PGY-2 Therapeutics Flashcards
1) What is the mechanism of action of oral prednisone? List 5.
- Inhibits NfKB and AP-1–> transcription factors that stimulate inflammatory cytokine production
- Induces apoptosis auto reactive T-cells, eosinophils
- Decreases Ig production from B-cells
- Inhibits phospolipase A2–> decreases productions prostaglandins, eicosanoids, leukotrienes
- Inhibits neutrophil apoptosis and margination and migration
2) List 3 absolute contraindication of oral prednisone.
Allergy/hypersensitivity
systemic fungal infection
HSV keratitis
3) List 8 relative contraindication for oral prednisone
- HTN
- Diabetes
- CHF
- Prior psychosis or seere depression
- Active peptic ulcer disease
- Active TB, + TB skin test
- Glaucoma
- Osteoporosis
4) What are the different route of administration of prednisone?
Topical, PO, IM, SC, IM, IV, intranasal, inhaled, ophthalmic
Prednisone only= PO
4) What are the different route of administration of prednisone?
5) List 4 drug-drug interactions for prednisone.
CYP3A4 inhibitors (increase prednisone):
Macrolides, azole antifungals, OCP
CYP3A4 inducers (decrease prednisone):
Rifampin, cholesytramine, phenytoin and other anti-epileptics
Warfarin-increase or decrease warfarin levels when on pred
Isoniazid-pred may decrease levels isoniazid
6) List 8 non-cutaneous side effects prednisone therapy.
Steroids withdrawal syndrome: fatigue, headache, lethargy
Addisonian crisis: hypotension, electrolyte imbalances
Brain: psychosis/depression, psudeotumor cerebri
Eyes: cataracts, glaucoma
GI: PUD, bowel perforation, GERD, fatty liver
Infection risk: OIs
MSK: Osteoporosis, myopathy, AVN, premature growth failure, epiphyseal plate closure
Metabolic: HTN, diabetes, weight gain, fluid retention, hyperglycaemia, hypokalemia, elevated TGs
7) List 10 cutaneous side effects of prednisone therapy.
Skin atrophy
Telangiectasias
Hirsutism
Telogen effluvium
Moon like facies/buffalo hump
Purpura
Striae
Non healing wounds
Steroid acne
Cutaneous infections
Acanthosis nigricans
Pustular psoriasis (withdrawal)
8) What investigations would you order for someone on prednisone therapy? Baseline and follow up
Baseline:
-BP, weight, height, DEXA scan, ophthalmoscope
Labs:
TBST, CXR, Hep B/C, HIV, strongy
TG, K, HbA1c
Monitoring:
BP, weight, ophthalmoscope
Labs:
K, Glucose, TGs
What do you order for Hep B serology
HepB sAg
Anti HB sAb
Anti HB cAb
What is the MOA of methotrexate? List 4.
- Inhibits DNA synthesis –> Inhibition DHFR and thymidylate synthase
- T-cell immune suppression: Decrease T-cell proliferation and migration into tissue
- B-cell Immunosuppresion: Decreases antibody responses
- Decreases inflammation through increases intracellular adenosine
What are 4 enzymes methotrexate inhibits
Dihydrofolate reductase
Thymidylate synthase
AICAR transformylase
Ecto 5’ Nucleotidase
List 3 absolute contraindications to MTX
Hypersensitivy/allergy
Pregnancy
Lactation
List 6 relative contraindications for MTX
Liver disease
Renal impairment
Immunodeficiency
Blood cell dyscrasia/cytopenias
Alcoholism
Active TB or Hep B/C
List 6 relative contraindications for MTX
Liver disease
Renal impairment
Immunodeficiency
Blood cell dyscrasia/cytopenias
Alcoholism
Active TB or Hep B/C
What are the different routes of administration of MTX? List 5
PO
SC
IM
IV
Intrathecal
Intra-arterial
List 3 categories of drug-drug interactions for MTX and 3 drugs in each category
- Increase risk cytopenias through concomitant folate reduction
-Sulfa drugs (sulfasalinze, sulfamethaxasole, dapsone), trimethoprim - Increase risk hepatoxicity
-Alcohol, retinoids - Increase MTX levels and toxicities
NSAIDS, doxy/minocycline, dipyramidole, furosemide
6) How long do men and women have to be off of MTX before conceiving?
- Women 1 ovulatory cycle
-Men 3 months
List 6 non cutaneous side effects MTX
Infection-OI’s like pneumocystis
Malignancy-increase risk lymphoma +KC
Pregnancy-teratogen
GI-N/V/Diarrhea/oral ulcers/anorexia
Lung-pneumonitis and pulmonary fibrosis
Liver-hepatitis and fibrosis/cirrhosis
Cytopenias
List 6 cutaneous side effects of MTX therapy
- Oral ulcers
- Alopecia
- Radiation or sunburn recall
- acral erythema
- papular eruption
- vasculitis
- cutaneous ulceration or epidermal necrosis
- Increased risk keratinocyte carcinomas
9) What investigations would you order for someone on MTX therapy?
a) at Baseline
b) Regular monitoring
Baseline:
Hep B/C, HIV, tbst, CXR
Cr/urea, LE, LFTs, CBC with differential
Monitoring:
Cr/urea, LE, LFT, CBC with diff
Liver biopsy at 3.5-4 grams cumulative dose (or 1.5 grams if high risk) and at each 1.5 gram interval subsequently, or consider Fibroscan yearly after 1 year of treatment
What is the mechanism of action of Azathioprine (AZT)? List 4
- Purine synthesis inhibitor/decreased cell proliferation : 6MP–> 6-TG via HGPRT–> purine analog.
