MCB Ch. 11

Define Chemotherapeutic drugs

Define Chemotherapeutic drugs

any chemical used to treat disease

Define prophylaxis

use of a drug to prevent imminent infection of a person at risk

Define antimicrobial chemotherapy

the use of chemotherapeutic drugs to control infection

Define antimicrobials

all-inclusive term for any antimicrobial drug

Define antibiotics

substances derived from living organisms that can inhibit or destroy other microbes

Define semisynthetic drugs

drugs made from a natural source, then chemically modified

Define synthetic drug

drugs entirely produced by chemical reactions

narrow vs. broad spectrum

Narrow: antimicrobials effective against a limited array of microbes.

Broad: wide variety

Broad spectrum antibiotics are the best!

T or F

Not always. A prolonged use of broad spectrum antibiotics can kill off your natural flora (get rid of the good bacteria)

Paul Ehrlich

• tested arsenic-containing compounds against Treponema palladium

• originated the concept of selective toxicity

Selective toxicity means

a drug should harm the pathogen and not the host

Toxic vs Therapeutic dose

toxic = harm to host

therapeutic = eliminated pathogens in the host

Characteristics of the Ideal Antimicrobial Drug

• selectively toxic

• microbicidal

• soluble

• remains potent for long enough

• does not lead to resistance

• complements or assists host’s defenses

• remains active

• readily delivered to site of infection

• reasonably priced

• doesn’t disrupt host’s health

E-test tests for…

what concentration is the best

MIC = minimum inhibitory concentration

Tube dilution tests

• tests for drug susceptibility

• more sensitive and quantitative than Disc-diffusion tests

List the Modes of Action for Antibacterial drugs

+ examples

1. Inhibition of cell wall synthesis

   • stop peptidoglycan from forming

   • ex. penicillin

2. Inhibition of protein synthesis

   • stops translation

   • ex. tetracyclines

3. Inhibition of nucleic acid replication and transcription

   • interfere with DNA synthesis by inhibiting topoisomerase. interferes with RNA synthesis

   • ex. rifampin

4. Injury to the Plasma membrane

   • destroy membrane structures and impair function

   • ex. polymyxin B

5. Inhibition of synthesis of essential metabolites

   • inhibit enzymes

   • ex. sulfanilamide

What inhibits the biosynthesis of peptidoglycan (cabin logs)?

ampicillin

What leads to antibiotic resistance

improper or excessive use

How Antibiotic resistance comes to be…

1. random mutation

   • some bacterial cells of the population has the mutation for resistance. this resistance is not used when the antibiotic is not present.

2. exposure

   • when the population is treated with antibiotics, the sensitive ones die off, the resistant ones thrive. the resistant gene becomes operative

3. resistance

   • the resistant bacteria now multiply and fill the environment

Define Superinfection

infection occurring after or on top of an earlier infection, especially following treatment with broad-spectrum antibiotics

What allows for resistant strains to overgrow susceptible ones?

unnecessarily large antibiotic doses

How can antibiotic resistance spread?

• meat consumption (antibiotics are used in livestock feed)

• bacterial cells passing resistance genes to other bacterial cells

What are some ways humans misuse antibiotics and encourage antibiotic resistance?

• stop taking the antibiotics before your prescription is empty.

• saving it for when you feel bad later

Mechanisms of antibiotic resistance

• new enzymes are synthesized, inactivating the drug

• permeability/uptake of drug is decreased

• drug is immediately eliminated (pumped right back out)

• decreased binding sites for drugs

• an alternative pathway is used (detour)

What is antibiotic inactivation?

• a mechanism of resistance

• enzymes destroy antibiotics or prevent them from binding to target sites

Antifungal Agents cause

• membrane damage. causes contents to leak out

• inhibit sterol synthesis

Nystatin is used for…

antifungal used against Candida albicans infections in the intestines or vagina

• topical (you physically apply it)

• affects cell membrane function

Amphotericin B is used for…

antifungal used against serious systemic fungal infections

• pill

• affects cell membrane function

The goal of antiprotozoal agents is to…

eradicate the parasite

Aminoquinolines (Quinine) is a…

• Antiprotozoal Agent

• Antimalarial drug that accumulates in parasitized red blood cells.

• Interferes with parasite’s ability to break down and digest hemoglobin

Nitroimidazoles is a…

• Antiprotozoal Agent

• interferes with DNA synthesis

• treats

  • amoebiasis

  • giardiasis

  • trichomoniasis

What can be used against African trypanosomiasis?

a derivative of arsenic

Name some Antihelminthic agents

Praziqyantel, mebendazole, Ivermectins

Praziqyantel does what?

changes membrane permeability in cestodes and trematodes

• causes contraction and paralysis in the parasite

Mebendazole does what?

inhibit nutrient uptake in worms

Ivermectins do what?

cause paralysis in roundworms

Actions of Antiviral Drugs

1. inhibition of virus entry (can’t enter new cells)

   • ex. Enfuvirtide

2. inhibition of nucleic acids (can’t replicate)

   • ex. Acyclovir

3. inhibition of assembly/release (can’t get out)

   • ex. Indinavir

How does the disk-diffusion method work to characterize antibiotic resistance?

If there is a zone of inhibition, the bacteria is susceptible and the antibiotic works. No zone of inhibition means the bacteria is resistant.

More than half our antibiotics are produced by _____

bacteria

Describe the problems of chemotherapy for viral, fungal, protozoan, and helminthic infections

Fungi, protozoa, and helminths are eukaryotes and have very similar cells to humans & it's hard to find things that are not toxic to us.

Viral infections are hard to treat because viruses control the human host cell to replicate the virus so it's hard to attack the virus without killing the healthy host cells

Define broad spectrum antibiotic

affect a broad range of gram-positive or gram-negative bacteria

Define spectrum of activity

The range of pathogens the drug is effective against

Why is it hard to target a pathogenic virus without hurting the host’s cells

the virus is in the cells

Describe two tests for microbial susceptibility to chemotherapeutic agents.

Disk-diffusion

• measure zone of inhibition

Tube dilution tests

• more sensitive & quantitative

• finds MIC

What does MIC and MBC stand for? what is the difference between the two?

MIC = minimum inhibitory concentration (inhibits growth)

MBC = minimum bactericidal concentration (kills bacteria)

Modes of action of current antihelminthic drugs

• Prevents ATP production

• Alters membrane permeability

• Interfere with nutrient absorption

• Paralysis of helminths