Common mechanisms of Drug resistance?
Spontaneous mutations in target proteins, Natural enzymes that inactivate agent, Spontaneous changes in membrane permaability
Molecular Targets for Antimicrobial drugs
Cell Wall synthesis, DNA gyrase, DNA-Direction RNA polymerase, Protein synthesis, Cell membrane, Folic acid metabolism, Periplasmic space
Gram negative vs Gram positive
Gram negative has small cell wall, gram positive have big cell wall
B-lactam anibiotic classes
Cephalosporins and penicillins
Mechanism of Beta-lactam Action
Bind to Pencillin binding proteins, Inhibits peptidoglycan synthesis, Stimulates Autolysins, results in cell lysis
Beta Lactams are inactivated by?Static or cidal?Most effective against Gram pos or Neg?
B-lactamASES, Gram positive but can have effect on negative
What is the allergen from Pencillins?
Penicillinoic acid
Natural Pencillins, Route, and Target, CNS penetration?
G, V, G (Benzathine), G is iv/im, V is oral, G B is IM long acting. Gram positive. No CNS
What does MRSA really stand for?
Resistant to all Beta lactams
Semisynthetic Pencillins ases resistant, route, used for? CNS penetration?
Nafcillin, Dicloxacillin.. Good CNS with meniges inflammation
Semisynthetic Pencillins (Extended spectrum). Route, Spectrum? Combination of?
Amoxicillin, Ampicillin, Piperacillin Extended to Gram + and some Gram -. Combination of minopencillin + Beta-lactamase inhibitor(Clavulanate, Sulbactam,Tazobactam)
Synthetic Penicillin-Like (Carbapenems), Spectrum? Co-admined with?
Imipenem/Cilastatin. Broadest spectrum Most + and - . Coadministered with Cilastatin. Inhibitor of the degradation renal enzymes
Semi-synthetic monobactams. Spectrum? Not affected by?What patients?
Aztreonam. Inhibits PBP of Gram NEGATIVE ONLY, beta lactamases. Good for B-lactam allergic patients with gram negative
Cephalosporins are used as what in hospital settings?Natural product of?
Prophylaxis, molds
1st Generation Cephalorsporins, Specrum, Used for?
Cephazolin (Ancef), Cephalexin (Keflex), Gram + and Some gram -, Surgical prophylaxis, UTI
2nd Generation Cephalorsporins, Spectrum? Used for?
Cerfuroxime (Zinacef), Cefuroxime axitel (Ceftin), Intermediate Spectrum. Gram + and extended Gram Negative.
Third Generation Cephalorsporins. Spectrum? Used for? Special consideration?
Ceftriaxone (Rocephin), Ceftazidime (Fortaz), Broad spectrum Gram + and Gram Negative. CNS penetration
Fourth Generation cephalosporins. Spectrum? Used for?
Cefepime (Maxiprime). Very broad Gram + and Negative. Aerobic. Used for limited resistants and nosocomial infections
B-Lactam adverse reactions. 3 stages and effects
1st immediate= anaphylaxis <72 hours Milder, maybe rash. 3rd is Late reaction Drug fever
Tetracycline bacteriostatic or bacteriocidal?
Static
Tetracycline mechanism
Blocks tRNA bind=Block protein synthesis 30s
Tetracycle spectrum? UV? Divalent metals?
Very broad spectrum. Forms complexes with Teeth and Bones. Absorbs UV causing inflammatory response
Chloramphenicol block wwhat ribsome?
50s
Chloramphenicol spectrum? Cidal or static? Alternative for?
Extremely broad. Static. Alternative to Beta lactams for CNS
Chloramphenicol side effects bone marrow? Babys?
Grey baby, Bone marrow toxicity
Macrolide/Ketolides block what ribsome?Static or cidal?Spectrum?
50S, static, NO CNS, Gram positive with limited negative
Macrolide and Ketolide Protoypes
Erythromycin, Azithromycin, Clarithrymycin, Telithromycin, Clindamycin
Polumyxin spectrum? Acts on? Static or cidal? ROUTE?
