Drugs Flashcards
1
Q
Greatest risk factor for non-melanoma skin cancer?
Melanoma?
A
UV radiation UV radiation (gene damage?)
2
Q
Effects of UV light on skin?
A
Immediate - erythema
Long-term - photo-aging, immunosuppression, carcinogenicity
*profound immune suppression (organ transplant) can increase skin cancer risk
3
Q
Substantivity
A
Sunscreens ability to remain effective under exposure to water and sweat
- Water resistint 40 min
- Very water resistent 80 min
4
Q
Imiquimod Mechanism
A
small molecule tumor-directed immune response initiator
- direct activation of Toll-like receptor 7/8
- involvement of adenosine receptor blockade
- activation of NF-kappaB - upregulation of cytokines (TNF-alpha/interleukins)
5
Q
Imiquimod Use
A
Basal Cell Carcinoma
Actinic Keratosis
HPV
6
Q
Imiquimod Med/Toxicity
A
topical agent, limited systematization
-benzyl alcohol/paraben may be allerginic
-mild-moderate localized skin reactions common
Increased Photosensitivity
Contact compromise condom & diaphragm integrity
7
Q
Vismodegib Mechanism
A
Oral SMO inhibitor
Lipophilic agent with extensive metabolism
8
Q
Vismodegib Toxicity
A
- Intrauterine fetal death
- Male-mediated teratogenicity
- Pregnancy-both male/female should use contraception
- Can’t donate blood for 7 months
- Alopecia
- GI toxicities (N/V, diarrhea, vomiting)
- Weight loss/fatigue
9
Q
Vismodegib Use
A
Basal Cell Carcinoma
10
Q
Aldesleukin Mechanism
A
Binds to cell surface IL-2 receptor
Induces proliferation/differentiation of B/T-cells, monocytes, macrophages, CTL (NK cells)
-IV or SC
11
Q
Aldesleukin Toxicity
A
Contraindicated: CNS, cardiac, pulmonary, renal, hepatic disease/organ transplant
- hypotension, S-TACH, peripheral vasodilation, SVT, decreased mental status, speech difficulties, cortical blindness, limb/gait ataxia, hallucinations, agitation, dyspnea, pulmonary congestion, rales, rhonchi, renal failure (capillary leak syndrome)
- effects all systems
12
Q
Aldesleukin Use
A
Melanoma
13
Q
Interferon-alpha 2 beta Mechanism
A
IV or SC administered immunomodulator
14
Q
Interferon Toxicity
A
Caution: Autoimmune Disease,Cardiac disease, depression (sucide), infection
- flu-like symptoms, fever, fatigue
- neutropenia, leukopenia, anemia, alopecia
- increased hepatic enzymes (LFT)
- cough/dyspnea, pneumonia, pneumonitis, infilatrates
15
Q
Interferon Use
A
Melanoma
16
Q
Ipilimumab Mechanism
A
Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) recombinant antibody
-Bolsters antitumor response of immune system
17
Q
Ipilimumab Toxicity
A
Severe/fatal immune-mediated adverse rxns due to T-cell activation and proliferation
- dermatitis (toxic epidermal necrolysis)
- most common:tiredness, diarrhea, itch, rash
Black Box: adrenal insufficiency, diarrhea, Guiliain-Barre syndrome, hepatitis, hyperthyroidism, hypopituitarism, hypothyroidism, myasthenia graivis, peripheral neuropathy, pregnancy, serious rash
18
Q
Ipilimumab Use
A
Melanoma
19
Q
Sorafenib Mechanism
A
Oral multi-kinase inhibitor (VEGF, PDGFR, KIT, Raf Kinase)
20
Q
Sorafenib Toxicity
A
Hepatic metabolism (LFT) Hand/Foot Rash/desquamation/anemia Bone marrow suppression/neurtopenia (CBC) Cat D bleeding in GI, respiratory, brain
21
Q
Sorafenib Use
A
Melanoma
22
Q
Trametinib Mechanism
A
Oral reversible MEK inhibitor
Patients with BRAF V600E or V600K mutations
-can’t have received BRAF-inhibitors before
23
Q
Trametinib Toxicity
A
Rapid skin toxicity (dermatitis, erythema, hand-foot) severe in 12%
GI:diarrhea, stomatitis, anemia
Decreased LVEF, require routine reassessment
Hypertension, hemorrhage
rare: cardiomyopathy, ILD, retinal pigment epithelial detachment
24
Q
Trametinib Use
A
Melanoma
25
Vemurafenib Mechanism
Oral inhibitor of mutated BRAF (BRAFV600E)
- genotyping required
- can cause paradoxical ERK activation of mutated RAS-driven growth
- resistance via alternative pathway activation
26
Vemurafenib Toxicity
*Hepatic metabolism, PGP/CYP interactions
Increased serum creatinine
QT prolongation and TP, ECG/ electrolyte monitoring
photosensitivity (avoid sun)
Cutaneous SCC in 1/4th
Severe dermatologic reaction (SJS)
Opthalmologic: uveitis, iritis, retinal vien occlusion
27
Vemurafenib Use
Melanoma
28
Carmustin Use
Melanoma; good b/c can cross blood brain barrier and treat brain metastases.
