Term
| list of bacteriostatic antibiotics |
|
Definition
| o Chloramphenicol, erythromycin, clindamycin, sulfonamides, trimethoprim, tetracyclines |
|
|
Term
| list of bactericidal antibiotics |
|
Definition
| o Aminoglycosides, beta-lactams, vancomycin, quinolones, rifampin, metronidazole |
|
|
Term
| - Drugs that pass the BBB (first line of treatment for meningitis) |
|
Definition
| chloramphenicol, sulfonamides, trimethoprim |
|
|
Term
| - Drugs that pass BBB only during inflammation |
|
Definition
| cefotaxime, ceftriaxone, ceftazidime |
|
|
Term
| second line of treatment for meningitis |
|
Definition
| chloramphenicol, sulfonamides and trimethoprim |
|
|
Term
| - The antibiotics that should be avoided during pregancny are: |
|
Definition
o Fluroquinolones, cartilage damage
o Chloramphenicol, gray baby syndrome
o Aminoglycosides, ototoxicity
o Tetracycline, bone growth inhibition
o Solfonamies, kernicterus |
|
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Term
| bacteria that are immune to cell wall synthesis inhibitors |
|
Definition
|
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Term
|
Definition
- Penicillin, cephalosphorin, carbapenems, monobactams.
- They all bind to the penicillin binding protein and inhibit the transpeptidase reaction and cross linking.
- bactericidal |
|
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Term
|
Definition
beta lactam bactericidal
- All are eliminated through the kidney, with the exception of nafcilin and oxacilin, which are more lipid soluble and are excreted though bile.
it’s excreted though the PSOASS, there is a completion between probenecid and penicillin.
can cause hypersensitivity, this can come in the form of macular popular rash, bronchospasm, urticaria (hives) or anaphylactic shock
exhibit crossallegenicity: an allergic reaction to penicillin will increase the chances of also having an allegic reaction to carbapenems and cephalosporins |
|
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Term
|
Definition
: Pen G and Pen V. They are the purest form of penicillin.
- They are beta-lactamase sensitive
they are combined with other things to make them last longer. Pen G procaine and Pen G benzathine
- Penicillin G is the treatment of choice of syphilis, which is caused by Treponema Pallidum. It is injected intra venously.
- bactericidal |
|
|
Term
| Anti Staph (oxypenicillins): |
|
Definition
Methicillin,(removed) Nafcillin, Oxacillin, cloxacillin, dicloxacillin.
are resistant to beta lactamases
used to treat gram + cocci (staphylococcus) except for MRSA.
- bactericidal |
|
|
Term
| - Extended spectrum (Aminopenicillins) |
|
Definition
Ampicillin, Amoxicillin
- They are more water soluble than the others and pass through the porin channels of some gram – organisms
- They are beta lactamase sensitive
- bactericidal |
|
|
Term
| treatment for pseudomembranous collitis |
|
Definition
metronidazole (DOC)
Vancomycin (alternative) |
|
|
Term
|
Definition
: carbenicillin, piperacillin, ticarcillin
- bactericidal
- These drugs are aimed at gram – bacteria that don’t have porin channels, they probably diffuse through the cell.
- Beta lactamase sensitive
- Mainly aimed at pseudomonas aeruginosa (gives a greenish bluish color to nails) |
|
|
Term
| beta lactamase inhibitors |
|
Definition
- Sulbactam, clavulonate, tazobactam
(can't combine with the natural penicillin’s and carbenicillin.) |
|
|
Term
|
Definition
- beta lactam bactericidal
- There are 4 generations. As the generation increases, the beta lactamase sensitivity decreases and the wider the spectrum for gram – bacteria.
- First generation are used for surgical prophylaxis.
