CH14: ANTIMICROBIAL DRUGS

what is the most important feature of an ideal antimicrobial drug

the most important feature is selective toxicity — the drug must harm or inhibit the microorganism without damaging the host's cells

what does it mean for an antimicrobial drug to be selectively toxic

selective toxicity means the drug specifically targets structures or metabolic processes unique to the microbe (such as the bacterial cell wall or bacterial ribosomes) that human cells do not have, allowing it to kill or inhibit microbes without harming the patient

how do antimicrobial drugs achieve selective toxicity

they exploit biochemical or structural differences between microbial cells and host cells

for example:

-some target bacterial cell walls (which humans lack)

-others target bacterial ribosomes (different from human ribosomes)

-some interfere with microbial enzymes that humans do not possess

what is the difference between microbicidal and microbiostatic drugs

-microbicidal drugs: kill the microorganism outright, eliminating it from the body

-microbiostatic drugs: only inhibit the growth or reproduction of the microorganism, allowing the body's immune system to finish clearing the infection

why is a microbicidal drug usually preferred over a microbiostatic one

because a microbicidal drug completely destroys the pathogen, reducing the chance of relapse or resistance, while microbiostatic drugs rely more heavily on the host's immune response to finish the job

why must an ideal antimicrobial drug remain potent for a sufficient amount of time

because the drug needs to stay active in the body long enough to reach the site of infection and fully kill or inhibit the microbes before being broken down or excreted

how do metabolism and excretion affect a drug's potency and duration

the body's metabolism can break down drugs into inactive forms, and excretion (often through the kidneys) can remove them too quickly

-if a drug is metabolized or excreted too fast, it wont remain at effective concentrations long enough to work properly. this s related to its half-life — how long it stays active in the body

what is antimicrobial resistance

antimicrobial resistance is when microbes develop the ability to survive exposure to a drug that once killed or inhibited them. this happens through genetic mutations or by acquiring resistance genes from other microbes

why is it important that the ideal antimicrobial drug is not easily susceptible to resistance

because resistance makes treatment ineffective, leading to persistent or recurring infections. a drug that microbes cannot easily develop resistance to will remain useful for longer periods and be more reliable in treatmen

how should an ideal antimicrobial drug interact with the host's immune defenses

it should complement or assist the immune system — not replace it. this means the drug should reduce the number of microbes, making it easier for the immune system to clear the infection, or make the microbes more vulnerable to immune attack

what is synergy between an antimicrobial drug and the immune system

synergy occurs when the drug and the immune system work together — for example, the drug weakens or reduces the number of microbes, allowing immune cells (like phagocytes) to destroy the remaining ones more effectively

why must the drug remain active even when diluted in body fluids and tissues

after absorption, drugs are distributed throughout body fluids such as blood and lymph. they become diluted during this process, so an ideal drug must maintain enough potency to stay effective even at lower concentrations in tissues

what does it mean for an antimicrobial drug to be "readily delivered to the site of infection"

it means that once administered, the drug must be able to travel through the bloodstream or tissues and cross necessary barriers (like cell membranes or the blood-brain barrier) to actually reach the location where the infection exists

why is drug distribution important in antimicrobial therapy

because some infections occur in areas that are difficult for drugs to reach (such as the brain, eyes, or joints). a drug that can't reach its target site in adequate concentrations won't be effective, even if it's potent in a lab test

why should an ideal antimicrobial drug be reasonably priced

because affordability ensures accessibility — patients and healthcare systems can obtain and use the drug widely and promptly. if a drug is too expensive, patients may delay or avoid treatment, leading to worse outcomes and continued spread of infection.

what does it mean for an antimicrobial drug to have minimal adverse effects

it means the drug should cause little to no harm to the patient, with a very low risk of side effects, allergic reactions, or damage to normal body functions

how can antimicrobial drugs cause allergic reactions

some people's immune systems recognize drug components as harmful substances, triggering an allergic response — ranging from mild rashes to severe reactions like anaphylaxis

what are secondary infections (superinfections), and how can they occur during antimicrobial therapy

a superinfection occurs when the normal microbiota (the beneficial bacteria that protect the body) are destroyed by broad-spectrum antibiotics, allowing other harmful microbes (like Candida or Clostridium difficile) to grow and cause new infections

why should the ideal drug avoid disrupting the host's normal microbiota

because the normal microbiota helps protect against invading pathogens, aids digestion, and supports immune function. disrupting it can lead to digestive issues, yeast infections, or antibiotic-associated diarrhea

summarize all the characteristics of the ideal antimicrobial drug

the ideal antimicrobial drug should: B

-be selectively toxic to microbes but safe for host cells

-be microbicidal, not just microbiostatic

-remain potent long enough in the body without being broken down or excreted too quickly

