Chapter 10 - Antimicrobials Flashcards
(159 cards)
1
Q
Antimicrobials
A
Drugs that kill or inhibit the growth of microorganisms, or microbes, such as bacteria, protozoa, viruses, and fungi
2
Q
Antibiotic
A
Often used interchangeably with antimicrobial - but specifically antibiotics describe a natural substance produced by one microorganism that suppresses growth of another microorganism
3
Q
Spectrum of Activity
A
Antibiotics are classified according to the type of microorganism it fights
4
Q
The suffix “ -cidal “ means ….
A
Drugs that kill the microorganism
5
Q
The suffix “ -static “ means ….
A
Drugs that inhibit replication and proliferating of microorganisms but do not directly kill them
6
Q
Pathogens
A
Disease-causing organisms
7
Q
Bacteriostatic Drugs
A
Temporarily inhibit the growth of bacteria, once the drug is removed the organism can begin to multiply again
8
Q
Because of their mode of action, do bacteriostatic drugs rely more on that than the animals immune system to fight systemic infections?
A
Bacteriostatic drugs depend far more on the animals functional immune system to ultimately defeat the organism
9
Q
What is the goal of antimicrobial therapy?
A
To kill or disable pathogens without killing the host
10
Q
What are the 3 things required for successful treatment with antimicrobial’s?
A
1) Microorganism must be susceptible to the drug
2) Drug must be able to reach the site of infection in high enough concentrations to kill or inhibit the microorganism
3) Animal must be able to tolerate the required high concentrations of the drug
11
Q
What are some of the less essential (but still important) conditions to choosing an appropriate antimicrobial treatment?
A
- Client compliance (following dosing instructions)
- Ease of administration
- Convenient dosage interval
- Dose form
- Cost
12
Q
Culture
A
Grow
13
Q
Process of identification and drug susceptibility testing is referred to as what?
A
Culture and sensitivity
14
Q
What does a culture and sensitivity test determine?
A
Susceptibility of of a bacterial strain to certain drugs by determining how much drug it takes to inhibit or kill the bacteria
15
Q
The lowest drug concentration needed to inhibit bacterial growth is called what?
A
Drug Minimum Inhibitory Concentration (MIC)
16
Q
The highest concentration of drug that can be tolerated by the animal before significant toxicity signs or adverse effects occur is referred to as what?
A
Maximum Tolerated Dose (MTD) drug concentration
17
Q
Resistant
A
If a drug’s MIC is more than the MTD, the microorganism is resistant to the drug
18
Q
Susceptible
A
If a drug’s MIC is less than the MTD, the microorganism is susceptible to the drug
19
Q
Means the drug’s MIC is close to the MTD.
A
Intermediate Resistance or Susceptibility
20
Q
Breakpoints
A
Mark a drugs MIC that differentiates between when a bacterial strain is considered susceptible, intermediate susceptible or resistant to that particular drug
21
Q
True or False
Unless the antimicrobials can reach the infection site at the needed concentrations to inhibit the bacteria, the antimicrobial will be ineffective
A
TRUE
22
Q
Minimum Bactericidal Concentration (MBC)
A
- Used to describe the ability of a drug to actually kill, versus inhibit the growth of a bacterial species.
- MBC concentration is typically higher than the MIC because they are not being held in a static condition, they are being killed
23
Q
Resistance
A
Bacterial and other microorganisms have developed the ability to survive in the presence of antimicrobial drugs designed to kill them
24
Q
What is the monitoring system the CDC has in place to track changes in bacterial susceptibility and resistance in the US?
A
National Antimicrobial Resistance Monitoring System (NARMS)
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What other groups does NARMS work with besides the CDC to collect its data to track bacterial susceptibility and resistances?
* State and local health departments
* FDA (Food and Drug Administration)
* USDA ( US Department of Agriculture)
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How does bacterial resistance occur?