29
Carmustine Mechanism
Alkylationa and carbomoylation of amino acids
30
Carmustine Toxicity
Myelosuppression
| CBC
31
Cisplatin Mechanism
Forms DNA intrastrand crosslinks
32
Cisplatin Toxicity
Renal tubular damage and failure
| Myelosuppression
33
Cisplatin Use
Basal Cell Carcinoma
| Squamous Cell Carcinoma
34
Cyclophosphamide Mechanism
Pro-drug of active alkylating moiety
35
Cyclophosphamide Toxicity
Myelosuppression
36
Cyclophosphamide Use
Basal Cell Carcinoma
37
Dacarbaxine Mechanism
Pro-drug of active alkylating moiety
38
Dacrbaxine Toxicity
Myelosuppression
39
Dacrbaxine Use
Melenoma
40
Trichloracetic Acid Mechanism
chemical peel: rapidly penetrates and cauterizeds skin, keratin, other tissue
41
Tirchloracetic Acid Toxicity
burning, inflammation, local tenderness
42
Tichloracetic Acid Use
Actinic Keratosis
43
Acyclovir Mechanism
Competitively inhibits viral DNA polymerase; competes with deoxyguanosine triphosphate for incorporation into viral DNA
44
Acyclovir Toxicity
- O-P
- Cross-hyper-sensitivity
- neurotoxicity incl seizures
- Little metabolism, renal elimination, dose adjustment in renal dysfunction or renal failure
45
Acyclovir Use
Varicella zoster
| Varicella chicken pox
46
Famciclovir Mechanism
Competitively inhibits viral DNA polymerase; competes with deoxyguanosine triphosphate for incorporation into viral DNA
47
Famciclovir Toxicity
-O-P
-Cross-hyper-sensitivity
Little metabolism, renal elimination, dose adjustment in renal dysfunction or renal failure
48
Famciclovir Use
Varicella zoster
| HHV-8
49
Ganciclovir Mechanism
Competitively inhibits viral DNA polymerase; competes with deoxyguanosine triphosphate for incorporation into viral DNA
50
Ganciclovir Toxicity
-O-P
-Cross-hyper-sensitivity
Little metabolism, renal elimination, dose adjustment in renal dysfunction or renal failure
-anemia, leukopenia, neutropenia, pancytopenia, thrombocytopenia, teratogen
51
Ganciclovir Use
HHV-6,8
| HHV-8 infection
52
Valacyclovir Mechanism
Competitively inhibits viral DNA polymerase; competes with deoxyguanosine triphosphate for incorporation into viral DNA
53
Valacyclovir Toxicity
-nephrotoxicity - monitor creatinine and urinary protein; probenecid hypersensitivity
Little metabolism, renal elimination, dose adjustment in renal dysfunction or renal failure
54
Valacyclovir Use
Varicella zoster
Varicella chicken pox
HHV-8
55
Cidofovir Mechanism
competitively inhibits viral DNA polymerase; competes with deoxyCYTOSINE triphosphate for incorpation into viral DNA
56
Cidofovir Toxicity
- nephrotoxicity - monitor creatinine and urinary protein; probenecid hypersensitivity
- Little metabolism, renal elimination, dose adjustment in renal dysfunction or renal failure
57
Cidofovir Use
Pox family
| HHV-6,7,8
58
Forscarnet Mechanism
selectively inhibits the viral specific DNA polymerases and reverse transcriptases at pyrophosphate-binding site; blocks chain elongation
59
Forscarnet Toxicity
- electrolyte imbalance - chelates Ca2+ ions
| - Little metabolism, renal elimination, dose adjustment in renal dysfunction or renal failure
60
Forscarnet Use
HHV-6
61
Malathion Mechanism
Ovide: topically applied organophosphate insecticide
- in louse, metabolized to malaoxon which inhibits acetylcholinesterase and causes neuronal hyperstimulation and paralysis
- in human, malathion is converted to inactive metabolites and excreted by kidney
62
Malathion Toxicity
Safe, not associated with significant topical cholinergic activity, but oral/pulmonary ingestion: increased GI peristalsis; miosis, decreased ocular accommodation/pain, rhinorrhea, chest tightness/wheezing, increased lacrimation, salivation, sweating, bradycardia, hypotension, confusion, convulsions, weakness, muscular paralysis, respiratory paralysis
***Treatment is atropine & pralidoxime***
63
Premethrin Mechanism
Synthetic pyrethrin - cause hyper-excitability and paralysis by binding voltage-gated sodium channels.