-resist the development of microbial resistance

-support and complement the host's immune defenses

-stay active even when diluted in body fluids and tissues

-be readily distributed to the site of infection

-be reasonably priced and widely accessible

-cause minimal side effects, no allergies, and no disruption of normal microbiota

what are antimicrobial drugs and what is their primary purpose

antimicrobial drugs are a diverse group of compounds used to kill or inhibit the growth of microorganisms, including bacteria, fungi, protozoa, and viruses, thereby treating infections caused by these organisms

how are antimicrobial drugs classified based on their origin

-natural: compounds originally produced by living organisms, such as penicillin from Penicillium mold

-synthetic: drugs entirely man-made in a laboratory, like sulfa drugs

-semisynthetic: natural compounds chemically modified to improve effectiveness, stability, or spectrum of action, like amoxicillin, a modified penicillin

how many antimicrobial drugs and drug families exist, and how are they classified

there are about 260 different antimicrobial drugs classified into 22 drug families. classification is based on

-chemical structure of the drug

-mechanism of action (how it kills or inibits microbes, e.g., damaging the cell wall, inhibiting protein synthesis, or interfering with DNA replication

how are antimicrobial drugs categorized based on the type of microbe they target

the four major groups are:

1) antibacterial drugs (antibiotics) - target bacteria

2) antifungal drugs - target fungi

3) antiprotozoal drugs - target protozoa

4) antiviral drugs - target viruses

what are antibacterial drugs and how do they function

antibacterial drugs, also called antibiotics, specifically target and treat bacterial infections. they may work by:

-disrupting cell wall synthesis

-inhibiting protein synthesis

-interfering with DNA or RNA replication

-blocking metabolic pathways unique to bacteria

what are antifungal drugs and why are they more challenging to develop than antibacterial drugs

antifungal drugs treat infections caused by fungi (mycoses), such as athlete's foot, ringworm, or systemic fungal infections. they are harder to develop because fungal cells are eukaryotic, like human cells, so drugs must target features unique to fungi without harming the patient.

what are antiprotozoal drugs and what challenges exist in their development

antiprotozoal drugs treat diseases caused by single-celled protozoa, such as malaria, giardiasis, and trichomoniasis. like antifungals, they are challenging to develop because protozoa are eukaryotic making selective toxicity essential to avoid harming the host

what are antiviral drugs

antiviral drugs target infection caused by viruses, which are obligate intracellular parasites (they require host cells to replicate)

how do antiviral drugs functions

they work by interfering with viral entry into host cells, replication of viral DNA or RNA, assembly and release of new viral particles

-examples of viral infections treated include HIV, influenza, and herpes

why is selective toxicity important for antifungal, antiprotozoal, and antiviral drugs

because these pathogens are eukaryotic (fungi and protozoa) or live inside host cells (viruses), drugs must be carefully designed to kill or inhibit the pathogen without causing damage to the host's cell

can the term "antibiotic" be used interchangeably with antibacterial drug

often yes, but technically an antibiotic refers to a natural compound produced by one microorganism to kill another, while antibacterial drugs include natural, semisynthetic, and synthetic drugs targeting bacteria

what are antibiotics and what is their biological origin

antibiotics are naturally occurring antimicrobial compounds produced as secondary metabolites by bacteria and fungi, used to inhibit or kill other microorganisms in their environment

what is primary metabolism, and how does it differ from secondary metabolism

primary metabolism involves essential processes like cellular respiration, amino acid synthesis, and fatty acid synthesis, which are necessary for immediate growth and survival. secondary metabolism involves biochemical pathways that are not essential for survival under normal conditions but give the organism a competitive ecological advantage, such as antibiotic production

under what conditions are antibiotics typically produced in microorganisms

antibiotics are often produced when nutrients become scarce or when microorganisms enter the stationary phase of growth. this production helps them compete for resources by inhibiting or killing nearby susceptible microbes

what is the ecological purpose of antibiotic production in microorganisms

the production of antibiotics serves as chemical competition. by releasing antibiotics, microorganisms can eliminate susceptible competitors in the environment, ensuring better access to nutrients and space

which bacterial genus is the most prolific source of naturally occurring antibiotics, and why

