med chem 2 final exam

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Flashcards on med chem 2 final exam, created by lola_smily on 04/05/2015.
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Flashcards by lola_smily, updated more than 1 year ago
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heparin anticoagulant parenteral mucopolysaccharide source: pig lungs, pig intestinal mucosa isolated from liver high/low (higher affinity) molecular weight acidic: carboxylic acid and sulfate groups anion: at physiological pH given as Na+ salt/poor GI absorption IV/SQ (not IM: cause hematoma) -MOA: accelerates binding of antithrombin to thrombin (inhibit it + inhibit factor 10a) -metabolism (partially): depolymerization, desulfuration --> inactive mtb (liver) -prolonged effect if: renal, hepatic dysfunction -SE: hemorrhage, alopecia (after 3-4m), thrombocytopenia if high dose (>50mg) --> heparin like effects -antidote: protamine sulfate
warfarin anticoagulant oral 4-hydroxycoumarin derivative racemic mixture: S(-)>R(+) given Na+, K+ salts bioavailability: 100% onset of action: 12-48h --> slow DOA: 2-5d MOA: vitamin K antagonist (inhibit vit K epoxide reductase, vit K quinone reductase, gamma carboxylation) --> reduce factors 10,9,7,2 metabolism: S--> CYP2C9/ R--> CYP2C19 2'-hydroxywarfarin (active) caution in pregnancy: crosses placenta SE: hemorrhage, skin rash, nausea, thrombocytopenia, diarrhea, skin necrosis antidote: blood transfusion, give factors
vitamin K
hemiketal form of warfarin similar to hemiketal form of vit K compete for same enzyme
hemiketal form of vit K share similarities with hemiketal form of warfarin
(S)-7-hydroxywarfarin metabolite of warfarin by CYP2C9
(S)-6-hydroxywarfarin metabolite of warfarin by CYP2C9
2'-hydroxywarfarin metabolite of warfarin active
(R)-warfarin can be metabolized by CYP2C19 on C7
anisindione anticoagulant oral 1,3-indandione derivative onset of action: 12-48h --> slow DOA: 2-5d MOA: same as warfarin alkaline urine (red-orange color)
phenindione anticoagulant oral 1,3-indandione derivative onset of action: 12-48h --> slow DOA: 2-5d MOA: same as warfarin alkaline urine (red-orange color)
citric acid in vitro anticoagulant chelate Ca2+ (inhibit factor 4)
EDTA in vitro anticoagulant chelate Ca2+ (inhibit factor 4)
aspirin (ASA) antiplatelet inhibit COX 1 irreversibly --> inhibit PGI2 and TXA2 acidic active as such GI disturbance
trifusal antiplatelet inhibit COX 1 inhibit PDE active as such metabolized to: deacetylated form (2-hydroxy-4-trifluromethylbenzoic acid HTB) --> active
sulfinpyrazone antiplatelet inhibit COX 1 reversibly metabolism: inactive metabolites--> p-hydroxysulfinpyrazone, sulfone, p-hydroxysulfide, sulfide
dipyridamole antiplatelet inhibit PDE (phosphodiesterase) --> increase cAMP --> inhibit release of aggregating agent inhibit adenosine reuptake --> increase cAMP
cilostazole antiplatelet quinolinone derivative inhibit PDE3A inhibit adenosine reuptake orally active well absorbed increase absorption with high fat meal metabolism: CYP3A4, CYP2C19--> active: DHC, HC
3,4-dehydrocilostazol antiplatelet major active metabolite of cilostazol by CYP3A4
4'-hydroxycilostazol antiplatelet minor active metabolite of cilostazol by CYP2C19
ticlopidine antiplatelet thienopyridine derivative prodrug orally active MOA: ADP pathway inhibitor, inhibit GP2b/3a receptor t1/2: 24-36h --> long onset of action: 48h --> slow metabolism (liver): 2-keto metabolite, thiol metabolite (active), M5 and M6 (toxic) SE: neutropenia, thrombocytopenia, skin rash, GI effects
clopidogrel antiplatelet thienopyridine derivative prodrug orally active MOA: ADP pathway inhibitor t1/2= 24-36h --> long metabolism: hydrolyzation of the thiol--> active metabolite (bind to P2Y and prevent binding of ADP--> t1/2= 8h) SE: rare neutropenia, thrombocytopenia, GI effects
prasugrel antiplatelet thienopyridine derivative orally active metabolism: hydrolyzed to thiolactone then thiol --> active used in combination with aspirin like clopidogrel: non competitive antagonist of P2Y12 (irreversibly)--> block ADP for the life of platelets (10days)
eptifibatide antiplatelet GP2b/3a receptor antagonist cyclic heptapeptide (KGD sequence) IV t1/2= 2.5h --> short excretion: renal
tirofiban antiplatelet GP2b/3a receptor antagonist non peptide (distance btw COO- and NH+ is identical to RGD sequence--> compete with fibrinogen) t1/2= 2h --> short IV excretion: renal (unchanged)
epoprostenol antiplatelet prostaglandin metabolite of arachidonic acid PGI2 potent vasodilator IV t1/2= 3-6min increase in cAMP--> decrease release of aggregation mediator
Abciximab antiplatelet GP2b/3a receptor antagonist monoclonal antibody IV short t1/2= 30min
urokinase fibrinolytic agent from human urine and renal cells act on plasminogen to produce plasmin nonantigenic
streptokinase fibrinolytic agent from hemolytic streptococci generates more plasmin than urokinase (via 2 steps) allergic reactions (due to Ab formation)
anistriplase fibrinolytic agent prodrug 2nd generation plasminogen activator acetylated-plasminogen-streptokinase-activator complex (APSAC) p-anisoyl derivative of Lys-plasminogen-streptokinase
alteplase fibrinolytic agent 2nd generation plasminogen activator tissue plasminogen activator (tPA) formed by recombinant DNA techniques
reteplase fibrinolytic agent 3rd generation plasminogen activator modified alteplase less affinity to fibrin clot than alteplase
ananase fibrinolytic agent mixture of proteolytic enzymes from pineapple plant non selective to fibrin clot anti-inflammatory agent cheap
tenecteplase fibrinolytic agent 3rd generation plasminogen activator composed of 527a.a.: 103 a.a: Thr--> Asp 117 a.a: Asp--> Glu 296-299 a.a: Lys-His-Arg-Arg--> Ala (x4) 15X higher fibrin selectivity elimination: hepatically
prostaglandin prostanoic acid derivative must have: 15-alpha OH 13-14 trans double bond alpha/beta chain: trans A,B,C,D,E,F,G,H,I (differ in C9-11)
PGD
PGE PGE1: dilation of bronchiol smooth muscle PGE2: dilation of bronchiol smooth muscle, dilation of blood vessel
PGF2alpha constriction of bronchiol smooth muscle, constriction of blood vessels
PGG/PGH
PGI2 (prostacyclin) from PGH2 inhibit platelet aggregation dilation of blood vessels
TXA2 from PGH2 aggregation of platelet constriction of blood vessels
arachidonic acid cis 5,8,11,14-eicosatetraenoic acid precursor of prostaglandins by COX and leukotrienes by LOX
acetanilide NSAID removed from market form: acetaminophen/ aniline --> toxic SE: methemoglobenemia, skin rash, jaundice
phenacetin NSAID removed from market form: acetaminophen/ aniline --> toxic SE: nephritis, carcinogenecity in rats
acetaminophen NSAID antipyretic, analgesic little antiinflammatory activity MOA: reversible inhibitor of COX3 (brain) metabolism: by CYP2E1--> N-acetylmidoquinone (reactive metabolite) by glucuronidation and sulfation
N-acetylimidoquinone (NAPQI) metabolite of acetaminophen metabolism: N-acetylcysteine, glutathione (renal excretion), hepatic protein (hepatic necrosis)
salicylic acid metabolite of aspirin