- T-cell function reduced
- Decreases Ab production
- Impairs antigen presenting cell function
Which 3 enzymes metabolize 6-Mercaptopurine?
Xathine oxidsase
TPMT-thiopurine methyltrasnferase
HGPRT (hypoxanthine guanine phosphoribosyl)
) List 3 absolute contraindication of AZT.
Pregnancy
Hypersensitivity
homozygous mutant TPMPT/no TPMT activity
List 4 relative contraindications to AZT
- Active infection: Active Tb or Hep B/C
- PAncytopenia
- Prior use alkylating agents
- Concomitant use allopurinol/febuxostat
What is the dosing for AZT?
Homozygous wild type TPMT (15-26): 2-2.5 mg/kg
Heterozygous wild type (6.3-15): 1 mg/kg
Hetero mutant (<6.3): Do not use
*2-4 for pemphigus
*Mufti says unless homo normal won’t use it at all
8 adverse events Azathioprine
a. Teratogenic
b. Increased risk opportunistic infections (HSV, scabies, HPV)
c. TB, Hep B, JC virus reactivation
d. Hepatotoxicity and hepatic vein occlusion
e. Hypersensitivity reaction
f. GI: nausea, vomiting, diarrhea, pancreatitis
g. Cytopenia
h. Malignancy: Increased risk lymphoma and SCC
Can a patient taking AZT take the following medications (provide reasoning if not)?
-Allopurinol
-Febuxostat
-ACEi
-TMP-SMX
No for all of them.
For allopurinol/febuxostat–> can technically take but need to dose reduce. Inhibit XO= increase through HGPRT pathway=increase levels 6-TG and bone marrow suppression
ACEi-increaase risk leukopenia
TMP-SMX-concmitant folate inhibitor, increase toxicity
List 10 derm related indications for AZT (on or off-label); ii) what is the FDA indication for AZT?
FDA indication: Organ transplant, RA
Derm:
i. Immunobullous diseases: PV, BP, Cicatricial pemphigoid
ii. Vasculitis conditions: PAN, LCV, GPA, EGPA, urticarial vasculitis
iii. Photodermatoses: Actinic dermatitis, PMLE
iv. Neutrophilic dermatoses: Behcets, PG
v. AI-CTD: SLE, DLE, DM, relapsing polychonditis, eosinophilic fasciitis
vi. Dermatitis/Papulosquamous: Contact dermatitis, atopic dermatitis, hand dermatitis, PsO/PsA, LP
vii. Others: Sarcoid, EM, vitiligo, GVHD, leprosy
What investigations would you order for someone on AZT therapy? Baseline and monitoring
Baseline:
Hep B (sAG, sAB, core Ab), Hep C Ab, HIV, TBSR and CXR
CBC, liver, kidney
UA
Pregnancy
TPMT level
Monitoring:
i. CBC with differential
ii. LFTs including AST/ALT
1Write a prescription for someone who will be starting AZT for the very first time. Indication is pemphigus vulgaris and the patient has no comorbidities.
Azathioprine 50 mg po daily. M: 4 weeks, no refills
Increase to 100 or 150 mg daily
What are 2 formulations of cyclosporine? What is the difference in their dosage and bioavailability
Neoral: microemulsion, more bioavailable due to better absorption
Dose: 2.5-4 mg/kg 10-50
Sandimmune: 2.5-5 mg/kg
-30%
NAme 3 MOA of cyclosporine
a. Completes with cyclophilin to inhibit calcineurin which inhibits NFAT-1 transcription factors which down regulates IL-2 production which decreases T-cell production
b. Inhibits IFN-Y production by T-lymphocytes reduced keratinocyte proliferation and HLA-DR positivity
c. Binds to receptor associated heat shock protein 56 inhibits transcription of proinflammatory cytokines such as GM-CSF, IL-3, 4, 5, 6, 8, TNF-alpha
5 absolute contraindications to CsA
- Renal dysfunction-severe
- Uncontrolled HTN
- Allergy/hypersensitivity
- Active infection
- Persistent malignancy
8 relative contraindicatons to CsA
Concomitant:
-puva
-radiation
-bosentan
-immunosuppresant
Malignancy (clinically cured or persistent) except NMSC (product monograph)
Immune deficiency
Pregnancy/lactation
Drugs that interact with CsA or nephrotoxic
Unreliable patient
How is cyclosporine metabolized (which enzyme? Organ?) and excreted? What is its half-life?
