Bisphosphonates Flashcards
1
Q
Bisphosphonates for Osteoporosis
A
- alendronate
- risedronate
- ibandronate
2
Q
Bisphosphonates for multiple myeloma and skeletal metastases of solid tumors
A
- zolendronic acid
- pamidronate
3
Q
Bisphosphonates for hypercalcemia of malignancy
A
- etidronate
- pamidronate
- zolendronic acid
4
Q
Bisphosphonates for Paget’s disease of bone
A
- alendronate
- risedronate
- tiludronate
- pamidronate
5
Q
CANT use for Paget’s disease of bone
A
teriperatide
6
Q
RANKL drug
A
Denosumab
7
Q
30S inhibitors
A
- aminoglycosides
- – blocks initiation, elongation -> termination, miscoding
- tetracyclines
- – blocks elongation
8
Q
50S inhibitors
A
- macrolides
- – inhibit elongation
- clindomycin
- – blocks translocation
- streptogramin
- – blocks translocation, inhibits elongation
- Linzolid
- – blocks initiation
9
Q
Linzolid
A
VRE
10
Q
Classical chemotherapy targets
A
limitless replicative potential
11
Q
taxanes a vinca are
A
natural substances
12
Q
Antifolates
A
- inhibit cell division by limiting availability of DNA precursors
- DHFR = folate -> tetrafolate -> tymine nucleotides/purines
- ** folate analog competitive inhibitors bind 100x tighter to DHFR ***
13
Q
Antifolates Toxicity
A
- myelosuppression
- mucositis
- nephrotoxicity
- hepatotoxicity
- neurotoxicity
- pulmonary and alleopecia (rare)
14
Q
Antifolate Resistance
A
- decreased metabolism
- change in DHFR
- decreased cell entry
- increased efflux
- increased folate salvage
15
Q
Leucovorin
A
- rescue
- reverses antifolate toxicity
16
Q
Bisphosphonates
anti-resorptive agent
A
- non-hydrolyzable PCP bond
- BIND CALCIUM and accumulate at remodeling sites
- PREVENT DIFFERENTIATION OF MACROPHAGES into osteoclasts; inhibit osteoclast activity and cause APOPTOSIS
- suppress remodeling and decrease number of remodeling units
-DRONATE
17
Q
Nitrogen containing BPs inhibit
A
- FPP, inhibiting osteoclast activity
18
Q
BP contraindications
A
- hypocalcemia
- GI disease
- esophageal abnormalities
- kidney disease
- pregnancy
19
Q
Compared to morphine, buprenorphine would be expected to
A
precipitate withdrawal in a herone addict
20
Q
Give something other than morphine to transition?
A
methadone (40?)
21
Q
D2
D3
A
D2: Ergocalciferol: from mushrooms/fish
D3: cholecalciferol: from skin after exposure to sun
22
Q
Calcitriol
A
- active form of Vit D
- kidney converts other D forms to calitriol
23
Q
Calcitonin
A
- salmon
- less critical for homeostasis
- reduces serum calcium and phosphorous by PROMOTING BONE DEPOSITION AND STIMULATING RENAL EXCRETION
- produced by thryoid gland
- inhibits bone resorption by DIRECTLY BLOCKING OSTEOCLAST ACTIVITY
24
Q
Summary of Calcitonin
A
- increases bone density, decreases fractures
- REDUCES ACUTE PAIN due to fractures/metastases
- DESTROYED QUICKLY IN GI TRACT: intrnasal spray or injection
- for those who can’t tolerate estrogen or BPs
- can worsen postmenopausal symptoms
- injected calcitonin also for symptomatic PAGET’s DISEASE OF BONE
- TOLERANCE is common
25
Sulfonamides
- PABA analogs that competitively inhibit dihydroptarate preventing creation of folate
- bacteriostatic
26
Trimethoprim
- selectively inhibits bacterial DHFR preventing creation of folate
- bacteriostatic
27
TMP-SMX
- bactericidal
- #1 UTIs
- short course
- allergic response common
28
Abaloparatide
- ONLY BUILDS bone; take with BPs
Contraindication: osteosarcoma
- after discontinue can have rebound bone loss -> intermittent treatment followed by BP to prevent this
29
Slerostin
- WNT signaling pathway
- -- stimulate osteoblast, inhibit osteoclast
- leads to decreased bone resorption and increased bone formation
- sclerostin deficiency inhibits WNT pathway
- -- sclerostin deficiency have high bone mass
- calcitonin increases sclerostin production
30
Romozumab
- antibody against sclerostin
- stimulate/restore WNT pathway
- stimulate increased bone formation and decreased resorption
CARDIOVASCULAR ADVERSE EFFECTS
31
Fluoroquinolones
- block bacteria DNA replication
| - block DNA gyrase
32
B-lactam mechanism
- all look like D-Ala--D-Ala
- -- transpeptidase reacts to D-ala-D-ala to make crosslinks = peptidoglycan
* ** transpeptidase attacks B-lactam instead of D-Ala--D-Ala ***
- -- transpeptidase and B-lactam not covalently linked and can't be separated
- enzyme dies
* ** can only kill growing cells! ***
33
Bacterial B-lactamases
- bacterial response to B-lactam antibiotic
34
B-lactamase inhibitors
* ** NO ANTIBACTERIAL ACTIVITY ***
- don't kill bacteria
- target and remove B-lactamases, freeing up initial drug to kill bacteria
- inactivate B-lactamases irreversibly
35
Amoxicillin
| Penicillin
- acid stable
- > activity against gram -
- inactivated by B-lactamases
- oral, IV, IM
- quickly broken down
- allergic responses; all penicillin cross reactive
36
Probenecid
- inhibits secretion of penicillin
37
Augmentin
penicillin + clavulanate
clavulanate = B-lactamase inhibitor
38
Benzomorphans
- 3 rings
| SIEZURE = answer?
39
6 rings
- don't breakdown = toxicities
40
Morphine
low bioavailability; short t1/2; bad withdrawal
- excreted via kidney - can cause renal failure
- chronic: pain for terminal illness, particularly cancer
41
Acute Morphine Toxicity
- coma
- pinpoint pupils
- life threatening respiratory depression
- ventilate
- reversible with antagonists