64
Premethrin Toxicity
Safe: human voltage-gated channels are not susceptible
Rare: asthma exacerbation in patients allergic to ragweed
-Systemic drug is inactivated by ester hydrolysis no effects
-Efficacy decreased b/c knock-down resistance (kdr) mutations of louse sodium channels
65
Lindane Mechanism
Disfavored: shampoo or lotion, only patients who can't use first line treatment
-when systemic, its a CNS stimulatent , similare effects to DDT (block GABA action)
66
Lindane Toxicity
-Seizures and deaths
Black Box: skin disease/conditions/neonatal prematurity will increase drug systematization
not for patients with uncontrolled seizure disorders
67
Lindane Use
Lice
68
Premethrin Use
Lice
69
Ivermectin Mechanism
- Pediculicidal (must dose 3 at 1 week intervals)
- orally and topically
- causes hyperexcitability and paralysis by binding selectively and with high affinity to glutamate-gated chloride ion channels present in invertebrate nerve and muscle cells
- no resistance
70
Ivermectin Toxicity
Elevate liver transaminases & Cross BBB in children only
| worsen bronchial asthma
71
Minoxidil Mechanism
(Rogaine) Topical-potent oral vasodilator
-mechanism is unknown:activate hair follicle directly or stimulate follicular microcirculation / may alter local androgen metabolism
72
Minoxidil Toxicity
Percutaneous abs poor, systemic effects unlikely
- skin abrasions/irritations (sunburn, psoriasis, excoriations) increase absorption
- must continue drug to get effect
73
Finasteride Mechanism
Oral (1mg for hair loss, 5mg for BPH)
Testosterone analog: blocks 5-alpha-reductase activity
Decrease scalp and serum DHT conc. - no effect on cortisol, estradiol, prolactin, TSH, thyroxine, cholesterol, PTH-axis
74
FInasteride Toxicity
Loss of libido, sexual dysfunction, feminization
| palmetto/finasteride similar so don't use together
75
Eflornithine Mechanism
Topical to reduce unwanted female facial hair
- related to decrease ornithine decarboxylase
- decrease cell division & differentiation
- produces typanostatic action, used against sleeping sickness
-limited absorption, not depilatroy, use chin/face, not eyes mucous membranes
76
Eflornithine Toxicity
Skin effects rarely: most mild, resolve without treatment or discontination
77
Methoxsalen Mechanism
Oral and topical pigmenting agent
- activated by exposure to UVA 9320-400nm (peak photosensitivity within 1-2 hours, persist for days)
- conjugation/cross-linking of DNA (Cell death)
78
Methoxsalen: what happens, uses?
- Delayed erythema followed over several weeks by increased epidermal melanization and thickening of stratum corneum
- Vitiligo, symptomatic relief of psoriasis, treatment of cutaneous T-cell lymphoma (mycosis fungoides), alopecia areata, inflammatroy dermatoses, eczema, lichen planus
- extent of topical abs is not known
79
Methoxsalen Mechanism
Oral and topical pigmenting agent
- activated by exposure to UVA 9320-400nm (peak photosensitivity within 1-2 hours, persist for days)
- conjugation/cross-linking of DNA (Cell death)
80
Methoxsalen: what happens, uses?
- Delayed erythema followed over several weeks by increased epidermal melanization and thickening of stratum corneum
- Vitiligo, symptomatic relief of psoriasis, treatment of cutaneous T-cell lymphoma (mycosis fungoides), alopecia areata, inflammatroy dermatoses, eczema, lichen planus
- extent of topical abs is not known
81
Daptomycin Mechanism
- cyclic lipopeptide abx
- rapidly disrupts bacterial cell membranes (depolarization and loss of membrane potential and K+ efflux)
- bactericidal-reduce resistance (rare, no mech)
82
Daptomycin Pharm
IV once a day (muscle toxicity in MI injection)
give after hemodialysis
Metabolism - 90% albumin bound
Elimination - renal (dose adjust for renal disease)
83
Daptomycin Toxicity
Muscle pain/weakness
-monitor for development due to serum creatine phosphokinase elevations
Drug interactions - none with cyp P450, use cautions with co-administration of statins
84
Daptomycin Uses
Aerobin gram +
- multi-drug reisitant staph, strep, enterococcus (MRSA VRSA)
- Complicated skin/soft tissue infections
- MSSA MRSA bactermia (right endocarditis)
* **DON'T GIVE SURFACTANT***
85
Linezolid (Oxazolidinones)
| Mechanism
Inhibits protein systhesis by binding to 23S RNA on 50 ribosomal subunit
- Bacteriostatic -staph/enterococci
- Bactericidal-strep
86
Linezolid Resistance
- Point mutation in 23S RNA
- No cross resistance with other classes
- Emerging with enterococcal and s. aureus
87
Linezolid Use
MRSA, enterococcus, S. aureus, S. epi, serious VRE infections
88
Linezolid Pharm
-Oral/Parenteral use
-100% oral abs
-Food delays abs
-Met. by non-enzymatic oxidation (give 2 inactive metabolites)
-Elim: renal/non-renal
no CYP450
-more dose after hemodialysis
89
Linezolid Toxicity
Well tolerated
diarrhea, headache, nausea/vomiting, myelosuppression if more than 2 weeks
Oral has aspartame (warn those with phenylketonuria)
*Non-selective inhibitor of monoamine oxidase, caution if coadminister with drugs metabolized by MAO
hypertension from decreased breakdown of tyramine absorbed from diet