aspirin NSAIDs MOA: irreversibly inhibits COX1 (10-100X)> COX2 enzymes by acetylating serine 530 pKa=3.49 salicylate anion essential for activity stable in dry condition -absorbtion: upper small intestine (depend on gastric pH, tablet formulation, presence of food in stomach) high pH: increase ionization--> more soluble --> less absorbed buffering agent: if high dose --> decrease absorption if low dose --> increase absorption -formulation: tablet of small particles --> absorbed faster absorption from rectal--> slow absorption after topical--> fast -metabolism: hydrolyzed to salicylic acid and acetic acid (in aqueous solution) by glucuronidation, glycine conjugation stable in: alcohol, glycerin -SE: GI disturbance, salicylism (high dose) --> tinnitis, fatal --> respiratory failure (medullary depression) at high dose, Reye's syndrome in children with viral infection :influenza, chicken pox (encephalopathy, liver damage, violent headache), GI: (PGs--> cryoprotective for the gastric mucosa) gastric distress/bleeding, acute hemorrhage (dose dependent)
salicylamide NSAIDs analgesic and antipyretic (not antiinflammatory) fairly stable to heat and moisture poor water solubility for aspirin sensitive patients no gastric irritation more CNS effect than aspirin metabolism: inactive --> not hydrolyzed to salicylic acid
salsalate NSAIDs dimer of salicylic acid insoluble in gastric acid juice -metabolism: partially hydrolized in intestine --> 2 salicylic acid molecules (site of absorption), forms less salicylic acid than aspirin (15%) -less gastric upset than aspirin
diflunisal NSAIDs analgesic, little antipyretic insoluble in water slightly more potent than aspirin t1/2= longer than aspirin -metabolism: ether/ester glucuronide not metabolized to salicylic acid--> no gastric upset -SE: few, GI disturbances, diarrhea, skin reaction
mesalamine NSAID 5-amino salicylic acid metabolite of sulfasalazine and olsalazine MOA: inhibit COX in the bowel mucosa--> decrease colonic inflammation inhibit LOX --> decrease leukotrienes
sulfasalazine prodrug precursor of mesalamine metabolized by azo reductase
olsalazine prodrug precursor to mesalamine in GI tract by bacterial flora act locally (not systemically)
phenylbutazone NSAIDs 4-butyl-1,2-diphenyl-3,5-pyrazolidinedione not a drug of choice analgesic, antipyretic, antiinflammatory slight water soluble -to treat: painful symptoms of gout (uricosuric), rheumatoid arthritis, bursitis -metabolism: to oxyphenbutazone (active NSAID), glucuronidation, gamma-hydroxyphenylbutazone (uricosuric), gamma-ketophenylbutazone (antiinflammatory) -SE: abdominal discomfort, nausea, skin rashes, peptic ulcer, blood disorder -contraindicated: in children <14y --> due to Na+ retention
oxyphenbutazone NSAIDs metabolite of phenylbutazone same potency as phenylbutazone same SE but with less GI effect
indomethacin NSAIDs arylalkonic acid indole acetic acid derivative most potent (analgesic agent: more than aspirin, antipyretic agent: more than phenylbutazone, antiiflammatory agent: more than phenylbutazone) weak water soluble light sensitive rapid absorption after oral dose highly bound to plasma protein metabolized to inactive SE: GI disturbance, headache, vertigo, dizziness, severe depression, suicide attempts
sulindac NSAIDs arylalkonic acid indene derivative prodrug water soluble (at alkaline pH) stable at alkaline aqueous solution, air, 100C t1/2= 8h (sulfide t1/2=16h) absorbed: as sulfoxide -metabolism: to sulfide derivative (in the cirulation) -analgesic activity: equal to indomethacin -antiinflammatory/antipyretic activity: less than indomethacin -for: rheumatoid arthritis, osteoarthritis, gouty arthritis, ankylosing spondylitis -SE: gastric irritation, headache, vertigo, dizziness, skin rash
sulfide NSAID active metabolite of sulindac t1/2= 16h
tolmetin sodium NSAIDs arylalkonic acid N-methylpyrrole acetic acid derivative very water soluble free acid form--> water insoluble t1/2= 1h --> short -potency: more than phenylbutazone, less than indomethacin -for: different types of arthritis -metabolism: to inactive metabolites -SE: GI disturbance (less than aspirin)
diclofenac sodium NSAIDs arylalkonic acid most used NSAID in the world poor water soluble complete absorption after oral dose highly bound to plasma protein 50% bioavailabilty (first pass) analgesic, antipyretic, antiinflammatory analgesic/antipyretic agent: more potent than aspirin more potent than indomethacin -MOA: inhibit COX1 and LOX inhibit arachidonic acid release, stimulate uptake --> decrease AA availability -for: rheumatoid arthritis, osteoarthritis, ankylosing spondylitis -metabolite: 4'OH (30-40%)--> weak act.
etodolac NSAIDs arylalkonic acid tetrahydropyrano acetic acid derivative rapid GI absorption highly bound to plasma protein -antiinflammatory: more potent than aspirin, sulindac less potent than indomethacin -racemate--> S(+) active -metabolized: to inactive
nabumetone NSAIDs prodrug non acid derivative water insoluble analgesic: less active than aspirin -metabolism (rapid): acetic acid derivative --> 6-methoxynaphtalene-2-acetic acid (6MNA) (38%) --> active -less gastric damage (absorbed as ketone, converted to 6MNA in circulation) -for: osteoarthritis, rheumatoid arthritis
6MNA active metabolite of nabumetone in circulation
ibuprofen NSAIDs arylpropionic acid 2(p-isobutylphenyl)propionic acid most used NSAID orally active -same effect as aspirin (less SE) racemic mixture--> S(+) more potent than R(-) -for: osteoarthritis, rheumatoid arthritis, antipyretic, mild to moderate pain -metabolism: to inactive metabolite give ibufenac (active)--> less potent, hepatotoxic -excretion: (+) isomer
ibufenac p-isobutylphenyl acetic acid active form of ibuprofen less potent hepatotoxic
fenoprofen calcium NSAIDs arylpropionic acid derivative 2(3'-phenoxyphenyl)propionic acid slightly water soluble rapid absorption after oral dose highly bound to plasma protein Na+ and Ca2+ salts (less hygroscopic): similar pharmacokinetic -antiinflammatory: less potent than ibuprofen PG synthesis inhibitor: more potent than aspirin, less potent than indomethacin metabolism: to inactive metabolites
ketoprofen NSAIDs arylpropionic acid derivative) 2(3'-benzoylphenyl)propionic acid insoluble in water and many organic solvent rapidly completely absorbed after oral dose -MOA: inhibit COX, inhibit LOX, lysosomal mb stabilizer--> decrease release of lysosomal enzymes--> decrease tissue damage -for: osteoarthritis, rheumatoid arthritis, antipyretic, mild to moderate pain, dysmenorrheal -metabolism: glucuronidation, carbonyl reduction, ring hydroxylation
naproxen NSAIDs arylpropionic acid derivative 2(6'-methoxy-2'-naphtyl)propionic acid both enantiomer marketed: (-)--> anaprox (naproxen Na+) complete GI absorption after oral dose 99% bound to plasma protein -PG synthesis inhibitor: more potent than aspirin, phenylbutazone, ibuprofen -antiinflammatory: less potent than indomethacin -analgesic/antipyretic: more potent than phenylbutazone, aspirin, indomethacin -ulceration: less--> than aspirin, indomethacin, ketoprofen, tolmetin more--> than sulindac -for: different types of arthritis, ankylosing spondylitis, tenditis, bursitis, mild-moderate pain -metabolism: to inactive--> glucuronidation and O-demethylation -SE: GI irritation, nausea, dizziness
suprofen NSAIDs arylpropionic acid 2(4'(2'thienyl carbonyl)phenyl)propionic acid removed from market because renal failure reintroduced as mydriatic agent: for ophtalmic use --> inhibit intraoperative miosis
flubiprofen NSAIDs arylpropionic acid derivative 2(2'-fluoro-4'-biphenyl)propionic acid Na+ salt: topical for ophtalmic use(ocufen)--> mydriatic agent (inhibit intraoperative miosis) free acid form: oral use (ansaid)--> top prescribed use (osteo, rheumatoid arthritis) well GI absorption after oral dose 99% bound to plasma protein antiinflammatory: more potent than aspirin, phenylbutazone antipyretic: more potent than aspirin analgesic: more potent than ibuprofen -metabolized: to inactive metabolite--> glucuronidation, sulfation, 4'OH, 3',4'OH, 3'OH, 4'-OCH3