Metabolized in liver, excreted in bile, half-life 5-18 hours
CYP 3A4
List 8 adverse effects of cyclosporine.
a. HTN
b. Renal impairment
c. Increased risk malignancy
d. Increased risk infection
e. GI: Nausea, vomiting, abdominal pain
f. Hepatotoxicity
g. MSK: Myalgia, lethargy
h. Neuro: tremor, headache, paresthesia, hyperesthesia
i. Cutaneous: see b
j. Hyperlipidemia
7) List 4 lab abnormalities that can be see with cyclosporine.
a. Hyperkalemia, hyperuricemia, hypomagnesia, hyperglycemia, hyperlipidemia
8) List 5 mucocutaneous side effects of cyclosporine.
a. Hypertrichosis
b. Gingival hyperplasia
c. Acne
d. Hirsutism
e. Alopecia
f. Keratosis pilaris
g. Sebaceous hyperplasia
h. Infections
i. Trichodysplasia spinulosa
j. Epidermoid cysts
k. Increased risk keratinocyte carcinoma
9) List 7 derm related indications for Cyclosporine (on or off-label)
What is the FDA derm indication for CsA
FDA: Psoriasis- SEVERE, RECALCITRANT, FAILED OTHERS-MAX 1 YR
Others:
AD
CSU
PG
BP
PV
PRP
LP
SJS/TEN
AI-CTD-lupus, DM
10) What investigations would you order for someone on Cyclosporine therapy
- BP x 2
- CBC + diff, LFT, Cr x 2, BUN, urinalysis
- Mg, K, uric acid, fasting lipid profile
- consider Ca2+, Tbili, HBV/HCV, HIV, U/A w Alb:Cr ratio, CXR + TB skin test/IGRA
Monitoring ix for CsA
i. BP measurement qvisit
ii. Cr, BUN, UA
iii. CBC, LE/LFTs
iv. Lipid profile
v. Mg, K, Uric acid
11) List 3 medications which interact with cyclosporine and lead to the following:
a. Increased toxicity (CYP3A4 inhibitors)
Azoles
Macrolides
CCB-diltiazem/verapamil
GRaprefruit juice
3 medications that lead to decreased efficacy of CsA
Carbamazepine
Phenytotin
Rifampin
3 medications that increase risk nephrotoxicity in CsA
NSAIDS
Aminoglycosides
Ampho B
1) List 4 benefits of using sunscreens
a. Carcinogensis prevention
b. Sunburn prevention
c. Photoaging prevention
d. Photoimmunologic suppression prevention
e. Prevent flares of photo dermatoses (e.g. PMLE, SLE, DM, etc.)
How is SPF calculated
ratio of duration of UV radiation exposure required to produce the minimal erythema dose (MED) in sunscreen-protected skin vs unprotected
*UVB
What is the CW
the wavelength below which 90% of the area under the absorbance curve resides.
What is the CW
The CW for a particular product is the wavelength at which the cumulative absorption of radiation above 290 nm is 90%.
What does broad spectrum refer to
Broad spectrum refers to a sunscreen for which the critical wavelength is 370 or above. It protects against UVB and UVA.
What is the mechanism of action of physical and chemical sunscreen agents?
a. Physical: Mostly reflect/scatter UV light, but also may absorb photons (especially micronized versions)
b. Chemical: Absorbs photons of UV light
List 5 UVB absorbers.
a. PABA and derivatives: PABA, padimate O
b. Cinnamates: Octinoxate, Cinoxate
c. Salicylates: Homosalate, Octisalate
d. Octocrylene
e. Ensulizole
List 5 UVA absorbers.
UVA “BEAMBS”
Bemotrizonol (Tinosorb S)
Ecamsule/Mexoryl SX
Avobenzone
Menthyl anthranilate (Meradimate)
Bisdizulizole/ Neo heliopan AP
List 4 UVA + UVB absorbers
BODI
–> UVA+B best for yuour BODI
A+ B= ZEE Best coverage
a. Oxybenzone and dioxybenzone (Benzopheone 3 and 8)
b. Iscotrizonol (Uvasorb HEB)
c. Drometrizole trisiloxane (Mexoryl XL)
d. Bisoctrizole (Tinosorb M)
What is helioplex
Avobenzone + Oxybenzone
List 3 physical sunscreens
a. Titanium dioxide
b. Zinc oxide
c. Iron oxides
d. Ferrous oxide
10) List 3 contraindications to using sunscreens.
- Known sensitivity to sunscreen or vehicle
- Kids < 6 mos of age
- As a sole component of photoprotection
1) What are the two broad categories of anesthetics?
Amides
Esters
Differentiate how esters and amides are metabolized (be specific) and list contraindications for each.
Amides:
CYP3A4 in liver
Contraindications: end stage liver dz
Esters:
Psuedocholinesterase, exerted by renal
Contraindications: psuedocholinesterase deficiency, renal insufficiency, PABA allergy
3) List 5 amide anesthetics. List 2-3 important points for each (if available).
Lidocaine/xylocaine -fastest onset, #1 preggo choice
Marcaine/Bupivicaine- longest duration w/ epi, highest risk cardiac toxicity, risk fetal Brady
“PREM”
Prilocaine
Ropivicaine- longest duration action w/out episode
Etidocaine
Mepivicaine
4) List 3 ester anesthetics.
