Antimicrobials

Pharmacology Exam 4

What are the 6 main antimicrobials?

Penicillin

Cephalosporins

Macrolides

Clindamycin

Tetracyclines

Metronidazole

A drug that destroys or inhibits the growth of microorganisms:

Antimicrobial drug

Antibacterial drug

Antibiotic

Bactericidal

Bacteriostatic

Antimicrobial drug

A drug that destroys bacteria or suppresses their growth or ability to reproduce:

Antimicrobial drug

Antibacterial drug

Antibiotic

Bactericidal

Bacteriostatic

Antibacterial drug

A drug with anti-bacterial action:

Antimicrobial drug

Antibacterial drug

Antibiotic

Bactericidal

Bacteriostatic

Antibiotic

Any agent capable of killing bacteria:

Antimicrobial drug

Antibacterial drug

Antibiotic

Bactericidal

Bacteriostatic

Bactericidal

Any agent capable of inhibiting the growth or reproduction of bacteria:

Antimicrobial drug

Antibacterial drug

Antibiotic

Bactericidal

Bacteriostatic

Bacteriostatic

What are the microorganisms of medical importance?

Bacteria

Viruses

Fungi

Parasites

Which are dependent on immune system to help eradicate the infection:

Antimicrobial drug

Antibacterial drug

Antibiotic

Bactericidal

Bacteriostatic

Bacteriostatic

Which type of bacteria does not have an outer membrane made of lipopolysaccharide and protein:

Gram positive

Gram negative

Gram positive

Which type of bacteria does have an outer membrane made of lipopolysaccharide and protein:

Gram positive

Gram negative

Gram negative

Which of these has an outer membrane and which one doesn't:

Gram positive

Gram negative

Gram positive does not have an outer membrane

Gram negative does have an outer membrane

What are examples of gram positive bacteria?

Staphylococcus aureus

Streptococcus pyogenes

Streptococcus mutans

Clostridiodes difficile

What are examples of gram negative bacteria?

Escherichia coli (E. Coli)

Pseudomonas aeruginosa

Actinomyces

Porphyromonas gingivalis

Bacteroides forsythus

Helicobacter pylori

What does susceptibility testing look for?

MIC (minimum inhibitory cone)

Levels of antibiotic that need to be present above that to be effective

If the sample is turbid and hard to see, there is bacteria

If clear, no bacteria

Microbial resistance has become and continues to be a major issue facing infectious disease therapy today

True or false

True

Microbial resistance to medicine is not a major issue

True or false

False

It is a MAJOR issue and many people die from resistance microbes

How many cases and deaths are there per year due to microbial resistance?

2 millions cases per year

23,000 deaths per year

WHO estimates that the current 700,000 deaths worldwide due to antibacterial drug resistance could rise to as many as 10 million in 2050

True or false

True

What are common names of resistant strains?

MRSA (methicillin resistant Staphylococcal aureus)

VRSA (vancomycin resistant Staphylococcal aureus)

How does antibiotic resistance happen?

1. Lots of germs. A few are drug resistant.

2. Antibiotics kill bacteria causing the illness, as well as good bacteria protecting the body from infection.

3. The drug-resistant bacteria are now allowed to grow and take over.

4. Some bacteria give their drug-resistance to other bacteria, causing more problems.

What are the 4 mechanisms of resistance?

Modification (mutation) of antibiotic binding sites

Impaired penetration

Antibiotic efflux

Enzymatic de-activation

How does the following mechanisms for resistance work:

Modification (mutation) of antibiotic binding sites

Microbes that are resistant to penicillin produce binding protein sites that have low affinity for penicillin

How does the following mechanism for resistance work:

Impaired penetration

Antibiotics enter some bacteria via porin

This porins can be poorly expressed or contain structural mutations in resistant strains

How does the following mechanism for resistance work:

Antibiotic efflux

Various cellular pumps transport antibiotics back across outer membrane and prevent entry into bacterial cell ("efflux")

How does the following mechanism for resistance work:

Enzymatic de-activation

Certain enzymes will degrade penicillins in inactive metabolites

B-lactamase enzymes (aka penicillinases) will degrade penicillin into inactive metabolites

How is penicillin affected by enzymatic de-activation?

The B-lactam ring of penicillin is hydrolyzed by bacterial b-lactamase enzymes to the inactive penicilloic acid metabolite

What do bacterial B-lactamase enzymes hydrolyze?

They hydrolyze the B-lactam ring of penicillin

What do B-lactamase enzymes do?

They hydrolyze the B-lactam ring of penicillin

This turns penicillin to the inactive penicilloic acid metabolite

How do we combat the resistance due to enzymatic deactivation (which involves the B-lactamase enzymes)?

To combat this, B-lactamase inhibitors are used in conjunction with penicillin's

What are B-lactamase inhibitors used for?

To combat the resistance by B-lactamase enzymes

B-lactase inhibitors provide antibacterial activity

True or false

False

They have weak, if at all, antibacterial activity by themselves

Which of the following B-lactamase inhibitors is orally absorbed:

Clavulanic acid

Sulbactam

Tazobactam

Clavulanic acid

What medication do we give to combat B-lactamase enzymes?

