13. Antibiotics Flashcards
• Antibiotic: Any chemical which at ____ attainable blood levels, inhibits the growth of or kills pathogenic microorganisms
○ Usually are from natural sources
○ Don’t want to injure kill the patient/host
• People that make serendipitous discoveries typically due something with the mistake
○ Seen with the discovery of penicillin
therapeutically
• ____: Actively kills the pathogen
○ Are preferred since they depend less on the host ____
○ Advantages of bactericidal over bacteriostatic antibiotics:
§ More ____ –> work better
§ Less dependent on host ____
• ____: Prevents further growth of pathogen
bacteriocidal immune response efficacious mechanisms bacteriostatic
Antibiotic Groupings
• Depending on the antibiotic and bacteria the effects of the antibiotic can be either bactericidal or bacteriostatic
○ Also depends on ____
Bacteriostatic: • \_\_\_\_ • Macrolides: ○ Erythromycin ○ Clarithromycin ○ Azithromycin • \_\_\_\_ • Sulfonamides
Bactericidal: • \_\_\_\_ • Cephalosporins • \_\_\_\_ ○ Good for strict anaerobes or infections that are facultative anaerobes ○ Typically given with a Penicillin –> makes it easier for metronidazole to penetrate the cell wall ○ Metronidazole then can fragment \_\_\_\_ • Quinolones –> Ciprofloxacin • \_\_\_\_
Rules for combining multiple antibiotics:
1. \_\_\_\_ Effect: Static + Static (1 + 1=2 ) 2. \_\_\_\_ Effect: Cidal + Cidal (1 + 1 > 2) 3. \_\_\_\_ Effect: Static + Cidal (1 + 1 < 2) • Odontogenic Infections: Require two different \_\_\_\_ antibiotics with different mechanisms
dose
tetracyclines
clindamycin
penicillin
metronidazole
bacterial DNA
aminoglycosides
additive
synergistic
antagnoistic
bactericidal
• Selective Toxicity: The antibiotics should be harmful to the pathogens but ____ to the host
○ No drug is completely innocuous to everyone, all drugs have potential ____
innocuous
side effects
Selective Toxicity
1. Cell Membrane Synthesis Inhibitors (____)
○ Bactericidal mechanism that targets ____ only found in bacterial membranes!
§ Will be given as a rinse or paste –> very polar so little gets absorbed into the blood
1. ____
2. Amphotericin B: Given via ____ only when there are life threatening fungal infections (HIV patients!)
§ Has some potential to be toxic to the liver
3. ____: Will target cell membranes if it gets into the blood
§ Targets ergosterol which is similar to cholesterol –> drug might accidentally target human cells that contain cholesterol
2. Protein Synthesis Inhibitors 30S (Lower level of selective toxicity) (\_\_\_\_) ○ Bacteriostatic 1. Aminoglycosides: Large polar molecules that are given via IV during life-threatening Gram \_\_\_\_ infections § Have a low \_\_\_\_ –> Can damage kidneys and cause ringing of the ears □ Typically prescribed or given in a hospital § 3D structures resembles curare –> can block \_\_\_\_ receptors due to structure! 2. \_\_\_\_
bacteriocidal ergosterol nystatin IV vancomycin
bacteriostatic
negative
therapeutic index
nicotininc M cholinergic
tetracyclines
- Protein Synthesis Inhibitors 50S (Lower level of selective toxicity) (____)
○ Bacteriostatic
1. ____
2. Clindamycin: Preferred over Erythromycin since it’s good against ____ infections (PA lesions/abscesses) and better at targeting ____- DNA Synthesis Inhibitors (____ )
- ____ : Fragments DNA
§ Typically given with Penicillin where the Penicillin allows it to penetrate the cell walls
§ Good against strict anaerobes, but not ____ anaerobes - Quinolones: Inhibit DNA ____ that are used to ease super-coiling, thus preventing the uncoiling of DNA
§ Good against facultative anaerobes, but not ____ anaerobes (opposite of Metronidazole) - ____: Given to fight TB or leprosy and is a CYP3A4 inducer (will degrade drugs like Warfarin or oral contraceptives as a result –> can get pregnant)
