Week 9 Flashcards
(159 cards)
1
Q
What is the overall purpose of Beta-Lactam treatment?
A
Prevention and treatment of bacterial infections.
2
Q
By what method is Penicillin administered?
A
Injection
3
Q
By what method are ampicillin, amoxycillin and cephalexin administered?
A
Orally
4
Q
What is the purpose of penicillin binding protein?
A
It creates cross-links within cell walls of bacterial cells therefore giving the cells formation and strength.
5
Q
What are the repeating units of bacterial cell walls?
A
N-acetylglucosamine and N-acetylmuramic acid.
6
Q
Describe the structure of N-acetylmuramic acid subunits.
A
Short peptide chains with 1 proximal L-alanine chain and 2 distal D-alanine chains.
7
Q
Outline the process by which Penicillin inhibits penicillin binding protein.
A
1) PBP binds to peptide side chains and forms cross links with the removal of D alanine from peptide side chains.
2) PBP dissociantes from the cell wall after the cross-links are formed.
3) Penicillin enters the active site of the PBP and reacts with a serine group (a amino acid used in the biosynthesis of proteins).
4) Beta-lactam ring of penicillin is irreversibly opened. Penicillin remains covalent linked to PBP which permanently blocks the active site.
8
Q
Describe the Pharmacokinetic properties of Penicillin G.
A
Acid Labile, widely distributed, rapid renal excretion.
9
Q
What is meant by a drug being acid labile?
A
It is easily destroyed in acidic envrionments.
10
Q
What is the common molecular structure of beta-lactam antibiotics?
A
4 atom ring
11
Q
By what process do beta lactase enzymes brea Beta-lactam rings?
A
Hydrolysis
12
Q
What penicillin type is known as ‘The prototype’?
A
Penicillin G
13
Q
Name a type of acid resistant penicillin.
A
Penicillin V
14
Q
Name a type of penicillin which is resistant to penicillinase.
A
Methicillin
Oxacillin
15
Q
Name some broad spectrum penicillins
A
Amoxicillin
Ampicillin
16
Q
Name some antipseudoma penicillins
A
Aziocillin
Piperacillin
17
Q
What type of antibiotic is Penicillinase?
A
Beta-lactamase
18
Q
What is meant by antibiotics having a broad spectrum?
A
They act on a wide range of disease causing bacteria - may be gram-positive or gram-negative.
19
Q
Describe the resistance of Oxacillin
A
Resistant to Penicilinase
20
Q
What type of bacteria does Oxacillin have an effect on?
A
Gram-positive only
21
Q
Describe the spectrum of Oxacillin
A
Narrow
22
Q
Describe the spectrum of Ampicillin
A
Wide
23
Q
What the of Bactria does Ampicillin have an effect on?
A
Mainly gram-negatives
24
Q
What type of Streptococci caused diseases are Penicillins used to treat?
A
Pneumonia, Meningitis, Pharyngitis, endocarditis, rheumatic fever.
25
What type of infections are caused by Staphylococci and treated by Penicillins?
Skin and wound infections
26
What type of diseases are caused by Costridia and are treated with Penicillin?
Tenatus and Gangrene
27
What type of disease is caused by H.influenzar and is treated by penicillin?
Pneumonia
28
What type of diseases are caused by E.coi and Pseudomonas Enterococci and are treated using Penicillin?
Urinary tract infections (acute only).
29
What are the possible adverse reactions to Penicillin?
Tissue toxicity.
Hypersensitivity.
Immediate anaphylaxis.
30
What is anaphylaxis?
An acute allergic reaction to an antigen.
31
What is the overall purpose of beta-lactam?
Inhibits synthesis of the peptidogycan layer in bacterial cell wall.
32
What is the overall purpose of beta-lactase enzymes?
Break the beta-lactam ring open via hydrolysis.
33
What is Augmentin antibiotic a combination of ?
Clavulanic acid and Amoxycillin
34
In an Augmentin antibiotic, what is the beta-lactam inhibitor?
Clavlanic acid
35
Describe the antibacterial activity of Clavulanic acid
Weak
36
What type of inhibitor is Clavulanic acid on beta-lactam?
Competitive and sometimes irreversible.
37
What is the main purpose of Cephalosporins?
Inhibit synthesis of bacterial cell walls.
38
Which drug do cephalosporins have similar ADME properties to?
Penicillins
39
What are the possible adverse reactions to Cephalosporins?
Hypersensitivity
Thrombophlebitis
Nephrotoxicity
40
What is hypersensitivity?
Un-desirable reactions produced by the immune system.
41
What is thrombphlebitis?
Inflammation of the wall of a vein associated with thrombosis.
42
What is nephrotoxicity?
