Antibacterials Drug Info Exam 2 Flashcards
Penicillin G PK features
- Poor oral absorption
- Unstable in acid environments
- Only given by injection, usually continuous IV
- Ordered in units
- Half-life is about 30 minutes due to rapid renal elimination. Dosage reduction if impaired renal function
Penicillin V PK features
- Acid-stable, oral use, should be taken on an empty stomach several times a day
- Half-life is about 30 minutes due to rapid renal elimination. Dosage reduction if impaired renal function
Which PCN(s) has the best oral absorption?
- oxacillin
- nafcillin
- dicloxacillin
Ampicillin route of administration
- oral and injected
- injection preferred
- take on empty stomach if taking oral
amoxicillin route of administration
oral only
piperacillin route of administration
injected only
Penicillin G route of administration
parenteral
Penicillin V route of administration
oral, empty stomach
Hypersensitivity Reactions of Penicillins
- Immediate (anaphylactic)
- Accelerated
- Delayed (most common; skin rashes)
- Assume 100% cross-allergic reactions among the penicillins
Theory for Hypersensitivity Reactions of Penicillins
when the β-lactam ring is opened and combines with a human protein
General PK of Cephalosporins
- incompletely absorbed after oral dose
- short half-life
- renal elimination
Hypersensitivity Reactions of Cephalosporins
Possible cross-allergic reaction with other β-Lactams
ADEs of PCN’s
- CNS Excitation / seizures at high conc.
- lower doses in case of renal impairment
- Diarrhea
- nausea
- superinfections
ADEs of Cephalosporins
- CNS excitation and seizures with high levels
- Renal toxicity
- Bleeding (Kill bacteria that synthetize Vit.K, potential problem with all extended and broad spectrum antibiotics, drug-drug interaction with warfarin that inhibit Vit.K synthesis)
Cefadroxil route of administration
- best absorbed after oral administration (has amoxicillin side chain)
Which First Generation Cephalosporins has the longest half life?
Cefazolin
Cefoxitin route of administration
parenteral
cefuroxime route of administration
oral prodrug and parenteral
cefaclor route of administration
oral
cefprozil route of administration
oral
Third Generation Cephalosporins route of administration
- Poor oral absorption, some pro-drug formulations can improve oral bioavailability
- Some injectable third generation Cephalosporins can cross the BBB
Cefotaxime route of administration
parenteral
Ceftriaxone route of administration
parenteral
Ceftazidime route of administration
parenteral
Cefotaxime PK
short half-life
Ceftriaxone PK
long halflife
Cefepime route of administration
parenteral
Ceftaroline route of administration
parenteral
Carbapenems PK
- Short half-life, quickly excreted in urine
* Poor oral absorption
Imipenem route of administration
parenteral
Imipenem PK
- rapidly degraded by the renal enzyme dehydropeptidase
- metabolites can cause kidney damage
meropenem, doripenem, ertapenem PK
- Chemically modified, resistants to dehydropeptidase
- Not available for oral use.
