1
Q
Penicillin Drugs
A
- penicillin (G and V)
- amoxycillin
2
Q
Beta Lactam Drugs
A
- Cephalosporin
- Carbapenems
3
Q
Cell Wall Attacking Drugs
A
- Vancomycin
- Bacitracin
4
Q
3 classes of drugs that attack cell wall
A
- penicillin
- beta lactam drugs
- other cell well inhibitors (not penicillin based)
5
Q
Penicillin
A
Mechanism - enters the cell, binds to PBP to inhibit it’s role in strengthening the peptidoglycan layer. Cell lysis.
- penicillin G breaks down in acid
- amoxycillin has a longer half life, has an effect o gram -‘ve bacteria, and has higher bioavailability. Better version of penicillin.
6
Q
What effects the activity of penicillin?
A
porins - improve effect
beta lactamase - inhibit effect
7
Q
Beta lactamase inhibitor
A
clavulanate
mechanism - occupies beta lactamase
8
Q
Cephalosporins
A
structure next to the beta lactamase ring is slightly different than penicillin. Makes it more resistant to beta lactamase.
9
Q
Carbapenems
A
- S in penicillin is changed to C in carbapenems - makes it beta lactamase resistant.
10
Q
Vancomycin
A
inhibits growth/elongation of peptidoglycan strands. Unable to make a rigid structure without long strands. Lysis.
11
Q
Bacitracin
A
works inside the cell (not at the location of the cell wal)) to inhibit cell wall formation
12
Q
Classes of Drugs that inhibit protein synthesis (effect ribosomal subunits)
A
- Chloramphenicol
- Erythromycin
- Aminoglycosides
- Tetracyclines
13
Q
Chloramphenical
A
binds to the 50S sunubit. Inhibits formation of peptide bonds between individual amino acids
- side effects - bone marrow disturbance, gray baby syndrome, serious drug interactions.
14
Q
Erythromycin
A
changes the 30S subunit, causing the mRNA code to be read incorrectly (wrong amino acid)
- unstable in acid
- a macrolide
- used if a penicillin resistance develops.
15
Q
Macrolide Drugs
A
Erythromycin < Clarithromycin < Azithromycin
16
Q
Clarithromycin
A
same effect as erythromycin but can be given orally
17
Q
Azithromycin
A
some effect on gram -‘ve
more potent
greater tissue penetration.
- better drug
18
Q
Aminoglycosides
A
bind 50S subunit - prevents ribosomal movement along mRNA.
- streptomycin, gentamicin
- hexose ring linked to an amino sugar by a glycosidic linkage.
- effective against gram -‘ve
- given via IV
- side effects - ototoxic, nephrotoxic.
19
Q
Aminoglycoside Mechanism (3)
A
- mRNA binds 30S, but 50S doesn’t join.
- miscoding in the polypeptide chain - causes the tRNA to hold the wrong amino acid
- blocks translocation
20
Q
Tetracyclines
A
interfere with the acceptor site
- absorption effected by milk and antacids
- accumulates in bones and teeth.
- shouldn’t be given to pregnant woman or children.
21
Q
Drugs that inhibit DNA Synthesis
A
sulfonamides
trimethoprim
22
Q
Folic acid pathway
A
PABA -(DHPS)-> folate -(DHFR)-> THF -> Purines for DNA
23
Q
Sulfonamide
A
Target and inhibit DHPS
24
Q
Trimethoprims
A
Target and inhibit bacterial DHFR (because DHFR is in human cells too)
25
Other DHFR inhibitors
protozoa - pyrimathamine
| cancer - methotrexate
26
DNA Replication inhibiting Drugs
Fluoroquinolones = fluorinated quinolones = ciprofloxacin
27
Activity of Fluoroquinolones
inhibit DNA gyrase/bacterial topoisomerase activity. DNA can't be uncoiled so it can't be replicated.
28
Problem with fluoroquinolones?
widespread resistance
29
Cell Membrane inhibiting Drugs
Polymyxins
30
Polymyxins
- detergent-like properties.
| - destroy phospholipid membrane by binding to PE in the membrane and cause disruption to the structure.
31
Problem with polymyxins?
also has the same effect on human cells.
| - can only be given topically. Never systemically
32
Common Combination Therapies
- chloramphenicol + aminoglycosides
- beta-lactam drugs + beta lactam inhibitors
- 2 beta lactam drugs that inhibit different PBPs
- sulfonamides and trimethoprims
33
Advantages of Combination Therapy
- wider spectrum
- can give lower doses
- synergism
34
Disadvantages of Combination Therapy
- antagonism
- adverse effects
- increased likelihood of resistance
35
Bacterial Resistance
- decreased entry
- efflux pump
- bypass pathway
- altered target proteins
- enzymes to degrade the drug
36
Examples of Bacterial Resistance
Sulfonamide resistance
| Trimethoprim resistance
37
Sulfonamide Resistance
- decrease membrane permeability
- increased PABA
- change DHPS so it nolonger binds to sulfonamide
38
Trimethoprim Resistance
- decrease membrane permeability
- increase DHFR
- change DHFR so it not longer binds to trimethoprim.
39
Drugs for Fungi
- ketoconazole - oral
- fluconazole - oral
- amphotericin B - IV
40
Fluconazole
inhibits fungal cytochrome P450 -> enzyme involved in making ergosterone
41
Amphotericin B
amphoteric - one end is hydrophilic and the other is hydrophobic. Therefore it happily spans the membrane.
makes pores by binding to ergosterol.