Kidney damage due to the kidney being exposed to a drug or toxin that causes damage.
43
What is the main benefit of using Cephalosporins over Penicillins?
They have a lower incidence of resistance.
44
How many generations of Cephalosporins exist?
4
45
What causes the different generations of Cephalosporins to be produced?
Modifications of side chains at positions 3 and 7 of the ring.
46
What are 2nd generation Cephalosporins?
Methyl group on the beta-lactam ring is removed.
They have similar structure to generate 1 but are more active against gram negative bacteria
47
What type of bacteria are 2nd generation Cephalosporins most active against?
Gram negative bacteria and Haemophilus influenzas.
48
What are 3rd generation Cephalosporins?
R1 and R2 group changes so they become stable without refrigeration.
Increase activity.
Decreased activity in Gram positive Staphylococci.
49
What are 3rd generation Cephalosorins often used to treat?
CNS infections
50
In wha type of bacteria do 3rd generation Cephalosporins have a reduced effect?
Gram postive Staphylococci
51
What additional feature does 4th generation Cephalosporins have in comparison to the other generations?
Quaternary N-methyl Pyrrolidine at R1
52
Describe the resistance of 4th generation Cephalosporins
Highly resistant to beta-lactase
53
Describe the spectrum of 4th generation Cephalosporins
Wide spectrum for both gram positive an gam negative bacteria
54
Why do 4th generation Cephalosporins have minimal beta-lactamase activity?
There is rapid periplasmic penetration and high penicillin binding protein access.
55
What is the effect of Isoniazid on bacteria
Inhibits cell wall (mycolic acid) synthesis
56
What % of bacterial cell walls is comprised of Mycolic Acid?
40
57
Describe the structure of Mycolic acid
Alpha-alkyl and beta-hydroxyl long chain fatty acids.
58
What is the mycobacterial enzyme?
Peroxidase
59
What does deletion of the peroxidase gene in bacteria cause?
Resistance to mycobacterial infections.
60
What side effects are caused by Isoniazid ?
Peripheral neuropathy and other nervous system issues.
61
What can be used to aid the effects of Isoniazid?
Vitamin B6
62
What is Rifampicin used to treat and how?
Used to treat cancer, tuberculosis and leprosy.
63
How is Rifampicin used to treat Mycobacterium infections?
It binds to RNA polymerase and inhibits bacterial RNA synthesis by inhibits the bacterial DNA dependent RNA polymerase
64
What are the side effects of Riampicin?
Hepatoxicity
65
What is hepatoxicity?
A substance which can be damaging to the liver cells
66
What effect does Chloramphenicol have as an antibiotic protein synthesis inhibitor ?
It binds to the 50s section of the ribosome and inhibits formation of peptide bonds. Affects translation.
67
What effect do Lincosamides have as antibiotic protein synthesis inhibitor?
They bind to the 50s section of ribosomes and inhibit the formation of peptide bonds. Affects translation.
68
What effects do Streptomycin have as antibiotic synthesis protein inhibitors?
Change the shape of the 30s portion of ribosomes and cause the mRNA code to change and be read differently.
Affects translation
69
What effects do Aminoglycosides have as antibiotic protein synthesis inhibitors?
They prevent f-met binding and the formation of the initiation complex during translation.
70
What type of antibiotic is erythromycin?
A macrolide
71
When is Erythromycin often used as an antibiotic treatment?
When people are allergic to penicillin
72
What treatment is often used for people who are allergic to penicillin ?
Erythromycin
73
How does Erythromycin work as an antibiotic inhibitor of protein synthesis?
It causes removal of the tRNA molecules and translocation of the peptide tRNA.
74
How does the synthesis of precursors cause antibiotic inhibition?
Prevents formation of purine and pyrimidine bases.
75
How do inhibitors of DNA replication act as antibiotic resistors?
They prevent the action of bacterial gyrase
76
How do inhibitors of RNA polymerase act as antibiotic inhibitors?
They prevent RNA synthesis and have a higher affinity to bacterial RNA polymerises.
77
What are the different classes of antiviral drug treatments used against HIV?
Enty Inhibitors
Protease Inhibitors
Nucleoside reverse transcriptase inhibitors and nucleotide reverse transcriptase inhibitors.
Non-nucleoside reverse transcriptase inhibitors.
78
How are entry inhibitors used to treat HIV?
They interfere with binding, fusion and entry of HIV to hose cells by blocking one of several targets.
79
How do protease inhibitors work when treating HIV?
Inhibit activity of protease
80
How do nucleoside reverse transcriptase inhibitors work to treat HIV?
Inhibit reverse transcription by incorporation into newly synthesised viral DNA strands as faulty nucleotides.