ketorolac NSAIDs arylpropionic acid derivative 5-benzoyl-2,3-dihydro-1-pyrrolidine-1-carboxylic acid orally active highly bound to plasma protein analgesic activity: comparable to morphine for: ophtalmic use, injection, for short term management of pain
oxaprozin NSAIDs arylpropionic acid derivative (not alpha methyl acetic acid derivative) complete absorption after oral dose highly bound to plasma proteins t1/2= 59h--> long onset: rapid long acting antiinflammatory: equal to aspirin -for: short, long term treatment of osteoarthritis, rheumatoid arthritis -metabolism: (in liver) p-hydroxylation --> active -SE: skin rash, mild photosensitivity
fenamic acid NSAIDs arylanthranilic acid derivatives antiiflammatory/analgesic activities: little or no advantage over salicylates -MOA (like salicylates): COX inhibition -SE (like salicylates): GI disturbances, headache, dizziness, skin rash, transient hepatic and renal abnormalities
mefenamic acid NSAIDs N(2',3'-xylyl)anthranilic acid Orally active water insoluble (except at high pH) Highly bound to plasma proteins analgesic (mainly), anti-inflammatory t1/2=2-4h --> short for short term pain management Metabolized: to inactive metabolites--> ester glucuronide, hydroxymethyl and dicarboxylic acid
meclofenamate sodium NSAID arylanthranilic acid derivative
meclofenamic acid NSAID arylanthranilic acid derivative Rapidly, completely absorbed after oral dose Highly bound to plasma proteins t1/2= 2-4h --> short -potency: 25% more than mefenamic acid -Metabolism: oxidation of methyl, ring hydroxylation and monodehalogenation
meclofenamic acid metabolite active by oxidation of methyl
piroxicam NSAIDs oxicam 4-hydroxy-1,2-benzothiazine carboxamides pKa=4-6 (acidic) orally active highly bound to plasma protein more potent than fenamate -potency: piroxicam> indomethacin> ibuprofen Long t ½ 38 hrs -anti-inflammatory agent: more potent than aspirin and phenylbutazone, equal to indomethacin analgesic agent: less potent than indomethacin, equal to fenoprofen, ibuprofen, naproxen and phenylbutazone -MOA: Inhibitor of COX, lysosomal enzymes release and migration of polymorphonuclear cells into inflammatory sites, inhibits collagen induced platelet aggregation -Metabolism: pyridine and aromatic benzothiazine ring hydroxylation (inactive metabolites) -SE: Same like other NSAIDs -for (most commonly used NSAIDs): osteoarthritis and rheumatoid arthritis, ankylosing spondylitis
meloxicam NSAIDs oxicam 4-hydroxy-1,2-benzothiazine carboxamides pKa=4-6 (acidic) orally active highly bound to plasma protein more potent than fenamate -MOA: selectivity to COX2 -metabolism: CYP2C9 (extensively) and CYP3A4 (less) -SE: Less GI side effects
celecoxib First NSAID marketed as selective COX-2 inhibitor Diarylpyrazole derivative does not contain carboxylate anion Orally active t1/2= 11h -metabolizm: into inactive metabolites -SE: Less GI disturbances than other NSAIDs, causes edema and hypertension (caution in case of CHF)
valdecoxib NSAIDs selective COX2 inhibitor oxazole moiety Orally active t1/2= 7-8h -metabolizm: by CYP3A4 and CYP2D6 (substrate and inhibitor of these enzymes)
parecoxib NSAIDs selective COX2 inhibitor Prodrug IV and IM (only parenterally administered coxib -metabolism: rapidly metabolized (in vivo) --> valdecoxib -analgesic: more potent than ketorolac
etoricoxib NSAIDs selective COX2 inhibitor Orally active t1/2= 22h --> long -metabolism: by CYP3A4 (but is not inhibitor)--> 6'-hydroxymethyl and 1-N-oxide , glucuronides-->inactive -excretion: mainly renal elimination as metabolites
prontosil antimetabolite sulfonamide prodrug ozo moiety only active in vivo metabolism: to sulfanilamide poor water soluble forms crystalluria
sulfanilamide antimetabolite aniline sulfonamides White colorless bitter tasting crystals weak acids water insoluble -More soluble in alkaline solutions than acidic -available as Na+ salts --> moderately water soluble -structurally analogues of PABA --> compete with dehydropteroate synthase (get incorporated in folic acid synthesis) -do not affect mammalian cells -cross placenta -metabolism (in liver): to inactive -Activity against: gram-ve/ gram +ve, E.coli, nocardia. -SE: urinary tract disturbances, hypersensitivity, hematopoietic disturbances rare: aplastic and hemolytic anemia, agranulocytosis, thrombocytopenia kernicterus and jaundice, anorexia, nausea, vomiting and diarrhea -DDI: Potentiation of sulfonylurea oral hypoglycemics, oral anticoagulants and hydantoin (due to displacement from plasma proteins) -Drug resistance: altered enzyme (major), overproduction of PABA, reduced cellular reuptake of drug, enhanced drug inactivation
sulfamethoxazole antimetabolite Sulfonamide rapidly absorbed and rapidly eliminated t1/2= 10h --> short ppb: 70% highly water soluble--> rarely produce crystalluria
sulfisoxazole antimetabolite Sulfonamide rapidly absorbed and rapidly eliminated t1/2= 6h --> short ppb: 90% highly water soluble--> rarely produce crystalluria
Sulfadiazine antimetabolite Sulfonamide rapidly absorbed and rapidly eliminated t1/2= 10-17h most active ppb: 45% --> low relatively water soluble --> crystalluria
sulfamethizole antimetabolite Sulfonamide rapidly absorbed and rapidly eliminated t1/2= 9h -->short ppb: 90% --> highly bound
sulfasalazine antimetabolite Sulfonamide poorly absorbed prodrug for: treating GI infections metabolizm: by bacteria flora
sulfapyridine toxic mtb of sulfasalazine absorption: from GI excretion: in urine
mesalamine 5-para-amino salycilic acid active mtb of sulfasalazine
sulfadoxine antimetabolite Sulfonamide rapidly absorbed (from GI) but very slowly eliminated ppb: 98% --> highly bound t ½ 7-10 days--> extraordinary
Silver sulfadiazine antimetabolite sulfonamide Topically administered their salts are very potent antimicrobial in the treatment of burns, scald & wound infection
sulfacetamide antimetabolite sulfonamide Topically administered their salts are very potent antimicrobial in the treatment of burns, scald & wound infection
Mafenide antimetabolite not a true sulfonamide Topically administered
trimethoprim antimetabolite Not a sulfonamide Trimethoxy benzyl diaminopyridine, Bacteriostatic -MOA: Potent inhibitor of DHF reductase, Similar antibacterial spectrum to sulfonamides Higher affinity to bacterial DHF reductase than mammalian -Mostly compounded with sulfamethoxazole TMP/SMX (Cotrimoxazole) oral and IV -potency: TMP (20-50X) > SMX -absorption: TMP well absorbed from GI -ppb: 60-70% -concentrated in prostatic fluid and vaginal fluid--> most used in UTI -excretion: mainly renal, small amounts biliary -SE:- Long term use: antifolate effects, folate deficiency, megaloblastic anemia, granulocytopenia, leucopenia (reversed by folinic acid), nausea, vomiting, fever, renal damage, skin rashes, CNS disturbances
polymyxin bacterial cell membrane disrupting agent Cyclic polypeptides (by Bacillus polymyxa, soil bacteria) polymyxin sulfate B (B1 and B2) Polymyxin E (E1, E2) --> colistin Bactericidal cationic detergent (5 + charges) -MOA: React with – charged phospholipids-->disrupt cell mb --> creates holes --> cell leakage -active against most Gram – (not against Gram + and anaerobics) -Pseudomonnas aeruginosa (only): elevated levels of Mg2+ and Ca2+ --> decrease activity -absorption: GI (not well), topically, IV and IM, (found in ophthalmic, otic) -for: bacterial diarrhea -poor distribution (don't enter CSF) -excretion:renal via GF -SE: topically (few), orally (high dose): nausea and vomiting ,IV: nephro and neurotoxicity (accumulates in renal tubules) Large dose: damage to mammalian cell membranes --> inhibit NMJ --> respiratory paralysis -DDI: Aminoglycosides + polymyxins--> increase risk of respiratory/renal dysfunction NMJ blockers + polymyxins--> increase effect of NMJ -Use of polymyxins--> overgrowth of non-susceptible--> superinfection
