Pharm antibiotics part 2 Flashcards
Antimicrobial agents- MOA
Part 1: cell wall synthesis and cytoplasmic membrane structure
* betalactams= Penicillins, Cephalosporins, Carbapenems, Monobactam
* glycopeptides= Vancomycin
* cyclic lipopeptide= Daptomycin
Part 1: target DNA or DNA replication
Antimetabolites: sulfonamides and trimethoprim
Fluoroquinolones: Ciprofloxacin, Levofloxacin, Ofloxacin
Now= block production of new proteins= bacterial ribosome
Aminoglycosides: neomycin, Gentamicin, Tobramycin, and amikacin, strptomycin
Tetracyclines: tetracycline, doxycycline, minocycline
Macrolides: Erythromycin, Clarithromycin, Azithromycin
Clindamycin
Linezolid
Chloramphenicol
Aminoglycosides types
- Gentamicin
- Tobramycin
- Amikacin
- Plazomicin
- Streptomycin
- Neomycin
- Paromomycin
Aminoglycosides MOA
- cause addition of incorrect aa resulting in synth of abn proteins
- cause misreading of mRNA and terminate protein synth
- Bind to 30S ribosomes and block the initiation of protein synth
Pharmacodyn and kinetic prop of Aminoglycosides
- Favorable target: Aerobic Gram - rods and mycobacteria
- Postantibiotic effect PAE= persistent suppression of growth after drug done
- Conc dependent killing characteristics-> higher conc induce more rapid killing
- Synergistic effect= in combo, MC cell wall active agents to help target gram positive bacteria
- Absorption= peak conc -> 30-60 min IV and 30-90 min IM
Aminoglycoside Toxicity
Nephrotoxicity
Ototoxicity
Neuromuscular blockade
Aminoglyc routes and indications
*Neomycin-> topical with Bacitracin and Polymyxin
* Gentamicin: topic, opth, systemic-> Group B streptococcus
* Tobramycin: Inhalation for CF patients with pseudomonas infections
* Streptomycin: second line drug for TB
General Aminoglycosides indications
- Septicemia
- Complicated UTI
- complicated Intraabdominal
- combo with others for drug resistant organisms
- topical drugs in conjunc for Otitis Externa
Otitis External- swimmers ear
mc: STAPH AUREUS AND PSEUDOMONAS AERUGINOSA
topical only: Fluoroquinolones ie
* ciprofloxacin
* Ofloxacin
AB with glucocorticoid: hydrocortisone, Dexamethasone, Prednisolone
* Neomycin
* Tobramycin
* Gentamycin
* allllllllll aminoglycosides
* combos: neomycin, polyyxin B, hydrocort= Cortisporin otic
* Combos: tobramycin and dexamth= Tobradex- opthalmic solution
Fluoroquinolones:
* Ciprofloxacin and Ofloxacin
* combos
ciprofloxacin and dexamethasone-Ciprodex
ciprofloxacin and hydrocortisone- Cipro HC Otic
DO NOT GIVE STEROID IN PERFORATED EAR DRUMS
Otitis External- swimmers ear
mc: STAPH AUREUS AND PSEUDOMONAS AERUGINOSA
topical only: Fluoroquinolones ie
* ciprofloxacin
* Ofloxacin
AB with glucocorticoid: hydrocortisone, Dexamethasone, Prednisolone
* Neomycin
* Tobramycin
* Gentamycin
* allllllllll aminoglycosides
* combos: neomycin, polyyxin B, hydrocort= Cortisporin otic
* Combos: tobramycin and dexamth= Tobradex- opthalmic solution
Fluoroquinolones:
* Ciprofloxacin and Ofloxacin
* combos
ciprofloxacin and dexamethasone-Ciprodex
ciprofloxacin and hydrocortisone- Cipro HC Otic
DO NOT GIVE STEROID IN PERFORATED EAR DRUMS
Tetracyclines types
- Chlortetracycline
- Minocycline
- Doxycycline
- Eravacycline
- Sarecycline
- Omadacycline
Tetracyclines MOA
- Bacteriostatic
- Passive diffusion and transporter uptake
- inhibit protein synthesis
- aerobic gram + and -
- Intracellular bacteria:
* rickettsiae
* chlamydiae
* mycoplasmas
Tetracyclines MOA
- Bacteriostatic
- Passive diffusion and transporter uptake
- inhibit protein synthesis
- aerobic gram + and -
- Intracellular bacteria:
* rickettsiae
* chlamydiae
* mycoplasmas
Pharmacokinetics Doxycycline and Minocycline
absorption, distribution, excretion, classification
Absorption
* 95-100% absorbed orally, duodenum, ALL TETRAC IMPAIRED BY MULTIVALENT CATIONS- Ca, Mg, Fe, Al
* Doxycycline and minocycline absorption NOT IMPAIRED BY FOODS
Distribution
* CROSS PLACENTA, NOT INDICATED IN PREGNANCY
* high tissue penetration except CSF
Excretion
* mainly in bile and urine
* Doxycycline: elim by nonrenal mechanisms, no dose adjustment required in renal failure
Classification:
* short acting- regular tetra: 6-8 hours
* long acting- doxy and mino: 16-18 hours