81
How are non-nucleoside reverse transcriptase inhibitors used to treat HIV?
They inhibit reverse transcriptase by binding to the allosteric site of the enzyme and acting as a non-competitive inhibitor of reverse transcriptase.
82
What is Acyclovir ?
A nucleoside reverse transcriptase inhibitor used to treat Herpes and HIV.
83
What is Acyclovir used to treat?
Herpes and HIV
84
What causes Acyclovir to be a prodrug?
After phosphorylation to acyclovir-GTP, it has a 100x greater affinity for viral polymerase.
85
How does Acyclovir work against Herpes and HIV?
Incorporation into viral DNA causes premature chain- termination and prevents viral replication.
86
What effect does Acyclovir have on HIV-1?
Its progress is delayed.
87
What are the possible mechanisms of antibiotic resistant?
Target site alteration.
Access to target site modification.
Inactivation of antibiotics.
Extrusion.
88
How does target site alteration act as a mechanism of antibiotic resistance?
Target site alteration is used to reduce the affinity of the antibiotic without impairing norma cellular function.
89
How does target site alteration of cell walls occur as a method of antibiotic resistance?
Penicillin binding proteins shit in the amino acid sequence and reduce the affinity for penicillin.
90
How does target site alteration of protein synthesis occur as a method of antibiotic resistance?
The covalent bonding in ribosomes is altered due to changes in the amino acid sequence. This reduces the affinity for Erythromycin and tetreacycline.
91
What effect does access to target side modification have on antibiotic resistance?
Affects the ability of an antibiotic to enter the bacterial cell and gain access to the target site.
92
How is the access to the target site of a bacterial cell altered as a mechanism of antibiotic resistance?
There are alterations to the composition of the bacterial membrane or cell wall which can reduce permeability for an antibiotic.
93
How is the inactivation of antibiotics caused by effecting cell walls?
Occurs as beta-lactamases inactvative penicillin by catalysing lactam ring cleavage.
94
How does inactivation of antibiotics occur due to affecting protein synthesis?
Aminoglycoside modifying enzymes and chloramphenicol transferases prevent disruption of protein synthesis by modifying antibiotic structure.
95
What is extrusion in terms of antibiotics?
Antibiotic enters bacteria, but rapid expulsion lowers cytoplasmic antibiotic concentration.
96
What is meant by specific drug resistance?
Organism resistant to one drug
97
What is multi drug resistance ?
Organisms resistant to more than one drug
98
Define Chemotherapy
The use of drugs to treat disease.
99
Define Antimicrobial
A drug that inhibits growth of microorganisms.
100
Define Antibacterial
Substances used to disinfect non-living surfaces.
101
Define antibiotic
Class of drugs used to treat bacterial infections by producing a microbe, in small amounts, that will inhibit another microbe.
102
Define anti-fungals
A class of drugs used to treat fungal infections.
103
Define antivirals
A class of drugs used to treat viral infections
104
In what year did Fleming discover Penicillin?
1928
105
Which strain of Penicillin did Fleming initially discover?
Peicillium Notatum
106
When were the first clinical trials of Penicillin carried out and by who?
1940 by Howard Florey and Ernst Chain
107
In the first treatment with Penicillin, what was used when the dose of Penicillin ran out?
The patients urine was purified and re-injected.
108
How are antibiotics classified?
By their mechanisms of action, their chemical structure, their spectrum of activity
109
What is meant by the spectrum of an antibiotic ?
The different types of microorganism (from gram-positive to gram-negative) that it can act on.
110
What are the possible target sites for antibiotics?
Inhibition of cell wall synthesis.
Inhibition of protein synthesis.
Inhibition of nucleic acid replication and transcription.
Injury to the plasma membrane.
Inhibition of synthesis of essential metabolites.
111
What are the desirable antimicrobial properties of an antimicrobial?
Selectivity
Broad Spectrum
'Cidal activity
112
What is 'cidal activity?
Kills bacteria without reliance on the patients immune system.
113
What are the desirable pharmacological properties of an antimicrobial?
Non-toxic to the host.
Good tissue distribution.
Low plasma protein binding.
Oral and parenteral dosing forms.
No interference with other drugs.
114
What is meant by the therapeutic index of a drug?
The ratio of the toxic dose and the therapeutic dose.
115
Define therapeutic dose of a antibiotic
The level of antimicrobial required for clinical treatment of a particular infection.
116
Define toxic dose of a antibiotic
The level of antimicrobial at which the antibiotic becomes too toxic for the host.
117
What is meant by antibiotics being bactericidal?
Antibiotics that target bacteria cell wall or membrane or interfere with enzymes have bactericidal activity.
118
What are antibiotics that are bacteriostatic?
They usually target protein synthesis in bacterial cells.
