Anti-Infective+Agents

**Use this site to develop the concepts surrounding anti-infective agents and their mechanism of action .**
=Anti-Fungal & Anti-Infective Medications=
 * Anti-fungal and anti-infective medications are used to treat fungal or bacterial infections.**
 * Some are applied topically, while others are administered orally.
 * Anti-infective drugs are substances from any source that inhibits or kills organisms that can produce infection, such as bacteria, protozoa, or viruses
 * Antibacterial drugs are substances that destroy or suppress the growth or multiplication of bacteria
 * Antiviral agents are substances that destroy or suppress the growth or multiplication of viruses.

=**Medications given to treat fungal or bacterial infections include:**=
 * Penicillin
 * Ampicillin
 * Amoxicillin (Amoxil)
 * Cephalexin (Keflex)
 * Cefuroxime (Ceftin)
 * Cefprozil (Cefzil)
 * Cefaclor (Ceclor)
 * Cefixime (Suprax)
 * Cefadroxil (Duricef)
 * Erythromycin
 * Clarithromycin (Biaxin)
 * Azithromycin (Zithromax)
 * Nitrofurantoin (Furaton, Macrobid)
 * Trimethoprim-suphamethoxazole (Septra, Bactrim, Cotrim)
 * Dicloxazcillin (Dynapen)
 * Mupirocin (Bactroban)
 * Ciprofloxacin (Cipro)
 * Minocycline
 * Ofloxacin (Floxin)
 * Tetracycline
 * Doxycycline
 * Metronidazole (Flagyl)
 * Bacitracin
 * Polymixin B
 * Triple antibiotic ointment with bacitracin zinc/neomycin sulfate/polymyxin B sulfate (Neosporin, Polysporin)
 * Fluconazole (Diflucan)
 * Terbinafine (Lamisil)
 * Mycostatin (Nystatin)
 * Clotrmazole (Mycelex)
 * Tolnaftate (Tinactin)

Four principal drug discovery approaches are employed in the search for new antiinfectives:
 * 1) The expansion of known drug classes to cover organisms resistant to earlier members of the class
 * 2) The reevaluation of underexplored molecules
 * 3) The classical screening of synthetic compounds and natural compounds isolated from fermentation broths of microorganisms, plants or other organisms
 * 4) The identification of novel agents active against previously not-exploited or even unknown (novel) targets within the pathogen.

There is increasing evidence for involvement of oxidative stress (OS) in the mechanism of action of a wide variety of physiologically active materials. Often the reactive oxygen species (ROS) are generated by electron transfer (ET) or other routes mediated by free radicals. Principal ET functionalities are quinones (or precursors), metal complexes, aromatic nitro compounds (ArNO2), and conjugated imines. These moieties are commonly found in the structures of anti-infective agents or their metabolites. In most cases, the ET functionalities display reduction potentials in the physiologically active range, i.e. more positive than approximately -0.5 V. Though the focus of this review is on OS and ET, a mode of action which emulates the natural immune system of the host, in some cases, this mechanism also appears to be involved in more generally accepted approaches, such as enzyme inhibition, adverse effects on membranes and DNA, or interference with DNA or protein synthesis. OS-ET represents a broad understanding of drug action that can aid in the design of new anti-infective agents. It is significant that a relatively simple unifying theme can be applied not only to the action of the predominant groups of anti-infective agents, but also more generally to other drug classes, toxins, carcinogens, enzymes, and hormones. PMID: 10637374 [PubMed - indexed for MEDLINE]

Mechanism of action: Some interfere with biosynthesis Bactericidal drugs are an aggressive antibiotic that causes death Bacteriostatic drugs are drugs the interfere with the cells ability to reproduce and replicate without killing the bacteria Broad spectrum drugs have an effect on many different drugs at the same time Narrow spectrum drugs effect specific bacteria types Some antibiotics change the permeability of the cell membrane Some antibiotics will inhibit the protein synthesis While others inhibit DNA synthesis