Gram Negative bacteria. Acts on lipid membrane. BacteriCIDAL, TOPICAL only
Bacitracin Route? Spectrum? Mechanism?
Topical only. Limited to Gram positive. Blacks cell wall synthesis
Vancomycin Route? Spectrum? Mechanism?
IV/IM, Limited to Gram positive. Blocks cell wall synthesis
Inhibitors of Cell wall synthesis?
Bactracin and vancomycin
Tigecycline is for? Spectrum? Mechamism?Class?
Resistant strains. Tetracyline. Blocks tRNA binding on 30s ribosome. Broad + and - spectrum
Quinupristin/Dalfopristin (Synercid). Spectrum? Class? Used for? Mechanism?
Blocks protein synthesis on 30s ribosome. Used for ONLY Gram positive. For resistant Vanomycin strains. Macrolide class
Linezolid. Spectrum?Class? Used for? Mechanism?
Oxazolidone class. Blocks protein synthesis at TRNA formation. Broad against Gram positive. For VRSA
Daptomycin. Class?Spectrum?Used for?
Natural derived class. Used for MRSA and VRE. Gram positive
Mercaptopurine mechanism, converted to?
Blocks purine synthesis by being an analog of purine bases hypoxanthine or adenine, T-IMP
Azathioprine is?
prodrug of 6-MP
Methotrexate mechanism, inhibits what enzyme and synthesis
Inhibits dihydrofolate redutase and inhibits synthesis of thymidine and purines
5-Flurouracil mechanism, inhibits what? Inhibits synthesis of what?
Inhibits thymidylate synthase, inhibiting synthesis of thymidine
Hydroxyurea inhibits what?
ribonucleotide reductase
Anti-microtubules are considered to be what phase specific agents?
M phase
Anti dna nucleotide synthesis is for what phase?
G1
Vinca alkaloids mechanism? Vincristine, Vinblastine, Vinorelbine
Binds to tubulin and inhibit tublin polymerization
Taxanes (Paclitaxel, Docetaxel) mechanism
prevent depolymerization
Anthracyclines (doxorubicin, Daunorubicin mechanism
Insert into DNA, inhibits topoisomerase II and induce production of ROS. Deforming DNA
Bleomycin (blenozane, Cipla, Bleocip), anesthesia concerns
Requires metal and oxygen for its activity, causes DNA damage by producing ROS. Causes pulmonary fibrosis
Nitroden mustards:cyclophosphamide
Alklyating agents, crosslinking DNA.
Tamoxifen is?
Selective estrogen receptor modulator for breast cancer
Aromtase inhibitor (Anastrozole)
Blocks estrogen synthesis
Imatinib (Gleevec)
Inhibits Tyrosine kinase inhibitor for Chronic myeloid leukemia
Trastuzumab (Herceptin)
Monoclonal antibody against HER2, for breast cancer, cardiotoxic
Bevacizumab (Avastin)
Monoclomal antibody againsst Angiogensis
FDA Pregnacy rating ABCDX
A, adequate studies show no risk, B Animal studies fail to show risk, no study in human. C-Animals positive, no studies Human. D-Positive in human studies but may be used. X-Animals/Human positive and risks outweight benefits. N-No classification
Thalidomide concerns, which enantomer?
Presciped for pregnacy associated nausea, bilateral limb reduction, kidney eyes ears heart deformities. S enantiomer
Diethylstilbesterol (DES)
Oral synthetic nonsteroidal estrogen analog, Use to prevent miscarriages. Teratogen seen 20-30 years later
Fetal Alcohol syndrome
Most common cause of mental retardation, completely preventable
Phenytoin (Dilatin)
Antiepileptic medicationm, will show and resemble FAS (feal alcohol syndrome), epoxide hydrolase 1. Fetal Hydantoin syndrome
Mechanism of Nicotine/Tobacco tetragenic effects
Growth retardation, restrictions uterine blood vessels chronic hypoxia and malnutrition
Retinoids Isotretinoin(acutane)
Vitamin A analog, for acne causing fetal abnormality
Gamma Globulin (IgG) mechanism viruses
Blocks the attachment of virus particles to host cells
Amantadine rimantadine
Targets m2 protein of influeza A virus and prevents uncoating of vesicle by blocking acidification of vesicle
Oseltamivir (Tamiflu
Targets influenza A and B and prevents replication and host cleavage from host cell nueraminidase inhibitor. Inhibits respiratory spread
Acyclovir mechanism, what is needed for it to work? Prodrug?
