Antibiotics Part 1 Flashcards
Sulfonamides include
Sulfamethoxazole-trimethoprim Others: Sulfamethoxazole Sulfisoxazole Sulfadiazine Sulfamethiozole
Mechanism of Action and Drug Effects: Sulfonamides
- Bacteriostatic (inhibits growth of bacteria)
- Inhibits folic acid synthesis (folic acid is required for proper synthesis of purines, a chemical component of nuclei can acids)
- Competitive inhibition (competes with PABA for bacterial enzyme tetrahydropteroic acid synthetase, which incorporates PABA into the folic acid molecule)
Indications for Sulfonamides
Broad spectrum: act against gram (+) and (-)
UTI’s
Respiratory Tract Infections
Pneumocystis Jerovecii (HIV associated pneumonia)
Skin and soft tissue infections
Infections due to Staph or MRSA
Contraindications to Sulfonamides
Allergy to sulfa
Cyclooxyrgenase-2 inhibitor (Celebrex)
Pregnant women at term and infants younger than 2 months
Sulfite so: preservatives in food, wine, injectable drugs.
Chemical components of folic acid
PABA
Adverse Effects of Sulfonamides
Allergic Reaction
Stevens Johnson Syndrome, Renal Damage from crystalluria, Kernicterus (bilirubin deposited in infants)
Delay cutaneous reactions, fever followed by rash
Photosensitive try reaction: skin reaction induced by exposure to sunlight, sunburn
Other: mucocutaneous, GI, hepatic, renal and hematologist complications
Immune mediated: involve production of reactive drug metabolites in the body
Interactions of Sulfonamides
Sulfonylureas, hypoglycemic effects in diabetes treatment
Phenytoin toxic effects
Warfarin anticoagulant effects hemorrhage
(Increased?) likelihood of cyclosporine-induced nephrotoxicity
(Decreased?)efficacy of oral contraceptives
Assessment of Sulfonamides
Drug allergies to sulfa type drugs or sulfites (oral sulfonylureas, thiazides diuretics)
Skin assessment during therapy d/t Stevens-Johnson syndrome
RBC count before therapy d/t possibility of drug related anemias
Renal function d/t potential for drug related crystalluria
Meds and med he for any manifestations of GSPD and slow acetylation.
Implementation of Sulfonamides
Avoid in pts w/ G6PD and slow acetylation
Fluids: 2000-3000 mL/24 hrs to prevent crytalluria
Take w/ food to minimize GI upset
Report: worsening abdominal cramps, stomach pain, diarrhea, blood in urine, severe or worsening rash, SOB, fever
Penicillins (PCNs) are divided into 4 subgroups
- Natural PCNs
- Aminopenicillins
- Penicillinase-resistant PCNs
- Extended spectrum PCNs
Natural PCNs include
Penicillin G and V
Aminopenicillins include
Amoxicillin
Ampicillin
Penicillinase-resistant PCNs include
Nafcillin
Dicloxacillin
Oxacillin
Cloacal lion
Extended spectrum PCNs include
Amoxicillin/clavulanic acid
Ampicillin/sulbactam
Ticarcillin/clavulanic acid
Piperacillin/tazobactam
Mechanism of Action and Drug Effects of PCNs
Bactericidal (kills a wide variety of gram (+) and some (-)
Inhibits cell wall synthesis -> formation of defective cells walls = cell death from lysis
Doesn’t affect human cells
Beta-Lactam Antibiotics have four major subclasses
- Penicillins
- Cephalosporins
- Carbapenems
- Monobactams
Beta-Lactam Antibiotics structure and MOA
Share a common structure and MOA
Inhibits synthesis of bacterial peptidoglycan cell wall.
Beta Lactamase inhibitors are added to
Penicillin AB. Makes drug more powerful against beta Lactamase bacterial strains. (Some bacterial strains produce enzyme: beta lactamase)
Beta Lactamase
Resists these antibiotics by breaking the chemical bond of C and N atoms in structure of beta-lactam ring loss of antibacterial efficacy.