Streptomyces, a genus of filamentous, Gram-positive Actinomycetes, is the most prolific source, accounting for over 70% of known naturally occurring antibiotics. This genus produces antibiotics through complex, regulated pathways often coordinated by small signaling molecules called autoregulators

example of antibiotics produced by Streptomyces

Streptomyces produces antibiotics such as Streptomycin, Erythromycin, and Tetracycline. one specific example is Actinorhodin, a blue-pigmented antibiotic with antimicrobial activity

which genus of bacteria produces peptide antibiotics, and what are some examples

Bacillus is known for producing peptide antibiotics. examples include Bacitracin and Polymyxin B, which are used to target various bacterial pathogens

which fungal genus produces Penicillin, and which species is commonly used for industrial production

Penicillium produces Penicillin, and the species Penicillium chrysogenum is commonly used for industrial production

what are some naturally occurring forms of Penicillin

Penicillin G (Benzylpenicillin) and Penicillin V (Phenoxymethylpenicillin) are naturally occurring forms of Penicillin

which fungal genus is the source of Cephalosporin antibiotics

Cephalosporium, now often referred to as Acremonium, is the mold that produces Cephalosporin antibiotics

what is the primary target of β-lactam antibiotics, and why is it effective

β-lactam antibiotics, including Penicillin and Cephalosporin, target the bacterial cell wall by inhibiting peptidoglycan synthesis. this is effective because peptidoglycan is essential for bacterial structural integrity, and humans lack this component, making it selectively toxic

how do β-lactam antibiotics interfere with peptidoglycan synthesis

tThey irreversibly bind to Penicillin-binding proteins (PBPs), including transpeptidase, which are enzymes responsible for cross-linking glycan strands and peptide chains, weakening the cell wall and causing bacterial lysis

what is the bactericidal effect of β-lactam antibiotics

by blocking cross-linking in peptidoglycan synthesis, β-lactam antibiotics make the bacterial cell wall structurally defective. the cell cannot withstand internal osmotic pressure and undergoes lysis, leading to death

why do β-lactam antibiotics exhibit high selective toxicity

they exhibit high selective toxicity because human and animal cells do not have peptidoglycan cell walls and therefore lack the PBP enzymes that are the target of β-lactam antibiotics

who discovered Penicillin, in what year, and under what circumstances

Alexander Fleming discovered Penicillin in 1928. He observed that a mold, Penicillium notatum, accidentally contaminated a Staphylococcus aureus culture plate, creating a clear zone (zone of inhibition) where bacterial growth was prevented

what is the primary action of antimicrobial drugs on infectious microorganisms

antimicrobial drugs either kill infectious microorganisms (bactericidal, fungicidal, or virucidal) or inhibit their growth (bacteriostatic, fungistatic), preventing them from multiplying

how do antimicrobial drugs disrupt cellular processes or structures in microorganisms

these drugs target essential structures and processes within microbial cells, such as the cell wall, cell membrane, protein synthesis machinery, or metabolic pathways, causing the cells to malfunction or die

why are bacterial cell walls a common target for antibiotics, and which drugs act on them

bacterial cell walls contain peptidoglycan, a structure absent in human cells. antibiotics like penicillins and cephalosporins inhibit peptidoglycan synthesis, causing the bacterial cell wall to weaken and the cell to lyse

how can drugs disrupt the bacterial cell membrane

certain antimicrobial drugs target the lipid components of bacterial cell membranes, disrupting membrane integrity and permeability, which leads to leakage of cellular contents and cell death

how do antibiotics target bacterial protein synthesis

antibiotics such as tetracyclines and aminoglycosides bind selectively to bacterial 70S ribosomes, which differ structurally from human 80S ribosomes, halting the production of essential proteins necessary for microbial growth

in what ways can antimicrobial drugs interfere with microbial metabolic pathways

drugs may inhibit synthesis of nucleic acids (DNA or RNA) or block the production of essential metabolites, like folic acid in bacteria, thereby preventing cell replication and survival

