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Pharma > FINALS: Anti Infective Drugs (p1) > Flashcards

FINALS: Anti Infective Drugs (p1) Flashcards

1
Q

What are the main components of the bacterial cell envelope?

A

Membranes, proteins, and other structures surrounding the cytoplasm.

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2
Q

What are the stages of bacterial cell wall biosynthesis?

A

Assembly: Formation of MurNAc and GlcNAc.
Transport: Movement of peptidoglycan units by bactoprenol.
Transglycosylation: Linking peptidoglycan units into chains.
Polymerization: Cross-linking to form two-dimensional sheets.

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2
Q

What are the targets for antibiotic agents in bacteria?

A

Cell walls and cell membranes.

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2
Q

How do beta-lactam antibiotics affect bacteria?

A

They are generally bactericidal and most effective against rapidly dividing bacteria, causing swelling, bursting, filamentation, or cessation of viability.

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2
Q

What happens during the cross-linking reaction in cell wall biosynthesis?

A

The transpeptidase displaces the final D-alanine from the D-ala-D-ala terminus, forming an acyl enzyme intermediate, which couples with the free amino group of the third residue (L-lysine) of an adjacent chain.

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2
Q

What are first-generation cephalosporins active against?

A

Gram-positive cocci (pneumococci, streptococci, staphylococci), E. coli, Klebsiella pneumoniae, and Proteus mirabilis.

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3
Q

What are the mechanisms of resistance to beta-lactam antibiotics?

A

Inactivation by beta-lactamases.
Modification of PBPs.
Impaired drug penetration (especially in gram-negative species).
Efflux pumps.

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3
Q

What types of penicillin are resistant to destruction by most beta-lactamases?

A

Penicillinase-resistant penicillins like oxacillin, cloxacillin, nafcillin, and dicloxacillin.

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3
Q

Name some first-generation cephalosporins.

A

Cefadroxil, Cefazolin, Cephalexin, Cephalothin, Cephradine, Cephapirin, Cephaloridine.

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3
Q

What are the pharmacokinetics of penicillins like dicloxacillin, ampicillin, and amoxicillin?

A

They are acid-stable and relatively well absorbed.
Nafcillin has erratic absorption and is not used orally.
Food impairs absorption (except for amoxicillin), so they should be given 1-2 hours before or after meals.

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3
Q

What organisms are resistant to first-generation cephalosporins?

A

MRSA, Pseudomonas aeruginosa, indole-positive Proteus, Enterobacter, Serratia marcescens, Citrobacter, Acinetobacter, and anaerobes like Bacteroides fragilis.

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3
Q

What is the role of beta-lactamase inhibitors like clavulanic acid, sulbactam, and tazobactam?

A

They inactivate beta-lactamases and extend the antibacterial activity of penicillins.

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4
Q

What are second-generation cephalosporins active against?

A

They have broader activity than first-generation cephalosporins and include drugs like Cefaclor, Cefuroxime, and Cefoxitin.

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4
Q

What are some adverse effects specific to certain penicillins?

A

Procaine Pen G: Pulmonary embolism and acute psychotic reactions.
Oxacillin, Nafcillin: Hepatitis and granulocytopenia.
Pen G Na: Hypernatremia, hyperkalemia, and Jarisch-Herxheimer reaction.
Ampicillin: Pseudomembranous colitis.

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4
Q

What is the clinical use of Cefazolin, a first-generation cephalosporin?

A

It is the drug of choice for surgical prophylaxis and for streptococcal and staphylococcal infections requiring intravenous therapy. It does not penetrate the CNS, so it cannot treat meningitis.

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4
Q

What are the second-generation cephalosporins?

A

Cefaclor, Cefamandole, Cefonicid, Cefuroxime, Cefprozil, Loracarbef, Ceforanide, and the cephamycins like Cefoxitin, Cefmetazole, and Cefotetan.

