

111
Q

What are the four main adverse effects of tetracyclines?

A
  1. GI upset (esp. colitis in horses)
  2. Nephrotoxicity (excreted unchanged)
  3. Hepatotoxicity
  4. Azotemia
112
Q

What are the two main drugs in the group Amphenicols?

A
  1. Chloramphenicol

2. Florfenicol

113
Q

Where do Amphenicols have their site of action?

A 
50S ribosome
(same action as tetracyclines but on the other subunit = 30S)
114
Q

Are Amphenicols -cidal or -static?

115
Q

What type of drug can block the action of Amphenicols?

A

Macrolides
Lincosamides
Type B Streptogramin
= MLS antibacterial drugs

116
Q

Which Amphenicol is banned from use in food animals and why?

A

Chloramphenicol causes aplastic anemia in 1/25,000 humans

117
Q

Which of the two main Amphenicols is more potent?

A

Florfenicol

118
Q

What are two bacteria that are resistant to Amphenicols?

A
  1. Nocardia

2. Mycobacteria

119
Q

How do resistent types of bacteria evade Chloramphenicol?

A

Acetylation of a hydroxyl group

120
Q

What is the oral bioavailability of Amphenicols in monogastrics and ruminants?

A 
Monogastrics = good
Ruminants = poor (inactivation)
121
Q

How good is the tissue penetration of Amphenicols?

A

Very good!
Reaches protected sites
(eye & CSF)

122
Q

What is the main mechanism of metabolism of Amphenicols?

A

Glucuronidation

123
Q

How are Amphenicols excreted?

A

Mostly renal

Some biliary

124
Q

What is Chloramphenicol typically used for in companion animals?

A

Empirical treatment of serious ANAEROBIC infection

125
Q

Can Florfenicol be used in food animals? If so for what infections?

A

Yes

Respiratory infections

126
Q

What are three main adverse effects of Amphenicols?

A
  1. Bone marrow suppression
  2. GI upset
  3. Hypotension
    (calves given drug IV)
127
Q

What three drugs are included in MLS antibacterial drugs?

A
  1. Macrolides
  2. Lincosamides
  3. Streptogramins
128
Q

What drug can be blocked from its binding site by MLS drugs?

A

Chloramphenicol

129
Q

What is the main mechanism of action of Macrolide drugs?

A

Interrupt protein synthesis

  1. Prematurely detach growing peptide chain
  2. Obstruct the exit of the peptide chain
130
Q

What is the main mechanism of action of Lincosamide drugs?

A

Interrupt protein synthesis

1. Inhibits tRNA transfer of AAs

131
Q

What is the main mechanism of action of Streptogramin drugs?

A

Interrupt protein synthesis

Uses both Macrolides and Lincosamides mechanisms

132
Q

Are Macrolides and Lincosamides acids or bases?

133
Q

Macrolides and Lincosamides penetrate tissue well except which tissue?

134
Q

Macrolides and Lincosamides have what spectrum of activity?

135
Q

What bacteria are usually not susceptible to Macrolides and Lincosamides?

A

Aerobic Gram negative bacteria

136
Q

What bacteria are typically susceptible to Macrolides and Lincosamides?

A

Gram positive bacteria
Mycoplasma
Some Gram negative anaerobes

137
Q

Are Macrolides and Lincosamides concentration- or time-dependant? -cidal or -static?

A

Time-dependant

Bacteriostatic

138
Q

What are some adverse effects of Macrolides and Lincosamides?

A
  1. Diarrhea

2. Enteric super infections esp. horses

139
Q

How are resistance genes transferred between bacteria for Macrolides and Lincosamides drugs?

A

Horizontal transfer!

Via mobile elements

140
Q

How to target modifications by bacteria affect resistance in the other MLS drug categories?

A

They are cross-resistant!

141
Q

Name three important Macrolides.

A
  1. Erythromycin
  2. Tylosin
  3. Tilmicosin
142
Q

Name three important Lincosamides.

A
  1. Lincomycin
  2. Clindamycin
  3. Pirlimycin
143
Q

Name one important Streptogramin drug?

A

Virginiamycin

144
Q

Name one important Pleuromutilin drug?

145
Q

Which Macrolide is destroyed by gastric acid?

A

Erythromycin

146
Q

What is important to know about the distribution of Macrolides in the body?

A

Drug concentration is higher in the tissues than in the body

147
Q

What is the major route of elimination of Macrolides?

A

Bile

some in the urine

148
Q

Which Lincosamide has the best oral bioavailability?

A

Clindamycin

149
Q

What bacteria is NOT susceptible to Macrolides and Lincosamides?

A

Gram negative bacteria

150
Q

What are Macrolides and Lincosamides used as a second choice in patients sensitive to the first choice drug?

A

Penicillin

151
Q

Which two MLS drugs are mostly used in companion animal medicine?

A
  1. Erythromycin

2. Clindamycin

152
Q

Which two MLS drugs are mostly used in food animal medicine?

A
  1. Tilmicosin

2. Lincomycin

153
Q

What MLS drug is used in many species?

154
Q

What MLS drug is used to treat Campylobacter enteritis in dogs and R. equi infections in foals?

A

Erythromycin

155
Q

What drug can be used as an alternative to Erythromycin and has greater activity against Gram negative bacteria?

A

Azithromycin

156
Q

What drug is effective for treating chronic colitis and acute lung infections in dogs & cats?

157
Q

What drug is good for treating recurrent skin Staphlococcal infections and other infections?

A

Clindamycin

158
Q

What drug is good for mastitis in ruminants and proliferative enteropathy in swine?

A

Erythromycin

159
Q

What drug is effective against mycoplasma infections?