- The third generation cephalosporins (ceftriaxone, cefotaxime, ceftazidime) all cross the BBB and are the treatment of choice for meningitis. |
|
|
Term
| - The most common organisms that cause meningitis |
|
Definition
| Neisseria Meningitidis (young adults), Haemophilus Influenza type B (toddlers) and Streptococcus Pneumoniae (elderly). Think NHS. |
|
|
Term
| cephalosporins that cause hypoprothrombinemia leading to prolonged bleeding and a disulfiram-like effect |
|
Definition
| Cefoperazone, Cefamandole, Cefotetan. |
|
|
Term
|
Definition
beta lactam bactericidal
broadest spectrum of all beta lactams
- They are excreted through the kidney but are not probenecid sensitive
- The most common adverse reaction is hypersensitivity and cross allergenicity.
beta lactamase resitant |
|
|
Term
|
Definition
beta lactam bactericidal
only work on gram – rods
- They are excreted through the kidney but are not probenecid sensitive
- The most common adverse reaction is hypersensitivity and cross allergenicity.
beta lactamase resistant |
|
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Term
|
Definition
| a carbapenem that is sensitive to renal dehydropeptidase 1. It is co administered with cilastatin since it inhibits the renal enzyme. The cleaved product of inipenem and renal dehydrogenase is toxic. |
|
|
Term
|
Definition
non beta lactam
Blocks the transportation of NAM-NAG complex through cell membrane
bactericidal |
|
|
Term
|
Definition
bins to D Ala – D Ala muramyl pentapentide inhibiting transglycosylation, and also interferes with cross linking of bacterial cell wall, making it a bactericidal.
- It is the drug of choice for MRSA, it is the second choice for Clostridium Difficile super infection and enterococcus (gram + bacteria) |
|
|
Term
| Reistance and side effects of vancomycin |
|
Definition
- There is some resistance by replacing one of the D Ala with D lactate
- Side effects the red man syndrome: because it is usually administered quickly through iv, mast cells degranuate and release histamine, causing flushing of head, neck and upper torso. Not an allergic reaction.
- Another side effect is ototoxicity and nephrotoxicity. It is not as common now because the drug is more pure but if you combine with other drugs that produce the same effects you are more likely to see this. |
|
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Term
|
Definition
| similar to vancomycin, but is less toxic since it has a shorter half life. |
|
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Term
|
Definition
-cell membrane inhibitor
Kills highly resistant gram + bacteria without cell lysis very effectively. The long chain binds to the cell membrane , with the help of Calcium, causes a depolarization (K comes out) , loses membrane potential and stops everything that goes on inside cell (DNA, RNA and protein synthesis)
- It’s used for complicated skin and skin structure infections.
- S. Aureus bacteremia. |
|
|
Term
|
Definition
Doxycycline, Minocycline, Tetracycline, Demeclocycline
- bacteriostatic
- Most common use is for acne and rosacea
- Also used for Mycoplasma Pneumonia, Chlamydial infections, Rocky mountain spotty fever, Lyme disease and cholera.
- Tetracyclines are chelators, they bind anything with a positive charge. Foods with high cation content will decrease the efficacy of the drug, preventing the drug from being absorbed.
- Tetracyclines are renally excreted, so they shouldn’t be used in patients with kidney failure (except Doxycycline) |
|
|
Term
|
Definition
| Binds to the 30S subunit Inhibiting the binding of amino acyl tRNA at the acceptor site. |
|
|
Term
|
Definition
o Active Efflux of drug
o Synthesis of a protein that covers the binding site of the tetracycline
o If a bacteria is resistant to one tetracycline its resistant to all |
|
|
Term
|
Definition
o Growth stunt in children, they bind to Ca in bone, not permanent.
o Discoloration of teeth, permanent,.
o Pregnancy category D
o Shouldn’t be administered while lactating
o Cause photosensitivity
o Demeclocycline can interfere with ADH receptors, leading to nephrogenic diabetes insipidus. However in patients with SIADH (syndrome of inappropriate secretion of ADH) since they make too much ADH. |
|
|
Term
|
Definition
amikacin, gentamycin, Netilmicin, neomycin, streptomycin, tobramycin
- The only bactericidal protein inhibitors |
|
|
Term
|
Definition
: Binds to the 30S subunit blocking the association with the 50S subunit , blocking formation of initiation of protein synthesis. Causes a misreading of the code and incorporation of incorrect amino acid, leading to a toxic product. This is why it’s bactericidal.