Clavulanic acid (which is a B-lactamase inhibitor) is orally absorbed

Clavulanic acid is combined with amoxicillin

Both of those combined is called AUGMENTIN

What is augmentin and what is it used for?

Amoxicillin + Clavulanic Acid

Helps protect the beta-lactam ring of penicillin

Where is penicillin derived from?

Blue and white colored mold found on rotting food

Penicillins contain a 4 member B-lactam ring attached to a thiazolidine (sulfur-containing) ring

True or false

True

What are the 4 classifications of penicillin?

Penicillin G and Penicillin V

Penicillinase-resistant penicillin

Aminopenicillins

Extended-activity penicillin (anti-pseudomonal)

What is Penicillin G known as?

Benzyl-penicillin

What is Penicillin V known as?

Phenoxy-methylpenicllin

What is Penicillin G known as?

What is Penicillin V known as?

G: Benzyl-penicillin

V: Phenoxy-methylpenicllin

Which is Phenoxy-methylpenicllin and which is Benzyl-penicillin:

Penicillin G

Penicillin V

G: Benzy-penicllin

V: Phenoxy-methylpenicllin

What is a type of penicillinase-resistant penicillins?

Dicloxacillin

What are the 2 types of amino-penicllins?

Amoxicillin

Ampicillin

What is a type of extended-activity penicillin?

Piperacillin

What is the mechanism of action of penicillin also called?

Cell wall inhibitors

What do penicillins inhibit?

They inhibit the trans-peptidation step during bacterial cell wall synthesis

Transpeptidation is a key step in forming peptidoglycan layer that surrounds the membrane of the bacteria and maintains cell shape and integrity

Penicillins are also called "cell wall inhibitors"

Key step in forming peptidoglycan layer that surrounds the cytosolic membrane of bacteria and maintains the cell shape and integrity:

What is that step called?

Transpeptidation

Peptidoglycan is the layer that surrounds the membrane of bacteria

What is the peptidoglycan layer made of and what are the base units?

It is made of cross-linked polymers of polysaccharides and polypeptides

The base units are N-acetyl-glucosamine (NAG) and N-acetylmuramic acid (NAM)

How does penicillin affect the peptidoglycan layer of bacteria?

Specifically, penicillin binding proteins (PBPs), also called "transpeptidases", remove the terminal alanine residue to form a crucial peptide cross link....

Penicillins bind to PBPs (transpeptidases), thereby blocking a vital transpeptidation step during cell wall synthesis

True or false

True

How can penicillin be adminstered?

Tablets, capsules, oral suspension

Which of these is acid-labile (easily changed) in the stomach and is not taken orally:

Penicillin G

Penicillin V

Penicillin G

Which of these is acid-stable and taken orally:

Penicillin G

Penicillin V

Penicillin V

Which of these is taken orally and which one isn't:

Penicillin G

Penicillin V

Penicillin G is NOT taken orally

Penicillin V is taken orally (voca/boca/mouth)

Absorption of most penicillin can be impaired by what?

It can be impaired by food

Are most penicillins taken on an empty stomach or with a meal?

Take with an empty stomach or take 2-3 hours after a meal

Absorption of most penicillins can be impaired by food, except for which penicillin?

Amoxicillin

For most penicillins, the unchanged drug is eliminated primarily by _______ _________

Renal excretion via proximal tubular secretion

Penicillins have the classical drug interaction between probenecid and penicillin (as well as other B-lactam antibiotics)

True or false

True

Probenecid inhibits the tubular secretion of penicillins and thus prolongs the elimination half-life and increases exposure (greater blood concs)

True or false

True

How many people are allergic to penicillin?

.7% to .8% of the population

What are risk factors for people who are allergic to penicillin?

Multiple allergies to other drugs

Atopic disease (asthma, allergic rhinitis, nasal polyps)

Repeated penicillin exposures

Anaphylactoid reactions occur in

True

Penicillin allergy is likely the most common cause of drug-induced anaphylaxis fatalities in the US

True or false

True

Which is the most common cause of drug-induced anaphylaxis fatalities in the US:

Penicillin

Cephalosporins

Macrolides

Clindamycin

Tetracyclines

Metronidazole

Penicillin

It accounts for 400-800 deaths per year

What do penicillin allergies manifest as?

Hives (urticaria)

Rash

Itching

Swelling

What is urticaria?

commonly referred to as "hives"; a kind of skin rash notable for pale red, raised, itchy bumps

What is a manifestation of penicillin allergy?

Urticaria (hives)

What is an immediately life saving agent in patients with anaphylaxis?

Epinephrine (EpiPen)

ADR of penicillins include GI upset and abdominal pain

True or false

True

Large IV doses of penicillins can penetrate the BBB, eliciting seizures, hallucinations, and general CNS excitation

True or false

True

Highest risk of penicillin ADR include compromised renal function and elderly

True or false

True

Ampicillin and amoxicillin are associated with mild pruritic rash that starts in the trunk and spreads over the body (not due to true drug allergy)
―occurs in approximately 5-10% of patients

True or false

True

What are two ADR of penicillin?