Penicillins were first derived from a
mold (fungus) seen on bread or fruit
Penicillinases
Beta lactamase that inactivates penicillin molecules
Three beta lactamase inhibitors
Cleveland acid
Tazobatam
Sulbactam
Natural Penicillin
Only 2 in clinical use
Pen G: injectable or IV/IM use
Pen V: PO (tablet & liquid)
Penicillinase-resistant drugs
Stable against hydrolysis of staphylococcal Penicillinases
Aminopenicillins
has amino group attached
? activity against gram (-) bacteria compared with natural penicillins
Extended spectrum drugs
Wider spectra of activity compared to all other penicillins
Combos of Penicillin + Beta-lactamase inhibitors
ampi + sulbactam
amoxi + clavulanic acid
ticar + clavulanic acid
pipera + tazobactam
Indications for Penicillins
- to prevent and treat infections caused by gram (+) bacteria (strepto, entero, and staphylo -end coccus
- for prophylaxis (i.e amoxicillin)
- extended spectrum penicillins have gram + and - and anaerobic coverage: used in HAI (pneumonia, intraabdominal infections and sepsis)
Contraindications for Penicillins
drug allergy: very common, incidence (0.7% - 4%)
Adverse Effects of Penicillin
Related to drug allergies/Type 1 hypersensitivity reactions
mostly GI effects such as diarrhea, N/V, taste alterations, oral candidiasis
How does penicillin affect the CNS?
causes lethargy, anxiety, depressions and seizures.
How does penicillin affect hematologic functions?
causes anemia, bone marrow depression and granulocytopenia
How does penicillin affect metabolic functions?
causes hyperkalemia and hypernatremia
alkalosis
How does penicillin affect the skin?
causes pruritus, hives and rash.
What drugs interact w/ penicillins?
Aminoglycosides (IV) and Clavulanic Acid Methotextrate NSAIDs Oral Contraceptives Probenecid Rifampin Warfarin
How does Aminoglycosides and Clavulanic Acid interact with penicillin?
Mechanism: Additive
Result: More effective killing of bacteria
How does Methotrexate interact with penicillins?
Mechanism: ? renal elimination of methotrexate.
Result: ? methotrexate levels
How do NSAIDs interact with penicillins?
Mechanism: Compete for protein binding
Result: More free and active penicillin
How do oral contraceptives interact with penicillins?
Mechanism: uncertain
Result: May ? efficacy of contraceptive
How does probenecid interact with penicillins?
Mechanism: competes for elimination
Result: prolongs effects of penicillins
How does rifampin interact with penicillins?
Mechanism: inhibition
Result: may inhibit the killing activity of penicillins
How does warfarin interact with penicillins?
Mechanism: ? vitamin K from gut flora
Result: enhanced anticoagulant effect of warfarin
Assessment for Penicillin Administration
Determine drug allergies and potential drug interactions
Hx: asthma, allergens, aspirin allergy and sensitivity to cephalosporins
Neuro, abdominal and bowel assessment (electrolyte disturbed, cardiac and renal disease pts.)