Procaine/novocaine
CHLOprocaine
Tetracaine
5) What is the maximum safe dose of lidocaine: i) with epinephrine; ii) without epinephrine; iii) tumescent.
with epi: 7 mg/kg
w/out epi: 4.5 mg/kg
Tumescent: 55mg/kg
6) What is the advantages, disadvantages and contraindications of using epinephrine as an additive in local anesthetics?
a. Advantages: Safer (more localized/less systemic absorption), longer duration, decreased bleeding, can use more
b. Disadvantages: Decreased uterine blood flow
c. Contraindications: pheochromocytoma, uncontrolled hyperthyroid
What is the advantages, disadvantages and contraindications of using sodium bicarbonate as an additive in local anesthetics
a. Advantages: Increased speed onset, decreased pain
b. Disadvantage’s: shorter shelf life ~1 weeks
c. Contraindications: none?
8) List 8 injections techniques that can be used to decrease pain for patients.
a. Buffer with bicarb
b. Small diameter needle-30 gauge
c. Warm to room temp
d. Mildly irritate surrounding skin
e. Inject slow into deep subQ, then more superficially as retract
f. Inject in previously anesthetized area then fan out
g. Pre-treat topical anesthetics
h. Slow injection
i. Distraction
9) List 3 reactions that can occur when a patient is injected with an anesthetic. How are heart rate and blood pressure affected in each? Briefly discuss how to manage each.
1- vasovagal -HR and BP down–> trendelenburg and cool compress
2-anaphylaxis - HR up, BP down –>
Management: Stop injecting, SC epinephrine 1:1000 0.3 mL, anti-histamines, steroids, oxygen, airway support
3-anesthetic OD- HR down, BP down
-Management: Reassurance, phentolamine, propranolol
10) Discuss the signs and symptoms of lidocaine overdose, management and affect on vitals for the following ranges:
1-6 mc/mlg
6-9
9-12
>12
a. i) 1-6 mcg/ml: Circumoral numbness, digital paresthesias, metallic taste, talkative, euphoria, light-headed,
b. ii) 6-9 mcg/ml: Nausea, vomiting, muscle twitching, tremors, blurred vision, slurred speech, tinnitus, excitement, psychosis
c. iii) 9-12 mcg/ml: seizures, cardiopulmonary depression
d. iv) >12 mcg/ml: coma, cardiopulmary arrest
> 12 coma and cardiopulmonary arrest
What is the mechanism of action of vismodegib?
SMO (smoothened receptor) inhibitor–> Prevents activation of transcription factors GLI
What is vismodegib used for?
a. Adults with
-metastatic basal cell carcinoma,
-with locally advanced basal cell carcinoma that has recurred following surgery
-who are not candidates for surgery and who are not candidates for radiation.
-gorlins off label
3) List 5 side effects for vismodegib. Which is the most common?
a. Muscle spasms #1
b. Alopecia #2
c. Dysgeusia #3
d. Weight loss, anorexia
e. Fatigue
f. Vomiting/diarrhea/abdominal pain
g. Headache
h. Arthralgia
i. Pruritus
j. delayed wound healing in select patients
List 2 BRAF inhibitors.
Vemurafenib
Dabrafenib
encorafenib
What is the MOA of BRAF inhibitors
a. BRAF is a serine-threonine kinase in MAPK pathway, important for cell division. BRAF inhibitors target the BRAF V600E mutation and interfere with the MAPK signalling pathway
List 5 side effects associated with BRAF inhibitors
Cutaneous: Keratotic lesions (verrucous keratoses, KA, SCC), papulopustular exanthem, photosensitivity, plantar hyperkeratosis, alopecia,
Arthralgia
Nausea
Fatigue
Diarrhea
QT prolongation
Retinal vein thrombosis
Palmar plantar erythrodysesthesia
List 2 MEK inhibitors.
Trametinib
Cobimetinib
What is the MOA of MEK inhibitors?
a. Inhibit MEK1/2 in the MAPK pathway
Name 5 side effects of MEK inhibitors
What are 2 serious side effects
GI most common -diarrhea, N/V
Hypoalbuminemia
Dysguesia
Xerostomia
Fever, chills
Fever, ILD, cardiomyopathy, retinal vein occlusion, retinal pigment epithelium detachment, serious skin rash (rash, acneiform dermatitis, palmar plantar erythrodysesthsia)
Give an example of a CTLA-4 inhibitor.
Ipilimumab
What is the MOA of CTLA-4 inhibitors?
IPiliumab prevent the inhibitory binding reaction of CTLA-4 on T-cells with B7 antigen on APCs in the lymph node, thereby allowing the new T-cell to become activated
List 5 side effects of CTLA-4 inhibitors. What is the most common and which is the most severe?
a. Skin
i. Rash (most common)-eczematous or maculopapular
ii. Alopecia
iii. Pruritus
iv. Hypopigmentation
b. GI
i. Diarrhea, constipation, bloating
ii. Colitis–> most life threatening
c. Hypothyroid, hypopituitarism
d. Transaminitis, hepatitis
List 2 PD-1 inhibitors
Pembrolizumab
Cemiplimab
NNivolumab
List 3 PDL-1 inhibitors:
Atezolizumab
Avelumab
Durvalumab
What is the MOA of PD-1 inhibitors?
