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Pharm > Antibiotics, Antiviral, and Antifungal > Flashcards

Antibiotics, Antiviral, and Antifungal Flashcards

1
Q

How do bacteria harm the host?

A

 Divert nutrition away from host, depriving cells of O2 and food
 Elaborate toxic chemicals
 Activate a harmful immune response

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2
Q

Not all bacteria are harmful…

A

 Source of vitamins (K) & essential fatty acids
 Prevent over-growth of harmful bacteria

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3
Q

How the body defends against bugs

A

 Infections are typically “partially controlled” by the
body’s own immune system
 The invading organism gets a “foot hold”, but
can’t flourish, except in overt infections

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4
Q

How do antibiotics works with the body’s immune system

A

 Most antibiotics “tip the scales” in favor of the
immune system
 “slow” bacterial spread and reproduction so immune system can kill it of

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5
Q

Bactericidal

A

kills bacterial D E A D
* Penicillins and Vancomycin

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6
Q

Bacteriostatic

A

Blocks replication of bacteria
* Tetracycline
* Chloramphenicol

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7
Q

In an “immunocompramized patient”, which is the preferred type of antibiotic, a bacteriosidal or a bacteriostatic agent?

A

Bactericidal

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8
Q

Bacteria - Prokaryotes

A
  • Cell wall
  • Cell membrane (unique phospholipids)
  • 60s (larger) ribosome
  • No nuclear membrane
  • Unique mechanism of RNA/DNA synthesis
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9
Q

Human Hosts (Eukaryotes)

A
  • No cell wall
  • Cell membrane (but different phospholipids compared to bacteria)
  • 50s (larger) ribosome
  • Nuclear membrane
  • standard eukaryotic RNA/DNA synthesis
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10
Q

What is selective toxicity

A

 Degree to which the drug impairs/kills invading
organism’s cells compared to the host’s cells –> similar to therapeutic window

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11
Q

When to use Broad spectrum antibiotics:

A

Useful when infection is caused by “unknown”
organism

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12
Q

Broad spectrum antibiotics side effects

A

 Kill off “good” bacteria”
 Predispose to resistance
 Typically strong medications with toxic side effects (except penicillins)

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13
Q

Narrow Spectrum Antibiotics

A

 Specifically target one type of bacteria
 May have better side effect profile
 Less resistance
 Less effect on normal bacteria in and on body

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14
Q

Mechanisms of antibiotic drugs

A

 Cell wall synthesis inhibitors
 Cell membrane inhibitors
 Protein synthesis inhibitors
 Metabolic and nucleic acid (RNA and/or DNA) synthesis inhibitors

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15
Q

Inhibition of Cell wall synthesis and function

A
  • bacteria have a rigid cell wall
  • Drugs targeting the synthesis of bacterial cell wall typically have good selective toxicity
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16
Q

Bacteria have a rigid cell wall -

A

 Key constituent is peptidoglycans
 Peptidoglycans are cross-linked in a way that
provides strength
 Any compromise of bacterial cell architecture
activates a suicide/autolysis pathway

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17
Q

One new antibiotic targets…..

A

bacterial lipid II and III, important precursor molecules for forming the cell wall

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18
Q

Bacterial Cell Wall Inhibitors

A

Beta-Lactam antibiotics
Cephalosporins & Penicillins

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19
Q

What is the first known antibiotic

A

Penicillins

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20
Q

How do penicillins work

A

Binds to a special bacterial cell wall enzyme (penicillin binding protein) used in peptidoglycan synthesis
 Bacteria develop a special enzyme that degrades penicillins (penicillinase)

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21
Q

Naturally occurring penicillins

A

Penicillin G & V
Narrow

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22
Q

Synthetic penicillins

A

Ampicillin & Amoxicillin
Broader

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23
Q

What penicillins have been developed that are resistant to breakdown or are combined with penicillinase-blocker

A

 Augmenten (Amoxicillin plus Clavulate, inhibits breakdown)