daptomycin bacterial cell membrane disrupting agent Novel cyclic lipopeptide antibiotic from Streptomyces sp. Consists of 13 a.a. bactericidal (dose dependant) -MOA: on Gram + (via acyl tail--> membrane depolarization), disrupts bacterial plasma mb function without penetrating into cytoplasm -MIC (minimal inhibitory concentration): for susceptible strains is 4X< vancomycin -post-antibiotic effect (PAE) -Synergism with gentamicin against staph. and enterococci IV ppb: 90% t1/2= 6.5-32h -excretion: mainly renal (80%)--> 2/3 intact -SE: Constipation, myopathy (dose dependent), GI discomfort, nausea, diarrhea, skin rash, headache, insomnia
6-aminopenicillanic acid (6-APA) beta-lactam fermentation derived not active: very minimal activity after acylation --> active compound (penicillin)
penam beta lactam antibiotic
penem beta lactam antibiotic 2,3-dihydrothiazole
carbapenem beta lactam antibiotic 2,3-dihydro-1H-pyrrole
cefem beta lactam antibiotic 3,6-dihydro-2H-1,3-thiazine
monobactam beta lactam antibiotic
carbacephems beta lactam antibiotic 1,2,3,4-tetrahydropyridine
oxacephems beta lactam antibiotic 3,6-dihydro-2H-1,3-oxazine
Pen G benzyl penicillin beta lactam antibiotic fermentation derived must be kept dry Na and K salts are crystalline, hygroscopic and water soluble orally and parenterally stable for a long time unless in solution improved acid stability (by addition of e- withdrawing grp on side chain) -excretion: renally by tubular secretion -MOA : cell wall inhibitor - inhibit PBPs, the cross linking of peptidoglycan matrix/ activate autolytic enzymes : degrade the already formed cell wall -SE: hypersensitivity / GI disturbances / neurotoxicity (seizures)
Pen V phenoxy methyl penicillin beta lactam antibiotic must be kept dry Na and K salts are crystalline, hygroscopic and water soluble orally and parenterally stable for a long time unless in solution improved acid stability (by addition of e- withdrawing grp on side chain) -excretion: renally by tubular secretion -MOA : cell wall inhibitor - inhibit PBPs, the cross linking of peptidoglycan matrix/ activate autolytic enzymes : degrade the already formed cell wall -SE: hypersensitivity / GI disturbances / neurotoxicity (seizures)
methicillin beta lactam antibiotic semi-synthetic penicillinase resistant (bulky group on diortho) parenteral contains e-donating groups --> not acid resistant -excretion: renally by tubular secretion -MOA : cell wall inhibitor - inhibit PBPs, the cross linking of peptidoglycan matrix/ activate autolytic enzymes : degrade the already formed cell wall -SE: Nephritis / hypersensitivity / GI disturbances / neurotoxicity (seizures)
nafcillin beta lactam antibiotic semi-synthetic penicillinase resistant (bulky group on diortho) parenteral contains e-donating groups --> not acid resistant -excretion: renally by tubular secretion -MOA : cell wall inhibitor - inhibit PBPs, the cross linking of peptidoglycan matrix/ activate autolytic enzymes : degrade the already formed cell wall -SE: hypersensitivity / GI disturbances / neurotoxicity (seizures)
oxacillin beta lactam antibiotic semi-synthetic penicillinase resistant improved acid stability oral -excretion: renally by tubular secretion -MOA : cell wall inhibitor - inhibit PBPs, the cross linking of peptidoglycan matrix/ activate autolytic enzymes : degrade the already formed cell wall -SE: hepatitis / hypersensitivity / GI disturbances / neurotoxicity (seizures)
cloxacillin beta lactam antibiotic semi-synthetic penicillinase resistant improved acid stability oral -excretion: renally by tubular secretion -MOA : cell wall inhibitor - inhibit PBPs, the cross linking of peptidoglycan matrix/ activate autolytic enzymes : degrade the already formed cell wall -SE: hypersensitivity / GI disturbances / neurotoxicity (seizures)
dicloxacillin beta lactam antibiotic semi-synthetic penicillinase resistant improved acid stability oral -excretion: renally by tubular secretion -MOA : cell wall inhibitor - inhibit PBPs, the cross linking of peptidoglycan matrix/ activate autolytic enzymes : degrade the already formed cell wall -SE: hypersensitivity / GI disturbances / neurotoxicity (seizures)
carbenizillin beta lactam antibiotic semi-synthetic carboxypenicillin penicillinase sensitive extended spectrum : antipseudomonas parenteral -excretion: renally by tubular secretion -MOA : cell wall inhibitor - inhibit PBPs, the cross linking of peptidoglycan matrix/ activate autolytic enzymes : degrade the already formed cell wall -SE: hypersensitivity / GI disturbances / neurotoxicity (seizures)
carbenicillin phenyl beta lactam antibiotic semi-synthetic carboxypenicillin penicillinase sensitive extended spectrum : antipseudomonas parenteral -excretion: renally by tubular secretion -MOA : cell wall inhibitor - inhibit PBPs, the cross linking of peptidoglycan matrix/ activate autolytic enzymes : degrade the already formed cell wall -SE: hypersensitivity / GI disturbances / neurotoxicity (seizures)
carbenicillin indanyl beta lactam antibiotic semi-synthetic carboxypenicillin penicillinase sensitive extended spectrum : antipseudomonas parenteral -excretion: renally by tubular secretion -MOA : cell wall inhibitor - inhibit PBPs, the cross linking of peptidoglycan matrix/ activate autolytic enzymes : degrade the already formed cell wall -SE: hypersensitivity / GI disturbances / neurotoxicity (seizures)
ticarcillin beta lactam antibiotic semi-synthetic carboxypenicillin penicillinase sensitive extended spectrum : antipseudomonas parenteral -excretion: renally by tubular secretion -MOA : cell wall inhibitor - inhibit PBPs, the cross linking of peptidoglycan matrix/ activate autolytic enzymes : degrade the already formed cell wall -SE: hypersensitivity / GI disturbances / neurotoxicity (seizures)
azlocillin beta lactam antibiotic semi-synthetic ureidopenicillin penicillinase sensitive extended spectrum : antipseudomonas parenteral -excretion: renally by tubular secretion -MOA : cell wall inhibitor - inhibit PBPs, the cross linking of peptidoglycan matrix/ activate autolytic enzymes : degrade the already formed cell wall -SE: hypersensitivity / GI disturbances / neurotoxicity (seizures)
mezlocillin beta lactam antibiotic semi-synthetic ureidopenicillin penicillinase sensitive extended spectrum : antipseudomonas parenteral -excretion: renally by tubular secretion -MOA : cell wall inhibitor - inhibit PBPs, the cross linking of peptidoglycan matrix/ activate autolytic enzymes : degrade the already formed cell wall -SE: hypersensitivity / GI disturbances / neurotoxicity (seizures)
piperacillin beta lactam antibiotic semi-synthetic ureidopenicillin penicillinase sensitive extended spectrum : antipseudomonas parenteral -excretion: renally by tubular secretion -MOA : cell wall inhibitor - inhibit PBPs, the cross linking of peptidoglycan matrix/ activate autolytic enzymes : degrade the already formed cell wall -SE: hypersensitivity / GI disturbances / neurotoxicity (seizures)
Ampicillin beta lactam antibiotic alpha-aminobenzylpenicillin semi-synthetic penicillinase sensitive broad spectrum oral improved acid stability excreted renally by tubular secretion MOA : cell wall inhibitor - inhibit PBPs, the cross linking of peptidoglycan matrix/ activate autolytic enzymes : degrade the already formed cell wall SE: hypersensitivity / GI disturbances / neurotoxicity (seizures)
