Pharmacology L10 Flashcards
Half of deadly bacterial infections due to 5 pathogens
Staphylococcus aureus
Escherichia coli
Streptococcus pneumoniae
Klebsiella pneumoniae
Pseudomonas aeruginosa
What is colistin
Last resort antibiotics to treat infections caused by multi-drug resistant Gram-negative bacteria
What is Antimicrobial Chemotherapy
Drug treatment of parasitic infections in which the parasites are destroyed or removed without injuring the host
Important microorganisms involved in infectious diseases
Bacteria, Viruses, Protozoa, Fungi, Worms
Potential issues with therapy:
- Drug delivery
- Drug retention
- Correct activity spectrum
- Toxic side effects
- Development of resistance
Increasing concentration of antimicrobial
agent leads to
Toxic side effects
concept of antimicrobial chemotherapy
In order to use chemotherapy successfully, we must look for substances that have an affinity for the parasite cells and have the power of killing them greater than the damage these cells cause to the organism ‘itself’
What performs the final elimination of infection
the human’s body defences
What is penicillin
Typical β-Lactam antibiotic that inhibits the formation of peptidoglycan cross-links in the bacterial cell wall
Bacteria
simple unicellular organisms without nuclear membrane
Fungi
Uni- or multi-cellular eukaryotes with a distinct nucleus
May look like plants, but can not perform photosynthesis
Protozoa
Unicellular eukaryotic microbes, amoebae
Viruses
DNA or RNA with protein coat structures; not cells
Helminths
Parasitic worms (flatworms or roundworms); multi-cellular
animal parasites - not strictly microorganisms
What are cancer cells
Host cells that have become malignant, thus ‘parasitic/foreign’ with respect to normal cellular control processe
Examples of Bacteria
- Gram-positive cocci, e.g. Staphylococcus
- Gram-negative cocci, e.g. Neisseria
- Gram-positive rods, e.g. Clostridium
- Gram-negative rods, e.g. Escherichia coli
- Spirochaetes, e.g. Treponema
Examples of viruses
- RNA viruses, e.g. rubella virus
- DNA viruses, e.g. herpes virus
Examples of fungi
Dermatophytes, e.g. tinea organisms
Examples of protozoa
- Plasmodium falciparum
- Pneumocystis carinii
- Entamoeba histolytica
- Leishmania organisms
- Trypanosomes
Examples of helminths
- Worms in alimentary canal, e.g. nematodes
- Worms in tissues, e.g. trematodes
Proper use of antimicrobial drugs:
-Diagnosis
-Removal of barriers to cure (abscesses)
-Necessity of chemotherapy (acute vs chronic infection)
-Selection of appropriate drug
-Combinations of antimicrobials
-Chemoprophylaxis and preemptive suppressive therapy
General problems with antimicrobial drugs:
Opportunistic infection
Allergic reactions
Treatment failure
Opportunistic infection
General suppression of part of normal bacterial flora of patient by antimicrobial
drugs may trigger proliferation of drug-resistant microorganisms in the absence of
proper competition
Treatment failure can include
Resistance to drugs
Wrongly diagnosed infectious organism(s)
Sub-optimal use of drug
Reduced host defenses
Selection of appropriate drug include
- Specificity
- Side effects
- Administration
- Dosage and dosing intervals
- Duration of treatment
- Test for cure
How is an accurate disease diagnosis obtained
- by determining the site of infection
- defining the host (eg, immunocompromised, diabetic, of advanced age)
- establishing, when possible, a microbiological diagnosis
Relationship between humans and microorganisms is affected by factors such as:
Natural distribution of microorganisms
Microbial pathogenicity
Susceptibility to infection
Classification of Antimicrobial Drugs
(i) Mode of action in target organism
(ii) Site of action in target organism
(iii) Type of organism against which they are active
(iv) Spectrum of antimicrobial activity
Mode of action in target organism
- Bacteriostatic: Arrest of bacterial growth
- Bactericidal: Killing of bacteria
Site of action in target organism
- Cell wall
- Cytoplasmic membrane
- Protein synthesis
- Nucleic acid metabolism
Type of organism against which they are active
- Antibacterial drugs
- Antiviral drugs
- Antifungal drugs
- Antiprotozoal drugs
Spectrum of antimicrobial activity
- Narrow-spectrum drug
- Broad-spectrum drug
example of Antibacterial drug, bacteriocidal, narrow-spectrum antibiotic, cell wall target
Penicillins
why are Inhibitors of Cell Wall Synthesis important
since human host cells lack a
cell wall
Cell wall synthesis inhibitors are
BACTERICIDAL on growing or multiplying bacteria!
How does penicillin and cephalosporin inhibit peptidoglycan synthesis
Inhibition of transpeptidation and thus no proper cross-linking of peptidoglycan
How does bacitracin Inhibition peptidoglycan synthesis
Inhibition of regeneration of lipid carrier due to blocking its de-phosphorylation
Parent substance: Penicillin G is obtained from
cultures of mold fungi Penecillium notatum
How does it disrupt cell walls
by inhibiting Transpeptidase
Bactericidal effect of penicillin
Since cell wall prevents rupture of the bacterial plasma membrane from a
high internal osmotic pressure, cell wall defects cause bacterial cells to swell and burst
Potential adverse effects of penicllin G
hypersensitivity,
neurotoxic effects,
anaphylactic shock
Disadvantages of Penicillin G
Cleavage of b-lactam ring by gastric acid
- Cleavage of b-lactam ring by bacterial enzymes (beta-lactamases)
- Narrow anti-bacterial spectrum (mostly against Gram-positive bacteria)
Penicillin derivatives
- Penicillin V
- Oxacillin
- Amoxicillin
- Amoxicillin plus Clavulanic Acid
Penicillin V
Acid resistance
Oxacillin
Penicillinase resistance
Amoxicillin
Extended activity spectrum, including also many gram-negative bacteria
Amoxicillin in combination with Clavulanic Acid
Protection against destruction by penicillinase
why is the Determination of the level of antimicrobial activity important
- Determine which agents are most effective against a particular pathogen of interest
- Estimate the proper therapeutic dose
effectiveness of a chemotherapeutic agent against a pathogen can be obtained
from determining:
(i) MIC Minimal Inhibitory Concentration
(ii) MLC Minimum Lethal Concentration
(i) MIC Minimal Inhibitory Concentration
Lowest concentration of a drug that prevents growth of a particular pathogen
(ii) MLC Minimum Lethal Concentration
- Lowest drug concentration that kills the pathogen
at what MIC do bactericidal drugs kill pathogens
at levels 2-4 times the MIC
at what MIC do bacteristatic drugs kill pathogens
only at much higher concentrations
Two established methods are often used to determine the level of antimicrobial activity:
-Mueller-Hinton broth dilution susceptibility assay
- Kirby-Bauer disk diffusion assay
