Pharmacology Tutoring- Antimicrobials 1

antimicrobial

any drug that kills or inhibits a "microbe"

Name 4 microbes

bacteria, viruses, fungi, protozoa

antibiotic- extra definition

-substances produces by one organism that acts against another microorganism

-loosely used to mean any drug that is used against bacteria

bactericidal

kills bacteria

bacteriostatic

inhibits growth of bacteria, but doesn't kill

-depends on the immune system to "finish the job"

fungicidal

kills fungi (mycotic agents)

virucidal

kills viruses

What are the 2 things antimicrobials are classified by?

1. whether the drug kills or inhibits

2. what microbes the drug kills or inhibits (drugs spectrum of activity)

bacteriostatic antibiotic

antibiotic drug keeps bacteria from dividing and growing but doesn't kill the bacteria outright (depends on the immune system)

bactericidal antibiotics

antibiotic drug that kills bacteria directly (from immune compromised patients

"cidal"

suffix meaning kill

"static"

suffix meaning inhibits

broad spectrum antibacterials

antibacterial that are active against bacteria belonging to AT LEAST 2 quadrants

narrow spectrum antibacterials

antibacterial effective against selective populations ( ONLY 1 or 2 quadrants

what is the goal of antimicrobial therapy?

kill or disable pathogen without killing the host

3 factors in order for antimicrobial therapy to be successful

-pathogen susceptible to the drug

-drug must reach site of infection at high enough concentrations to kill or inhibit pathogen

-patient needs to tolerate the high concentration

What is Minimum Inhibitory Concentration (MIC)?

lowest drug concentration at which the bacteria are inhibited (NOT killed)

What is Minimal Bactericidal Concentration?

Lowest drug concentration at which the bacteria are killed

What is Maximum Tolerated Dose?

Highest drug concentration before toxicity or side effect signs become unacceptable

what would the chart of bacterial effect (culture) look like for bacterial that is SUSCEPTIBLE to the drug?

MTD (maximum tolerated dose) and MBC (minimum bacterial concentration) are far apart

what would the chart of bacterial effect (culture) look like when drug doses are only bacteriostatic?

the MTD (max tolerated dose) and MBC (min bacterial concentration) are really close together

(narrow therapeutic index)

what would the chart of bacterial effect (culture) look like when the bacteria is RESISTANT to this drug?

the MTD (max tolerated dose) is BELOW the MIC (min inhibitory concentration)

why might the drug not work, even if the culture and susceptibility says it will?

location:

- trachea (drugs in blood cant reach)

- brain (drugs are hydrophilic, drugs can't penetrate blood brain barrier)

- urine (drug is secreted in the urine and achieves too high concentration to be tolerated in blood)

What is resistance?

ability to survive in the presence of antimicrobials designed to kill them

What are 3 things that antimicrobial resistance is caused by?

-inherited genetic mutation

-acquire from transfer of DNA from resistant bacterium

-picks up DNA from environment

presence of antibiotics does apply ___________ ___________ to allow the most resistant bacteria to proliferate

selective pressure

What are the ways to reduce selection pressure?

-use appropriate dose

-administer drug long enough

-educate clients to treat for entire dosage regimen

-don't use antibiotics to treat non-bacterial infections like virus infections

-be aware of your patients immine status

Residues

trace amounts of drug, chemical, or the metabolites

Withdrawal time

-designed to allow all drug to leave the body before the animal is harvested or its milk/eggs are sold for human food

What can happen if residues of antibiotics are left in human food?

-allergic reactions

-continued low exposure can result in selective pressure on bacteria allowing for naturally resistant bacteria to survive

What are the 3 modes of action for antimicrobial drugs

1. physically damage cell wall or membrane

2. disrupt organelles inside bacterium

3. metabolic or enzymatic processes

What cells don't have cell walls?

mammaliam cells

What antimicrobials target cell enzymes used for wall formation?

penicillins, cephalosporins and bacitracin

What is the topically applied antibiotic used in vet med to work via cell membrane?

polymyxin B (neosporin)

What are the drugs that work by targeting ribosomes (preventing protein creation) and are bactericidal or bacteriostatic?

aminoglycosides, macrolides, tetracyclines, lincosamides

What is the drug class that disrupts replication of DNA?

quinolones

What is the drug that forms unstable DNA only in anaerobic bacteria and protozoa?

metronidazole

What is the drug class that interferes with formation of folic acid synthesis?

sulfonamides

What effect do sulfonamids normally have?

bacteriostatic

If sulfa drugs are combinded with trimethoprim (which inhibits another step in folic acid synthesis), what happens?