- They require O2 for uptake, which means they’re ineffective in anaerobic bacteria.
- Work in aerobic gram negative rods
- Has a synergistic effect with cell wall inhibitors (like beta lactams) |
|
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Term
|
Definition
| bacteria make conjugation enzymes that deactivate the aminoglycoside. |
|
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Term
|
Definition
| attaches to the cell wall, lets solutes in and cell bursts. Only applied topically because it’s nephrotoxic. Can also produce contact dermatitis once applied to skin. |
|
|
Term
|
Definition
Can cause nephrotoxicity, related to damage of mitochondrial ribosomes.
Can cause ototoxicity. First loss of high frequency hearing then low frequency. Irreversible. Can also affect the uterus.
Class D pregnancy
Can cause paralysis through NMJ blockage. This occurs because it causes a decrease in Ach levels increasing the risk of myasthenia gravis. |
|
|
Term
|
Definition
- Thromycin ending: (azithromycin, clarithromycin, erythromycin, telithromycin)
- Macrolides are used frequency in outpatient setting due to their broad spectrum or respiratory pathogens. Used in lower/upper respiratory infections. |
|
|
Term
|
Definition
| Binds to 50S subunit and inhibits translocation from peptidyl tRNA from A to T site |
|
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Term
|
Definition
| : bacteria methylates the drug, decreasing its affinity to the 50S subunit (except Telithromycin) |
|
|
Term
|
Definition
Should not be used in patients with liver problems (erythromycin and Azithromycin)*
Should not be used in patients who have kidney problems (clarithromycin)
They all interfere with CYP 450drug metabolism (except azithromycin). Can increase the effects of warfarin.
They are motilin agonists, hence they cause GI distress.
Ototoxic |
|
|
Term
|
Definition
| bacteriostatic protein synthesis inhibitor |
|
|
Term
|
Definition
binds to the 50S subunit inhibiting the translocation step of protein synthesis.
- Mainly used for the treatment of anaerobic bacteria. |
|
|
Term
|
Definition
Mainly it can cause pseudomembranous colitis due to overgrowth of C. Difficile. Since it’s a broad spectrum drug and is poorly absorbed.
Osteomyelitis, since it has a high affinity for bone and retains its properties. |
|
|
Term
|
Definition
bacteriostatic protein synthesis inhibitor
- Broad spectrum antibiotic restricted to life threatening infections
- Very lipid soluble and crosses BBB
- Is extensively metabolized in liver by glucoronyl transferase in order to be made water soluble.
- Intereferes with CYP450 metabolism. Increases warfarin effect. |
|
|
Term
|
Definition
| : Binds to the 50S subunit, inhibiting the activity of peptidyl transferase, inhibiting transpeptidation reaction. |
|
|
Term
|
Definition
GI stress
Anemia due to bone marrow toxicity (dose dependent)
Gray baby syndrome: chloramphenicol stays lipid soluble since glucoronyl transferase is not developed in babies. Crosses the BBB and produces symptoms similar to cyanide poisoning (hypotension, hypothermia and hypothormis)
Class D pregnancy drug and not for children |
|
|
Term
|
Definition
binds to the 50S subunit, inhibiting tRNA from initiating protein synthesis.
- They’re used in the treatment of vancomycin resistant enterococci and vancomycin resistant staph aureus, since they mutate one of the D Ala to D Lactate |
|
|
Term
| streptogramines (quinopristin/dalfopristin) |
|
Definition
bind to the 50S subunit, inhibiting tRNA biding to acceptor site.