amoxicillin beta lactam antibiotic alpha amino-p-hydroxybenzylpenicillin semi-synthetic penicillinase sensitive broad spectrum oral improved acid stability -excretion: renally by tubular secretion -MOA : cell wall inhibitor - inhibit PBPs, the cross linking of peptidoglycan matrix/ activate autolytic enzymes : degrade the already formed cell wall -SE: hypersensitivity / GI disturbances / neurotoxicity (seizures)
Bacampicillin beta lactam antibiotic penicillin prodrug hydrolyzed by non specific esterase --> unstable products that form active free carboxylic acid SE: hypersensitivity / GI disturbances / neurotoxicity (seizures)
Pivampicillin beta lactam antibiotic penicillin prodrug hydrolyzed by non specific esterase --> unstable products that form active free carboxylic acid SE: hypersensitivity / GI disturbances / neurotoxicity (seizures)
Talampicillin beta lactam antibiotic penicillin prodrug hydrolyzed by non specific esterase --> unstable products that form active free carboxylic acid SE: hypersensitivity / GI disturbances / neurotoxicity (seizures)
Pen G procaine beta lactam antibiotic amine salt of Pen G low water solubility given IM : local depot: slow dissolution and release --> prolong blood levels -excretion: renally by tubular secretion -SE: hypersensitivity / GI disturbances / neurotoxicity (seizures)
Pen G benzathine beta lactam antibiotic diamine salt of Pen G very water insoluble given IM : local depot: slow dissolution and release --> prolong blood levels for more than a week -excretion: renally by tubular secretion -SE: hypersensitivity / GI disturbances / neurotoxicity (seizures)
Clavulanic acid beta lactamase inhibitors weak affinity to PBPs high affinity to beta lactamase irreversible beta lactamase inhibitor (adjunct therapy) produced from streptomyces clavuligeris 1-oxopenam lack 6-amino group has 2-hydroxyethylidene moiety formulated with amoxicillin SE: hypersensitivity / GI disturbances / neurotoxicity (seizures)
Sulbactam beta lactamase inhibitor weak affinity to PBPs high affinity to beta lactamase irreversible beta lactamase inhibitor (adjunct therapy) semi-synthetic 1,1-dioxopenicillanic acid formulated with ampicillin SE: hypersensitivity / GI disturbances / neurotoxicity (seizures)
Tazobactam beta lactamase inhibitor weak affinity to PBPs high affinity to beta lactamase irreversible beta lactamase inhibitor (adjunct therapy) semi-synthetic 1,1-dioxopenicillanic acid formulated with pipericillin SE: hypersensitivity / GI disturbances / neurotoxicity (seizures)
Cephalosporin C beta lactam antibiotic Isolated from C.acremonium Not potent enough to be clinically as an antibiotic Precursor to develop useful derivatives
7-ACA beta lactam antibiotic 7-aminocephalosporanic acid formed by the removal of the side chain from cephalosporin C analogous to 6-APA used to prepare semi-synthetic analogs Its 7-phenylglycine derivatives are orally active
7-ADCA beta lactam antibiotic 7-Amino-3-deacetoxy-cephalosporanic acid metabolite of pen V reduced acetoxy methyl of 7-ACA Its analogs are orally active
Cephapirin beta lactam antibiotic first generation cephalosporin parenteral agent sodium salt MOA : inhibit cell wall synthesis/similar to penicillins : inhibit PBPs & activate autolytic enzymes (inhibit the last stage: stage 3) Renal excretion via tubular secretion
Cefazolin beta lactam antibiotic first generation cephalosporin parenteral agent sodium salt 5 membered ring (thiadiazole) --> increase potency MOA : inhibit cell wall synthesis/similar to penicillins : inhibit PBPs & activate autolytic enzymes (inhibit the last stage: stage 3) Renal excretion via tubular secretion
Cephalexin beta lactam antibiotic first generation cephalosporin oral agent because it contains an alpha amino benzyl substituent HCl salt MOA : inhibit cell wall synthesis/similar to penicillins : inhibit PBPs & activate autolytic enzymes (inhibit the last stage: stage 3) Renal excretion via tubular secretion
Cefadroxil beta lactam antibiotic first generation cephalosporin oral agent because it contains a p-hydroxybenzyl substituent MOA : inhibit cell wall synthesis/similar to penicillins : inhibit PBPs & activate autolytic enzymes (inhibit the last stage: stage 3) Renal excretion via tubular secretion
Cephradine beta lactam antibiotic first generation cephalosporin oral and parenteral agent it contains an alpha amino benzyl substituent MOA : inhibit cell wall synthesis/similar to penicillins : inhibit PBPs & activate autolytic enzymes (inhibit the last stage: stage 3) Renal excretion via tubular secretion
Cefamandole nafate beta lactam antibiotic second generation cephalosporin parenteral agent contains NMTT --> bleeding problems and disulfiram side effects MOA : inhibit cell wall synthesis/similar to penicillins : inhibit PBPs & activate autolytic enzymes (inhibit the last stage: stage 3) Renal excretion via tubular secretion
Cefonicid beta lactam antibiotic second generation cephalosporin parenteral agent MOA : inhibit cell wall synthesis/similar to penicillins : inhibit PBPs & activate autolytic enzymes (inhibit the last stage: stage 3) Renal excretion via tubular secretion
Cefuroxime beta lactam antibiotic second generation cephalosporin parenteral agent MOA : inhibit cell wall synthesis/similar to penicillins : inhibit PBPs & activate autolytic enzymes (inhibit the last stage: stage 3) Renal excretion via tubular secretion
Cefoxitin beta lactam antibiotic second generation cephalosporin parenteral agent Cephamycin : produced by Streptomyces species posses 7 alpha methoxy substituent => more resistance to beta lactamases MOA : inhibit cell wall synthesis/similar to penicillins : inhibit PBPs & activate autolytic enzymes (inhibit the last stage: stage 3) Renal excretion via tubular secretion
Cefotetan beta lactam antibiotic second generation cephalosporin parenteral agent contains NMTT --> bleeding problems and disulfiram side effects Cephamycin : produced by Streptomyces species posses 7 alpha methoxy substituent => more resistance to beta lactamases MOA : inhibit cell wall synthesis/similar to penicillins : inhibit PBPs & activate autolytic enzymes (inhibit the last stage: stage 3) Renal excretion via tubular secretion
Cefmetazole beta lactam antibiotic second generation cephalosporin parenteral agent contains NMTT --> bleeding problems and disulfiram side effects Cephamycin : produced by Streptomyces species posses 7 alpha methoxy substituent => more resistance to beta lactamases MOA : inhibit cell wall synthesis/similar to penicillins : inhibit PBPs & activate autolytic enzymes (inhibit the last stage: stage 3) Renal excretion via tubular secretion
Cefaclor beta lactam antibiotic second generation cephalosporin oral agent because it contains an alpha amino benzyl substituent MOA : inhibit cell wall synthesis/similar to penicillins : inhibit PBPs & activate autolytic enzymes (inhibit the last stage: stage 3) Renal excretion via tubular secretion
Loracarbef beta lactam antibiotic second generation cephalosporin oral agent because it contains an alpha amino benzyl substituent carba analogue of cefaclor : sulfur atom replaced by carbon --> less potent MOA : inhibit cell wall synthesis/similar to penicillins : inhibit PBPs & activate autolytic enzymes (inhibit the last stage: stage 3) Renal excretion via tubular secretion
