Antimicrobial Drugs bacterial

Selective Toxicity

selectively finding and destroying pathogens without damaging the host

The use of chemicals to treat a disease

Chemotherapy

A substance produced by a microbe that in small amounts, inhibits another microbe

Antibiotic

synthetic substance that interferes with any sort of microbe ex helminths, parasites etc.

Antimicrobial drugs

1928 Fleming

discovered penicillin, produced by Penicillium

1932 Prontosil red dye

used for streptococcal infections

First clinical trials of penicillin

1940

Currently in the history of chemotherapy

Growing problem of antibiotic resisitance

What is found in the soil and makes most of our antibiotics?

Streptomyces

drugs affecting a narrow range of microbial types (only kills either gram pos or gram neg)

Narrow spectrum of microbial activity

affecting a broad range of gram pos or gram neg bacteria

Broad -spectrum antibiotics

Superinfection

An overgrowth of normal microbiota that is resistance to antibiotics

Bactericidal

directly kills microbes

Bacteriostatic

-Prevents microbes from growing

• Allows the immune system to take over and kill off bacteria eventually

1. Inhibition of cell wall synthesis

2. Inhibition of protein synthesis

3. Inhibition of nucleic acid replication and transcriptions

4. Injury to plasma membrane

5. Inhibition of essential metabolite synthesis

what are the 5 modes of actions of antimicrobial drugs

What drug targets and inhibits cell wall synthesis and how

• Penicillin- It prevents peptidoglycan walls from joining together , thus the cell wall is weakened.

• Only actively growing cells affected

• Best on gram positive ( think breaks links of a chain fence)

• little toxicity to host

• Targets bacterial 70S ribosomes

• Blocks or prevents 1 part of the following

• DNA/RNA/Transcription /Translation

• Prevents amino acid chain formation

How does inhibiting protein synthesis work?

Examples of synthesis protein blocking drugs

• Chloramphenicol

• Erythromycin

• Streptomycin

• Tetracyclines

How do antimicrobials injure the plasma membrane?

• Polypeptide antibiotics change the membrane permeability

• Antifungal drugs combine with membrane sterols - only plants have sterols not bacterial cells

• Ionophores (not for humans but cattle) allow uncontrolled movement of cations

How does antimicrobial drugs inhibit nucleic acid synthesis?

Interferes with DNA replication and transcription

Sulfa drugs

inhibiting the synthesis of essential metabolites

antimetabolite

competes with normal substrates for an enzyme

Without the correct enzyme fitting, cell cannot continue to replicate

sulfas competes with PABA stopping the synthesis of folic acid

folic acid is needed because

This is a precursor for DNA and RNA replication

without folic acid

DNA/RNA cannot be created in order to replicate

competing for PABA , sulfa is what action of antimicrobial drugs

Inhibition of creating and synthesizing nucleic acid

Penicillin- disrupts cell wall synthesis because

contains a B -lactam ring

B Lactam rings are

chemical sides attached to the side of the ring and prevent peptidoglycans to link together (think of chain link fence, each individual link is the peptidoglycan)

penicillinase

arch enemy of penicillin

enzyme that can work around the action of penicillin

allows peptidoglycan to hook up

is a limitation of natural penicillin

synthetic penicillins

lab created penicillin that can resist penicillinase

examples of synthetic penicillin that can resist penicillinase

• methicillin

• oxacillin

  (think MO)

These have B lactam ring inhibitors

another name for broad spectrum

extended spectrum

clavulanic acid

The superhero that can inhibit the evil penicillinase and put in broad spectrum antibiotics

Methicillin is

The first penicillinase - resistant drug to be developed

carbapenems

• Changes structure to penicillin

• Adds double bonds to penicillin nucleus

• Substitutes C and S

• This makes it harder to break down the penicillin

• Broad spectrum

Primaxin, doripenem

Examples of carbapenems (penicillin with stronger bonds)

Monobactam (single ring)

• Penicillin with single ring instead of B lactam double ring

• Low toxicity

• only works against gram negatives

Aztreonam is an example of what kind of penicillin?