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24
Q

Imipenem

A

Relatively narrow spectrum penicillin

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25
Cilastatin
a compound that prevents the excretion of impenem from the kidney, thus trapping it
26
Primaxin
- a combination of Imipenem and Cilastatin that has very broad spectrum antibiotic activity  Active against > 90% of all clinically important bacterial infectious agents  Overcomes resistance in many infectious agents  Acts synergistically with aminoglycside antibiotics
27
Uses of Penicillins
 Still one of the most useful classes of antibiotics  Mainstay of therapy for skin, respiratory, GI infections  Generally well tolerated  Very high therapeutic window
28
Limitations of Penicillins
 Methicillin-resistant S. aureus (MRSA) --> Other beta-lactam resistant strains have also developed  Allergic reactions --> Type II hypersensitivity reactions; Potential for anaphylactic shock and bronchospasm  Prolonged use: CNS & hematological side effects
29
Cephalosporins
Different class, but similar mechanism as penicillins
30
3 generations of drugs within cephalosporins
 1st- narrow, mainly gram +  2nd-broader,gram + & -  3rd-broad against gram -, but no effect on gram +  4th generation, but mainly used in Europe
31
Uses of Cephalosporins
 Drug of choice for UTIs, prophylaxis post-surgery  Alternative or “second line” of defense if penicillin fails
32
1st Generation Cephalosporin
Cefazolin
33
Limitations of Cephalosporins
 Most cephalosporins are well tolerated  Produce type-II hypersensitivity reaction, similar to penicillins  Often there is “Cross-reaction” with penicillins (i.e. if patients is allergic to one, greater chance they are allergic to the other)  Susceptible to resistance if infection is resistant to penicillin (Methicillin)
34
Polymixins
- Bacterial Cell Membrane Inhibitors - Cationic compounds attracted to the bacterial cell phospholipid membrane (more than the host’s cell membrane) - Directly “Punch holes” in the cell membrane layer - Results in connection between inside and outside: creates a “leak” that is fatal - Rapidly lethal to bacteria - Not very selectively toxic (i.e. many adverse/side effects)
35
Vancomycin
- Bacterial Cell Membrane Inhibitors - Reserved for serious life-threatening infections (C-diff, staph, endocarditis) - Ototoxic and nephrotoxic
36
Bacitracin
- Bacterial Cell membranes inhibitors - Useful for STDs and a wife variety of infections, but limited by side effects when given systemically - Used topically for burns and skin infections
37
How to bacterial protein synthesis inhibitors work
 Most bind to bacterial ribosomes  Inhibit polypeptide synthesis or leads to misreading of mRNA  May be bacteriostatic or bactericidal
38
Largest subclass of bacterial protein synthesis inhibitors
Aminoglycosides - very broad spectrum - toxicity problems, monitors liver enzymes
39
Macrolides/Erythromycins
- Bacterial Protein Synthesis Inhibitors - good for gram +’s, but side effects include hepatitis - Bacteriostatic at low dose, bactericidal at high dose
40
Azithromycin
- Macrolides/Erythromycin - ear & respiratory tract infections - Has added benefit of being packaged as a “Z-pack” allowing short duration of Rx
41
Tetracyclines
- Bacterial Protein Synthesis Inhibitors - broad spectrum, in general can’t be taken with Ca foods - Doxycycline (Vibramycin)- broad spectrum bacteriostatic agent
42
Chloramphenicol
- Bacterial Protein Synthesis Inhibitors - Broad spectrum, severe infections
43
Uses and Limitations of Tetracycline
 Useful for hard to Rx infections like Chlamydial and Rickettsia and spirochetes  Limited by development of tetracycline- resistant bacteria strains
44
Ethionamide
- inhibits bacteria protein synthesis - used as a second line of defense to treat tuberculosis or Hansen's disease
45
How do Bacterial RNA/DNA Synthesis Inhibitors work?
 May bind bacterial DNA directly preventing replication or bind to and inhibit enzymes used in replication or transcription  Mainly as “back up” antibiotics (when there is resistance or reaction) or for severe infections
46
