Exam IV Flashcards
daunorubicin
mech, admin, SE
intercalates with DNA→produces free radicals
given IV
♥ muscle degeneration
migraine agents (7)
mech, admin, SE
TRIPTANS (sumatriptan, rizatriptan, zomitriptan, naratriptan, almotriptan, eletriptan, frovatriptan)
serotonin receptor agonist
admin oral/IV/nasal spray
synergistic effect with MAOIs or SSRIs→serotonin syndrome
(hyperthermia, muscle twitching)
abatacept
mech, use
inhibits CD80 and CD86 receptors
treats RA
vincristine
mech, admin
binds to microtubules→blocks cell mitosis
given IV
behavioral changes associated with glucocorticoid uses (3)
euphoria/depression, psychosis, emotional lability
ustekinumab
mech, use
binds to IL-12 and IL-23 molecules
psoriasis
Cyclosporine
mech, use, SE (7)
binds to CYCLOPHYLLIN protein→COMPLEX inhibits calcineurin phosphatase
eventually incapacitates T-Cells
tx transplants, psoriasis, dry eye
metab by CYP450
nephrotoxicity, hepatotoxicity
cosmetic changes: hypertrichosis, gingival hyperplasia
↑cholesterol, mild HTN
leucovorin
mech
a tetrahydrofolic acid analog which requires DHF Reductase
rescues cells methotrexate toxicity
middle potency glucocorticoids
prednisone (a prodrug→no topical admin), prednisolone, triamcinolone
ISA:4
MCA: 0.25
duration 18-36h
ATGAM antithymocyte globulin
mech, use, SE
polyclonal antibody
treats acute renal transplant rejection
↑risk for allergic response
methotrexate
mech, SE
folic acid antimetabolite inhibiting dihydrofolate reductase
myelosuppression (inhibition of blood cell formation)→fixed with leucovorin
erbulin
mech
inhibits microtubules→prevents mitosis, causes apoptosis
GI side effects of glucocorticoids (3)
↑risk of ulcers, gastritic, GI bleeding
the methylxanthine used for asthma
mech, SE (5)
theophylline
inhibits cAMP phosphodiesterase ENZYME (relaxes smmm by ↓cAMP breakdown)
♥ arrythmias (from heart stimulation)
CNS: tremors, insomnia, seizures
GI upset
ibritumomab
SE
its pure mouse, so superduper antigenic
etanercept
mech, admin, use
binds to TNF
given subq
RA
certolizumab
mech, use
binds to TNF molecule
RA, Chrohn’s Dx
first generation antihistamines (6)
mech? clinical use for each? tox? SE (4)
block both central and peripheral H1 receptors
diphenhydramine (sedative, motion sickness)
clemastine (motion sickness)_
chlorpheniramine (NOT A SEDATIVE, uticaria, motion sickness)
hydroxyzine (sedative, uticaria)
promethazine (STRONG sedative, STRONG antiemetic)
tripelennamine (sedative, local anaesthetic)
high TI
dry mouth, blurred vision, constipation (antimuscarinic efx)
synergistic with CNS depressants
topotecan
mech
topoisomerase I inhibitor
everolimus
mech, use, SE (3)
BINDS to FK-BINDING PROTEIN→COMPLEX inhibits a kinase required for IL-2 induced transcription of cytokines
tx transplantation, psoriasis
renal toxicity
lung toxicity
metab by CYP 450
adalimumab
mech, use
binds to TNF molecule
RA
Which agent for asthma treatment is the least selective in its method of action? Which receptors does it bind? What are some side effects (2)? How is it administered?
epinephrine
activates ALL α and ß receptors
inhaled or IV
SE: ↑HR (from ß1) and ↑BP (from α1 induced vasoconstriction)
ocular side effects of glucocorticoids (2)
cataracts, glaucoma
rituximab
mech, use
blocks CD20 receptor
tx Chronic lymphocytic leukemia, RA
rilonacept
mech, use, admin, SE
binds to IL-1 molecule!