- sometimes binds to cholesterol in humans - super dangerous - nephrotoxicity.
42
Causes of Cancer
Genetics
- oncogenes
- tumor suppressor genes
Environment - most important
43
Cancer Pathophysiology
1) Initiation - 1 cell gets mutated
2) Promotion - proliferation
3) Progression - malignant.
44
3 ways we treat cancer
1) surgery
2) radiation
3) chemotherapy
45
Traditional Cancer Treatments
Alkylating & Platinum Agents - target the DNA molecule itself.
Antimetabolites - target DNA synthesis
Antobiotics and Topoisomerase inhibitors - target transcription
Vinca Alkaloids & Taxanes - target the mitotic spindle.
46
Alkylating & Platinum Agents
alkylating - cyclophosphamide
platinum - cisplatin
mechanism - both bind the DNA strand, are detected as damage and cause DNA molecule death.
Cl is removed and 2 (incorrect) DNA base pairs covalently bind - destroyed.
Negative side effects - can also bind to other similar structures like lipids ad proteins - problematic for other bodily cells.
47
Antimetabolites
Purine antagonists - mercaptopurine
Pyrimidine antagonists - fluorouracil
Folic Acid antagonists - methotrexate
cell cycle specific - S phase drugs.
48
Mercaptopurine
- looks like adenine.
- inserts itself where adenine would bind in DNA and RNA.
- DNA enzymes recognize that DNA is wrong and destroy it.
49
Fluorouracil
- looks like U/T
- binds to thymidylate synthase, preventing thymidine form being made.
- can't make any new DNA
50
Methotrexate
- inhibits cancer cell specific DHFR
| - unable to make new nucleotides.
51
Antibiotic & Topoisomerase Inhibitors
Topoisomerase I inhibitors - topotecan
Topoisomerase II inhibitors - doxorubicin
Antibiotics - anthracycline
52
Topotecan
binds topoisomerase I, produces a fixed complex, inhibits DNA unwinding.
- leads to cell death
53
Doxorubicin
Binds topoisomerase II, prevents religation of DNA
| - leads to cell death
54
Anthracycline
wedges itself between DNA, stabilized topoisomerase II complex, preventing religation.
- produces free radical
- unique cardiotoxicity
55
Vinca Alkaloids & Taxanes
Vinca Alkaloid - vincristine
| Taxane - docetaxel
56
Vincristine
blocks assembly of microtubules in mitotic spindle.
57
Docataxel
blocks disassembly of microtubules in mitotic spindle.
58
Adverse effects of Traditional Antineoplastics?
- non-specific
- small therapeutic window
- immuno-suppressant
59
Combination Drugs
- must be effective by themselves
- should have similar recovery intervals/rates
- pick drugs with different aide effects so not to be additive.
60
Combination Therapy Example
CAV for lung cancer
C - cyclophosphamide
A - adriamycin (brand name for doxorubicin
V - vincristine
61
Targeted Anticancer Drugs - 5 targets
1) Cellular Markers
2) New Blood Vessel Growth - angiogenesis
3) Growth and Proliferation
4) Survival Proteins
5) Hormone Sensitive Cancer
62
Cellular Markers
CD-20 is a common cancer cell marker
also found on mature B cells
- monoclonal antibody - flags for immune system.
- conjugated radiation - kills cells with radiation that antibody binds to.
- conjugated cytotoxicity - kills cells through antimicrotubule action (eg. vincristine)
63
Tositumomab
radiation conjugated, monoclonal antibody targeted to CD-20.
64
Sipuleucel-T
anti-cancer vaccine.
| virus expressing CD-20, activates immune system to respond to cells presenting CD-20
65
Bevacizumab
monoclonal antibody against VEGF.
- similar to VEGF, binds the VEGFR to inhibit binding and downstream signaling.
- inhibit angiogenosis
66
Sorafenib & Gefitinib
Small molecule TK inhibitor. Binds intracellular part of the tyrosine kinase to inhibit autophosphorylation and activation
- specific to receptor tyrosine kinases like HER-2
- inhibit angiogenesis
67
Trastuzumab
blocks EGF receptors.
- EGF - epidermal growht factors stimulates growth and proliferation of cancer cells.
- can be conjugated (cytotoxic) or unconjugated (just antagonistic)
- inhibits growth and proliferation
68
Imatinib
Bcl-2 is a survival protein that allows cells to ignore the apoptosis signal.
Bcl-Abl is a cytoplasmic TK involved in Bcl-2 upregulation.
Imatinib binds to Bcl-Abl, so the normal ligand can not bind/activate it. (anagonist)
- inhibits survival proteins
69
Hormone Sensitive Cancer Drugs
- Leuprolide
- Letrozole
- Tamoxifen
70
Leuprolide
looks like GnRH, involved in the production of testesterone and estrogen.
- effective against both breast cancer and prostate cancer
71
Letrozole
inhibits aromatase involved in estrogen conversion
| - specific to breast cancer
72
Tamoxifen
estrogen receptor antagonist
| - specific to breast cancer
73
1st line therapy
```
Old + New
Eg. R-CHOP
R - rituximab
C - cyclophosphamide
H - hydroxydaunorubicin (doxorubicin)
O - oncovin (vincrisitne)
P - prendisone adjuvant (reduce side effects)
```
PHAC 3001
flashcards
Decks in class (1)
# Cards