The drug becomes bactericidal

What does it mean that penicillins are "beta lactams?"

They are antibiotics that have a beta-lactam ring structure

Name the 4 types of penicillins

1. Natural penicillins

2. Aminopenicillins

3. Penicillinase-resistant penicillins

4. Extended spectrum penicillins

Natural penicillins

penicillin G

Aminopenicillins

amoxicillin, ampicillin

Penicillinase-resistant penicillins

-oxacillin, cloxacillin, dicloxacillin, methicillin

-naturally resistant to beta lactamase enzymes

Extended spectrum penicillins

-piperacillin, ticarcillin, carbenicillin

Are penicillins bactericidal or bacteriostatic?

bactericidal

What are penicillins working primarily against?

aerobic gram positive bacteria and some gram negatives

What do penicillins target?

bacterial cell wall formation, transpeptidase enzyme

How do penicillins work?

-bind and inhibit the transpeptidase enzyme that normally links peptidoglycan strands

-prevents fusing of peptidoglycan strands

What are the only bacteria killed by penicillins?

actively dividing bacteria

What would occur if bacteriostatic antibiotics are used at same time as penicillins?

static drug would halt replication and prevent penicillins from working

Which penicillin is given by injection only and why>

Penicillin G because it is inactivated by gastric acid

Do penicillins penetrate BBB?

no

Most penicillins are excreted via what organ?

kidneys (very effective against most bacteria in urine)

True or False: If a bacterial strain is resistant to one of the penicillins, it is likely resistant to many of the penicillins

True

What enzyme created by bacteria like staphylococci, breaks apart the penicillin's beta-lactam ring (central part)?

-it is then attacked by penicillinases

beta-lactamase enzyme

Name the "penicillinase-resistant" or "beta-lactamase resistant" penicillins.

oxacillin, cloxacillin, dicloxacillin, methicillin

What is the significant disadvantage of "penicillinase-resistant" or "beta-lactamase resistant" penicillins?

Narrow spectrum of activity against bacteria

What 2 substances might be added to penicillin (like amoxicillin), to convert resistance against bacterial beta-lactamase enzyme?

clavulanic acid and sulbactam

what bacteria is penicillin's kryptonite?

Pseudomonas : have an outer capsule that surrounds bacteria and prevents drug accessing the wall

Penicillin's are considered to be "safe", but what are we concerned about after administering them to our patient?

allergic or immune mediated reactions

True or False: if a patient has an anaphylactic reaction after giving penicillin in their chart, we are still able to give the drug, with close monitoring?

False: 2nd exposure can result in severe systemic anaphylaxis and death

What is another disadvantage of penicillins, which is especially a concern in guinea pigs, ferrets, hamsters, and rabbits?

-alter microflora of GI tract: kill of gram positive = gram negative proliferate

What are the term(s) for pathogenic gram negative proliferation due to penicillin administeration producing GI disease?

superinfection or suprainfection

What is the only natural penicillin used in vet med?

Penicillin G

What are the 3 forms of penicillin G?

1. aqueous solution

2. suspension combined with procaine

3. suspension combined with benzathine (3-5 days)

What are the aqueous forms of penicillin G usually compounded with? What route can they go?

-sodium or potassium

-IV only

name 2 aminopenicillins, that have a broader spectrum than natural (more gram negatives)

amoxicillin and ampicillin

What are beta-lactamase resistant penicillins used for?

Staph mastitis with intra-mammary teat infusions

Name the class of beta lactam antibiotics that target cell wall formation (inhibit enzymes)

-susceptible to bacteria's beta lactamase enzyme

- classified by generations

cephalosporins

Name the first gen cephalosporins

cefadroxil, cephapirin, cephalexin, cefazolin

Name the third generation cephalosporins

cefovecin, cefpodoxime, ceftiofur

As the generations of cephalosporins increases, what happens to the activity?

the activity against gram negative bacteria increases

(meaning it may lose some effectiveness against gram positive bacteria)

What are the 3 generation cephalosporins effectice against?

Pseudomonas bacterial infections

Are the 2nd generation cephalosporins used in vet med?

No

What are cephalosporinases?

beta-lactamase enzymes that work against cephalosporins but leave penicillins alone

What can occur if cephalosporins are given PO?

causes bacterial overgrowth in GI tract

-vomiting and diarrhea

Cephalosporins are prohibited from extra-label use in what species?

cattle, swine, chickens and turkeys