admin subQ
RA; admin with methotrexate
NOT USED with TNF inhibitors (synergistic)
bleomycin
mech, SE
intercalates with DNA→strand breakage
pulmonary fibrosis
hydroxychloroquine
mech, SE (3)
taken up by macrophages, concentrated in lysosomes, and interferes with antigen processing
GI dysfunction, dermatitis,
irreversible retinal damage
ergot alkaloids (2)
mech, SEs (2)
ergotamine, dihydroergotamine
partial 5HT receptor agonists
synergistic with 5HT agonists (MAOIs/SSRIs)→serotonin syndrome
(HTN, fever, confusion, muscle twitch/rigidity, severe vasospasm)
pregnancy category X
imitinib
mech, use, admin, SE
protein kinase inhibitor of a kinase which turns off cell apoptosis
tx chronic myelogenous leukemia (CML)
given orally→causes edema
trastuzumab
mech, use
blocks a HR2 receptor (a tyrosine kinase)
tx breast cancer
tocilizumab
mech, use
binds to IL-6 receptors on T-cells
RA
5-fluorouracil
mech
pyrimidine analog inhibiting thymidylate syntetase→inhibits thymidine synthesis
ixabepilone
mech
binds to microtubules
natalizumab
mech, use, SE
inhibits to α-integrins (INHIBITS RECEPTORS) on CD4 T-Cells
Crohn’s Dx, MS
linked with progressive multifocal leukoencephalopathy (viral dx of CNS)
anastrozole
mech, use
inhibits aromatase enzyme (which converts testosterone to estrogen)
treats ladycancers
specific H2 blockers (4)
mech, SE
blocks peripheral H2 receptors (doesn’t cross BBB)
cimetidine (has antiandrogenic efx→gynecomastia/galactorrhea)
ranitidine
tamotidine
nizatidine
aspirin
where most readily absorbed? mech?
most readily absorbed in stomach (weak acid)
inhibits cyclooxygenase (both COX1 adn COX2)→ ↓prostaglandin synthesis
golimumab
mech, use
binds to TNF molecule
ulcerative colitis, psoriatic arthritis, RA
What are the desired effects of aspirin and other NSAIDs (4)? What are the SE/toxicities (8)? Where is it contraindicated (2)?
antipyretic effects (for fever px only)
limited analgesia (due to ↓prostaglandins)
antiinflammatory
anticlotting (irreversible inhibitor of platelet COX2→↓TXA2)
GI upset (gastric irritant→↓PG production via intestinal mucosa)
tinnitus
↑respiration
↓miosis, ↓kidney perfusion, hypersensitivity, bronchospasms, inhibits labor
contrx with clotting deficiencies
contrx in children with viral infections (→Reyes sx)
What is the mechanism of action for glucocorticoids?
enter target cell and binds to cytoplasmic receptor
steroid-receptor complex dimerizes and binds to steroid response element in DNA
lipocortin I is induced→activity of phospholipase A2 is inhibited
↓↓synthesis of prostaglandins and leukotrienes→inhibits immune response
NIBs
mechanism
kinase inhibitors
etoposide
mech
inhibits topoisomerase II→irreperable DNA breaks
propionic acid derivatives (7)
mech, SE
PROs (ibuPROfen, naPROxyn, fenoPROfen, ketoPROfen, flurbiPROfen, oxaPROzin, suPROfen)
cyclooxygenase inhibitors (COX1 and COX2)
[see aspirin]
also in ↑doses: ↑MI, ↑stroke (due to greater effect on PGI prod. than TXA2)
irinotecan
mech
topoisomerase I inhibitor
omalizumab
mech, admin?