PD-1 is an immune checkpoint inhibitor expressed by activated T-cells, puts brake on immune system. Binds to PDL-1 or PDL-2 on tumor cels, inactivated T-cells. PD-1 inhibitors prevent T-cell deactivation = increased immune mediated tumoricidal
List 5 side effects of PD-1 inhibitors.
Fatigue- most common in bold
Cutaneous: Pruritus, Rash
Pneumonitis
Colitis
Hepatitis
Nephritis
Thyroid dysfunction
What are the uses for:
BRAF inhibitors
MEK inhibitors
CTLA-4 inhibitors
PD-1 inhibitors:
PD-L1 inhibitors
a. BRAF inhibitors: Melanoma
b. MEK inhibitors: Melanoma
c. PD-1 inhibitors: Melanoma, merkel cell carcinoma, BCC and SCC (cemiplimab)
d. PDL-1 inhibitors: Merkel cell carcinoma (Avelumab)
e. CTLA-4 inhibitors: Melanoma
List 4 systemic therapies that can be used to treat infantile hemangioma (IH).
Propranolol
Prednisone
Vincristine
Rapamycin
What baseline investigations would you consider in someone who you would like to treat with propranolol?
Cardiac exam, BP/HR, consider EKG
If PHACES–>MRI/MRA head/neck, echocardiograms
List 4 contraindications for propranolol.
HR< 80
BP< 50/30
Asthma
Decompensated heart failure
Heart block > 1st degree
List 5 side effects of propranolol therapy.
a. Bronchospasm
b. Hypoglycemia
c. Disrupted sleep
d. Bradycardia
e. Hypotension
f. Diarrhea
g. Somnolence
What is the initial dosing of propranolol (mg/kg/day)?
What is target dosing?
1 mg/kg/day in divided doses
2-3 mg/kg/day, max 3.4
Can propranolol be used for RICH/NICH?
n0
8) During which phase of the natural history of a hemangioma is the use of propranolol most beneficial?
proliferative
early proliferative 0-3 months, late proliferative 3-8 months
9) When should propranolol typically be administered during the course of the day?
W/ feeds
10) List 4 early and 4 late signs of hypoglycemia.
Early: shaking, fussy mood, irritable, tachy, diaphoretic
Late: Poor appetite, lethargy, seizures, hypothermia
What are the 3 interconvertable forms of Vitamin A/retinoids?
Retinol–> Retinal–> Retinoic acid
What are 3 dietary sources of retinoids? Where retinoids/derivatives stored in the body? How are they transported?
Orange/yellow vegetables, dairy, fish, meat, eggs, leafy greens
Stored in liver
Transported by retinol binding protein and transthyretin
What are the 2 broad categories of retinoic acid reecptors? How many isotypes are contained within each group?
RAR
RXR
Each have alpha beta gamma isomer
In 3-4 bullet points, explain the MOA of retinoids once inside the cell and any downstream effects.
- Inhibits transcription factors AP1 and NF-IL-6, TLR2 = decreases inflammation and cell proliferation
-Increases Th1 and decreases Th2 responses (e.g. effective against CTCL)
-↓tumorigenesis and induces apoptosis
- Antikeratinization by downregulating K6 and K16
-Inhibits ornithine decarboxylase
How do retinoids act in the cell? Describe MOA
a. Once in cytosol, transported to nucleus via Cytosolic Retinoic Acid Binding Protein (CRABP)
b. In nucleus bind to TF’s RAR and/or RXR, which bind to “RARE= retinaoic acid response elemtns” in genes regulated by these TFs
List 3 first generation retinoids, 2 second generation retinoids and three third generation retinoids. Which ones are oral and which ones are topics?
TIA AcE BATT:
1st gen both, 2nd gen oral, 3rd gen topical *except box
a. First generation:
i. Tretinoin – topical (oral does exist)
ii. Alitretinoin – oral (topical does exist)
iii. Isotretinoin – oral (topical does exist)
b. Second generation:
i. Acitretin - oral
ii. Etretinate - oral
c. Third generation:
i. Adapalene - topical
ii. Tazarotene - topical
iii. Bexarotene – oral and topical
6) What is Aklief? What is name of the retinoid in aklief?
Trifarotene
Topical retinoid for face/body acne
7) What are 5 FDA approved indications for topical retinoids?
a. Acne vulgaris (tret, adapalene, tazarotene, trifarotene)
b. Psoriasis <20% BSA (Tazarotene)
c. AIDS-related Kaposis Sarcoma (alitretinoin)
d. Fine lines/wrinkling/mottled pigmentation/rough texture (tret, tazaoretene)
e. CTCL (IA/IB) (bexarotene)
8) What are 3 FDA approved indications for systemic retinoids?
a. Psoriasis-Acitretin
b. CTCL-Bexarotene
c. Acne-Isotretinoin
Toctino/alitretinoin-hand dermatitis
List 10 adverse effects of topical retinoids (126.6).
a. Erythema
b. Scaling
c. Peeling
d. Drying
e. Pruritus
f. Burning
g. Photosensitivity
h. Hypo or hyperpigmentation
i. Ectropion
j. ACD
k. Sticky skin
What are 4 systems (broadly) are affected in retinoid embryopathy?