Monobactam

• Bacitracin

• Vancomycin

• Teixobactin

Examples of polypeptide antibiotics that inhibit cell wall synthesis

works against gram positive and topical (OTC)

Bacitracin

Vancomycin

• Glycopeptide

• Last line of defense against MRSA

Teixobactin

New class of antibiotics fights gram positive

Antimycobacterial antibiotics

Prevents mycolic acid formation in the acid fast positive bacterial strains from forming

Isoniazid (INH)

Inhibits mycolic acid synthesis

Ethanbutal

allows for mycolic acid to be made but does not allow it to be used in the actual cell wall

Attacks & effects either 30S, 50S ribosome disrupting protein synthesis

How antimicrobics work against protein synthesis

What drug is converted to intermediates targeting ribosomal proteins?

Nitrofurantoin

methods of how antibiotics target growth

How to remember what drug effects what ribosome

50S ribosomal unit and 30 ribosomal unit in prokaryote cells

what are peptide bonds?

The bonds that links the amino acids so they stay together in formation

Chloramphenicol

• drug that prevents peptide bonds from forming

• binds to the 50S (big unit) of the entire ribosome

• Broad spectrum

Chloramphenicol side effects

1. suppress bone marrow

2. affect blood cell formation

Aminoglycosides

• Blocks tRNA from brining in amino acid sequence so protein sequence cannot be created

• Bacteriostatic

• Changes shape of the 30S (bottom) ribosomal unit

Aminoglycoside examples and side effects

• streptomycin, neomycin, gentamycin

• can cause permanent auditory damage

Streptomyces spp produces what?

Tetracyclines

Tetracycline action and is

Does not allow for the tRNA to attach to the ribosome

Broad spectrum & penetrates tissues

Because tetracycline is broad spectrum and penetrates tissues it is used for ____________ and side effect is _______________

against rikettsias, chlamydia and side effect is suppression of normal microbiota

Glycyclines

Newer class of protein synthesis inhibor

Binds to 30S ribosomal unit
Administered via IV

Useful against MRSA

Macrolides

Freezes the 50S ribosomal unit from moving along to read the mRNA unit, thus preventing the formation of proteins

Contains a macrocyclic lactone ring

Narrow spectrum - Gram pos targets

an example of a macrolide drug

Erythromycin

S.O.P (Last resort of drugs if other drugs used did not work in order of severity)

Bringing out the big guns

Inhibitors of protein synthesis

• Streptogramins

• Oxazolidinones

• Pleuromutilins

Streptogramins mode of action

Attach to the 50S subunit

work against gram positives resistance to other antibiotics

Oxazolidinones mode of action

Bind to both 50S and 30S ribosomal unit

Combat MRSA

Pleuromutilins

Retapamulin: Topical and effective against gram pos.

Treats impetigo

Lipopetides

effects the plasma cell membrane

Daptomycin

Polymyxin B

Polymyxin E

All drugs that affect the plasma membrane

Daptomycin

Treats only gram +

Attacks the bacterial cell membrane

Produced by streptomycetes

for skin infections

Polymyxin B (B negative)

• Topical

• Bacteriocidal

• Fights Gram negative

• OTC combined w/bacitracin and neomycin ointments

Polymyxin E (colistin brand name)

Effective against gram negative

mostly to fight resistance / respirators and more broad

Nucleic Acid Synthesis Inhibitors

prevents mRNA from doing its job during transcription thus preventing new DNA from being formed

• Rifamycin

• Quinolone and Fluoroquinolones

Examples of drugs blocking nucleic acid synthesis

Inhibits mRNA synthesis

penetrates tissues

antitubercular activity ( fights TB)

side effect of turning urine orange

Rifamycin uses and mechanism of action

Quinolone and Fluoroquinolones examples and uses

• Nalidixic acid- synthetic, inhibiting DNA gyrase

• Norfloxacin and ciprofloxacin- Broad spectrum, relatively non toxic