160
Q

What drug is approved for use only in swine?

161
Q

In which species are MLS antibiotics contraindicated? Why?

A
  1. Pocket pets
  2. Rabbits
  3. Horses
    = causes GI superinfections
162
Q

What is a side effect of Macrolides?

A

Diarrhea

macrolides are motilides!

163
Q

What drug causes lip-smacking and salivation in cats?

A

Clindamycin

164
Q

What adverse reaction can occur with high doses of Tilmicosin given i.v.?

A

Cardiotoxicosis

165
Q

What is the main use of Streptogramins?

A

Livestock growth promoter

166
Q

What is another drug used as a growth promoter?

A

Macrolide Tylosin

167
Q

What is the oral bioavailability of Streptogramins?

A

Poor

confines drug to GI tract

168
Q

What is a specific Streptogramin drug?

A

Virginiamycin

169
Q

What is the Pleuromutilin drug Tiamulin commonly used for?

A

Treatment of infections in swine

170
Q

How many layers of Peptidoglycan are in Gram negative bacteria? Gram positive bacteria?

A

Gram negative = one layer

Gram positive = many layers < 40

171
Q

How to B-Lactams act against the bacteria’s cell wall?

A
  1. Penetration of bacterial cell wall
  2. Binding to penicillin-binding proteins
  3. Interruption of peptidoglycan cross-linkage
  4. Arrest in cell wall formation
  5. Cell lysis!
172
Q

What protein does the B-Lactam ring structure inhibit?

A

Bacterial transpeptidases

= penicillin binding proteins (PBPs)

173
Q

Are B-Lactam drugs time- or concentration-dependant? -cidal or -static?

A

Time-dependant

Bactericidal

174
Q

What role do Autolysins have a cell wall breakdown?

A

B-Lactams inhibit cell wall synthesis allowing autolysins to degrade cell wall membrane unchecked

175
Q

Can B-lactam drugs reach intracellular bacteria?

176
Q

Which bacteria are most susceptible to B-lactam drugs?

A

Gram positive

177
Q

What are three main mechanisms of bacterial resistance to B-lactam drugs?

A
  1. Restrict drug access (Gram negative)
  2. Change PBP target molecule
  3. Produce B-lactamases that breakdown the drug’s ring
178
Q

What type of B-lactamase enzyme expression is clinically important?

A

Plasmid-associated B-lactamases

179
Q

How does the location of the B-lactamase differ between gram negative and gram positive bacteria?

A

Gram negative = periplasmic space

Gram positive = extracellular space

180
Q

Which groups of B-lactamases are insensitive to clavulanic acid?

A

Group 1 & 3

181
Q

Which drug is still able to escape B-lactamase activity?

A

Carbapenems

newest drugs

182
Q

What is a gram positive bacteria that produces B-lactamases?

A

Staphlococcus

183
Q

What types of Gram negative bacteria produce B-lactamases?

A

Enterobacteriaceae

E. coli, pseudomonas, proteus, salmonella, etc

184
Q

What are two B-lactamase inhibitors?

A
  1. Clavulanic acid

2. Tazobactum

185
Q

What animals should not receive Clavulanic acid?

A

Pocket pets!

Use caution in herbivores and horses

186
Q

How do B-lactamase inhibitors affect the MIC value?

A

Reduce the MIC value

187
Q

What are 4 important categories of B-lactam drugs?

A
  1. Penicillin = wide
  2. Cephalosporin = narrow-wide
  3. Carbapenems = wide
  4. Monobactams = narrow
188
Q

What is the spectrum of activity of Penicillin G?

A

Narrow

Mostly Gram negative bacteria

189
Q

What is the spectrum of activity of cloxacillin?

A

Narrow

But works against MSSA (staphylococci)

190
Q

What is the spectrum of activity of Ampicillin, Amoxicillin, Piperacillin, Ticarcillin?

A

Broadest

Even works against Pseudomonas, Proteus, Klebsiella

191
Q

Which generation of cephalosporins are better against gram negative bacteria?

A

Newer generations

4th & 5th

192
Q

What is a first generation cephalosporin?

A

Cephalexin

mostly Gram positive

193
Q

What is a third generation cephalosporin?

A

Ceftiofur
Cefovecin
Cefpodoxime
(more Gram negatives and pseudomonas)

194
Q

What is the spectrum of activity of Carbapenems?

A

Broadest of all B-Lactam drugs

Least sensitivity to B-Lactamases

195
Q

Are penicillins acids or bases?

196
Q

How are penicillins stored?

A

As dry powder

197
Q

What is the distribution of penicillins?

A

Low Vd!

Poor penetration

198
Q

How are penicillins secreted?

A

90% in the urine

199
Q

Are cephalosporins acids or bases?

A

Also acids = low oral bioavailability

200
Q

Are carbapenems also acids?

A

Yes!

Also Low Vd, short T1/2, excretion in the urine

201
Q

Which B-Lactam is best for urinary tract infections?

A

Carbapenems

active in urine

202
Q

How do cephalosporins relate to penicillins in effectiveness?

A

Cephalosporins are one step ahead of penicillins

203
Q

Which drug is used to treat serious pseudomonas infections in small animals?

A

3rd generation cephalosporins

204
Q

Why should B-lactam drugs not be used at high doses even though the dose is safe for the patient?

A

High doses can produce bacteriostatic effects

Limiting bactericidal effects

205
Q

What drugs should only be considered after first-line drugs have failed in small animal patients?

A

Carbapenems

206
Q

What are some adverse effects of B-lactam drugs?

A
  1. Hypersensitivity reactions
  2. Disruption of commensal flora
  3. Nephrotoxicity
  4. Blood dyscrasias

Pharmacology (9 decks)

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