Antibiotic associated diarrhea

Pseudo-membranous colitis

What is the most severe form of antibiotic associated diarrhea?

Psudeo-membranous colitis

What is given to treat pseudomembranous colitis?

Fidaxomicin (dificid)

Metronidazole is no longer recommended t treat PMC

What happens if a patient is taking a bacteriostatic antibiotic and a bactericidal antibiotic at the same time?

Bacteriostatic antibiotics antagonize the effects of bactericidal antibiotics

Bactericidal agents work better when bacteria are actively multiplying

Probenecid impedes renal tubular secretion of penicillins by blocking the organic anion transporter (OAT)

True or false

True

How do penicillins and warfarin interact?

Penicillins reduce intestinal bacteria that synthesize vitamin k (which are involved in pro-coagulation pathway)

How does penicillin react with oral contraceptives?

Penicillins reduce intestinal flora responsible for the hydrolysis of the conjugated hormone, which results in greater fecal loss of hormones and lower plasma levels

What are the types of penicillin drugs?

Penicillin G and Penicillin V

Penicillinase-resistant penicillin

Aminopenicillins

Extended-activity penicillin (anti-pseudomonal)

Which of these have activity against mostly gram positive and some gram negative bacteria:

Penicillin G and Penicillin V

Penicillinase-resistant penicillin

Aminopenicillins

Extended-activity penicillin (anti-pseudomonal)

Penicillin G and V

Clinical use has dropped dramatically over the years due to emergence of resistant strains, many of which express B-lactamase:

Penicillin G and Penicillin V

Penicillinase-resistant penicillin

Aminopenicillins

Extended-activity penicillin (anti-pseudomonal)

Penicillin G/V

Penicillin G/V works against which bacteria?

―Streptococcus pyogenes infections such as 'strep throat'

―Streptococcus pneumoniae infections

―Infective endocarditis caused by Staphylococcus and Streptococcus spp.

―Treponema pallidum (syphilis)

―Actinomyces spp. that cause actinomycosis (lumpy jaw)

Which are resistant to hydrolysis by staphylococcal penicillinase (b-lactamase):

Penicillin G and Penicillin V

Penicillinase-resistant penicillin

Aminopenicillins

Extended-activity penicillin (anti-pseudomonal)

Penicillin-resistant penicillin

Penicillinase-resistant penicillin are resistant to what?

They are resistant to hydrolysis of staphylococcal penicillinase

Which bacteria are resistant to the antibiotic "penicillinase-resistant penicillin"?

Bacteria that express extended spectrum β-lactamases (ESBL) are resistant to this class of penicillins

What is an example of a penicillinase-resistant penicillin drug?

Dicloxacillin

Dicloxacillin is which type of penicillin:

Penicillin G and Penicillin V

Penicillinase-resistant penicillin

Aminopenicillins

Extended-activity penicillin (anti-pseudomonal)

Penicillinase-resistant penicillin

Aminopenicillins include _______ and ________

Amoxicillin and ampicillin

Which of these include amoxicillin and ampicillin:

Penicillin G and Penicillin V

Penicillinase-resistant penicillin

Aminopenicillins

Extended-activity penicillin (anti-pseudomonal)

Aminopenicillin

Aminopenicillins generally have a modestly extended antibacterial spectrum beyond penicillin G/V, including a little more gram-negative coverage

True or false

True

Aminopenicillins are administered with what?

With B-lactamase inhibitor such as Augmentin (which is a amoxicillin and clavulanic acid combination)

Also with Unasyn (which is ampicillin and sulbactum)

Which of these are administered with the B-lactamase inhibitors Augmentin or Unasyn:

Penicillin G and Penicillin V

Penicillinase-resistant penicillin

Aminopenicillins

Extended-activity penicillin (anti-pseudomonal)

Aminopenicillin

What is the only antipseudomonal penicillin?

Piperacillin

Piperacillin is the only type of which penicillin:

Penicillin G and Penicillin V

Penicillinase-resistant penicillin

Aminopenicillins

Extended-activity penicillin (anti-pseudomonal)

Anti-pseudomonal penicillin

What is piperacillin combined with?

Combined with B-lactamase inhibitor tazobactum

Which is combined with B-lactamase inhibitor tazobactam:

Penicillin G and Penicillin V

Penicillinase-resistant penicillin

Aminopenicillins

Extended-activity penicillin (anti-pseudomonal)

Anti-pseudomonal penicillin

The only one of its class is piperacillin

So, piperacillin is combined with tazobactum

Which antibiotics are no longer recommended for antibiotic prophylaxis prior to dental treatment:

A.Penicillin VK

B.Azithromycin

C.Clarithromycin

D.Clindamycin

E.Cephalexin

F.Erythromycin

A. Penicillin VK

D. Clindamycin

F. Erythromycin

What is infective endocarditiis antibiotic prophylaxis?

When dentists prescribe antibiotics prior to certain dental procedures to decrease risk of bacterial infestations such as the heart