Cardiac/vascular
CNS
Craniofacial
Pharyngeal pouches
11) List 6 acute effects of systemic retinoids as it pertains to each of the following systems:
Mucocutaneous
Ocular
Systemic
lab
i. Xerosis with pruritus
ii. Cheilitis
iii. Skin fragility
iv. Dry eyes, mouth, nose with epistaxis
v. Retinoid dermatitis
vi. Palmar plantar peeling
vii. Granulation tissue with pyogenic granuloma like lesions
viii. Nail fragility
ix. Photosensitivity
x. Alopecia/telogen effluvium
xi. Sticky skin syndrome
i. Decreased night vision
ii. Xeropthalmia (dry eye)
iii. Blepharoconjuctivitis
iv. Blurred vision
v. Photophobia
vi. Keratitis
vii. Corneal ulceration
i. Arthralgia/myalgia
ii. Pseudotumor cererbri
iii. Worsening depression/suicidality
iv. Anorexia, nausea, diarrhea, abdo pain
v. Fatigue, lethargy, irritable
vi. Toxic hepatitis
vii. Hypothyroid Bexarotene
viii. Pancreatitis/TG elevation
d. Laboratory:
i. Hyperlipidemia: major concern TGs, can see elevated LDL, cholesterol, decreased HDL
ii. Transaminitis
iii. Agranulocytosis (Bexarotene)
iv. Leukopenia (Bexarotene)
v. Decreased T4 (Bexarotene)
vi. Thrombocytopenia/thrombocytosis
vii. Elevated CK
viii. Hypercalcemia (rare)
12) List 3 chronic mucocutaneous effects of systemic retinoids.
Alopecia
Dry eye
Corneal opacities
13) List 5 chronic systemic effects of oral retinoid use.
a. DISH-like bony changes
b. Osteophyte and bony bridge formation
c. Anterior >posterior ligament spinal calcification
d. Premature epiphyseal closure
e. Periosteal thickening
f. Myopathy
g. Osteoporotic changes in long bones
What are the contraindications for systemic retinoid use?
Absolute:
-Pregnant
-breastfeeding,
- hypersensitivity
isotret-paraben anf soybean oil, epuris also soy, Clarus soy nd paragons
Relative:
i. Leukopenia
ii. Severe hypertriglyceridemia or hypercholesterolemia
iii. Significant liver or renal impairment
iv. Hypothyroid-bexarotene
v. Psuedotumor cerebri
vi. Depression
List 4 important drug interactions when prescribing oral retinoids.
a. Vitamin A: hypervitaminosis)
b. Alcohol: liver risk, converts acitretin into etretinate
c. Tetracyclines: increased risk pseudotumor cerebri
d. Methotrexate: liver impairment, can be use in certain situations
e. Macrolide, Azalide antibacterials (Erythromycin»_space; Clarithromycin > Azithromycin): CYP3A4 inhibitors which ↑ retinoids drug levels and resultant toxicity—lipids, liver toxicity, etc.; given that systemic retinoids do not have a narrow therapeutic index, thus more moderate risk vs. CsA.
What is the typical therapeutic target dose for Accutane? What would be the target dose for a 75kg male who is about to initiate therapy with Accutane?
a. Total target: 120-150 mg/kg total 9000-11250
b. Target daily dose: 0.5-2 mg/kg/day Target dose up to 150 mg po daily (this is quite high, most would target 75 mg daily but technically up to 2 mg/kg allowed)
What is the wavelength range of UVA?
320-400
What is the wavelength range of UVB?
280-320
What is the definition of minimal erythema dose (MED)?
a. the lowest dose that causes a minimally perceptible erythema reaction at 24 hours after irradiation.
How are doses of light therapy generally determined?
70% MED or by skin type
What is the mechanism of action of psoralens + UVA?
a. Psoralens activated by UVA photons, results in 2 reactions
-Type I reaction (direct) results in photoaddition of the compound to pyrmidines in DNA, forming monofunctional adducts and crosslinking DNA = DNA synthesis suppression.
-Type II (indirect) results in generation of ROS that causes cell membrane/constituent damage
iii. Also stimulated melanocytes, selective immunosuppression
What are the side effects of PUVA? List 5
i. Pruritus
ii. Erythema
iii. Ankle edema
iv. Phototoxic reaction
v. Koebner phenomenon
vi. Friction blisters
vii. HSV recurrences
viii. Photosensitive eruptions’
ix. Due to methoxsalen alone
1. Nausea/GI disturbance
2. CNS disturbance
3. Hepatic toxicity
4. Cardiovascular stress
5. Bronchoconstriction
6. Drug fever
7. Exanthem
i. Photoaging
ii. NMSC
iii. Melanoma-controversial
PUVA increases risk for which NMSC?
SCC
What ocular issues are there with PUVA
cataracts
What are the contraindications of PUVA? Name 5 absolute, 5 relative
Hypersensitivity to psoralens
Pregnant/Breast feeding
Lupus, XP, BP, PV, OCA, porphyria
Relative:
Hx skin cancer
Photoaggravated condition/photodermatosis
Cardiac, liver, renal dysfunction
Prior radiation or arsenic exposure
What is wavelength nvUVB
311-313
What are the side effects of NBUVB?