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4
Q

What is the function of efflux pumps in bacterial resistance to beta-lactam antibiotics?

A

Efflux pumps in gram-negative bacteria transport beta-lactam antibiotics from the periplasmic space back across the outer membrane, reducing the drug’s effectiveness.

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4
Q

What is the mechanism of action for beta-lactam antibiotics?

A

They inhibit bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), preventing the cross-linking of peptidoglycan chains, which leads to bacterial cell lysis.

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5
Q

What are the adverse effects of penicillins?

A

Hypersensitivity reactions.
Seizures following rapid IV administration.
Nerve dysfunction with accidental injection into the sciatic nerve.
Superinfection and hepatitis with chronic use.
Gastrointestinal upset (nausea, vomiting, diarrhea).

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5
Q

What are the four types of penicillin based on their spectrum of activity?

A

Natural penicillins (e.g., Penicillin G, Penicillin V).
Aminopenicillins (e.g., Amoxicillin, Ampicillin).
Penicillinase-resistant penicillins (e.g., Oxacillin, Dicloxacillin).
Antipseudomonal penicillins (e.g., Ticarcillin, Piperacillin).

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5
Q

Which penicillins are preferred for the treatment of severe systemic staphylococcal infections?

A

Oxacillin and Nafcillin, typically administered via IV infusion.

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5
Q

What are the pharmacokinetics of Penicillin G?

A

Penicillin G is administered intravenously (IV) due to poor oral absorption and is rapidly excreted by the kidneys. Dose adjustments are necessary in cases of renal insufficiency.

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5
Q

What second-generation cephalosporin is particularly effective against anaerobes?

A

Cefoxitin, a cephamycin, is effective against anaerobes and is used in certain abdominal infections.

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6
Q

What are beta-lactamase inhibitors, and how do they work?

A

Beta-lactamase inhibitors (e.g., Clavulanic acid, Sulbactam, Tazobactam) resemble beta-lactam molecules and inactivate beta-lactamases, preventing the destruction of beta-lactam antibiotics and extending their spectrum of activity.

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6
Q

What are some adverse effects specific to Methicillin?

A

Methicillin can cause interstitial nephritis, a serious kidney inflammation.

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6
Q

What is the role of PBP modification in bacterial resistance to beta-lactam antibiotics?

A

Modified PBPs have low affinity for beta-lactam antibiotics, leading to resistance in organisms like methicillin-resistant Staphylococcus aureus (MRSA) and penicillin-resistant pneumococci.

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7
Q

What adverse effect is associated with Ceftriaxone in neonates?

A

Ceftriaxone has a high affinity to serum albumin, potentially displacing bilirubin, which can cause jaundice in neonates.

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7
Q

Which cephalosporin is the drug of choice for gonorrhea and severe Lyme disease?

A

Ceftriaxone is the drug of choice for all forms of gonorrhea and severe forms of Lyme disease.

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7
Q

What organisms are second-generation cephalosporins active against?

A

Second-generation cephalosporins are active against organisms inhibited by first-generation drugs, extended gram-negative coverage, and β-lactamase-producing H. influenzae and Moraxella catarrhalis.

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7
Q

What is the clinical use of Cefoxitin and Cefotetan?

A

Cefoxitin and Cefotetan are used for mixed anaerobic infections like peritonitis, diverticulitis, and pelvic inflammatory disease.

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8
Q

Which cephalosporins are anti-pseudomonal?

A

Ceftazidime (3rd generation), Cefepime (4th generation), Ceftazidime/avibactam, Ceftolozane/tazobactam, and Cefiderocol are anti-pseudomonal cephalosporins.

8
Q

What is the mechanism of action for Vancomycin?

A

Vancomycin inhibits the transglycosylase enzyme, preventing the elongation and cross-linking of peptidoglycan, weakening the bacterial cell wall, and leading to cell lysis.

9
Q

Which cephalosporins are safe for use in pregnancy for treating UTIs?