how do antiviral drugs inhibit virus replication

antiviral drugs target specific steps of the viral life cycle, including attachment/entry into host cells, uncoating of viral genetic material, nucleic acid synthesis using viral enzymes, and assembly or release of new viral particles

what is selective toxicity in the context of antimicrobial drugs

selective toxicity is the ability of a drug to kill or inhibit a pathogen without harming host cells. drugs achieve this by targeting molecular structures or pathways unique to the pathogen

why do drugs that target bacterial cell walls exhibit high selective toxicity

human cells lack peptidoglycan cell walls, so drugs targeting this structure can kill bacteria effectively without affecting human cells

when is selective toxicity more difficult to achieve, and why does this lead to side effects

selective toxicity is harder when pathogens share many structures or metabolic pathways with host cells. drugs that affect these shared components may damage host cells, causing side effects

why do antibacterial drugs generally have higher selective toxicity than antifungal or antiprotozoal drugs

bacteria are prokaryotes with many targets absent in human cells (like 70S ribosomes and cell walls). fungi and protozoa are eukaryotes and share many cellular structures and pathways with humans, reducing selective toxicity and increasing side effect risk

how do antifungal drugs achieve selective toxicity, and why can side effects occur

antifungal drugs often target ergosterol in fungal cell membranes, which is similar to human cholesterol. this similarity can lead to some disruption of human cell membranes and more frequent side effects

why are antiprotozoal drugs considered the least selectively toxic

protozoa are highly similar to human cells, so drugs targeting them often affect human cells as well, leading to a higher incidence of significant side effects and limiting long-term use

why do antiviral drugs often have toxicity concern

viruses rely on host cell machinery for replication, so drugs that inhibit viral replication can inadvertently interfere with the host cell's processes, leading to potential toxicity

what determines the potential for selective toxicity and the likelihood of side effects in antimicrobial therapy

the degree of difference between the pathogen and host cell dictates selective toxicity. the more similar the pathogen is to the host, the harder it is to find unique targets, increasing the risk of collateral damage to host cells

summarize the relationship between pathogen type, selective toxicity, and drug effectiveness

bacteria, as prokaryotes, provide the most unique targets for drugs, allowing high selective toxicity and effective treatment. fungi and protozoa, being eukaryotic like humans, share structures with host cells, reducing selective toxicity. viruses, as intracellular parasites, often require drugs that affect host cell machinery, which increases potential toxicity

what is the primary target of antimicrobial drugs that inhibit cell wall synthesis

these drugs target the bacterial cell wall, specifically the peptidoglycan layer, which provides rigidity and protection against osmotic pressure

how do drugs that inhibit cell wall synthesis work

they interfere with the synthesis, transport, or cross-linking of peptidoglycan monomers, preventing the cell wall from forming properly and weakening its structure

what happens to bacteria when their cell wall synthesis is inhibited

the weakened cell wall can no longer resist internal turgor pressure, causing the bacterial cell to undergo osmotic lysis (bursting)

why does inhibition of a cell wall synthesis have high selective toxicity

human cells do not have a peptidoglycan cell wall, so these drugs specifically target bacterial cells without harming human tissues

what are examples of drug classes that inhibit cell wall synthesis

Penicillins, Cephalosporins, and Vancomycin are major classes that block peptidoglycan synthesis in bacteria

what are the main target of antimicrobial drugs that inhibit protein synthesis

these drugs target bacterial ribosomes, which are responsible for translating mRNA into proteins

how do protein synthesis inhibitors achieve selective toxicity

bacteria have 70S ribosomes, while human cells have 80S ribosomes. the structural difference allows drugs to bind selectively to bacterial ribosomes without affecting human ones significantly

what is the mechanism of action for protein synthesis inhibitors

these drugs bind to the 30S or 50S subunits of bacterial ribosomes, disrupting translation by interfering with initiation, elongation, or mRNA reading, halting protein production

why can protein synthesis inhibitors still cause mild toxicity in humans

human mitochondria contain ribosomes that resemble bacterial 70S ribosomes, so these drugs can occasionally interfere with mitochondrial protein synthesis, leading to limited host toxicity

what are examples of antimicrobial drug classes that inhibit protein synthesis

Aminoglycosides (like Streptomycin), Tetracyclines, and Macrolides (like Erythromycin)

what is the target of antimicrobial drugs that inhibit nucleic acid synthesis and transcription

these drugs target enzymes involved in DNA replication and RNA transcription, such as DNA gyrase and RNA polymerase