Cefprozil beta lactam antibiotic second generation cephalosporin oral agent because it contains a p-hydroxybenzyl substituent MOA : inhibit cell wall synthesis/similar to penicillins : inhibit PBPs & activate autolytic enzymes (inhibit the last stage: stage 3) Renal excretion via tubular secretion
Cefotaxime beta lactam antibiotic third generation cephalosporin parenteral agent contains an alkoxyimino substituent => resistant to beta lactamases MOA : inhibit cell wall synthesis/similar to penicillins : inhibit PBPs & activate autolytic enzymes (inhibit the last stage: stage 3) Renal excretion via tubular secretion
Ceftizoxime beta lactam antibiotic third generation cephalosporin parenteral agent contains an alkoxyimino substituent => resistant to beta lactamases MOA : inhibit cell wall synthesis/similar to penicillins : inhibit PBPs & activate autolytic enzymes (inhibit the last stage: stage 3) Renal excretion via tubular secretion
Ceftriaxone beta lactam antibiotic third generation cephalosporin parenteral agent contains an alkoxyimino substituent => resistant to beta lactamases MOA : inhibit cell wall synthesis/similar to penicillins : inhibit PBPs & activate autolytic enzymes (inhibit the last stage: stage 3) Biliary excretion
Ceftazidime beta lactam antibiotic third generation cephalosporin parenteral agent contains an alkoxyimino substituent => resistant to beta lactamases MOA : inhibit cell wall synthesis/similar to penicillins : inhibit PBPs & activate autolytic enzymes (inhibit the last stage: stage 3) Renal excretion via tubular secretion
Cefoperazone beta lactam antibiotic third generation cephalosporin parenteral agent MOA : inhibit cell wall synthesis/similar to penicillins : inhibit PBPs & activate autolytic enzymes (inhibit the last stage: stage 3) Biliary excretion
Cefixime beta lactam antibiotic third generation cephalosporin oral agent contains an alkoxyimino substituent => resistant to beta lactamases MOA : inhibit cell wall synthesis/similar to penicillins : inhibit PBPs & activate autolytic enzymes (inhibit the last stage: stage 3) Renal excretion via tubular secretion
Ceftibuten beta lactam antibiotic third generation cephalosporin oral agent MOA : inhibit cell wall synthesis/similar to penicillins : inhibit PBPs & activate autolytic enzymes (inhibit the last stage: stage 3) Renal excretion via tubular secretion
Cefpodoxime proxetil beta lactam antibiotic third generation cephalosporin oral agent contains an alkoxyimino substituent => resistant to beta lactamases ester prodrug MOA : inhibit cell wall synthesis/similar to penicillins : inhibit PBPs & activate autolytic enzymes (inhibit the last stage: stage 3) Renal excretion via tubular secretion
Cefdinir beta lactam antibiotic third generation cephalosporin oral agent contains an alkoxyimino substituent => resistant to beta lactamases MOA : inhibit cell wall synthesis/similar to penicillins : inhibit PBPs & activate autolytic enzymes (inhibit the last stage: stage 3) Renal excretion via tubular secretion
Cefditoren pivoxil beta lactam antibiotic third generation cephalosporin oral agent contains an alkoxyimino substituent => resistant to beta lactamases ester prodrug MOA : inhibit cell wall synthesis/similar to penicillins : inhibit PBPs & activate autolytic enzymes (inhibit the last stage: stage 3) Renal excretion via tubular secretion
Cefepime beta lactam antibiotic fourth generation cephalosporin parenteral agent exist as zwitterion contains an alkoxyimino substituent => resistant to beta lactamases More gram -ve (against P. aeruginosa) and greater beta lactamase resistance MOA : inhibit cell wall synthesis/similar to penicillins : inhibit PBPs & activate autolytic enzymes (inhibit the last stage: stage 3) Renal excretion via tubular secretion
Cefelidine beta lactam antibiotic fourth generation cephalosporin parenteral agent exist as zwitterion contains an alkoxyimino substituent => resistant to beta lactamases More gram -ve (against P. aeruginosa) and greater beta lactamase resistance MOA : inhibit cell wall synthesis/similar to penicillins : inhibit PBPs & activate autolytic enzymes (inhibit the last stage: stage 3) Renal excretion via tubular secretion
Cefpirome beta lactam antibiotic fourth generation cephalosporin parenteral agent exist as zwitterion contains an alkoxyimino substituent => resistant to beta lactamases More gram -ve (against P. aeruginosa) and greater beta lactamase resistance MOA : inhibit cell wall synthesis/similar to penicillins : inhibit PBPs & activate autolytic enzymes (inhibit the last stage: stage 3) Renal excretion via tubular secretion
Cefozopran beta lactam antibiotic fourth generation cephalosporin parenteral agent exist as zwitterion contains an alkoxyimino substituent => resistant to beta lactamases More gram -ve (against P. aeruginosa) and greater beta lactamase resistance MOA : inhibit cell wall synthesis/similar to penicillins : inhibit PBPs & activate autolytic enzymes (inhibit the last stage: stage 3) Renal excretion via tubular secretion
Cefluprenam beta lactam antibiotic fourth generation cephalosporin parenteral agent exist as zwitterion contains an alkoxyimino substituent => resistant to beta lactamases More gram -ve (against P. aeruginosa) and greater beta lactamase resistance MOA : inhibit cell wall synthesis/similar to penicillins : inhibit PBPs & activate autolytic enzymes (inhibit the last stage: stage 3) Renal excretion via tubular secretion
Ceftobiprole beta lactam antibiotic fifth generation cephalosporin parenteral agent More gram -ve (against P. aeruginosa) and greater beta lactamase resistance activity against MRSA MOA : inhibit cell wall synthesis/similar to penicillins : inhibit PBPs & activate autolytic enzymes (inhibit the last stage: stage 3) Renal excretion via tubular secretion
Ceftaroline fosamil beta lactam antibiotic fifth generation cephalosporin parenteral agent More gram -ve (against P. aeruginosa) and greater beta lactamase resistance activity against MRSA MOA : inhibit cell wall synthesis/similar to penicillins : inhibit PBPs & activate autolytic enzymes (inhibit the last stage: stage 3) Renal excretion via tubular secretion
Thienamycin beta lactam antibiotic carbapeneme Natural : streptomyces cattleya broad spectrum hydroxyethyl at C-6 --> resistant to beta lactamase chemically unstable : -undergoes beta lactam ring opening => inactive -form a dimer => inactive MOA : inhibit cell wall synthesis
Imipenem beta lactam antibiotic carbapenem addition of N-formiminoyl moiety to Thienamycin --> less Nu semi-synthetic more chemically stable not orally active hydrolyzed by dehydropeptidase DHP enzyme in renal tubule => inactive and nephrotoxic metabolites formulated with cilastatin (inhibitor of DHP) MOA : inhibit cell wall synthesis
Meropenem beta lactam antibiotic carbapeneme synthetic same activity as Imipenem not hydrolyzed by DHP => no need for formulation with cilastatin MOA : inhibit cell wall synthesis
Ertapenem beta lactam antibiotic carbapenem synthetic same activity as Imipenem not hydrolyzed by DHP => no need for formulation with cilastatin MOA : inhibit cell wall synthesis
Biapenem beta lactam antibiotic carbapenem synthetic same activity as Imipenem not hydrolyzed by DHP => no need for formulation with cilastatin MOA : inhibit cell wall synthesis
Aztreonam beta lactam antibiotic monobactam synthetic chemically stable for 48h strong e-withdrawing sulfamic acid => less stable alpha methyl at C2 --> beta lactamase resistant given by injection active against gram -ve bacteria
Tigemonam tigemonam beta lactam antibiotic monobactam synthetic highly resistant to beta lactamase similar spectrum to aztreonam orally active, excellent bioavailability MOA : inhibit cell wall synthesis