- They’re used in the treatment of vancomycin resistant enterococci and vancomycin resistant staph aureus, since they mutate one of the D Ala to D Lactate. |
|
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Term
|
Definition
| blocks dihydropteroate synthetase which catalyzes reaction pteridine + PABA -> dihydropteroid acid which only occurs in bacteria |
|
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Term
|
Definition
o Steven-Johnson’s syndrome
o Crystalluria (which damages the kidneys)
o Phototoxicity
o Should not be used in newborns or pregnant women
o Has a high affinity for albumin, so watch out for bilirubin levels (kernicterus) and warfarin levels (increase bleeding)
- in patients in tolbutamide, it causes hypoglycemia since its also displaced from albumin.
o It causes hemolytic anemia in patients with glucose 6 phosphate dehydrogenase deficiency. |
|
|
Term
|
Definition
o blocks dihydrofolate reductase which catalyzes the reaction dihydrofolic acid -> tetrahydrofolic acid.
can cause anemia due to a decreased level of THF since both bacteria and humans have the dihydrofolate reductase enzyme. Treatment with folinic acid alleviates this. |
|
|
Term
|
Definition
(-floxacin)
- Broad spectrum antibiotic used mainly for gram – bacteria.
- Used for the treatment of UTI, STD, GI, Skin and soft tissue infection |
|
|
Term
|
Definition
o Fluoroquinolones interfere with topoisomerase II (DNA Gyrase) and IV by binding on them and interfering with bacterial DNA replication.
o DNA Gyrase neutralizes positive supercoils by introducing negative supercoils mainly in gram –
o Topoisomerase IV decatenates DNA mainly in gram + bacteria |
|
|
Term
|
Definition
| they alter topoisomerases and decreasing accumulation by changing the porin channel so that the fluoroquinolones cannot enter the cell |
|
|
Term
|
Definition
o Not to be used in pregnant women, nursing women and children under 18 due to cartilage erosion
o Most common side effects are nausea and vomiting
o Photosensitivity
o In adults there can be rupturing of tendon
o Should not be used in patients with arrhythmias (increases QT interval)
o Interfere with CYP450 metabolism |
|
|
Term
| - First drug of choice for Influenza A and B |
|
Definition
| Oseltamivir (orally active pro drug) |
|
|
Term
| Alternatives for Influenza A and B |
|
Definition
| Zanamivir: Very potent. inhaled, It can cause some respiratory irritation. It is contraindicated in people with COPD or asthma. It’s not administered to children younger than 7 since they have a narrow respiratory tract. |
|
|
Term
| Oseltamivir and Zanamivir MOA |
|
Definition
| sialic acid analogues that inhibit the neuraminidase from cleaving the bond between sialic acid and hemagluttinin. They block the release of the virus |
|
|
Term
| Oseltamivir and Zanamivir MOR |
|
Definition
| mutations of neuraminidase |
|
|
Term
| Rimantadine and Amantadine MOA |
|
Definition
| - They block the AM2 capsid which allows H+ to come in at low pH (in endosomes) oreventing the proteins to denature and uncoating to occur. |
|
|
Term
| Rimantadine and Amantadine MOR |
|
Definition
| Mutations in Amino acid sequence of AM2 channel. |
|
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Term
|
Definition
o Used to treat respiratory syncytial virus (RNA virus)
o Guanosine nucleoside analog that is activated by cellular kinases to the active tri phosphate form.
o It blocks RNA dependent RNA polymerase.
o It indices dose dependent anemia and elevated bilirubin levels.
o Contraindicated in pregnancy
o Also used in the treatment of Lassa Fever. High mortality, essentially bleed to death if not administered between 24-48 hrs
o Also used to treat Hepatitis C virus, along with endogenous interferon a. (endogenous interferon a or lamividine treats Hep B) |
|
|
Term
|
Definition
treats HSV and VZV
inhibits viral DNA polymerase
o This is an excellent drug since it has 3000x more affinity to the viral thymidine kinase than to the host kinase.
o It also has 100x more affinity to the viral DNA polymerase than to the host DNA polymerase.
o It’s well tolerated, nephrotoxic and ototoxic at high dosages.