Serum Na+ and K+ levels: an ? in levels can exacerbate a patient w/ HF, fluid overload or cardiac dysrhythmias
Don’t always end in cillin; zosyn and augmentin
Implementation of penicillin
Consumption of probiotics: lactobacillus or dairy products (yogurt, buttermilk, kefir)
Oral: 6oz of water, NOT juices
Penicillin V, amoxicillin and amoxicillin-clavulanate: given w/ water 1 hour before or 2 hours after meals
Procaine and Benzathine salt penicillins (thick): give as ordered IM, 21 gauge
Reconstitute IM imipenem/cilastatin in sterile saline w/ plain lidocaine
Anaphylactic Reaction: give epinephrine or other emergency drugs w/ supportive treatment @ all times(O2)
Cephalosporins: First-Generation
cefadroxil
cefazolin
cephalexin
cephradine
Cephalosporins: Second-Generation
cefactor ceforetan cefoxitin cefprozil cefuroxime
Cephalosporins: Third-Generation
cefdinir cefditoren cefixime cefoperazone cefotaxime cefpodoxime ceftazidime ceftibuten ceftizoxime ceftriaxone
Cephalosporins: Fourth-Generation
cefepime
First Generation Cephalosporin drugs
have the most gram (+) coverage, later generations have more gram (-) coverage
Anaerobic coverage is found only in
second generation drugs
Ceftaroline
newest cephalosporin
5th generation
broad spectrum and covers gram + and MRSA
Cephalosporins are NOT active against
fungi and viruses.
Mechanism of Action: Cephalosporin
Bactericidal
Disrupt bacterial cell wall = lysis and death
Depends on generation, level of coverage increases as generation increases.
Cephalosporin Indications
moderate to severe infections and choice of drug depends on pathogens and generation
Contraindications for Cephalosporins
Allergy to cephalosporins and PCNs, renal disease
Adverse Effects of Cephalosporins
similar to PCNs
What drugs interact with cephalosporins?
ethanol
antacids, iron
probenecid
oral contraceptives
How do cephalosporins interact with ethanol?
accumulation of acetaldehyde metabolite ethanol = acute alcohol intolerances after drinking ale, beverage w/in 24 hours of taking cefotetan
symptoms: stomach cramps, N/V diaphoresis, pruritus, headache and hypotension
How do cephalosporins interact with antacids and iron?
? absorption of certain oral cephalosporins (cefdinir, cefditoren) = ? effectiveness of drug
How do cephalosporins interact with probenecid?
? renal excretion = ? cephalosporin levels
How do cephalosporins interact with oral contraceptives?
enhanced OC metabolism = ? risk for unintended pregnancy
First Generation cephalosporins
Active against gram + and limited activity to gram -.
Parenteral and Oral forms
Cefazolin: for surgical prophylaxis and susceptible staphylococcal infections: (P) form
Cephalexin: (O) form
Second Generation Cephalosporins
Active against gram + and enhanced activity of gram -.
P/O forms
Second Generation Cephalosporin: Cefoxitin
-(P) form, used as prophylactic AB in pts undergoing abdominal surgery because it can effectively kill intestinal bacteria
Second Generation Cephalosporin: Cephamycins
coverage of anaerobic bacteria (cefoxitin and cefotetan)
Second Generation Cephalosporin: Cefuroxime
prodrug, doesn’t kill anaerobes, little antibacterial activity until hydrolyzed in liver to its active form. (O) form
Third Generation Cephalosporins
The most potent of the 1st three generations in killing gram - but less active against gram +.
Kills pseudomonas
Third Generation Cephalosporin: Ceftriaxone
-long acting, once a day, treats most infections
-able to pass through blood brain barrier treating meningitis
-(IV/IM) form
NOT given to hyperbilirubinemic neonates or liver dysfunction pts.
Third Generation Cephalosporin: Ceftazidime
difficult to treat infections like pseudomonas.
Fourth Generation Cephalosporins
? activity against enterobacter gram negative and gram positive organisms
Fourth Generation Cephalosporins: Cefepime
treats complicated/uncomplicated UTIs, uncomp. Skin and skin structure infections and pneumonia
Fifth Generation Cephalosporins
newest
adjust dose for ? renal function
injectable form
Fifth Generation Cephalosporin: Ceftaroline
S. aureus MRSA, acute skin and skin structure infections and CAP
Cephalosporin Assessment
Allergies, allergy to penicillin d/t cross sensitivity
Note generation of cephalosporins; different effects
Implementation of Cephalosporins
give w/ food to avoid GI upset
avoid alcohol and alcohol containing products - potential disulfiram like reaction (acute alcohol intolerance)