- Sulfonamides: Inhibits the synthesis of ____ from PABA (Para amino benzoic acid) and are used in the treatment of UTIs and opportunistic infections in AIDs patients
§ Most oral bacteria are ____ to Sulfonamides
§ Bacteria make Folic Acid, humans must consume it –> ____ Toxicity
§ If given a local ____ –> can increase the [Sulfonamides] as a byproduct
Why you don’t give people esters anymore like Procaine (Novocain
- ____ : Fragments DNA
- DNA Synthesis Inhibitors (____ )
bacteriostatic
erythromycin
bone
anaerobes
bacteriocidal metronidazole facultative gyrase/topoisomerase strict rifampin folic acid resistant selective anesthetic
Rifampin & Oral Contraceptives
• Breakthrough \_\_\_\_ –> Ovulation • 38/51 women on concomitant oral contraceptive therapy experience breakthrough bleeds • 68/88 women on concomitant oral contraceptive therapy experience breakthrough bleeds and resulted in 5 pregnancies • 76% of all alleged antibiotic/oral contraceptive interactions involve Rifampin • When taken off of Rifampin for a month –> oral contraceptive blood levels double ○ Confirmed with 99% significance
YAY
bleeds
- Rifampin is involved in many drug reactions and can decrease the blood levels of many drugs
- ____: Anticholinesterase used to treat Parkinson’s Disease
- *= drugs used in dentistry
tacrine
Antibiotic & Oral Contraceptive Controversy
• Rifampin reduces oral contraceptive blood levels via enzyme \_\_\_\_ • Reports with all other antibiotics are \_\_\_\_ (should be studied) • NEVER scientifically documented for \_\_\_\_ antibiotics • Normal oral contraceptive failure rates are between 1-3% ○ 4-8% failure rate for teens in the US due to non-compliance –> must miss a couple of pills
inducer
anecdotal
dental
• Estrogen and Progestin doses in oral contraceptives have been decreasing over the years
○ Estrogen + Smoking –> increased risk of thrombus formation since Estrogen inhibits ____
§ Increased risk of pulmonary embolism and stroke
• If you’ve been on oral contraceptives for 8+ years there has been shown to be a 20-30% increased risk of acquiring ____
anti-thrombin III
breast cancer
• 60-70% of oral surgeons will prescribe antibiotics before, during, or after impacted ____ molar extraction
○ People aren’t really at high risk for dangerous infections, the infections can be controlled and treated rather easily
third
Enterohepatic Recirculation Theory
• EE: Ethylene estradiol in oral contraceptives ○ Oral contraceptives target the Pituitary and Hypothalamus • Believed that \_\_\_\_ or \_\_\_\_ is added to EE inactivating the molecules ○ Believed normal \_\_\_\_ will cleave the Glucuronic Acid or Sulfate allowing EE to dissolve into the blood to the Pituitary or Hypothalamus ○ Once on antibiotics the normal flora is \_\_\_\_ resulting in improper removal of Glucuronic Acid or Sulfate from EE –> vulnerable to pregnancy
glucuronidation
sulfate
flora
inhibited
• ____ are prescribed at a much higher rate than anticonvulsants
○ Meaning the number of pregnancies while on ____ is rather alarming
antibiotics
anticonvulsants
• Doxycycline is a major drug that Periodontists use that is ____ spectrum
○ No change in ____ & progestin blood levels before or after taking Doxycycline
• Low N however (low amount of people tested)
○ Medically and legally must tell them about the very low chance of them becoming pregnant
○ Still take oral contraceptives and use condoms
§ Include this in the chart to prevent yourself from getting sued
broad
estrogen
• Tetracycline is ____ spectrum
○ Slight drop in oral contraceptive blood levels after one day but they rise again
• Broad spectrum antibiotics are more likely to eliminate the normal ____
