MECHANISM OF ACTION Flashcards
causes degenerative alterations in the tegument and intestinal cells of the worm by binding to the colchicine-sensitive site of tubulin, thus inhibiting its polymerization or assembly into microtubules.
MEBENDAZOLE
The loss of the cytoplasmic microtubules leads to impaired uptake of glucose by the larval and adult stages of the susceptible parasites and depletes their glycogen stores.
The loss of the cytoplasmic microtubules leads to impaired uptake of glucose by the larval and adult stages of the susceptible parasites and depletes their glycogen stores.
Degenerative changes in the endoplasmic reticulum, the mitochondria of the germinal layer, and the subsequent release of lysosomes result in decreased production of adenosine triphosphate (ATP), which is the energy required for the survival of the helminth.
Due to diminished energy production, the parasite is immobilized and eventually dies.
Adverse Effects
Diarrhea, abdominal pain
Symptoms of overdose include** elevated liver enzymes, headaches, hair loss, low levels of white blood cells (neutropenia)**, fever, and itching
By promoting the release of acetylcholine, inhibiting cholinesterase, and stimulating ganglionic neurons, serves as a depolarizing neuromuscular blocking agent in helminths
PYRANTEL PAMOATE
This causes extensive depolarization of the helminth muscle membrane, resulting in tension to the helminth’s muscles, leading to paralysis and release of their attachment to the host organism’s intestinal walls
GABA receptor agonist
PIPERAZINE
binds directly and selectively to muscle membrane GABA receptors, presumably causing hyperpolarization of nerve endings, resulting in flaccid paralysis of the worm.
PIPERAZINE
While the worm is paralyzed, it is dislodged from the intestinal lumen and expelled live from the body by normal intestinal peristalsis.
Mechanism of action is thought to involve sensitizing the microfilariae to phagocytosis
is an inhibitor of arachidonic acid metabolism in microfilariae.
DIETHYLCARBAMAZINE
This makes the microfilariae more susceptible to innate immune attack but does not kill the parasites outright
Host destruction of parasites results, depending on the parasite, in severe but reversible reactions, including leukocytosis, retinal hemorrhages and ocular complications, tachycardia, rash, fever, encephalitis, and lymph node enlargement and swelling.
binds selectively and with high affinity to glutamate-gated chloride ion channels in invertebrate muscle and nerve cells of the microfilaria.
also is believed to act as an agonist of the neurotransmitter gamma-aminobutyric acid (GABA), thereby disrupting GABA-mediated central nervous system (CNS) neurosynaptic transmission
IVERMECTIN
works by causing severe spasms and paralysis of the worms’ muscles. This paralysis is accompanied - and probably caused - by a rapid Ca 2+ influx inside the schistosome
Secondary effects are inhibition of glucose uptake, lowering of glycogen levels, and stimulation of lactate release
PRAZIQUANTEL
Inhibits parasite respiration.
It is an alternative for Fasciola hepatica (sheep liver fluke infection) and an alternative to praziquantel for acute pulmonary paragonimiasis
BITHIONOL
Acts by the uncoupling of the electron transport chain to ATP synthase.
The disturbance of this crucial metabolic pathway prevents the creation of adenosine triphosphate (ATP), an essential molecule that supplies energy for metabolism.
NICLOSAMIDE
inhibits oogenesis and spermatogenesis.
The compound also inhibits thephosphofructokinaseenzyme, leading to glycogen depletion.
NIRIDAZOLE
Niridazole hascentral nervous systemtoxicity and can cause hallucinations.
Also, it may cause allergic reactions in sensitive people.
Agonistic activity towards the L-subtype nicotinic acetylcholine receptors in nematode muscles
This agonistic action reduces the capacity of the males to control their reproductive muscles and limits their ability to copulate.
LEVAMISOLE
Levamisole is an immunostimulant that has been shown to increase NK cells and activated T-cells in patients receiving this adjuvantly along with 5FU for Stage III colon cancer.
An antibiotic that binds to ergosterol, a major component of fungal cell membranes. It forms pores that alter membrane stability and allow leakage of cellular contents.
AMPHOTERICIN B
selectively inhibit the cytochrome P–450-mediated sterol demethylation of lanosterol to ergosterol in fungal membranes
inhibits the transformation of yeast cells into hyphae, the invasive and pathogenic form of the parasite
AZOLE ANTIFUNGALS
Prevents the synthesis of ergosterol, the fungal equivalent of cholesterol, thereby increasing membrane fluidity and preventing growth of the fungus
KETOCONAZOLE
noncompetitively inhibit the synthesis of a major fungal cell wall component, β-(1,3)-d-glucan, which is not present in mammalian cell walls.