Inhibits viral dna polymerase, requires viral hymidine kinase for activation. Used for herpes infections
Forscarnet mechanism and uses
Effective against herpes simplex virus that are deficient in thymidine kinase, used for cytomegalovirus reitinitis and acyclovir ressitant herpes
Ribavirin uses
Used for chronic treatment of hep C and respiratory syncytial virus
Zidovudine (AZT)
Emtricitabine-reverse transcriptase inhibitors
Fuzeon mechanism
Interferes with Entry of HIV-1 into cells. Inhibits fusion or viral and cellular membranes
Amophotericin B spectrum and mech, side effect
broad spectrum severe antifungal agent, big ring structure and one side is hydrophobic because it binds to membrane creating a channel to lose intracellular components. Renal toxicity
Griseofukvin mechanismm spectrum?
Binds to microtubules causing nterference with mitotic spingle formation and dividing cells, narrow spectrum, atheletes foot
Azole mechanism
Inhibits ergosterol synthesis, leading to damaged and leaking cell membranes
Fluconazole mechanism, spectrum class
Very broad spectrum for most candida. single oral fose for yeast infection. For fungal meningiutis, high concentration in CNS. Triazoles
Voriconazole for what?
active against molds such as aspergillus, for invasive aspergillosis
Itraconazole spectrum, interesting properities?
broad spectrum, low gastric pH for absorption
Posaconazole uses
prevent candida and aspergillus infections in immunocompromised patients
Ketoconazole what class? For?
Class imidazole, broad spectrum effective against fungi
Amtimetabolite drug, uses in combination with
for systemic fungal infection such as cryptococcal menigitis, combination with amphotericin B
New class of antifungal agents
Glucan synthase inhibitors, the echinocandins
Enchinocandins, Glucan synthase inhibitors
Caspofungin, blocks cell wall synthesis, micafungin, anidulafungin
Schedule I drugs
High potential for abuse and no approved medical use such as heroin
Schedule II drugs
high potential for abuse but has accepted medical use such as morphine, oxycodone. No automatic refills
Scheduled III drugs
Moderate potential for abuse and refills can happen 5 times in 6 months
Schedule 4 drugs
lower potential for abuse and same regulations as 3
Schedule V drugs
limited potential for abuse, no dispense and refils
IND application is?
Investigational New drug. Preclinical data, trial design, informed consent form
Phase 0 clinical trials
microdosing trials, sub therapeutic dose and kinetic and dynamic data
Phase 1 clinical trials
Tests safety of drug not efficiacy.
Phase 2 trials
Tests for safety and efficacy,
Phase 3
Randomized efficacy is compared to the standard treatment
NDA is?
establishment of DA sets standards for the safety of the ingredients of the drug, labeling and package insert
Phase 4 clinical trial
additional safety data, or additional uses or in combination with other drugs, increase the “label” of the drug
5 Diuretic classes
Carbonic anhydrase inhibitor, thiazides, osmotics, K sparing, loops
2 high ceiling dieurtics
Loop and osmotics
3 low ceiling dieurtics
K sparing, carbonic anhydrase inhibitor, thiazides
Carbonic anhydrase inhibitor site of action and mechanism. Prototype
Increased bicarb rentention in the proximal tubule, Acetazolamide
Osmotic dieuretic protoype and location and mechanism
Proximal tubule and descending loops of henle, Mannitol, increases water excretion
Loop dieurtic protoype, site of action, mechianism
Furosemide (Lasix), loop of henle. Blocks na k and cl reabsorption
Thiazides site of action, mechanism, protoype, side effect
Distal tubule, blocks Na cl co transporter.hypokalemia. Hydrochlorothiazide
K+ sparing dieurtics, mechanism, site and prototype
Collecting duct, blocks Na+ channel, can cause hyperkalemia. Triamteren and amiloride
K+ sparing dieurtic that Is an antagonist of aldosterone receptor
Spironolactone
How do dieurtics cause hypokalemia?