Tetracyclines- Side effects
- Photosensitivity- doxy is biggest culprit
- GI disturbances- dose related, abdominal discomfort, food decrease symptoms
- Hepatotoxicity- rare
- Audiovestibular- dizziness, vertigo, tinnitis= Doxy and mino
- Teeth and bone- calcium attaches to and deposit in bone
Doxycycline/Minocycline indications
broad uses
- Acne
- Rosacea
- URI
- Pneumonia CAP
- Chlamydia
- Syphilis
- GU
- Anthrax
- Malaria
- tick borne disease
- H. Pylori
- other= ehrlichiosis, anaplasmosis, plasmodium, mycobacteria
Helicobacter Pylori
H. Pylori
4 drug therapy:
1. Proton pump inhibitor PPI
2. Bismuth subsalicylate
3. Tetracycline
4. Metronidazole
Bismuth Quadruple Therapy for 10-14 days
Macrolides types
- Erythromycin
- Clarithromycin
- Azithromycin
Macrolides MOA
inhibit bacterial synthesis
Macrolides AE
- GI upset
- acute cholestatic hepatitis-> fever, jaundice, imparied liver fxn
- Prolonged QT interval- effect potassium ion channels
- hearing loss and exacerbation of Myasthenia Gravis
Macrolides MOR
- Target site modification by methylation or mutation= prevents binding of ab to its ribosomal target
- Efflux via active pumping
- Inactivation via enzymatic process
Erythromycin clinical indications
- conjunctivitis/Pneumonia in neonates= Erythromycin ethylsuccinate or estolate
- Off label as Promotility agent for pt with gastroparesis= helps with constipation too
- diptheria
- chlamydia
Azythromycin info
Z pack
- long half life and tissue levels
- short rx course and improved compliance
- avoid antacids
- Doesn’t inhibit CYPS
- Overuse is a problem
some use for Viral too and coincidently feel better @ 5 days
Azythromycin info
Z pack
- long half life and tissue levels
- short rx course and improved compliance
- avoid antacids
- Doesn’t inhibit CYPS
- Overuse is a problem
some use for Viral too and coincidently feel better @ 5 days
Azythromycin indications
- Chancroid (Haemophilus Ducreyi - Gram Neg Bacillus)
- Cat scratch disease (Bartonella Henselae)
- Community Acquired pneumonia- outpatient
- Nongonococcal urethritis
- Cervicitis chlamydia trachomatis
- others= exacerbations of chronic bronchitis, streptococcal pharyngitis
Chancroid- Haemophilus Ducreyi
Gram Negative Bacillus
- STD- painful soft ulcer with erythema surrounding
- Adenitis- unilateral tender matted nodes, overlying erythema
- Men= penile
- women= labia majora (kissing lesions) transfers to other lip
TX: Azythromycin oral single dose or Ceftriaxone IM
Cat scratch disease
lymphadenopathy, mastoiditis?
tx: Azythromycin
CAP- community acquired
STreptococus pneumoniae, mycoplasma pneumoniae
No comorb, no recend ab in 90 days:
* amoxicillin
* Doxycycline
* Macrolide
Duration= treat 5 days
Comorbid of heart disease, kidney
* Macrolid or Doxy PLUS Oral Beta lactam
* monotherapy with Fluoroquinolone
Nongonococcal urethritis and cervicitis chlamydia trachomatis
Azithromycin single dose, safe for prego
Azithromycin warnings
- Potentially fatal irregular heart rhythm- mostly for those with pre existing heart disease
- pyloric stenosis in neonates given azith for pertussis
Clarithromycin
- Initial metab is hepatic but PRIMARY metabolite cleared by kidney= need dosing adjustment for renal failure
- Less GI SE but no sig difference from erythromycin
- higher cost
- highly stable in gastric acid
- same drug interactions as erythromycin= WATCH PROLONGED QT
Indications:
* mycobacterium avium complex- mac
* CAP
* Acute exacerbation of chronic bronchitis
Clarithromycin BLACK BOX WARNING
*heart disease= potential increased risk of heart problems or death that can occur years later
Macrolides Drug interactions
Erythromycin and Clarithromycin inhibit CYP3A4-> may increase conc of many drugs such as
* alfentanil and sufentanil
* Oral anticoagulants- warfarin
* glibenclamide
* Azithromycin not reported to have significant interactions
Clindamycin
lincomycin derivative
spectrum: strep, staph, pneumococcus, anaerobes
DO NOT PENETRATE GRAM NEG ORGANISMS BC OF OUTER MEM
Indications:
* skin, soft tissue
* with aminoglyc/cephalosporin= penetrating gut wounds, pelvic abscess, septic abortion
* Dental prophylaxis in endocarditis
* MRSA
Chloramphenicol