HSV recurrence
burning
pruritus
photoaging
Blpeharitis
bullae on psoriatic plaques
PMLE
Name 5 conditions for nbUVB
Psoriasis
AD
Vitiligo
LP
PR
GA
PMLE
Excimer laser wavelength
308
What is benefit of excimer laser
High dose in localized area w
Contraindications for NBUVB
a. Absolute: Pemphigus, pemhigoid, lupus, XP
b. Relative: Hx or fam hx of NMSC, melanoma, photodamage
List 3 oral antiviral medications commonly used.
Acyclovir
Valacyclovir
Famciclovir
What is the mechanism of action of acyclovir
Undergoes phosphorylation by viral thymidine kinase to acyclovir monophosphate, then 2 additional phosphorylations by host enzyme to become acyclovir triphosphate
inhibits viral DNA polymerase by serving as DNA obligate chain terminator (competes with deoxyguanosine triphosphate) = decreased viral replication
What is one mechanism of resistance to acyclovir? What 2 medications can you use instead?
If resistance emerges, often due to thymidine kinase mutation,
can still use foscarnet and cidofovir that act direct on DNA polymerase
What are the dermatological uses of acyclovir? List 3.
HSV-first episode, recurrence, suppressive,
Varicella zoster
Herpes zoster
Recurrent EM proven to be associated with HSV
What are some side effects of acyclovir therapy?
N/V
Diarrhea
Headache
Phlebitis if IV
renal failure with rapid IV
What is the mechanism of action of cidofovir? How is it different from other antiviral agents?
Does NOT rely on phosphorylation by viral thymidine kinase
MOA:
-Nucloeside phosphate analog of deoxycytodine monophosphate = competes with substrate for viral DNA polymerase, incorporates into DNA and inhibits DNaAsynthesis and replication
What are 5 indications for cidofovir
CMV retinitis
HSV
Orf
HPV
Molluscum
What is the mechanism of action of Foscarnet?
Pyrophosphate analog, binds and prevents DNA polymerase from DNA elongation
What are 2 indications for foscarnet
CMV retinitis in AIDS
Acyclovir resistant HSV
5 side effects foscarnet
Nephrotoxicity
Electrolyte abnormalities-
including hypocalcaemia, hypophosphatemia, hyperphosphatemia, hypomagnesaemia, and hypokalemia
Thrombophlebitis
Seizures
Penile erosion
What are the s/e of Cidofovir?
Alopecia
Neutropenia
Nephrotoxicity
Cardiomyopathy
iritis
What is 1 s/e of cidofovir
Nephrotoxicity
What are the 3 side tx for warts other than imiqimod and 5-fu
Podophylotoxin
Sinecathecins
Cantharadin
What is the MOA podofilox
Anti-mitotic agent that binds to tubular, cell arrest in metaphase
What is the FDA indications podophylotoxin
genital warts
What is the MOA cantharadin? where is it derived from? What is a side effect
Blistering agent- disrupts desmosomes and causes intraepideraml pacantholysis
Spanish fly/blister beetle/Lytta Vessicatoria
Can lead to ring wart formation
What is veregen
Sinecathecin
derived from green tea leaves- derived polyphenol epigallocatechin gallate
What is the MOA and indication for veregen
• Green tea (Camellia sinensis)–derived polyphenol epigallocatechin gallate → apoptosis, inhibition of telomerase, and an antioxidant effect on cells
• Approved for genital/perianal warts; SEs are local (e.g., upain, itch, and swelling)
What are 3 examples of commonly used azoles
Fluconazole
Itraconazole
Ketoconazole *less often
What are 3 examples of commonly used azoles
Fluconazole
Itraconazole
Ketoconazole *less often
2) What is the MOA of azole antifungals?
Inhibits 14 alpha demethylase, prevents conversion of lanosterol into ergosterol import for cell membrane synthesis
How is itraconazole metabolized and what is necessary for its absorption?
Liver-Cyp 3a4
acidic
What are the FDA approved indications for itraconazole
Onychomycosis-dermatophte
Oropharyngeal candida
Aspergillosis, Blasto, histo
Dosing for itraconazole for onychomycosis
200 mg daily x 3 month
or
200 BID x 1 week x 2-4 pulses
What are itraconaolze contraindications
CHF, ventricular dysfunction,
Pregnancy
Hypersneisivity to itoa or prior azaleas
Concomitant medications: c yp3a4 substrates
See below
Name the contraindicated medications for itraconazole use?
CYP3A4 substrates as it is a CYP3A4 inhibitor and will increase levels of the medications, can lad to prolonged QT and tornadoes
i. Cardiac: Statin (simva, lova), warfarin, riva, quinidine, dofeletide/disopyramide/dronedarone (anti-arrhythmics)
ii. Abx: Clarithro/erythro
iii. Immune modulators: Tacro, CsA, dapsone, colchcine,
iv. Psych: midaz, triazolam, Methadone, luradisone, Pimozide (Tics)
v. Misc: cisapride (GERD, off market), ergot alkaloids (PPH, migraines)
NAME 8:
Cisapride
Pimozide
Quinidine
Statins
Erythro/clarithro
Dapsone, colchicine, tacro, csa
Dofeletide,
Ergot alkalooids
Midaz
Lurasidone
nisoldipine
What are the common side effects of itraconazole therapy?
a. Common/nuisance: GI (nausea, vomiting, diarrhea, abdominal pain), cutaneous (rash), neuro (headache), edema, LE rise, rhinitis, fever
b. Serious/rare: Neuro (hearing loss, peripheral neuropathy), CV events/CHF (torsades, QT prolong), GI (dysgeusia, hepatotoxicity, pancreatitis) labs (neutropenia/leukopenia, hypokalemia), pulmonary edema,
How is Fluconazole metabolized and what is necessary for its absorption?