Typically resistance occurs as the result of a genetic mutation in the Deoxyribonucleic Acid (DNA) of bacteria
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Vertical Transmission of Resistance
Passing of this resistant genetic trait to the daughter cells and all subsequent generations of the original bacterium
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Plasmid
- Extrachromosomal self-replicating structure found in bacterial cells that carries genes for a variety of functions
- Can be transferred from one cell to another by conjugation and by transduction
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Horizontal Transmission or Resistance
Occurs when some bacteria make physical contact with another bacterium and transfer plasmid-containing resistant DNA across a cell membrane
30
Besides Vertical and Horizontal transmission list 2 other ways cells can transfer DNA
1) Pick up DNA with resistant genes left in the environment after death and lysis of another bacterial cell
2) Receive resistant DNA by a bacterial virus (bacteriophage) that transfers DNA from one bacterium to another
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True of False
If a low dose of antibiotic is administered, only the weakest bacteria are going to be inhibited, while all the more resistant bacteria to the drug will survive
TRUE
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Selection Pressure
Does not create mutations or speed up the rate at which mutations occur, it only helps resistant bacterial proliferate and emerge into a clinical disease that is resistant to treatment
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Bacteriostatic drugs that are required to remain at high concentrations at the infection site continuously to be effective in eliminating bacterial infections
Time Dependent Drugs
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Bactericidal agents must either achieve a peak drug concentration far exceeding the MIC or maintain a high level of concentration for a longer period of time to be maximally effective
Concentration Dependent Drugs
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Post-Antibiotic Effect
Continued killing effect in the absence of drug concentrations above the MIC (concentration dependent effect)
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Residue
Presence of a drug, chemical, or its metabolites in animal tissues or food products (caused by administration directly to animal or contamination during food processing)
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What are the two effects that exposure to low levels of antimicrobials from ingested food can cause?
1) Allergic reaction (hypersensitivity) to the antimicrobial
| 2) Selection for resistant bacteria in the intestinal tract
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Gut Flora
Composition of bacteria and protozoa in the intestinal tract
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List the 5 sites antimicrobials exert their effects on microorganisms
1) Cell Wall
2) Cell Membrane
3) Ribosomes
4) Critical Enzymes or Metabolites
5) Nucleic Acid
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True or False
Antimicrobials that interfere with bacterial cell wall formation only work while the wall is forming during bacterial cell division
TRUE
If these drugs are used once the cell wall is constructed then the microorganism is not readily affected by the antimicrobial drugs
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Bacteriostatic Drugs
Biological or chemical agent that stops bacteria from reproducing
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What are the 2 drug classes of antimicrobials that act by disruption of new cell wall formation?
1) Penicillin
| 2) Cephalosporins
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When antimicrobials attack and damage the cell membrane what occurs?
Membrane becomes leaky, allowing either the antimicrobial drug molecules to more readily enter the bacterial or allowing vital cytoplasmic components to escape
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True or False
| Antimicrobials that act by damaging the cell wall can only work when the cell membrane is dividing
FALSE
| These antimicrobials can exert their effect on both dividing or static (non-dividing) bacteria
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This is a common ingredient in topically applied first aid creams and it works by damaging the cell membrane
Polymyxin B
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List 2 of the antimicrobials that act by blocking production of essential proteins (which causes the cell to stop dividing or die)
1) Lincosamides
2) Macrolides
3) Tetracyclines
4) Aminoglycosides
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What antimicrobials work by interfering with critical enzymes needed by pathogenic bacterial to produce essential nutrients or substances they need to survive?
Sulfonamide Antibiotics
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What antimicrobials interfere with the production of bacterial nucleic acids (RNA + DNA) altering the ability of the cell to divide or produce critical proteins needed by the cell?
Fluoroquinolones (Enrofloxacin)
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Because of a particular ring-like structure in their chemical composition, Penicillin's are also referred to as what?
Beta-lactum or B-lactam Antibiotics
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Besides Penicillins, what is the other group of antibiotics that also has a B-lactam ring?
Cephalosporin Antibiotics
51
List the broad spectrum aminopenicillins used in vet med
Ampicillin
| Amoxicillin
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List the Penicillinase-resistant or B-lactamase-resistant Penicillins
Cloxacillin
Dicloxacillin
Oxacillin
Methicillin
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List the extended-spectrum penicillins
Ticarcillin
Carbenicillin
Piperacillin
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Penicillins are generally effective against many gram- ________ bacteria and a lesser number of gram- ________ bacteria
Gram-positive
| Gram-negative
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True or False
Penicillins are bacteriostatic
FALSE
| Penicillins are bactericidal - so they are only effective against an actively dividing colony of bacterial
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What does MRSA stand for?
Methicillin-Resistant Staphylococcus Aureus
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Bacteriostatic antimicrobials should not be used simultaneously with with ____________ antibiotics
B-lactam antibiotics (because B-lactam abx need the bacterial colony to be actively replicating)
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What are the 3 areas penicillins will typically not reach therapeutic concentrations because of the cellular barriers between the tissue and blood supply
Globe of the eye
Brain
Prostate Gland
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Why are penicillins commonly used to treat bacterial cystitis caused by bacterial infection?