- Very broad spectrum: + - and anaerobes
- res from special plasmid encoded enzyme= acetyltransferase
- Rare use: rickettsiae, menigococcus, plage
- SE: BM suppression, aplastic anemia, Gray baby syndrome- drug accum lead to cardiovascular collapse- monitor peak/trough levels
- otc in mexico
Linezolid
bacteriostatic and oxazolidinone
Indications: Pneumonia, skin infections, mrsa- reserve for multidrug res
SE: thrombocytopenia, neutropenia, peripherla and optic neuropathy
SEROTONIN SYNDROME->avoid tyramine= weak monomine oxidase inhibitor
No renal adjustment needed
tyramine is a monamine compound and acts as a catecholaine releasing agent
* cured meats, chocolate, beer, most cheese, fava beans, snow peas, avocados, bananas, pineapples, plums, raspberries
linezolid inhibits both forms of monamine oxidase
Nitrofurantoid
UTI
Metab: liver 75% and 25% urine
Indications: UTI, prophylaxis for recurrect UTI (simple cystitis)
pseudomonas and proteus resistance
SE: GI, Caution iwth G6PD and elderly with pulmonary fibrosis
Mupirocin
topicals
topical: cream, ointment, intranasal- not in us
Indications:
* impetigo
* surgical prophylaxis in MRSA carriers
* Elimination of MRSA colonization
AE: burning/stinging, rhinitis, headache
MOA: inhibition of protein synthesis
COVERS BOTH STAPH AUREUS AND STREP PYOGENES, MOST STREP
Bacitracin
topical
used for PRevention of disease
Usually with neomycin and/or polymyxin B= neomycin is very sensitizing topically= allergic reaction so dont use unless need it
MOA: inhibits cell wall synth
Targets= +
clean area and apply small amount
Acne Vulgaris
very common
Disorder of pilosebaceous unit
abn desquamation of keratinocytes lining sebaeous follicle= microplug
increase in circulating androgens stim the production of sebum into unit
favorable for colonization of Cutibacterium acnes
C. acnes-> stim t cells and mac-> inflamm and chemotactic factors-> local inflam and induce keratinocyte hyperprolif
can effect any age
Lifestyle tx of acne
- wash your face
- friction and trauma from headbands/straps
- application of comedogenic topical agents
- chronic exposure to certain industrial compounds
- Steroids (topicl, systemic) or PCOS bc tx will solve
- other meds: lithium, isoniazid
- low glycemic diet
Acne tx overview
- Comedonal acne
* topical retinoids
* benzoyl peroxide - Papular or Cystic inflammatory acne
* topicals clindamycin phosphate and erythromycin with benzyl peroxide
* oral ab- tetracyclines, tmp-smz, cephalosporins - Severe acne
* isotretinoin
* intralesional injection of triamcinolone acetonide
Tretinoin
acne tx
what is it? vitamin A derivative= mods epithelial growht and diff
Prego safe? NO, TETRAGENIC EFFECTS IN PREGO
Peds? OK in 8 yoa and up
SE?- Dryness, redness, swelling, blisters, warmth
Strengths? adapalene to tretinoin
Patient Education: may flare be4 clinical different in 4 weeks, may start 1-2 times weekly and work up to nightly use to tolerate
Benzyl peroxide
acne tx
how does it work? releases free radical oxygen which oxidized bacterial proteins in sebaceous follicles decreasing number of anaerobic bacteria and decreasing irritating type FA
warnings= bleaching effects
SE: dryness, irritation, itching, peeling, may be combined
bleaches sheets
Tx for Comedonal acne
- Topical retinoids: Tretinoin, can flare
- Benzoyl Peroxide- OTC
Topical antibiotics
topical clindamycin and erythromycin is combined with benzyl peroxide in order to prevent development of bacterial resistance
Papular or cystic inflammatory acne
resistant to topicla therapy with retinoids or benzoyl peroxide
mild acne: topical antibiotics-> erythromycin or clindamycin
Moderate acne: oral-> Doxycycline or mInocycline or TMP-SMX
Isotretinoin
Acutane
most clearing, quickest, not come back
SEVER ACNE:
MOA: vitamin A analog
Contraindications: PREGO CAT X, BREASTFEEDING
AE: Dry, photosensitive
Monitoring: CMP and lipids, PREGNANCY EVERY TIME
TWO FORMS OF BIRTH CONTROL MUST BE USED
ENROLLED IN MONITORING PROGRAM IPLEDGE
Clincal spectrum of acne
comedonal acne
neonatal acne
rhinophyma
acne rosacea
acne conglobata
Hormonal Acne tx
- Spironolactone
* MOA: decreases testosterone production - OCP-
* estrogen containing cpc