• Low N however (low amount of people tested)
○ Medically and legally must tell them about the very low chance of them becoming pregnant
○ Still take oral contraceptives and use condoms
§ Include this in the chart to prevent yourself from getting sued
broad
flora
• Ampicillin is similar to amoxicillin
○ Amoxicillin has better ____ stability and less likely to be degraded by stomach acid
○ 6-7% decrease in oral contraceptive blood levels
• Low N however (low amount of people tested)
○ Medically and legally must tell them about the very low chance of them becoming pregnant
○ Still take oral contraceptives and use condoms
§ Include this in the chart to prevent yourself from getting sued
acid
• Metronidazole showed essentially no difference in ____ blood levels
• Low N however (low amount of people tested)
○ Medically and legally must tell them about the very low chance of them becoming pregnant
○ Still take oral contraceptives and use condoms
§ Include this in the chart to prevent yourself from getting sued
oral contraceptive
• Spectrum: The range of pathogenic organisms against which an antibiotic is active
○ Broad vs narrow spectrum
• Principle: Use the ____ spectrum antibiotic directed against the specific pathogen
○ Want to use this especially when working with ____ infections
§ Penicillins and Amoxicillins are great
§ Mainly dealing with staph and some anaerobes
narrowest
odontogenic
Problems with Broader Spectrum Antibiotics • \_\_\_\_ complaints • \_\_\_\_ • Superinfections: ○ \_\_\_\_ overgrowths ○ \_\_\_\_ (C dificle) § Resistant to \_\_\_\_
GI diarrhea candida pseudomembranous colitis antibiotics
Penicillins I
• Mechanism –> Inhibition of ____ synthesis
○ ____ against actively growing cells
○ Most are inactivated by ____ (β-lactamase)
• Elimination –> Kidney remains unchanged
• Toxicity –> Low especially with ____ (narrow spectrum)
• Βeta-lactam ring:
○ Cleaved by:
§ Low ____
§ ____
cell wall bacteriocidal penicillinase penicillin V pH penicillinases
Penicillin Subclasses
• Narrow spectrum: ○ \_\_\_\_: Benzyl penicillin § First one discovered and \_\_\_\_ (destroyed by stomach acid) □ Given \_\_\_\_ as a result ○ \_\_\_\_: Phenoxy methyl penicillin § More acid stable and taken \_\_\_\_
• Broad spectrum: ○ \_\_\_\_ (Omnipen ®) ○ \_\_\_\_ (Trimox ®, Amoxil ®) § More superinfections than compared to Penicillin V which is narrow spectrum § Drug of choice for dentists replacing Penicillin V: □ Longer \_\_\_\_ than Penicillin V and given every 8 hours (taken 3 times a day) □ Used for infective \_\_\_\_ • Broadest spectrum: ○ \_\_\_\_ (Geopen ®) ○ \_\_\_\_ (Ticar ®) ○ Used for people who have suffered from burns to prevent \_\_\_\_ infections
• Penicillinase Resistant: ○ \_\_\_\_ (Staphcillin ®) § \_\_\_\_ is resistant to this ○ \_\_\_\_ (Bactocil ®) § Other "oxa" penicillins
penicillin G acid labile IM penicillin V orally
ampicillin amoxicillin half-life endocarditis carbencillin ticarcillin pseudomonas methicillin MRSA oxacillin
Narrow Spectrum Penicillins
• Penicillin G ○ Acid \_\_\_\_ –> resistant to corrosion via acid ○ Unpredictable oral absorption § Typically given \_\_\_\_ or IV ○ \_\_\_\_ or Benzathine suspensions –> Extended duration preparations (300K-600K U/mL) § Divide by 1,598 to get mg • Penicillin V (Pen VK ®) ○ Acid \_\_\_\_ ○ Better \_\_\_\_ absorption ○ Drug of choice for mild/moderate \_\_\_\_ infections
labile
IM
procaine
stabile
oral
odontogenic
Bacterial Susceptibility: Penicillin G and V
• Most important thing to do during dental infections is to remove the source of the infection • Gram positive bacteria: ○ \_\_\_\_ ○ Non-\_\_\_\_ producing Staphylococci § Typically in more immune resistant people • Gram negative cocci: ○ \_\_\_\_ • Some anaerobes: ○ \_\_\_\_ ○ Porphyromonas