Are Bacterial RNA/DNA Synthesis Inhibitors bacteriostatic or bactericidal?
Most are bacteriostatic
47
Characteristics of Bacterial RNA/DNA Synthesis Inhibitors
- low selective toxicity/many side effects - very diverse family - Mainly as "back up" antibiotics (when there is resistance or reaction) or for severe infections
48
RNA/DNA Synthesis Inhibitor Drug
Ciprofloxacin (Cipro): useful for a variety of infections including UTI Class: Floroquinolene: inhibits DNA gyrase, blocking DNA coiling
49
Antibiotic Resistance
- Antimicrobial Resistance is accelerating: MRSA, VRE, MDRSA, MDRTB - New drug development is not keeping pace
50
Solutions to antibiotic resistance
 Eliminating antibiotics from livestock feed  Decreasing use of antibiotics for self-limiting infections  Eliminating use of antibiotics for viral infections
51
Do the matching the antibiotic with the correct cellular mechanism thing
52
Virus mechanisms
 Work by being incorporated into host’s cell DNA and directing their self replication and dispersal  Can be either DNA or RNA based  Usually have a protein coat, but can also have a lipid/glycoprotein envelope
53
How to anti-viral drugs work
by inhibiting the DNA polymerase enzyme
54
Acyclovir (Zovirax)
- Anti-viral - Treats Herpes infection - In infected cell converted to acyclovir triphosphate (ATP) by viral thymidine kinase enzyme - ATP inhibits the DNA polymerase enzyme - ATP is also incorporated into viral DNA strands, further inhibiting function - Only effective in preventing or “limiting” infection… does not kill off dormant virally infected cells
55
Side effects of Acyclovir
impaired renal function hematological GI and CNS disturbances
56
Antivirals to treat AIDS
- Zidovudine - Inhibits the reverse transcriptase enzyme used to convert viral RNA to DNA
57
Saquinavir Mesylate
 Anti-retroviral, protease inhibitor used to Rx AIDS  Prevents cleavage of viral polypeptide such that mature viruses cannot be formed  Used exclusively in advanced HIV infection with low CD4 count  Many side effects including CNS disturbances  N&V and GI problems common  Pancytopenia- may be lethal
58
Terminology for AIDS therapies
 cART = combination antiretroviral therapy  HART = highly active antiretroviral therapy These are synonymous and the specific combination of antiviral drugs differs ** These are synonymous and the specific combination of antiviral drugs differs
59
How many Hepatitis-B medications are out there
7 approved anti-viral drugs for chronic hepatitis B infection
60
Standard therapy for hepatitis B
Interferon - 2b (interferon A)
61
Side effects of hepatitis medications
 Flu-like symptoms: pyrexia, myalgia and headache  Adverse effects Rx with NSAIDS Other AE: dizziness, fatigue, arthralgia, diarrhea, anorexia, neutropenia and leukemia, irritability & depression
62
What does hepatitis b medication result in
clearance of serum HBV DNA in 25% and 63% of patients with HBeAg+ and HBeAg- hepatitis B, respectively
63
Remdesivir
 In October 2020, FDA approved remdesivir to Rx COVID-19 in adults and children > 12 y/o.  Clinical trials suggest remdesivir may modestly speed recovery  Mechanism: nucleoside analog and inhibits the RNA-dependent RNA polymerase of SARS-CoV-2
64
Adverse Effects of Remdesivir
pain, bleeding, bruising of the skin, soreness, or swelling near the place where the medication was injected
65
Fungi
- ubiquitous throughout the soil, water and air… about 100,000 species - normally harmless, but when immune fx is impaired, they may cause pathology
66
Primary fungi infections in humans
Aspergillosis, Blastomycosis, Cryptococcosis and Histoplasmosis
67
What is Mycosis
infections caused by fungi
68
minor fungal infections are typically controlled by...
immune system
69
Amphotericin B
 Most common antifungal agent prescribed (Amphocin)  Useful for Candida and Cryptococcus  Administered by slow IV infusion or by local or topical administration  Binds to fungal cell membrane lipid leading to increased permeability and death  Many side effects including HA, fever, muscle & joint pain, weakness, N&V, nephrotoxicity

Pharm (12 decks)

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