** Mechanism of action of certain antibiotics **
|| ** = ** Example **=** || ** = ** Mechanism of Action / Notes **=** || neomycin || Inhibit protein synthesis by binding to a portion of the bacterial ribosome. Most of them are bacteriocidal (cause bacterial cell death). || cephalosporins carbapenems monobactams || Group of antiobiotics which contain a specific chemical structure (a beta-lactam ring) || The have structural similarities to penicillins and many people with allergies to penicillins also have allergic reactions to cephalosporins. || The cell wall is a needed protective casing for the bacterial cell wall. ||
 * = Agent =
 * **Aminoglycosides** || streptomycin
 * **Bacitracin** ||  || Inhibits cell wall production by blocking a step in the process (recycling of the membrane lipid carrier) which is needed to add on new cell wall subunits. ||
 * **Beta-lactam antibiotics** || penicillins
 * **Cephalosporins** ||  || Similar to penicillins in their mode of action, but they treat a broader range of bacterial infections.
 * **Chloramphenicol** ||  || Inhibits protein synthesis by binding to a subunit of bacterial ribosomes (50S). ||
 * **Glycopeptides** || vancomycin || Interferes with cell wall development by blocking the attachment of new cell wall subunits (muramyl pentapeptides). ||
 * **Macrolides** || erythromycin || Inhibit protein synthesis by binding to a subunit of the bacterial ribosome (50S). ||
 * **Lincosamides** || clindamycin || Inhibit protein synthesis by binding to a subunit of the bacterial ribosome (50S). ||
 * **Penicillins** ||  || Inhibit formation of the bacterial cell wall by blocking cross-linking of the cell wall structure.
 * **Quinolones** ||  || Block DNA synthesis by inhibiting one of the enzymes (DNA gyrase) needed in this process. ||
 * **Rifampin** ||  || Inhibits RNA synthesis by inhibiting one of the enzymes (DNA-dependent RNA polymerase) needed in this process. RNA is needed to make proteins. ||
 * **Tetracyclines** ||  || Inhibit protein synthesis by binding to the subunit of the bacterial ribosome (30S subunit). ||
 * **Trimethoprim** and **Sulfonamides** ||  || Blocks cell metabolism by inhibiting enzymes which are needed in the biosynthesis of folic acid which is a necessary cell compound. ||

Note: These cells are bacterial cells**
 * These are diagrams that visually demonstrate the mechanism of action of various antibiotics.



=Antibiotic Resistance - Diagram= 1. decreased permeability of the antibiotic 2. bacterial enzymes inactivate the antibiotic 3. target site of antibiotic is altered and so binding of antibiotic to target does not occur. Imagine a key, the antibiotic, does not fit into the key hole, the target site, because the key hole (target site) has been altered. 4. the antibiotic is actively transported out of the bacterial cell due to an efflux pump.
 * There are four antibiotic resistance can occur:**




 * All of these adaptations to antibiotics, or antibiotic resistance, can occur because of acquired genes, and these genes give rise to the 4 mentioned adaptations. These genes can be located on a plasmid, which is not apart of bacterial DNA. Plasmids are circular DNA. These adaptations can also occur due to mutations of genes that the bacteria already possess. Antibiotic resistance genes can either integrate into bacterial DNA or contained in acquired plasmid.**

**Diagram of how antibiotic resistance genes are tranfered among bacterial cells**



 * Activity Spectrum of Certain Antibiotics and Antimicrobial Drugs**






 * Narrow Spectrum Antibiotics **
 * ** Drug name: ** || ** Prescribed for: ** ||
 * Isoniazid || Tuberculosis ||
 * Ethambutol || Tuberculosis ||
 * Penicillin V & G || Acintobactor ||
 * Vancomycin || MRSA ||
 * Cephalosporin 1st generation ( || Bacterial Endocarditis ||
 * Metroidazole || Infection of the vagina, stomach, skin, joints, and respiratory tract ||
 * Penciclovir || Herpes ||
 * Augmentin || Lower respiratory tract infection ||


 * Broad Spectrum Antibiotics **
 * ** Drug Name: ** || ** Prescribed for: ** ||
 * Erythromycin || Strep throat ||
 * Clindamycin || If allergic to penicillin ||
 * Rifampin || Tuberculosis ||
 * Tetracycline || Acne ||
 * Chloramphenizol || Salmonella ||
 * Nitrofurantoin || E-coli ||
 * Penicillin VK || Ear infection ||
 * Ciprofloxacin || Respiratory tract infection ||
 * Cephalosporin 4th generation (Cefepime) || bacteremia ||

Adverse reactions to antibiotics
 * allergy or a hypersensitivity reaction
 * super infections
 * organ toxicity