o Resistance occurs when there is a mutation is viral DNA polymerase or viral thymidine kinase. |
|
|
Term
|
Definition
o Used in treatment of cytomegalovirus retinitis
o Not as much affinity to viral DNA polymerase as acyclovir, can induce bone marrow suppression and mucositis. |
|
|
Term
|
Definition
o A pyrophosphate analog that acts as a cofactor that is needed for DNA polymerase function.
o It inhibits the pyrophosphate binding site on viral DNA polymerase halting DNA elongation.
o Works at low concentrations which don’t interfere with human DNA polymerase.
o Used as an alternative in the treatment of cytomegalovirus retinitis, HSV and VZV
o Also used in the event that herpes simplex or varicella roster is resistant to acyclovir
o Does not need activation
o Dose limiting nephrotoxicity due to the Ca buildup
o Due to liberation of phosphate group, it binds to Ca and leads to hypocalcemia
o No bone marrow suppression |
|
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Term
|
Definition
o Blocks the CCR5 receptor in the host cell, blocking attachment.
o Not the main drugs used, it is used when the standard therapy has failed. |
|
|
Term
|
Definition
o It binds to viral gp41, preventing membrane fusion
o Only given IV
o Also given in case of failure of standard |
|
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Term
|
Definition
- NRT-I
dose limiting hematotoxicity, due to bone marrow suppression. Thymidine analog |
|
|
Term
|
Definition
- NRT-I
about 20% peripheral neuropathy and 7% pancreatitis. Guanosine analog. |
|
|
Term
|
Definition
-NRT-I
peripheral neuropathy when it’s administered by itself and lipoatrophy. Thymidine analog. |
|
|
Term
|
Definition
- NRT-I
Generally safe, 5% hypersensitivity reaction involving multi organ systems. If continued use of the drug despite symptoms it can evolve into a more serious problem. However in HLAB5701 genotype patients their lymphocytes release excess tumor necrosis factor which is a life threatening side effect that can result in shock. Patients are screened for this genotype prior to taking the drug. Guanosine analog. |
|
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Term
|
Definition
- NRT-I
Also used in Hep B treatment |
|
|
Term
|
Definition
- NRT-I
Fluoro analog of lamivudine. |
|
|
Term
| Nucleotide(side) reverse transcriptase inhibitors |
|
Definition
- work for both HIV 1 and 2
- Have similar chemical properties to nucleotides and integrate themselves into the viral reverse transcriptase bind to the active site and blocking it.
- They first need to be activated to the active tri phosphate form by host kinases
- Although they prefer to bind to reverse transcriptase the nucleotides can also bind to the gamma DNA polymerase in the mitochondria of the host, causing side effects like bone marrow suppression, nerve peripheral neuropathy and pancreatitis |
|
|
Term
| non nucleoside reverse transcriptase inhibitors |
|
Definition
- Only HIV 1 specific
- They do not bind to the active site, non-competitive inhibitors of HIV1 reverse transcriptase, inducing a conformational change.
- They do not need to be activated to the tri phosphate form since they’re not nucleotide analogs
- They do not suppress bone marrow
- All undergo 3A4 metabolism, so whatch out for the inhibitors (azole antifungals, cimetidine, ciprofloxacin, erythromycin, grapefruit juice) will increase the levels of the NNRT and the inducers (rifampin, carbamazepine, phenytoin, St John’s Wort) will decrease the levels of the NNRT.
- All have a 4-6 week lasting rash |
|
|
Term
|
Definition
NNRT-I
rash and hepatitis side effect |
|
|
Term
|
Definition
|
|
Term
|
Definition
NNRT-I
CNS complications like concentration loss, heaches, insomnia and vivid dreams which go away after a month. |
|
|
Term
|
Definition
Integrase Inhibitior
- blocks the catalytic activity of HIV integrase which integrates the viral DNA into host DNA |
|
|
Term
|
Definition
- All end in –navir
- blocks the process of maturation, inhibiting the cell for infecting other cells
- All are substrates and inhibitors of 3A4 |
|
|
Term
|
Definition
Protease inhibitor
mildest inhibitor of 3A4 |
|
|
Term
|
Definition
protease inhibitor
most potent inhibitor of 3A4 |
|
|
Term
| side effects of protease inhibitors |
|
Definition
o lipodydystrophy, where the normal distribution of adipose tissue is distorted. Creates buffalo humps and crix belly.