Most penicillins are excreted by the kidney intact without being metabolized and are actively transported (secreted) by the renal tubules into the forming urine
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Aerobic bacteria
Require oxygen
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Anaerobic bacteria
Do not require oxygen
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Empiric treatment/therapy
Selection of a particular antimicrobial drug before the results of a culture are returned
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Porins
Special capsule openings (like pores)
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True or False
If a bacteria develops resistance to one type of penicillin, the bacteria will often also be resistant to many of the other penicillins
TRUE
This is known as Cross-Resistance
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Penicillinases/B-lactamases
Bacterial enzymes that specifically attack penicillins
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Clavulanic acid and Sulbactum are added to penicillin drugs (amoxi, ampi) for what purpose?
To produce a potentiated penicillin compound capable of withstanding bacterial B-lactamase enzymes
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Penicillins are quite safe drugs for pets because they target bacterial ____ _____s and mammalian cells only have _____ ________s
Cell walls
| Cell membranes
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Urticaria
Hives
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Cross-Reactivity
If an animal exhibits hypersensitivity to one type of penicillin, the animal is likely to react adversely to other penicillin drugs
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Superinfection or Suprainfection
When penicillins are given orally they may destroy beneficial gram-positive bacteria residing in the lumen of the intestinal tract, allowing more pathogenic bacterial (which are generally more penicillin resistant) to proliferate
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Suprainfection can cause death in some species, such as:
Guinea pigs
Rabbits
Ferrets
Hamsters
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Penicillins should be used cautiously in:
Snakes
Birds
Turtles
Chinchillas
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Natural Penicillin
Penicillin that is the same penicillin that is produced by mold - most bacterial are now resistant to this penicillin
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Aminopenicillins
Have a wider effective spectrum against gram-negative bacterial than PenG
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B-Lactamase-resistant penicillins
Naturally resistant to the effects of this bacterial enzyme
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Extended-spectrum penicillins
Have a wider spectrum than other penicillins, most used in humans and very expensive
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Potentiated
When a drug is combined with another compound producing a stronger, modified effect
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Procaine
Combined with Penicillin G allows the drug to remain at effective blood concentrations for 24 hours
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Benzathine
Combined with Penicillin G allows the drug to remain at effective blood concentrations for 3-5 days
80
Cephalosporins
Bactericidal B-lactam antimicrobials that function by disrupting bacterial cell wall formation during cellular division and are only effective against actively dividing bacterial colonies
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First generation cephalosporins are generally effective against ...
Gram-positive bacteria
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Third generation cephalosporins are generally effective against ...
Gram-negative bacteria
83
True or False
| There are no FDA approved veterinary drugs classified as second generation cephalosporins
TRUE
84
Cephalosporinases
Bacterial B-lactamases specific for cephalosporins
85
Aminoglycosides
Bactericidal antimicrobials that act on the bacterium's ribosomal production of essential proteins. Aminoglycosides must be actively transported by a carrier into the bacterium
86
Postantibiotic Effect
Extends the drugs killing activity for the full 24 hours between doses regardless of the low antibiotic concentrations. To achieve this the drug must achieve a very high peak concentration
87
Time-Dependent Drugs
Drugs that need to be 'on site' continuously to be bactericidal
88
Concentration-Dependent Drugs
Drugs that only need to hit a critically high peak concentration for a short period of time
89
True or False
| Topically applied aminoglycosides should be considered the same as SQ administered drugs if the skin barrier is broken
TRUE
90
What are the 2 most common adverse side effects you may see with administration of Aminoglycosides?
- Nephrotoxicity
| - Ototoxicity
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What is an early sign of nephrotoxicity in animals being treated with aminoglycosides?