Increased NA reabsorption causes excess K excretion
Aminoglycosides cidal or static? Mechanism?
Cidal, block protein synthesis
Aminoglycosides used for?
Aerobic gram negative bacteria
Streptomycin history and primary use
Multidrug resistant TB, first amingolycoside to be developed
Isoniazid use, mechanism
mycolic acid synthesis inhibition, for TB
Rifampin mechanism and uses, side effects
TB gram +- and inhibits RNA synthesis and inhibits RNA polymerase in prokaryotic cells, liver toxicity
Ethambutol used for only? Static or cidal, indications for use
Only for mycobacteria, bacteriostatic, has to be used in combination
Pyrazinamide uses, mechanism and interesting factor
active at acidic ph, used for TB, inhibits fatty acid synthesis
Is combination therapy mandatory for TB?
Yes
Lunelle dosage and frequency
Estradiol and medroxyprogesterone injection every ~30 days
Nuvaring contents
Ethinyl estradiol
Orthoevra contents, rsk
E+ P, worn for 7 days, patch risk of blood clots
Ctinuous E + p pill, no period
Lybrel
Yasmin contents and side effects
drospirenone plus ethinlestradiol, hyperkalemia, heart problems DVT
Progrestin alone therapy does what
Endometrial changes, thickening of mucus, prevents ovulation
Progesterin only drugs
Minipill, depo provera, mirena, implanon
Clomiphere uses and mechianism
fertility pill, estrogen receptor antagonist
Tamoxifen class, what for
SERM, breast cancer
Raloxifene for? Does what
Estrogen antagonist in breast and uterin, agonist in bone. Prevents osteroporosis post menopausal
Femara use, mechanism
Aromatase inhibitor, reduces estrogen production for breast cancer treatment
4 synthetic corticosteroids
prednisone, prednisolone, dexamethasone, betamethasone
Echanism of action of corticosteroids
gene regulation
Is alderstrone part of the pituary axis?
no, renin angiotensin
Treatment of adrenocortical insuffieciency
cortisol
Treatment of inflammation and immunosuppression
Intermediate and long acting
Mineralcorticoids effects
salt rention and hypertension
Most widely used mineralcorticoid
fludrocortisone
Inhibition of adrenal cortical steroids
aminoglutethimide
Treatment of hypothroidism
Levothryoxine or Liothyronine, Synthroid or L-t3
Graves is?
caused by hyperthroidism
Drug of choice for thryoid storm
propanolol
Sulfonamides inhibti what? Clinical use?
synthesis of dihydropteroate, burn patients, inflammatory disorder of GIT, respiratory infection UTI
Trimethoprime mechanism, incombination with
inhibits reductase enzyme for tetrahydrofolate, co0trimoxazole
Fluoroquinolones mechanism, spectrum?
inhibit DNA gyrase, Gram negative aerobic
Fluoroquinolones drugs
Ciprofoxacin (anthrax),
How does mylanta work?
decrease acid in stomach
Mucosal protectants from acid in stomach
Peptobismol, Misoprostol, Sucralfate
H2 receptor antagonist
Cimetidine, Rantitide, Famotidine, Nizatidine
Proton pump inhibitors, pro drugs?7
Omeprazole (Prilosec, Lansoprazole Rabeprazole, esomeprazole, all pro drugs
Eradication of h.pylori always requires?
multidrug therapy such as PPI, antibiotic 1 and 2, amoxicillin clarithromycin and omeprazol