o Metabolic syndrome: central obesity, high BP, high TG, low HDL, and insulin resistance, at high risk for CV diseases
o Diarrhea and night sweats |
|
|
Term
|
Definition
| 2 NRTI and 1 PI or 2 NRTI 1 NNRTI |
|
|
Term
| - combinations to avoid in HIV therapy: |
|
Definition
| Stavudine and Didanosine since they have additive toxicity neuropathy , Stavudine and Zidovudine since they are both thymidine analogs and Abacavir and Didanosine since they are both Guanosine analogs |
|
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Term
|
Definition
yeast (oval)
shows up orally |
|
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Term
|
Definition
yeast (oval)
: think pigeon or chicken droppings. Inhaled. Had high CNS affinity and bad for people with AIDS. |
|
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Term
|
Definition
Mold (filamentous strands = hyphae)
widespread. Inhaled. Associated with construction work or contaminated vent systems. |
|
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Term
|
Definition
Dimorphic
Common in Ohio and Mississippi river valley |
|
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Term
|
Definition
Dimorphic
Common in Central and SE states |
|
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Term
|
Definition
Common in SW states.
San Joaquin Valley Fever. |
|
|
Term
|
Definition
Dermatophyte (anamorphic)
Ringworm’s Disease and Athlete’s foot |
|
|
Term
|
Definition
Cell wall targets
o Target β(1,3) D Glucan Synthase
o All end in –fungin: anidulafungin, micafungin, caspofungin
o Only iv
o Well tolerated
o No coverage for Cryptococcus neoformans |
|
|
Term
|
Definition
Cell membrane antifungals
o For systemic infections
o Bind to lanosterone demethylase and inhibit the conversion of lanosterol to ergosterol
o Cross reactivity with mammalian CYP450
o Contraindicated to use azole antifungals and ampho B, since azoles decrease ergosterol and ampho B needs ergosterol to function. |
|
|
Term
|
Definition
• Azole Antifungals
Oldest, only one with two N’s. Used in mucosal infections only. Poor absorption. High protein binding, hepatic, bile and kidney elimination. Inhibition of CYP450 and decreased testosterone synthesis. Metabolized by 3A system |
|
|
Term
|
Definition
• Azole Antifungals
better tolerated but resistance is increasing
narrow spectrum |
|
|
Term
|
Definition
• Azole Antifungals
taste disturbances, larger spectrum. |
|
|
Term
|
Definition
• Azole Antifungals
most modern. Visual disturbances. |
|
|
Term
|
Definition
• Alilamines (cell membrane antifungals)
Inhibits squalene epoxidase preventing the conversion of squalene to ergosterol |
|
|
Term
|
Definition
Cell membrane antifungal
o Used in invasive fungal infection that is resistant to other drugs
o Polyene antibiotic
o Binds to ergosterol, creating a transmembrane leakage.
o Active against most fungus except Aspergillus terreus and Scedosporium spp
o Has some serious toxic side effects: Cytokine storm, nephrotoxicity, hepatotoxicity, hypokalemia.
o Not absorbed in GI, so only iv
o Unknown metabolic fate, accumulates |
|
|
Term
|
Definition
Cytosol antifungals
o Microtubule inhibitor
o CYP inducer |
|
|
Term
|
Definition
Nucleus antifungals
o Fluorinated pyrimidine
o Affects DNA synthesis
o Not for monotherapy since resistance develops. Administer with ampho B or fluconazole |
|
|
Term
|
Definition
Third generation azole antifungal
among broadest spectrum |
|
|
Term
| Alternatives that only work in influenza A |
|
Definition
| Amantadine and Rimantadine |
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|