-Appearance of casts or protein in the urine
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Nystagmus
Repetitive, rapid eye movements
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True or False
Presence of cellular debris (pus) at the infection site can block aminoglycosides from reaching the bacteria in the infection site
TRUE
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Pyogenic
Pus producing
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Pyoderma
Infection of the skin involving pus
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Fluroquinolones
Bactericidal (concentration-dependent) antimicrobials that are used for treating serious aerobic gram-negative bacterial infections. They act by interfering with the DNA gyrase, preventing bacterial DNA supercoiling and subsequently disrupting DNA functions which rapidly kills the bacterium
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DNA Gyrase (topoisomerase II)
Enzyme that facilitates the unwinding of DNA strands so they can be recoiled into tighter supercoils
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10-40 % of Enrofloxacin is actually metabolized to ____________ for part of enrofloxacins antibacterial activity
Ciprofloxacin
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Relatively Contraindicated
The drug may be given if the benefit outweighs the risk
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Absolute contraindication
The drug should not be given under any circumstances
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Why should Quinolones not be administered to young animals during times of rapid growth?
They adversely affect developing joint cartilage and can cause bubble-like lesions to form on the joint cartilage potentially causing joint degeneration and arthritic changes as the animal grows older
102
Are Quinolones safe to be administered in epileptic animals?
Contraindicated - studies have shown at high doses quniolones can inhibit the inhibitory neurotransmitter GABA, allowing over-excitement of the CNS
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What adverse reaction can occur in cats that are administered Quinolones?
Permanent or temporary blindness due to sever changes in the retina (at high doses)
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Tetracyclines
- Bacteriostatic antimicrobials
- have unique abilities to accumulate within mammalian cells and reach organisms that hide within these cells - work by binding to bacterial ribosomes and prevent t-RNA from linking to the ribosome and disrupting protein synthesis
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Wolbachia
Gram-negative bacteria that live within canine heartworms and contribute to canine heartworm disease - they are dependent on the worms and also appear to contribute to the health of heartworms
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Chelate
Bind to and precipitate out of solution
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Enterohepatic Circulation
Movement of a drug from liver to intestinal tract and back to liver
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At what age should tetracycline's not be administered to animals?
Between 4 to 16 weeks when adult teeth are developing because they bind with calcium and cause a yellow discoloration - calcium binding can also cause slow bone development
109
What should a cat owner who needs to administer doxycycline know to always relay to the owner?
After pill/capsule is administered the cat must be given several mls of water after to prevent esophagitis/erosion and in some cases a stricture due to the highly acidic nature of doxy
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Precaution should be taken with horses being administered doxycycline, why is this?
IV doxy can cause collapse, fatal arrhythmia's and death - PO administration does not result in the same symptoms
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Sulfonamides
Bacteriostatic antimicrobials that disrupt the essential process of synthesizing folic acid by inactivating a key enzyme involved in this synthesis
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Which sulfonamide is used for its antiinflammatory effect in the colon to treat colitis
Sulfasalazine
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Can Sulfonamides penetrate difficult areas such as the prostate gland, blood-brain barrier and the CNS and CSF?
Yes
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What is the most common reaction seen in dogs who are administered Sulfonamides?
Keratoconjunctivitis Sicca (KCS)
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Drug Eruption
Skin reactions to drugs
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Dermatophytes
skin fungus
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Thrombocytopenia
Decreased platelets
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Leukopenia
Decreased white blood cells
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Crystalluria
Crystals in the urine
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Which Sulfonamide can cause a salicylate (aspirin) toxicity in cats?
Sulfasalazine
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Lincosamides
Bacterial protein inhibitors and can be bacteriostatic or bactericidal, depending on the concentrations attained at the infection site
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Which Lincosamide drug is different from the other drugs in its class because it has good efficacy against many anaerobic bacterial, making it an effective drug for treating deep pyodermas
Clindamycin
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What animals are Lincosamides contraindicated for use in?
Ruminants (animals that rely on fermentation for digestion) because it alters GI flora and allows Clostridium bacteria to proliferate and produce toxins
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Which Lincosamide is used exclusively in dairy cattle and what is it used for?
Pirlimycin - mammary infusion for mastitis
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Macrolides
Broad class of chemically related bacteriostatic drugs primarily used to treat gram-positive respiratory disease.
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By what mechanism do Macrolides work?
Macrolides inhibit bacterial protein synthesis and share similar spectra of antibacterial activity and bacterial cross-resistance
127
Erythromycin is similar in molecular structure to what compound?
Motilin - compound found in the intestinal tract that stimulates intestinal motility
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Macrolide drug approved for treatment of bovine respiratory disease, is incredibly well known to cause deaths in livestock handlers from accidental injection and it has also been used as a suicide drug
Tilmicosin (Micotil)
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Metronidazole
Bactericidal antimicrobial that is also effective against protozoa that cause intestinal disease (Giardia, Amebiasis, Trichomoniasis and balantidiasis) it is only effective against anaerobic bacteria
130
What is metronidazole most often used to treat?