A

fosfomycin, approved for a single 3g dose, is safe for use in pregnancy for treating uncomplicated lower urinary tract infections in women.

10
Q

How does Bacitracin inhibit bacterial growth?

A

Bacitracin interferes with the dephosphorylation and recycling of the lipid carrier involved in moving the peptidoglycan precursors through the cell membrane.

10
Q

What are the main adverse effects of Imipenem?

A

Imipenem can cause nausea, vomiting, diarrhea, skin rashes, reactions at infusion sites, and high levels in patients with renal failure may lead to seizures.

11
Q

What class of drug is Aztreonam, and what is its spectrum of activity?

A

Aztreonam is a monobactam and is active against aerobic gram-negative organisms, including Pseudomonas aeruginosa, but has no activity against gram-positive bacteria or anaerobes.

11
Q

Why is Daptomycin not used to treat pneumonia?

A

Daptomycin should not be used to treat pneumonia because pulmonary surfactant antagonizes its action.

11
Q

What is the mechanism of action of Amphotericin B?

A

Amphotericin B binds to ergosterol in fungal cell membranes, forming pores that disrupt membrane function, leading to leakage of cellular components and cell death.

12
Q

What is the primary clinical use of Bacitracin?

A

Bacitracin is mainly used topically to suppress mixed bacterial flora in surface lesions of the skin, wounds, or mucous membranes.

12
Q

What clinical use is Daptomycin approved for?

A

Daptomycin is approved for the treatment of infections caused by vancomycin-resistant enterococci and Staphylococcus aureus bacteremia.

12
Q

What is the mechanism of action for Fosfomycin?

A

Fosfomycin inhibits the enzyme enolpyruvate transferase, preventing the formation of N-acetylmuramic acid, a precursor of peptidoglycan, thereby interfering with cell wall synthesis.

12
Q

What is the mechanism of action of Daptomycin?

A

Daptomycin binds to the bacterial cell membrane via calcium-dependent insertion of its lipid tail, depolarizing the membrane, and leading to potassium efflux and rapid cell death.

13
Q

What are the most common adverse effects of Amphotericin B?

A

Adverse effects of Amphotericin B include infusion-related reactions (fever, chills, muscle spasms), nephrotoxicity, and electrolyte imbalances like hypokalemia and hypomagnesemia.

13
Q

What are some adverse effects associated with Polymyxin B and Polymyxin E (colistin)?

A

Adverse effects include dose-related nephrotoxicity, neurotoxicity (manifesting as muscle weakness and apnea), and interactions with neuromuscular blocking agents.

13
Q

What adverse effect is associated with the use of azole antifungals like voriconazole?

A

Voriconazole can cause visual disturbances, including blurred vision, photophobia, and altered color perception

13
Q

What is the mechanism of action of Echinocandins like Caspofungin?

A

Echinocandins inhibit the synthesis of β-glucan, an essential component of the fungal cell wall, thereby disrupting cell wall integrity and leading to cell death. What is the clinical use of Caspofungin?

13
Q

What are Polymyxins, and how do they work?

A

Polymyxins are cationic detergents that attach to and disrupt the bacterial cell membranes, particularly in gram-negative bacteria, leading to cell death.

13
Q
A
13
Q

What is Flucytosine’s mechanism of action in antifungal therapy?

A

Flucytosine is converted to 5-fluorouracil (5-FU) inside fungal cells, which then inhibits fungal RNA and DNA synthesis, leading to fungal cell death.

13
Q
A
13
Q

Which antifungal agents inhibit ergosterol synthesis by inhibiting fungal cytochrome P450 enzymes?

A

Which antifungal agents inhibit ergosterol synthesis by inhibiting fungal cytochrome P450 enzymes?

13
Q

What is the clinical use of Caspofungin?

A

Caspofungin is used for the treatment of invasive candidiasis and aspergillosis in patients who are intolerant to or have failed other antifungal therapies.