ADEs with Carbapenems
- Possible cross-allergic reactions
* CNS excitation, seizures more of a concern with Carbapenems
Aztreonam route of administration
parenteral
Monobactams (Aztreonam) PK
- Short half-life, quickly excreted in urine
- Poor oral absorption
- Because of unusual ring structure, no cross-allergic reactions with other β-lactams
Food with β-lactams
Oral absorption is reduced by food (except for amoxicillin)
Glycopeptides / lipoglycopeptides history
- Not widely used at first because of renal toxicity and hearing loss
- Big polar molecule
- Used as last resort
Vancomycin PK
- not absorbed reliably from GI tract
- Renal clearance (glomerular filtration)
- half-life 4-6 h
Vancomycin route of administration
- intravenously
- oral available too
ADE of Glycopeptides
- Nephrotoxicity
- Ototoxicity with high circulating levels
- Infusion-related effects: chills, fever rash, flushing; due to histamine release from mast cells; infuse slowly to avoid
Lipoglycopeptides PK
- Lower MIC values
- Less adverse effects
- Longer half-lives
Telavancin route of administration
- Administered by injection once a day
- half-life: 9h
Oritavancin route of administration
- Administered by injection once a week
- half-life: 195h
Dalbavancin route of administration
- Administered by injection once a week
- half-life: 346h
Lipopeptides uses
- Last resort antibiotic
- MRSA and VRSA
Lipopeptides route of administration
- injected IV once daily
Lipopeptides PK
- half-life 8-9h
- Renal elimination
Lipopeptides ADE
- Some apparent muscular toxicity
- drug-drug interaction with statins
Oxazolidionones uses
Last resort drugs
Linezolid PK
broken down in the liver by non-enzymatic oxidation, eliminated in urine, short half-life, administered twice daily
Tedizolid PK
sulfated in the liver and excreted mainly in bile, longer half-life, administered once daily
Oxazolidionones ADE
- Bone marrow suppression resulting in low platelet count
- Peripheral neuropathy (tingling sensation, numbness, burning)
- Weak monoamine oxidase inhibitor, interaction with other drugs like serotonine reuptake inhibitors used for depression
Streptrogramins route of administration
Must be given intravenously
Streptrogramins PK
- Rapidly metabolized in liver
- Short half-lives, administered 3-4 times daily
- Excreted in the bile
- No dosage adjustments required in case of poor renal function
- Dosage adjustment in case of hepatic impairment
Streptrogramins ADE
- Discomfort at injection site
- Some joint and muscle pain
- Potential for drug interactions involving CYP3A4 (these rx are inhibitors)
Lincosamide uses
- Penicillin substitute for G+ cocci, useful for some MRSA infections
- Anaerobic infections
- Infections of bone and joint
Clindamycin PK
- given at 6-8 h intervals
- Excellent penetration into bone, abscesses, macrophages but not CNS
- Metabolized in liver but to a small extent
- Few drug-drug interactions
- Parent drug and active metabolites mainly excreted into bile
Lincosamide ADE
- Rash, Nausea, Diarrhea (usually mild, self-limiting)
- Increased risk for Clostridium difficile colitis (Gram + anaerobe, NOT sensitive to Clindamycin)
- Weak neuromuscular blocking activities, drug-drug interaction with other neuromuscular blocking drugs that are used during surgery
Erythromycin route of administration
- injection
- poor oral absorption, very unstable in acidic conditions, given orally only as enteric-coated tablets
Erythromycin PK
- Pro-drug formulations for better absorption and stability.
- Short half-life ~1.4 h
- metabolized in the liver by CYP3A4
Clarithromycin PK
- stable in acidic conditions
- half-life ~3.7h
- metabolized in the liver by CYP3A4
Azithromycin route of administration
- etter oral absorption on an empty stomach
- stable in acidic conditions
Azithromycin PK
- long half-life ~68h
Macrolides ADE
GI intolerance
Azithromycin ADE
Increased risk for Clostrodium difficile colitis
Telithromycin ADE
- hepatotoxicity
- prolonged QT interval
- visual disturbances
- loss of conciousness
Sulfamethoxazole plus trimethoprim route of administration
oral and parenteral
Sulfamethoxazole plus trimethoprim route of administration
oral and parenteral
Sulfamethoxazole plus trimethoprim PK
- Hydrophobic, well absorbed orally
- Bound to plasma proteins in the blood, potential for drugdrug interaction
- Sulfonamides metabolized by acetylation, some glucuronidation and CYP oxidation, potential for drug-drug interaction
- Mostly renal excretion by glomerular filtration and/or tubular secretion, potential for drug-drug interaction
Sulfamethoxazole plus trimethoprim ADE
- Hypersensitivity or allergic reactions at high doses
- Crystalluria at high doses
- Aplastic anemia at high doses
- Do not use in late 3rd trimester of pregnancy or in neonates!