Very little hepatic metabolism
What are the FDA approved indications for fluconazole? Off-label?
a. Oropharyngeal/esophageal/vaginal candidiasis, cryptococcal meningitis
b. Off label: tinea, cutaneous candida, systemic candida, onychomycosis (150-300 mg once a week for 3-6 months or 9-12 months for toes), coccoidal meningitis
What CYP does fluconazole inhibit
CYP 2C9
Name the contraindications to fluconazole
Known hypersensitivity to fluctuate or other azaleas
o Do NOT administer with pimozide, quinidine, cisapride, erythromycin, TERFENADINE, astemizole, voriconazole, or statins or 2c9 substrates
What are the common side effects of fluconazole therapy?
Common: GI, headache, skin rash 9exfoliative)
Serious:
GI: hepatotoxicity, dysguesia
CV: Cardiac toxicity e.g., Torsades
Skin: Severe skin
Neuro: seizures
Blood-cytopenias
Labs: Hyperlipidemia
Compare and contrast itraconazole in terms of cardiac toxicity, liver toxicity and medication interactions, and neurological s/e
effectiveness on sites
Cardiac: Both increases risk arrhythmia, itra CHF is contraindicated
Liver: higher risk itraconazole
Drugs: higher risk itra (at doses of flu 200)
ITRACONAZOLE risks of cytopenias, hearing loss, neuropathy vs. seizures w/ fluc
OVerall: Fluconazole best tolerated, secreted into sweat glands, great for skin, candida good,but not good for nails. Less liver toxic.
Itra better for nails, also good Canada, higher risk liver. take with coke. more drug interactions. More cytopenias, hearing loss, neuropathy.
13) What are some unique side effects of voriconazole therapy?
Photoxicity
XP-like changes
Increased risk SCC
Psuedoporpyria
14) What is the MOA of allylamines?
a. Inhibits squalene epoxidase prevents conversion of squalene to lanosterol, squalene builds up=toxic and decreases cell membrane synthesis
15) How is terbinafine metabolized
Liver- CYP 2D6
What are the indications FDA for terbinafine
Dermatophyte onychomycosis
Tinea capitis
Off-label: tinea infections, subcutaneous/systemic mycoses (e.g., histoplasmosis and chromoblastomycosis), and other types of onychomycosis (good for Aspergillus, but not Candida)
List 3 systemic antiparasitic agents and 4 topical antiparasitic infections.
Albendazole
Ivermectin
THiobendazole
Topical:
Permethrin
Malathion
Albendane
Spinosad
lindane
What is the MOA of ivermectin?
Binds glutamate gated chloride ion channels in parasite nerve and muscle cells, hyper polarizes and can cause cell death
What is the FDA indication for ivermectin- 2
Strongyloides
Onchocerciasis
What are off label uses of ivermectin
Larva migrans
pediculosis
scabies
What are important s/e of ivermectin, what is the mazotti reaction and how is it treated
Rash
itch
Fever
LAD
Death and encephalopathy in those w/ loiasis
Mazotti:
urticaria
fever
edema
hypotension
arthralgia
abdominal pain
ocular sx
- more common when treating onchocerciasis,
can tx w/ doxy
MOA albendazole
Stops tubular polymerization–> causes immobilization and death
NAme 2 FDA indications albendazole and 4 off label indications
FDA:
Neurocystisercosis, Hyatid disease
Off label:
Strongyloides stercoralis, Giardia, scabies, Necator americanus (hookworms)
Others:
Ascaris lumbricoides, Trichuris trichiura, Enterobius vermicularis, Ancylostoma duodenale and Taenia,
8) What are important side effects of albendazole?
Bone marrow suppression: aplastic anemia and agrnaulocytosis
Hepatotoxicitty
MOA permethrin
Disabels sodium transport channels on cell membrane–> paralysis
What are 2 uses of permethrin and how are they applied
Scabies
Pediculosis capitis
Apply to entire body neck down, x 2, 1 week apart, 8-12 hrs
5% for scabies, 1% pediculosis
What is the MOA of malathion? List 4 side effects. list the main use
Malathion- Organophosphate that inhibits acetylcholinersterase in arthropods- leads to paralysis
Use: pediculossis capitis
S/e: Flammable, local irritation, malodorous, when ingested organophosphate poisoning
MOA of lindane
Organochloride-decreases neurotransmission via inhibitions gaba gated chloride channel- paralysis
What is lindane used for?
pediculosis as 2nd line agent
what is permethrin mc used for
scabies, pediculosis
13) What is an important side effect of Lindane?
seizures/neurotoxic, aplastic anemia, leukemia
NAme 4 tx for pediculosis
malathion
permethrin
lindane
spinosad
Name 2 treatments for scabies
permethrin topical
oral ivermectin