13
Q

What is the difference between bacteriostatic and bactericidal antibiotics?

A

Bacteriostatic: Inhibits bacterial growth; reversible effect.
Bactericidal: Kills bacteria; irreversible effect.

14
Q

Why should bacteriostatic and bactericidal antibiotics not be given together?

A

Bacteriostatic drugs may antagonize bactericidal antibiotics by halting bacterial replication, which bactericidal agents require for action.

14
Q

What are examples of cell wall synthesis inhibitors?

A

: Penicillins, Cephalosporins, Carbapenems, Vancomycin, Fosfomycin, Bacitracin.

14
Q

What is the mechanism of action for penicillins?

A

They bind to penicillin-binding proteins (PBPs) and inhibit peptidoglycan cross-linking, weakening the bacterial cell wall.

14
Q

What is the mechanism of action of Terbinafine?

A

Terbinafine inhibits the enzyme squalene epoxidase, leading to an accumulation of squalene, which is toxic to fungal cells, and interfering with ergosterol synthesis.

14
Q

What is the spectrum of activity for first-generation cephalosporins?

A

: Active against gram-positive cocci (e.g., Staphylococcus, Streptococcus), and some gram-negative bacteria (E. coli, Klebsiella).

15
Q

Which antibiotic causes Red Man Syndrome and how can it be prevented?

A

Vancomycin causes it. Prevention: Slow infusion rate and premedication with antihistamines.

15
Q

What are the uses of tetracyclines?

A

Rickettsial infections, Chlamydia, H. pylori ulcers, acne.
Doxycycline: Malaria prevention, Lyme disease, MRSA.

16
Q

Name three examples of macrolides.

A

Erythromycin, Azithromycin, Clarithromycin.

16
Q

What is the major adverse effect of tetracyclines in children?

A

Permanent teeth discoloration and bone growth inhibition due to calcium chelation.

17
Q

What infections are treated with macrolides?

A

Respiratory infections (e.g., Mycoplasma, Legionella).
Pertussis, Chlamydia, and H. pylori-induced peptic ulcers (Clarithromycin).

18
Q

What is the primary mechanism of aminoglycosides?

A

They bind to the 30S ribosomal subunit, causing mRNA misreading and inhibiting protein synthesis.

19
Q

What are common adverse effects of aminoglycosides?

A

Ototoxicity (hearing loss).
Nephrotoxicity (acute tubular necrosis).

20
Q

What is the main use of clindamycin?

A

Treats anaerobic infections (e.g., Bacteroides).
Used as a backup for MRSA and prophylaxis for endocarditis in penicillin-allergic patients.

20
Q

What mechanism allows bacteria to resist beta-lactam antibiotics?

A

Production of beta-lactamases, which hydrolyze the beta-lactam ring.

21
Q

What are the treatments for MRSA?

A

Vancomycin, Linezolid, Daptomycin, Tigecycline, Ceftaroline, Doxycycline.

22
Q

What are strategies to prevent antibiotic resistance?

A

Targeted therapy, avoiding overuse, and educating patients.

23
Q

Which antibiotics are contraindicated in pregnancy?

A

Aminoglycosides (ototoxicity).
Tetracyclines (bone/tooth effects).
Fluoroquinolones (collagen effects).
Sulfonamides (kernicterus risk).

24
Q

What are the common toxicities associated with chloramphenicol?

A

Aplastic anemia, Gray Baby Syndrome, and bone marrow suppression.

25
Q

Which antibiotics treat vancomycin-resistant enterococci (VRE)?

A

Linezolid, Daptomycin, Tigecycline, Streptogramins (Quinupristin/Dalfopristin).

26
Q

What is the treatment of choice for pseudomembranous colitis caused by C. difficile?

A

Vancomycin (oral), Metronidazole, or Fidaxomicin.

27
Q
A
28
Q
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