ECHINOCANDINS
CASPOFUNGIN, ANIDULAFUNGIN, AND MICAFUNGIN
intrafungally converted into the cytostatic fluorouracil which undergoes further steps of activation and finally interacts as 5-fluorouridinetriphosphate with RNA biosynthesis thus disturbing the building of certain essential proteins
also undergoes conversion into 5 fluorodeoxyuridinemonophosphate which inhibits fungal DNA synthesis
FLUCYTOSINE
The drug binds to tubulin, interfering with microtubule function, thus inhibiting mitosis.
It binds to keratin in keratin precursor cells and makes them resistant to fungal infections.
GRISEOFULVIN
Inhibit squalene epoxidase, resulting in the accumulation of squalene inside the fungal cells.
Decrease the ability of fungi to make sterols
TERBINAFINE, TOLNAFTATE
exerts its effects by reversibly inhibitingDNA-dependent RNA polymerase, which further inhibits bacterial protein synthesis and transcription.
Rifampin
pro-drug that is converted to its active form metabolite by catalase-peroxidase and exerts its action by further inhibiting the biosynthesis of mycolic acid.
Isoniazid
converted to its active form pyrazinoic acid and exerts its effect by inhibiting trans-translation and possibly coenzyme A synthesis needed for the bacteria to survive.
Pyrazinamide
inhibits the enzyme arabinosyltransferases andpreventsthe biosynthesis of the mycobacterial cell wall.
Ethambutol
binding to the 30S subunit of ribosomes and inhibiting the protein synthesis of the mycobacteria.
Aminoglycosides (Streptomycin,Kanamycin, Amikacin)
inhibiting DNA gyrase and topoisomerase IV, further inhibiting DNA synthesis within the bacteria.
Fluoroquinolones(Levofloxacin, Moxifloxacin, Gatifloxacin)
Forms a covalent adduct with bacterial nicotinamide adenine dinucleotide (NAD), PTH-NAD, which competitively inhibits 2-trans-enoyl-ACP reductase (inhA), an enzyme essential for mycolic acid synthesis; results in increased cell wall permeability and decreased resistance against cell injury eventually leading to cell lysis.
A thioamide derivative with antitubercular activity
PROTIONAMIDE
An analog of the amino acid D-alanine with broad-spectrum antibiotic activities
Interferes with bacterial cell wall synthesis by competitively inhibiting two enzymes, L-alanine racemase and D-alanine: D-alanine ligase, thereby impairing peptidoglycan formation necessary for bacterial cell wall synthesis
CYCLOSERINE
In addition, D-cycloserine is an excitatory amino acid and partial agonist at the glycine binding site of the NMDA receptor in the central nervous system (CNS); binding to the central NMDA receptor may result in amelioration of neuropathic pain
Blocks theproton pumpforATP synthaseof mycobacteria
ATP production is required for cellular energy production and its loss leads inhibition of mycobacterial growth
BEDAQUILINE
- Dihydro-nitroimidazooxazole derivative
- A pro-drug which gets activated by the enzyme deazaflavin dependent nitroreductase (Rv3547)
- It acts by inhibiting the synthesis of mycobacterial cell wall components, methoxy mycolic acid and ketomycolic acid.
DELAMANID
Prodrug which is metabolically activated by a
nitroreductase enzyme
MA: inhibits mycolic acid biosynthesis, thereby blocking cell wall production
PRETOMANID
- Completelysyntheticdrug
- Bacterial protein synthesis inhibitorand a weak,non-selective,reversiblemonoamine oxidase inhibitor
- Stops the growth and reproduction of bacteria by disruptingtranslationofmessenger RNA(mRNA) intoproteinsin bacterialribosomes
LINEZOLID
- Highly lipophilic antimicrobial riminophenazine dye
- Binds to the guanine bases of bacterial DNA, thereby blocking the template function of the DNA and inhibiting bacterial proliferation.
- Also increases activity of bacterial phospholipase A2, leading to release and accumulation of lysophospholipids, which are toxic and inhibit bacterial proliferation
- Also exerts anti-inflammatory properties due to the suppression of T-lymphocyte activity
CLOFAZIMINE
- Diaminodiphenyl sulfone
- As anantibacterial, inhibitsbacterialsynthesis ofdihydrofolic acid, via** competition withpara-aminobenzoatefor the active site ofdihydropteroate synthase**, thereby inhibiting nucleic acid synthesis
- As ananti-inflammatory, inhibits the myeloperoxidase-H2O2-halide-mediated cytotoxic system in polymorphonucleocytes
DAPSONE
which uniquely binds to the 23S ribosomal RNA of the 50S subunit to inhibit protein synthesis
LINEZOLID
binds the 50S ribosomal subunit and is bactericidal for most organisms. It inhibits CYP 3A4 and may influence the metabolism of various drugs. Adverse effects include complex arthralgia-myalgia.