Ansamycins PK
- Well absorbed after oral administration, take on an empty stomach
- Deacetylated in liver, active metabolites
- Not substrates of CYP450 enzymes
- Enterohepatic circulation
- Half-life 1.5 – 5 hours, take once a day
- About 30% renal elimination, 70% feces
- Tuberculosis treatment can take several months or longer
Ansamycins ADE
- Some hepatotoxicity
- Gastrointestinal intolerance
- Colors urine and other body fluids red or orange, not harmful
Rifampin PK
Rifampin is a powerful inducer of CYP3A4
Rifabutin PK
- Longer half-life
- Less induction of CYP3A4
- Is effective against some rifampin-resistant strains
Rifaximin uses
- Orally administered to treat traveller’s diarrhea caused by E. coli
- Does not need to be taken on an empty stomach
- Can be used for C.diff
ozenoxacin uses
treatment of impetigo
Fluoro/quinolones PK
- Good oral absorption, best oral drugs for P. aeruginosa!
- Third generation are better absorbed and have longer half-lives
- Chelate metal ions in food and antacids, decreases absorption
- Excreted in urine, lower dosage when renal insufficiency. Moxifloxacin is excreted in the bile.
- Good antibacterial activity in bowel in spite of good oral absorption (enterohepatic circulation)
- Excellent penetration in tissues (bone, prostate, etc), but not in CNS, delafloxacin has the best intracellular penetration
Fluoro/quinolones ADE
- Serious adverse effects in tendons, muscles, joints, nerves. Not recommended during pregnancy or in children.
- CNS excitation and seizures
- Peripheral neuropathy (pain, burning sensations, numbness)
- Diarrhea, due to broad antibacterial spectrum and superinfection with C. difficile
- FLUOROQUINOLONES with most serious toxicity have been withdrawn from the market
Tetracycline PK
poor oral absorption further decreased by food and dairy products because it forms insoluble, non-absorbed chelates with metal ions from food. Not metabolized, eliminated by urine, short half-life 6-8 h.
Doxycycline PK
excellent oral absorption. Partly metabolized, excreted by the bile, long half-life 18-20 h
Minocycline PK
excellent oral absorption. Partly metabolized, excreted by the bile, long half-life 18-20 h and fully metabolized by the liver
Tigecycline, omadacycline and eravacycline PK
Tigecycline, omadacycline and eravacycline are given intravenously, omadacycline can also be given orally, eliminated by feces and urine, longest half-life 36 h
Tetracycline ADE
- Usually uncommon, mostly diarrhea, super-infections of nonsusceptible organisms (Candida, C. difficile) due to broad antibacterial spectrum
- Teeth discoloration, chelate calcium, discoloration when exposed to light, not used during pregnancy or in children younger than 8
- Hypersensitivity to sunlight
- Tigecycline is associated with slightly increased risk of death relative to other antibiotics, only used when no other alternative.
Aminoglycosides PK
- Poor oral absorption, administered by injection, or used orally for GI infections
- Very hydrophilic drugs, dosage adjusted to the lean body mass not total body mass
- Excreted in urine (UTI), renal function must be checked during long-term therapy
- Half-life is short but they can be administered only once a day because these drugs remain active long after plasma level decrease below MIC level (post-antibiotic effect), due to the irreversible binding.
Aminoglycosides ADE
- Renal toxicity can occur during long-term treatment
- Neuromuscular junction blockade can occur with high doses. Stop treatment before surgery (when using other neuromuscular blockers)
- Ototoxicity, vestibular function, loss of balance may be permanent
- Toxicity is not increased when administered only once a day at a higher dose
Polypeptide PK
- No oral absorption, IV injection, aerosol (for Cystic Fibrosis)
- Short half-life
- Excreted in urine
Polypeptide ADE
- Was abandoned at first because of its kidney toxicity and neurotoxicity
- Used as last resort drug since the emergence of multidrug resistant G
- Used only for serious cases of resistant infections and for Cystic Fibrosis
Nitromidazoles PK
- Food does not affect oral absorption
- Administer every 6-8 h (metronidazole) or once (secnidazole)
- Excreted in urine
- Mild adverse effects
Nitromidazoles route of administration
Oral, IV, and topical administration