anti IgE mAB
IV only
tacrolimus
mech, use, SE (5)
binds to FK-BINDING PROTEIN→COMPLEX inhibits calcineurin phosphatase
tx transplants
nephrotoxic
neurotoxic
alopecia, diabetes
metab by CYP450
(ultimately prevents activation of Tcells; more efficacious than cyclosporin)
non propionic acid, non acetic acid derived (6)
mech, SE
pyroxicam, diclofenac, bromfenac, nepafenac, etodolac, nabumetone
cyclooxygenase inhibitors (COX1 and COX2)
[see aspirin]
also in ↑doses: ↑MI, ↑stroke (due to greater effect on PGI prod. than TXA2)
inhibitors of leukotriene system (3)
mech
zileuton inhibits E2 5-lipoxygenase in immune cells
zafirlukast, montelukast block leukotriene receptors on pulmonary smmm
bortezomib
mech, use
inhibits proteasome→inhibits antigen presentation by APCs
tx multiple myeloma
prednisone
mech, use
inhibits immune functioning
treats neoplasia of immune system (like leukemias, lymphomas)
basiliximab
mech, use, SE (4)
mAB that blocks IL-2 receptor
used with cyclosporine A
hypersensitivity rxns (chimeric) HTN, bronchospasms, pulmonary edema
leuprolide
mech, use
stimulates GnRH receptor→initially ↑testosterone, then downregulates receptor and then ↓↓↓testosterone synthesis
tx prostate tumors
infliximab
mech, use, SE (5), admin
mAB binding to TNF molecule
RA, Chrohn’s disease
admin IV
hypersensitivity (chimeric MAB);
itching, hypotension, fever
worsens TB/fungus infections
tamoxifen
mech, use, SE (2)
blocks estrogen receptor
treats ladycancers
retinal changes, ↑cataract formation
longer acting agents for asthma treatment
mech, admin, SE (3)
formoterol, arformoterol, salmeterol, indicaterol
specific ß2 agonist
inhaled usually
tremor, tachycardia, ♥ palpitations (due to ß1 effect)
Cholinergic blockers for COPD treatment (2)
mech? SE?
ipratropium, tiotropium
muscarinic receptors blockers on pulmonary smmm
dry mouth
highest potency glucocorticoids
dexamethasone, betamethasone
ISA:25
MCA: 0.01
duration 36-54h
carfilzomib
mech, use
inhibits proteosomes→inhibits antigen presentation by APCs
tx multiple myeloma
fulvestram
mech, use, SE (2)
blocks estrogen receptor
treats ladycancers
retinal changes, cataract formation
mast cell inhibitors (2)
mech
cromolyn sodium, nedocromil
inhibits release of mediators from immune cells by INHIBITING Cl- CHANNELS, which ↓Ca++ uptake
azathioprine
mech, use, SE
prodrug converted to 6-mercaptopurine→inhibits synthesis of purines; inhibits enzymes responsible for GMP synthesis
transplants, RA, Crohns
Bone marrow depression (→thrombocytopoenia, megaloblastic anemia, leukopenia)
leflunomide
mech, SE (4)
antimetabolite of pyridine inhibiting dihydroorotate dehydrogenase
diarrhea, abdominal pain
teratogen (especially for lymphocytes)
inhibits CYP450
sirolimus
mech, use, SE (3)
BINDS to FK-BINDING PROTEIN→COMPLEX inhibits a kinase required for IL-2 induced transcription of cytokines
tx transplantation, psoriasis
renal toxicity
lung toxicity
metab by CYP 450
skeletal side effects of glucocorticoids (3)
osteoporosis
osteonecrosis
↓growth in children
vinblastine
mech, admin
binds to microtubules→blocks cell mitosis
given IV
Shorter acting agents for treatment of asthma (1+5)
mech? admin? SE (3)?
isoproterenol (less selective)
albuterol, pirbuterol, bitolterol, levalbuterol, terbutaline
specific ß2 agonists (RECALL: any agent which acts to activate a receptor can cause downregulation and loss of effect!)
admin via inhalation
tremor, tachycardia, ♥ palpitations (due to ß1 effect)
teriflunomide
mech, SE
prodrug; converted to antimetabolite of pyridine inhibiting dihydroorotate dehydrogenase
diarrhea, abdominal pain
teratogen (especially for lymphocytes)
flutamide
mech, use
blocks intracellular androgen receptor
tx prostate tumors
abiraterone
mech, use
inhibits 17-hydroxylase lyase (CYP17)→ ↓testosterone synthesis
tx prostate tumors
THE non-narcotic analgesic
mech, tox (2)
acetaminophen
NOT AN NSAID→NO antiinflammatory or NO antiplatelet efx
specific COX2 inhibitor?
fewer GI upset than NSAIDs
acute liver failure (↓↓glutathione tx with N-acetyl cysteine)
bevacizumab
mech
blocks VEGF (vascular endothelial growth factor)→inhibits formation of blood supply to tumors
glucocorticoids used for asthma tx (7)
mech? clinical use? admin? SE (2)?