Treatment of protozoal infections of the large bowel and enteric bacterial infections caused by anaerobic bacteria
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What is the exact mechanism of Metronidazole?
Its exact mechanism is unknown, but it may be metabolized to a form that can disrupt synthesis of DNA and nucleic acids
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Chloramphenicol
Antimicrobial - bacteriostatic at low concentrations and bactericidal at higher concentrations. Works by binding to ribosomes in sensitive bacteria and disrupting bacterial protein synthesis. Banned for use in cattle!
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Aplastic anemia
Decreased production of red blood cells, white blood cells, and platelets
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Florfenicol
Newer antibiotic related to chloramphenicol - it is bacteriostatic, disrupts protein synthesis at the bacterial ribosomes and penetrates tissues well. But this drug is approved for use in cattle because it does not contain the component that makes chloramphenicol toxic to human bone marrow
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Rifampin
Bactericidal or bacteriostatic antimicrobials - used almost exclusively in horses (especially young foals) and almost always used in conjunction with aminoglycosides, B-lactam, or doxycycline
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Rifampins mechanism of action
suppresses formation of the RNA chain by inhibiting an RNA polymerase enzyme needed by bacteria to synthesize RNA
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What is a commonly seen side effect with Rifampin that should be mentioned to owners administering the drug?
Imparts a reddish-orange color into urine, tears, sweat and saliva (and in some cases plasma may also appear this color and should be distinguished from hemolysis)
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Bacitracin
Antibiotic that inhibits the formation of bacterial cell walls - it is limited to topical use because of its potential to produce nephrotoxicity
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Superficial Mycoses
Fungal skin infections
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Deep or Systemic Mycoses
Fungal infections within the body
141
Amphotericin B
Potent Antifungal for treatment of deep mycoses. Works by binding to and damaging a specific molecule Ergosterol (a major component of fungal cell membranes) creating holes and allowing critical cellular components to leak from the cell
142
Amphotericin B can cause several serious side effects by combining with ____________ in the mammalian cell membranes and producing a similar toxic effect as that observed with fungal cell membranes
Cholesterol
143
What organ should be closely monitored during Amphotericin B administration?
Kidney/Renal function
144
Why is the liposomal form of Amphotericin B safer than the old formulation?
The drug itself is encapsulated in a lipid "capsule" that reduced nephrotoxicity by better delivering the drug directly to the fungal element membrane (rather than potentially attacking mammalian cell membranes)
145
Azoles (Imidazole Derivatives)
Antifungal agents
146
Imidazoles
Contain 2 nitrogen atoms
147
Triazoles
Contain 3 nitrogen atoms
148
Imidazole derivatives mechanism of action
Interfere with the enzyme that synthesizes ergosterol (key component of fungal cell membranes) causing leakage
149
True or False
| Imidazole derivatives have a much faster onset of action than Amphotericin B
False
Imidazole derivatives = 5 to 10 days
Amphotericin B = hours
150
Ketoconazole and Itraconazole need a ________ pH environment in the GI tract to be absorbed when given PO
Acidic
151
Teratogenic Effects
Creates birth defects
152
Clotrimazole and Miconazole are recommended for use with what?
Topical yeast infections and superficial dermatophytes
153
Why may Ketoconazole be used in the treatment of cushings disease?
Interference with Cytochrome P450 also interferes with conversion of basic sterol molecule into cortisol by the adrenal gland and reducing production of cortisol by the adrenal gland, controlling overproduction
154
What hormone can Ketoconazole cause a decrease in?
Interferes with Cytochrome P450 enzyme that converts progesterone to testosterone - resulting in decreased testosterone levels
155
Griseofulvin
Fungistatic Drug used primarily to treat infections from Trichophyton and Microsporum species of dermatophytes - works by impairing microtubules that make up the structure of the fungal cell and provide a major part of the mechanism by which a replicating cell divides in half
156
True or False
| Griseofulvin is only effective when given topically
False - only effective when given systemically, otherwise it will not penetrate the skin sufficiently to reach the dermatophytes
157
Griseofulvin is available in....
Microsized powder, tablets, ultramicrosized powder
158
Terbinafine
Topically applied antifungal used in human medicine (Lamasil)
159
Nystatin
Topical antifungal often included with topical antibiotic/corticosteroid ointments - the drug is extremely nephrotoxic and restricted to topical use