QUINUPRISTIN and DALFOPRISTIN
polypeptide that acts as a deterrent to disrupt the cell membrane functions of gram-negative bacteria (bactericidal).
Polymyxin
Inhibit the bacterial DNA gyrase or the topoisomerase IV enzyme, thereby inhibiting DNA replication and transcription
FLUOROQUINOLONES
structural analogs of para-aminobenzoic acid (PABA).
As such, they compete with endogenous bacterial PABA to inhibit the activity of dihydropteroate synthase and prevent the synthesis of dihydrofolic acid that is essential for the production of nucleic acid (purines and pyrimidines) and amino acids, and thus bacterial growth.
Sulfonamides
- enter the bacterial cytoplasm through permeases of the inner cell membrane, where they bind to the 50S subunit of assembled ribosome-mRNA complexes
- block the translocation of the ribosome along the mRNA to the next codon, thus leading to the inhibition of protein synthesis
MACROLIDES
Erythromycin
Clarithromycin
Azithromycin
Telithromycin
enters the bacterial cytoplasm through permeases of the inner cell membrane, where it binds to the 50S subunit of assembled ribosome-mRNA complexes
blocks the conjugation of the previously coded aminoacyl-tRNA with the presently coded aminoacyl-tRNA, thus leading to the inhibition of protein synthesis
CHLORAMPHENICOL
Tetracycline binds reversibly to the 30S subunit of bacterial ribosomes. This prevents the binding of aminoacyl tRNA to the acceptor site on the mRNA- ribosome complex and the addition of amino acid to the growing peptide, thus inhibiting bacterial protein synthesis; these agents are bacteriostatic.
TETRACYCLINES
Tetracycline
Oxytetracycline
Demeclocycline
Doxycycline
Minocycline
Tigecycline
inhibit bacterial protein synthesis; they are bactericidal against most gram-negative aerobic bacteria.
passively diffuse via porin channels through the outer membrane of gram-negative aerobic bacteria. Transport across the inner membrane requires active uptake that is dependent on electron transport (gram-negative aerobes only), the so-called energy-dependent phase I transport.
Inside the cell, these agents interact with the receptor proteins on the 30S ribosomal subunit. This “ freezes” the initiation complex and leads to a buildup of monosomes; it also causes translation errors
Aminoglycosides
Gentamicin
Tobramycin
Amikacin
Kanamycin
Neomycin
Netilmicin
Streptomycin
inhibits the enzyme enolpyruvate transferase and thereby interferes downstream with the bacterial cell wall-specific N-acetylmuramic acid.
FOSFOMYCIN
bactericidal agent that binds to and depolarizes the cell membrane, resulting in loss of membrane potential and rapid cell death.
DAPTOMYCIN
inhibits alanine racemase and the incorporation of alanine into the peptidoglycan pentapeptide
CYCLOSERINE
inhibits dephosphorylation and reuse of the phospholipid required for acceptance of N- acetylmuramic acid pentapeptide, the building block of the peptidoglycan complex.
BACITRACIN
Binds to the terminal end of the peptidoglycan to prevent further elongation and cross-linking due to inhibition of transglycosylase; this results in decreased cell membrane activity and increased cell lysis.
VANCOMYCIN
Irreversibly inhibits β- lactamase; when administered with penicillins,
exposes penicillinase-producing organisms to therapeutic concentrations of penicillin.
Clavulanic acid
Hydrolyzed in the mammalian kidney by a dehydropeptidase enzyme to a nephrotoxic intermediate, and thus is co-formulated with the dehydropeptidase inhibitor cilastatin
Imipenem
Stable to mammalian dehydropeptidases and does not require co-administration of cilastatin
Meropenem
exhibit good activity against anaerobes such as Bacteroides fragilis
CARBAPENEMS
is a naturally occurring monobactam lacking the thiazolidine ring that is highly resistant to β- lactamases
AZTREONAM
Inactivate bacterial transpeptidases and prevent the cross-linking of peptidoglycan polymers which is essential for bacterial cell wall integrity. This results in a loss of rigidity and susceptibility to rupture.
PENICILLINS