beclomethasone, budesonide, fluticasone, mometasone, ciclesonide (all inhaled)
prednisone, dexamethasone (not inhaled)
bind to intracellular receptors→alter DNA trxn→↑lipocortin→inhibits PLA2 synth
DOC for chronic asthma
infections in mouth (thrush), dysphonia (abnormal speech)
CV side effects of glucocorticoids (5)
stroke, CHF, MI, HTN, ↑intracranial pressure
celecoxib
mech, use, SE
specific COX2 inhibitor
used to treat arthritis
↑MI, ↑stroke due to greater effect of drug on PGI2 than TXA2
second generation antihistamines (4)
mech? difference from first gen? tox? SE (3)?
loratadine, fexofenadine, desloratadine, cetirizine
block peripheral H1 receptors ONLY
do not cause drowsiness (don’t enter CNS)
high TI
dry mouth, blurred vision, constipation (antimuscarinic efx)
least potent glucocorticoids
cortisone (a prodrug→no topical admin), hydrocortisone
ISA:1
MCA: 1
duration 8-12h
cisplatin
mech, SE(2)
alkylates DNA
renal damage, ototoxicity
paclitaxel
mech
forms abnormal microtubules
doxorubicin
mech, admin, SE
intercalates with DNA→produces free radicals
given IV
♥ muscle degeneration
What are the clinical uses of antihistamines (4)? What are they ineffective in treating?
dermatoses (itching, insect bites)
allergic rhinitis/conjunctivitis→ ↓ congestion, sneezing
antiemetic/antinausea→tx motion sickness
sedatives
DO NOT TREAT ASTHMA or COMMON COLD
What is the synthetic path for glucocorticoids? Which reactions require P450?
cholesterol → pregnenolone → 17-OH pregnenolone → 17-OH progesterone →11-deoxycortisol → cortisol
all require CYP450 except the pregnenolone→17OHpregnenolone reaction
What are the effects of the H1 blockers (6) and H2 blockers (1)?
H1 Blockers: CNS: sedation, anti-nausea
drying of mucous membranes
local anaesthesia
dilates bronchial smmm
inhibits secretion of interleukins→ ↓↓immune/inflammation
H2 Blockers: inhibits acid secretion from parietal cells
betalacept
mech, use, SE
inhibits CD80, CD86 receptors
for renal transplants
↑malignancy associated
cyclophosphamide
mech, admin
prodrug which alkylates DNA
oral/IV
N-acetyl cysteine
mech
used to treat acetaminophen overdose
a reducing agent to ↑glutathione (GSH) levels in liver
metabolic side effects of glucocorticoids (3)
weight gain
fat redistribution (to abdomen, moon face, buffalo hump)
muscle wasting (thin arms, growth inhibition in children)
methotrexate
mech, use, SE
antimetabolite for folic acid inhibiting dihydrofolate reductase
DOC for early tx of RA
affects cells with rapid turnover (GI, bone marrow, fetal development)
(eventually ihiits cell division)
acetic acid derivatives (3)
mech, SE
indomethacin, tolmetin, sulinadac
cyclooxygenase inhibitors (COX1 and COX2)
[see aspirin]
also in ↑doses: ↑MI, ↑stroke (due to greater effect on PGI prod. than TXA2)
Indomethacin is extremely potent COX inhibitor:
used for newborns with patent ductus arteriosus
causes thrombocytopoenia, aplastic anemia, corneal opacities
dactinomycin
mech
intercalates with DNA→interferes with RNA synthesis
cytarabine
mech
pyrimidine analog inhibiting DNA polymerase
Skin/mucosal damage associated with glucocorticoids (4)
easy bruising (skin thinning)
poor wound healing
acne
increased incidence of infection (eg: thrush)
anakinra
mech, admin, use, SE
blocks IL-1 receptor
admin subcutaneously
RA; admin with methotrexate
NOT USED with TNF inhibitors (synergistic)
6-mercaptopurine
mech
prodrug purine analog inhibiting enzymes required for purine synthesis
mycophenolate mofetil
mech, use, SE
specific antimetabolite inhibiting inosine monophosphate dehydrogenase →inhibiting guanosine synthesis
transplants, lupus
GI cell disruption bonemarrow depression (→thrombocytopoenia, megaloblastic anemia, leukopenia)
lomustine
mech, admin
prodrug which alkylates DNA
given IV
tolfacitinib
mech, SE
inhibits Janus Kinase→prevents effect of cytokines on gene expression (JAK-STAT)
↑infection chance, ↑malignancy