119
Are bactericidal or bacteriostatic drugs generally more effective?
Bactericidal
120
What value is used to determine the effectiveness of an antibiotic?
The MIC (Minimum inhibitory Concentration).
121
What is the MIC (Minimum Inhibitory Concentration) of an antibiotic ?
The west concentration of an antibiotic that prevents growth of the bacterium.
122
Name factors that affect antibiotic concentration.
```
Dose
Route of Administration
Absorption
Extent of Protein Binding
Rate of metabolism
Rate of excretion
```
123
What concentration must an antibiotic have in the body to be effective?
Must have a concentration at the site of infection that is above the MIC of the bacterium it is targeting.
124
In what year was antibiotic inhibition of bacterial cell wall synthesis discovered?
1947
125
Outline the mechanism for antibiotic inhibition of bacterial cell wall synthesis.
Selectively acts on membranes rich in phosphatidlethanolamine.
126
What type of bacteria does the method of antibiotic inhibition of cell wall synthesis work on?
Works on many gram-negative rods but is ineffective against gram-positives.
127
Describe the effectiveness of antibiotics crossing cell membranes.
Very poor
128
Where are antibiotics excreted in the body?
Via the kidneys
129
Describe the distribution properties of antibiotics
Don't distribute very well
130
What locations are antibiotics which inhibit bacterial cell wall synthesis usually used in?
Used in topical locations
131
What are the adverse reactions of antibiotics which inhibit cell wall synthesis?
Nephrotoxicity and Neurotoxicity
132
Outline the mechanism of action of Polymyxin B
After binding Lipopolysaccharides in the outer membrane of gram-negative bacteria, Polymxins disrupt both the outer and inner membranes of bacteria.
133
Why is the hydrophobic tail of Polymyxin B important to inhibiting cell wall synthesis of bacterial cells?
Is causes membrane damage with a detergent-like model of action.
134
Which is the cell wall an ideal target for chemotherapy?
Cell walls are present in bacterial and fungal cells but not in mammalian cells.
135
Where does peptidoglycan precursor formation for bacterial cell wall production occur ?
Inside the cell
136
What inhibitor is used to block peptidoglycan precursor formation when forming bacterial cell walls?
Cycloserine
137
Where in a bacterial cell does transport and peptidoglycan formation occur?
Cell membrane
138
What inhibitor is used to inhibit transport and peptidoglycan formation in bacterial cells?
Bacitracin Vancomycin
139
Where in bacterial cells does cross linking of peptidoglycan chains occur?
Outside the cell
140
What inhibitor is used to inhibit the cross linking of peptidoglycan chains in bacterial cell walls?
Penicillins Cephalosporins
141
What are cycloserine structurally similar to?
D-alanine
142
In what type of organisms is cycloserine found?
Gram positive peptidoglycan tetra peptide
143
What are the clinical uses Cycloserine?
Used in tuberculosis treatment.
144
What is the purpose of Bacitracin in bacterial cells?
It is requires as a carrier during peptidoglycan synthesis.
145
How does Bacitracin create a carrier for bacteria?
Inhibits the dephosphorylation of udecaprenyl phosphate to produce a carrier.
146
Outline the mechanism by which Vancomycin inhibits cell wall production in bacterial cells.
It is a glycopeptide which binds with high affinity D-ala-D-ala terminus of the cell wall precursor units.
This prevents cross-linking and disrupts peptidoglycan synthesis.
147
What type of molecule is Vancomycin?
Glycopeptide
148
Describe the spectrum of Vancomycin
Narrow
149
What are the side effects of Vancomycin as an antibiotic?
It can be Ototoxic
150
What is Ototoxicity?
Toxic to the ear
151
What are the clinical uses of Vancomycin?
Used to treat MRSA
152
How does Vancomycin affect sensitive bacteria?
It binds to 2 D-ala residues on the ends of peptide chains. This prevents the peptide chains from interacting with cell wall cross-linking enzymes. The cell wall strands are synthesises but not cross linked, so the cell walls fall apart.
153
How does Vancomycin affect resistant bacteria?
Vancomycin cannot bind D-lactate residues, peptide chains interact with cell wall cross-linking enzymes and form stable cross-links.
154
What is the structure of beta-lactam?
A 4 membered cyclic amide ring.
155
What are beta-lactam's attached to a 6 membered ring called?
Cephalosporins
156
What are beta-lactam's attached to a 5 membered ring called?
Penicillins or Penems
157
What are beta-lactams attached to no rings called?
Monobactams
158
Why are penicillin binding proteins essential for cellular survival and growth in bacteria?
They create cross links in cell walls.
159
How can Penicillin binding proteins be identified?
By the binding of radioactive benzylpenicillin.