how do nucleic acid synthesis inhibitors work

they bind to and inhibit key bacterial enzymes like DNA gyrase (needed for DNA replication) or RNA polymerase (needed for transcription), blocking the bacterium's ability to replicate or produce mRNA

what is the result of inhibiting bacterial nucleic acid synthesis

the bacterium cannot replicate its DNA or make mRNA, which halts growth, reproduction, and protein production

why is nucleic acid synthesis inhibition selectively toxic to bacteria

bacterial enzymes like DNA gyrase and RNA polymerase are structurally different from those in eukaryotic cells, allowing for selective targeting

what are examples of drugs that inhibit nucleic acid synthesis

Fluoroquinolones inhibit DNA gyrase, while Rifamycins inhibit bacterial RNA polymerase

what is the target of antimicrobial drugs that cause injury to the plasma membrane

these drugs target the bacterial cell membrane (plasma membrane), which regulates the entry and exit of substances

how do drugs that damage the plasma membrane work

they act like detergents or insert themselves into the lipid bilayer, disrupting the membrane's structure and increasing permeability

what is the result of disrupting a bacterial cell's membrane integrity

leakage of vital cellular contents such as ions and macromolecules occurs, leading to loss of homeostasis and cell death.

why do drugs that damage the plasma membrane have lower selective toxicity

human cells also have plasma membranes made of similar lipids, so these drugs can affect host cells as well, increasing potential toxicity

what are examples of antimicrobial drugs that target cell membranes

Polymyxins (effective mainly against Gram-negative bacteria) and Daptomycin (used against Gram-positive bacteria)

what is the target of drugs that inhibit the synthesis of essential metabolites

these drugs target bacterial metabolic pathways necessary for producing key molecules such as folic acid

how do metabolic inhibitors work to stop bacterial growth

they act through competitive inhibition, mimicking the structure of natural substrates and binding to enzyme active sites, blocking the normal metabolic reaction

what happens when a bacterium's essential metabolic pathway is blocked

the bacterium cannot produce necessary metabolites (like folic acid), which are needed for DNA and RNA synthesis, leading to cell starvation and death

why is the inhibition of essential metabolite synthesis highly selective

many bacteria must synthesize their folic acid, while human cells obtain preformed folic acid from the diet and use a different pathway, making this drug target specific to microbes

what are examples of drug classes that inhibit the synthesis of essential metabolites

Sulfonamides (Sulfa drugs) and Trimethoprim, which are often used together to synergistically block folic acid synthesis

which mode of antimicrobial action generally has the highest selective toxicity, and why

inhibition of cell wall synthesis has the highest selective toxicity because the bacterial cell wall is unique to prokaryotes and absent in human cells

which mode of antimicrobial action usually has the lowest selective toxicity, and why

injury to the plasma membrane tends to have the lowest selective toxicity because human and bacterial membranes share similar lipid structures, making host damage more likely

how do Sulfonamides and Trimethoprim work synergistically

Sulfonamides block an earlier step in folic acid synthesis, while Trimethoprim blocks a later step, creating a double blockade that enhances antibacterial effectiveness.

why are metabolic pathway inhibitors generally bacteriostatic rather than bactericidal

these drugs inhibit growth and reproduction by starving the bacteria of essential metabolites, but they do not directly kill existing cells

how does selective toxicity influence the choice of antimicrobial drug

drugs with higher selective toxicity are preferred becayse they effectively kill pathogens while minimizing harm to human cells, reducing side effects and toxicity risk

what is the main target of cell wall synthesis inhibitors

peptidoglycan, the main structural polymer in bacterial cell walls

why are cell wall inhibitors selectively toxic to bacteria

human cells lack cell walls, so these drugs don't harm human cells

what are the major classes of β-lactam antibiotics

Penicillins, Cephalosporins, Monobactams, and Carbapenems

what is the mechanism of β-lactam antibiotics

they block peptidoglycan cross-linking, weakening the wall and causing ceel lysis

which β-lactam antibiotic is often used for patients allergic to penicillin

cephalosporins

which antibiotic is used as a last resort for MRSA infections

vancomycin (a glycopeptide)

why is Bacitracin usually used topically

its toxic if taken systemically but safe on skin

what is the bacterial ribosome type targeted by these drugs

70S ribosome (30S + 50S subunits)