Drug interactions Epilepsy medication (Tegretol, Dilantin)- Some seizure medications can affect the way the body reacts to antibiotics. The reverse is also true and some antibiotics affect the levels of the seizure medication putting the patient at a greater risk of reaching the threshold for a seizure. Cipro and doxycycline have these effects on seizure medications. The patient's physician must monitor the effects of antibiotics while taking the seizure medication.
 * Oral contraceptives- the evidence does not show indefinitely but it is recommended that a patient that is taking oral contraceptives and antibiotics should use another form of contraceptive in order to prevent pregnancy. It is thought that antibiotics reduce the effectiveness of oral contraceptives.
 * Warfarin- when a patient is taking antibiotics and warfarin their INR should be monitored closely. This is especially a greater concern in the elderly patients. Some antibiotics that increase the effects of warfarin are: ciprofloxacin, erythromycin and fluconazole. Antibiotics increase the patient's INR and are therefore a great concern for an increase in bleeding. These reactions are seen more often in patients 65 and older as they are more sensitive to the effects of medications.


 * ANTIFUNGAL

These medications are used to treat fungal infections such as candidiasis. These drugs act by being able to determine between mammalian and fungal cells in order to kill the fungal cells and not self. Due to both the body's cells and the fungal cells being eukaryotes and have organized DNA into chromosomes and ridding the body of the fungal cells can be difficult. Therefore it is difficult to find or design a drug that is going to target only fungal cells and not self. Due to this concept is why so many fungal drugs have adverse reaction. **

Polyene antifungals- such as amphoericin B act by binding to ergosterol int he fungal membrane causing depolarization of the membrane and formation of pores. Stimulation of the host immune cells by amphotericin B causes release of inflammatory cytokines by circulating monocytes resulting in fever, chills, rigor, nausea, vomiting, myalgias, arthralgias, and headache during intravenous infusions. At higher concentrations, amphotericin B binds to cholesterol in mammalian cell membranes leading to various organ toxicities, most importantly nephrotoxicity.

Azole antifungals- inhibit the fungal cytochrome P-450 3-A dependent ezyme 14-alpha demehylase which inhibits the synthesis of ergosterol. This then cause depletion of ergosterol in the cell membrane, and accumulation of intermediate sterols, causing increased membrane permeability and inhibition of fungal growth.






 * Antiviral Drugs for HIV **

nucleoside analogues, nukes || 1987 || NRTIs interfere with the action of an HIV protein called reverse transcriptase, which the virus needs to make new copies of itself. || non-nucleosides, non-nukes || 1997 || NNRTIs also stop HIV from replicating within cells by inhibiting the reverse transcriptase protein. ||
 * ~ Antiretroviral drug class ||~ Abbreviations ||~ First approved to treat HIV ||~ How they attack HIV ||
 * Nucleoside/Nucleotide Reverse Transcriptase Inhibitors || NRTIs,
 * Non-Nucleoside Reverse Transcriptase Inhibitors || NNRTIs,
 * Protease Inhibitors || PIs || 1995 || PIs inhibit protease, which is another protein involved in the HIV replication process. ||
 * Fusion or Entry Inhibitors ||  || 2003 || Fusion or entry inhibitors prevent HIV from binding to or entering human immune cells. ||
 * Integrase Inhibitors ||  || 2007 || Integrase inhibitors interfere with the integrase enzyme, which HIV needs to insert its genetic material into human cells. ||

Reverse Transcription: Converting viral RNA into DNA
Reverse transcriptase is the enzyme that transcribes the RNA sequence of HIV into DNA. Without reverse transcriptase, the viral genome couldn't become incorporated into human cells, and couldn't reproduce. Reverse transcriptase sometimes makes mistakes reading the RNA sequence. This means that newly reproduce viruses are slightly different from each other. Therefore, they end up with a variety of subtle molecular differences in their surface coat and enzymes. Vaccines, which induce the production of antibodies that recognize and binding to very specific viral surface molecules, are an unlikely player in fighting HIV, because throughout infection, HIV surface molecules are continually changing.

AZT-like Drugs Inhibit Reverse Transcription



 * Reverse Transcriptase Inhibitor (red) ||

The first major class of drugs found useful in slowing HIV infections are collectively called "reverse transcriptase inhibitors". These include AZT, 3TC, d4T, ddc, and ddl that act by blocking the recoding of viral RNA into DNA. The chameleon-like nature of HIV, however, limits their continued effectiveness

How HIV infects human cells []

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