Vancomycin non beta lactam antibiotic glycoprotein, cyclic peptide from Nocardia orientalis given parenterally MOA: inhibit cell wall synthesis through inhibition of transglycosylation step --> inhibition of elongation of peptidoglycan matrix active against MRSA SE : hypersensitivity / nephro and ototoxicity
Teicoplanin non beta lactam antibiotic glycoprotein, cyclic peptide from Actinoplanes teicomyceticus given parenterally MOA: inhibit cell wall synthesis through inhibition of transglycosylation step --> inhibition of elongation of peptidoglycan matrix active against MRSA SE : hypersensitivity / nephrotoxicity
Bacitracin non beta lactam antibiotic cyclic peptide produced from Bacillus subtilis inhibits dephosphorylation of the phospholipid carrier responsible for trnsporting the disaccharide across plasma membrane (late stage 1) SE: hypersensitivity / nephro and neurotoxicity ONLY topical route and IM with caution
Cycloserine non beta lactam antibiotic analog of D-ala produced by streptomyces sp. MOA: competitive inhibitor of D-ala-D-ala synthetase and D-ala racemase orally active SE : - CNS effects : tremor/seizure/confusion/hallucination/psychosis - occasional hepatic damage and peripheral neuropathy
naphtacene
tetracycline backbone
Tetracycline Tetracycline antibiotics Bacterial protein synthesis inhibitors octahydronaphtacene Natural (from streptomyces spc) or from chlortetracycline (by hydrogenolysis) Crystalline amphoteric compounds (form acid/base salts) Low water solubility (HCl salts-->water soluble) Orally active Undergoes chelation with di/trivalent cations (contraindication with dairy food and antacids) -In acidic condition: epimerization:epitetracyclin (4-beta): inactive, -H2O:anhydrotetracycline (deeper color) (double bond on C5a): inactive, formation of epianhydrotetracycline:hepatotoxic -In basic condition: lactone formation:isotetracycline: inactive Bacteriostatic (higher affinity to bacteria) -MOA: active against gram+ and gram-, aerobic and anaerobic-->broad spectrum of activity Enter by passive/active diffusion:bind to 30S subunit:inhibit protein synthesis -t1/2=6-8h-->short widely distributed (low to CSF) cross placenta excretion: renal SE: GI discomfort, discoloration of teeth, hepatotoxic at high dose, vertigo, superinfection
Demeclocycline Tetracycline antibiotics Bacterial protein synthesis inhibitors octahydronaphtacene Natural (from streptomyces spc) Crystalline amphoteric compounds (form acid/base salts) Low water solubility (HCl salts:water soluble) Orally active Undergoes chelation with di/trivalent cations (contraindication with dairy food and antacids) -In acidic condition: epimerization:epitetracyclin (4-beta): inactive, -H2O:anhydrotetracycline (deeper color) (double bond on C5a): inactive, formation of epianhydrotetracycline:hepatotoxic -In basic condition: lactone formation:isotetracycline: inactive Bacteriostatic (higher affinity to bacteria) -MOA: active against gram+ and gram-, aerobic and anaerobic:broad spectrum of activity Enter by passive/active diffusion:bind to 30S subunit-->inhibit protein synthesis -t1/2=12h--> intermediate widely distributed (low to CSF) cross placenta excretion: renal SE: GI discomfort, discoloration of teeth, hepatotoxic at high dose, vertigo, superinfection, photosensitivity
Minocycline Tetracycline antibiotics Bacterial protein synthesis inhibitors octahydronaphtacene Semi-synthetic Crystalline amphoteric compounds (form acid/base salts) Low water solubility (HCl salts:water soluble) Orally active Undergoes chelation with di/trivalent cations (contraindication with dairy food and antacids) Stable in acidic and basic condition More lipophilic Bacteriostatic (higher affinity to bacteria) MOA: active against gram+ and gram-, aerobic and anaerobic:broad spectrum of activity Enter by passive/active diffusion:bind to 30S subunit:inhibit protein synthesis t1/2=16h-->long completely absorbed widely distributed (to CSF:for meningitis) cross placenta excretion: biliary SE: GI discomfort, discoloration of teeth, hepatotoxic at high dose, vertigo, superinfection
Sancycline Tetracycline antibiotics Bacterial protein synthesis inhibitors octahydronaphtacene Semi-synthetic Slightly more active (than tetracycline) Crystalline amphoteric compounds (form acid/base salts) Low water solubility (HCl salts:water soluble) Orally active Undergoes chelation with di/trivalent cations (contraindication with dairy food and antacids) Bacteriostatic (higher affinity to bacteria) MOA: active against gram+ and gram-, aerobic and anaerobic:broad spectrum of activity Enter by passive/active diffusion:bind to 30S subunit:inhibit protein synthesis widely distributed (low to CSF) cross placenta excretion: renal SE: GI discomfort, discoloration of teeth, hepatotoxic at high dose, vertigo, superinfection
Chlortetracycline Tetracycline antibiotics Bacterial protein synthesis inhibitors octahydronaphtacene Natural (from streptomyces spc) Crystalline amphoteric compounds (form acid/base salts) Low water solubility (HCl salts:water soluble) Orally active Undergoes chelation with di/trivalent cations (contraindication with dairy food and antacids) -In acidic condition: epimerization:epitetracyclin (4-beta): inactive, -H2O:anhydrotetracycline (deeper color) (double bond on C5a): inactive, formation of epianhydrotetracycline:hepatotoxic -In basic condition: lactone formation:isotetracycline: inactive Bacteriostatic (higher affinity to bacteria) -MOA: active against gram+ and gram-, aerobic and anaerobic:broad spectrum of activity Enter by passive/active diffusion:bind to 30S subunit:inhibit protein synthesis t1/2=6-8h -->short least absorbed widely distributed (low to CSF) cross placenta excretion: renal SE: GI discomfort, discoloration of teeth, hepatotoxic at high dose, vertigo, superinfection
Oxytetracycline Tetracycline antibiotics Bacterial protein synthesis inhibitors octahydronaphtacene Natural (from streptomyces spc) Crystalline amphoteric compounds (form acid/base salts) Low water solubility (HCl salts:water soluble) Orally active Undergoes chelation with di/trivalent cations (contraindication with dairy food and antacids) -In acidic condition: epimerization:epitetracyclin (4-beta): inactive, -H2O:anhydrotetracycline (deeper color) (double bond on C5a): inactive, formation of epianhydrotetracycline:hepatotoxic -In basic condition: lactone formation:isotetracycline: inactive Bacteriostatic (higher affinity to bacteria) -MOA: active against gram+ and gram-, aerobic and anaerobic:broad spectrum of activity Enter by passive/active diffusion:bind to 30S subunit:inhibit protein synthesis t1/2=6-8h--> short widely distributed (low to CSF) cross placenta excretion: renal SE: GI discomfort, discoloration of teeth, hepatotoxic at high dose, vertigo, superinfection
Methacycline Tetracycline antibiotics Bacterial protein synthesis inhibitors octahydronaphtacene Semi-synthetic Crystalline amphoteric compounds (form acid/base salts) Low water solubility (HCl salts:water soluble) Orally active Undergoes chelation with di/trivalent cations (contraindication with dairy food and antacids) Exception: not stable in acidic and basic condition (undergoes hydration) Bacteriostatic (higher affinity to bacteria) -MOA: active against gram+ and gram-, aerobic and anaerobic:broad spectrum of activity Enter by passive/active diffusion:bind to 30S subunit:inhibit protein synthesis t1/2=12h--> intermediate widely distributed (low to CSF) cross placenta excretion: renal SE: GI discomfort, discoloration of teeth, hepatotoxic at high dose, vertigo, superinfection