streptococci
penicillinase
neisseria
fusobacterium
Dosing of Penicillin V
• Adult: ○ \_\_\_\_mg every 6 hours every 7-10 days ○ 1,000mg stat for more severe infections § Loading dose • Child ○ \_\_\_\_mg/lb ○ Every 6 hours for 7-10 days • Try to take it an hour or 2 \_\_\_\_ meals
500
3-6
after
Broad Spectrum Penicillins
• Medical indications: ○ \_\_\_\_ (Urinary Tract Infections) ○ URI (Upper Respiratory Tract Infections) ○ \_\_\_\_ infections • Less effective than Penicillin V against \_\_\_\_ ○ More effective than Penicillin V against \_\_\_\_ and bacilli • Ampicillin (Amcill ®, Omnipen ®): Erratic \_\_\_\_ absorption • Amoxicillin (Amoxil ®, Trimox ®): Well absorbed by the \_\_\_\_ ○ Drug of choice for infective endocarditis prophylaxis (2 grams) § Don't need to take as frequently as Penicillin V ○ Penicillin V is still the drug of choice for most \_\_\_\_ infections § Amoxicillin has more adverse drug reactions than Penicillin V because of its \_\_\_\_ spectrum ○ Neither Amoxicillin or Penicillin V are effective in infections harboring \_\_\_\_ producing pathogens
UT gonococcal gram positive cocci oral mouth odontogenic broader penicillinase
Extending the Spectrum of Amoxicillin
• Combine Amoxicillin with \_\_\_\_ and related compound sublactam to target penicillinase producing bacteria • On its own Clavulanic Acid lacks any effects ○ Resembles a \_\_\_\_ ring of Penicillins and are targeted instead of Amoxicillin § Clavulanic Acids are β-lactam inhibitors • Reserved for specialized instances (\_\_\_\_ infections) or when a culture and sensitivity dictates its use
clavulanic acid
beta-lactam
maxillary sinus
Broadest Spectrum Penicillins
• Medical indications: ○ Serious Gram Negative infections: § \_\_\_\_ –> seen in burn victims § Proteus § \_\_\_\_ fragilis infections possibly in bone • UTI and \_\_\_\_ infections • Inactivated by β-lactamases • Includes: ○ \_\_\_\_ ○ \_\_\_\_
pseudomonas bacteroides GI carbenicillin ticarcillin
Penicillinase Resistant Penicillins
• Sole indications: ○ Infections harboring penicillinase producing pathogens § \_\_\_\_ and some Gram Negative \_\_\_\_ • Less \_\_\_\_ than Penicillin V against Streptococci and other organisms typically found in odontogenic infections • \_\_\_\_ (Staphcillin ®): Poor oral absorption and nephrotoxic ○ Targets Staphylococcus • Oxa, Cloxa, Dicloxa, Floxa -\_\_\_\_ –> better \_\_\_\_ absorption ○ Bactocil ® –> target \_\_\_\_ ○ Prostaphlin ® –> targets \_\_\_\_
staphylococcus aureus bacilli active methicillin cillins oral bacteriodes staphylococcus
Staphylococcal Strain Resistance • ALL: ○ \_\_\_\_ § Including penicillinase resistant ○ Cephalosporins ○ \_\_\_\_ ○ Tetracyclines ○ \_\_\_\_ ○ Clindamycin
penicillins
aminoglycosides
erythromycin
Mechanisms of Resistance
Enzymes that destroy drugs
Done to ____
Decreased cell permeability or increased efflux
Done to ____
Altered antibiotic targets
Done to ____
Change in ribosomal ____ structure
penicillins
tetracyclines
erythromycin 50S
Mechanisms of Resistance Transfer • \_\_\_\_ mutation • Conjugation (“X” rated figure) • \_\_\_\_ • R-factors
sponataneous
plasmids
Penicillin Toxicity
Mild ____ disturbances, Candida overgrowths
____ > Penicillin V
Drug Allergy: Allergic to one, then allergic to ____
o Rash, hives, uticaria
o ____ Sickness
o Anaphylaxis
Incidence: up to 1:10 patients – ____
1:10,000 patients – ____
GI amoxicillin all serum mild anaphylaxis
Drug Allergy or Hypersensitivity
Requires \_\_\_\_ exposure (sensitizing dose) Independent of d\_\_\_\_ Antigen-Antibody Rxn > Mediator release A. \_\_\_\_ B. Complement C. \_\_\_\_ D. Leukotrienes E. \_\_\_\_ Skin/Bronchioles/Cardiovascular System
previous dose histamine heparin PAF, ECF