Doxycycline Tetracycline antibiotics Bacterial protein synthesis inhibitors octahydronaphtacene Semi-synthetic Crystalline amphoteric compounds (form acid/base salts) Low water solubility (HCl salts:water soluble) Orally active Undergoes chelation with di/trivalent cations (contraindication with dairy food and antacids) Stable in acidic and basic condition More lipophilic Bacteriostatic (higher affinity to bacteria) -MOA: active against gram+ and gram-, aerobic and anaerobic:broad spectrum of activity Enter by passive/active diffusion:bind to 30S subunit:inhibit protein synthesis t1/2=16h-->long completely absorbed widely distributed (low to CSF) cross placenta excretion: biliary SE: GI discomfort, discoloration of teeth, hepatotoxic at high dose, vertigo, superinfection, photosensitivity
tigecycline Tetracycline antibiotics (new) Bacterial protein synthesis inhibitors 9-dimethylglycylamino substituent (DMG) Semi-synthetic Crystalline amphoteric compounds (form acid/base salts) Low water solubility (HCl salts:water soluble) Poor oral/ given IV Undergoes chelation with di/trivalent cations (contraindication with dairy food and antacids) Stable in acidic and basic condition More lipophilic Bacteriostatic (higher affinity to bacteria) -MOA: active against gram+ and gram-, aerobic and anaerobic:broad spectrum of activity Enter by passive/active diffusion:bind to 30S subunit (5X more):inhibit protein synthesis t1/2=36h--> long widely distributed (low to CSF) cross placenta/ excreted in milk excretion: biliary SE: GI discomfort (nausea, vomiting), discoloration of teeth and bone
streptamine diaminoinositol moiety of aminoglycoside
2-deoxystreptamine diaminoinositol moiety of aminoglycoside
spectinamine diaminoinositol moiety of aminoglycoside
streptidine diaminoinositol moiety of aminoglycoside
Neomycin B Aminoglycoside (amino sugar connected to aminocyclitol) From streptomyces Have a pentose lacking amino group Topically, parentarely Bactericidal (exception) MOA: active against gram- : bind irreversibly to 30S subunit: inhibit bacterial protein synthesis (mistranslation of RNA templates: insertion of wrong amino acid: holes) Most toxic Active eventhough low plasma level (post antibiotic effect) Poor GI absorption Poor distribution Poor ppb Low CSF levels (if no meningitis) Accumulation: in renal cortex and inner ear (ototoxicity) Cross placenta Excretion: renal (unchanged) SE: nephrotoxicity/ototoxicity (the higher the nb of amino group: the more toxic), NMJ blockers, teratogenic effect, rare allergic reaction
gentamycin C Aminoglycoside (amino sugar connected to aminocyclitol) From micromonospora basic, polar, acid (salts) Bactericidal (exception) MOA: active against gram- : bind irreversibly to 30S subunit: inhibit bacterial protein synthesis (mistranslation of RNA templates: insertion of wrong amino acid: holes) Active eventhough low plasma level (post antibiotic effect) Poor GI absorption Poor distribution Poor ppb Low CSF levels (if no meningitis) Accumulation: in renal cortex and inner ear (ototoxicity) Cross placenta Excretion: renal (unchanged) SE: nephrotoxicity/ototoxicity (the higher the nb of amino group: the more toxic), NMJ blockers, teratogenic effect, rare allergic reaction
tobramycin Aminoglycoside (amino sugar connected to aminocyclitol) From streptomyces basic, polar, acid (salts) Bactericidal (exception) MOA: active against gram- : bind irreversibly to 30S subunit: inhibit bacterial protein synthesis (mistranslation of RNA templates: insertion of wrong amino acid: holes) Active eventhough low plasma level (post antibiotic effect) Poor GI absorption Poor distribution Poor ppb Low CSF levels (if no meningitis) Accumulation: in renal cortex and inner ear (ototoxicity) Cross placenta Excretion: renal (unchanged) SE: nephrotoxicity/ototoxicity (the higher the nb of amino group: the more toxic), NMJ blockers, teratogenic effect, rare allergic reaction
neltimicin Aminoglycoside (amino sugar connected to aminocyclitol) From micromonospora basic, polar, acid (salts) Bactericidal (exception) MOA: active against gram- : bind irreversibly to 30S subunit: inhibit bacterial protein synthesis (mistranslation of RNA templates: insertion of wrong amino acid: holes) Active eventhough low plasma level (post antibiotic effect) Poor GI absorption Poor distribution Poor ppb Low CSF levels (if no meningitis) Accumulation: in renal cortex and inner ear (ototoxicity) Cross placenta Excretion: renal (unchanged) SE: nephrotoxicity/ototoxicity (the higher the nb of amino group: the more toxic), NMJ blockers, teratogenic effect, rare allergic reaction
amikacin Aminoglycoside (amino sugar connected to aminocyclitol) From micromonospora basic, polar, acid (salts) Bactericidal (exception) MOA: active against gram- : bind irreversibly to 30S subunit: inhibit bacterial protein synthesis (mistranslation of RNA templates: insertion of wrong amino acid: holes) Active eventhough low plasma level (post antibiotic effect) Poor GI absorption Poor distribution Poor ppb Low CSF levels (if no meningitis) Accumulation: in renal cortex and inner ear (ototoxicity) Cross placenta Excretion: renal (unchanged) SE: nephrotoxicity/ototoxicity (the higher the nb of amino group: the more toxic), NMJ blockers, teratogenic effect, rare allergic reaction
kanamycin A old Aminoglycoside (amino sugar connected to aminocyclitol) From streptomyces basic, polar, acid (salts) Bactericidal (exception) MOA: active against gram- : bind irreversibly to 30S subunit: inhibit bacterial protein synthesis (mistranslation of RNA templates: insertion of wrong amino acid: holes) Active eventhough low plasma level (post antibiotic effect) Poor GI absorption Poor distribution Poor ppb Low CSF levels (if no meningitis) Accumulation: in renal cortex and inner ear (ototoxicity) Cross placenta Excretion: renal (unchanged) SE: nephrotoxicity/ototoxicity (the higher the nb of amino group: the more toxic), NMJ blockers, teratogenic effect, rare allergic reaction
Macrolides Bacterial protein synthesis inhibitor large-membered lactone rings 14 or 15-membered rings attached to deoxy sugars from propionic acid units substituted amino group on sugar → weakly basic (pKa = 8) not very water soluble salt formation with glucoheptanoic and lactobionic acids increase water soluble stearate and laurylsulfate salts decrease water solubility
Erythromycin macrolide natural (from Streptomyces erythreus) bacteriostatic active against gram+, aerobic well distributed (except to brain, CSF) cross placenta found in breast milk penetrates the prostatic fluid MOA: bind to 50S (reversibly): inhibit protein synthesis More effective at alkaline pH Free base form: inactivated by gastric acid, form cyclic ketal (given as enteric coated) Stearate: slightly susceptible to gastric acid inactivation ethylsuccinate preparation: absorbed first and hydrolyzed in blood to liberate free erythromycin estolate preparation (laurylsulfate propionate): more acid resistant lactobionate: suitable for IV administration t1/2= 1.2-2h enterohepatic circulation metabolism: partially excretion: biliary (95% in active form) SE: safe, GI disturbances (nausea, vomiting, anorexia, diarrhea, abdominal cramps), cholestatic hepatitis (with estolate ester), rare allergic reaction, ototoxicity (reversible at high dose) DDI: CYP3A4 inhibitor CI: with liver dysfunction patients
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