two types of anti-inflammatory agents for the skin
topical corticosteroids and tar compounds
variation on steroid transdermal absorption based on region
high: face, scalp, armpits, groind
medium: chest, back, abdomen
low: hand, feet, arms, legs
low potency topical steroid
intermiediate
high
highest
triamcinolone
hydrocortisone
desoximetasone
clobetasol
what skin conditions are coal tar used for
issues
psoriasis, lichenified dermatitis for anti-itch effect
messy, can be irritating
three ingredients of triple abx ointment
neomycin, bacitracin, polymyxin
what is mupirocin used for
atabax
gram + (impetigo)
also impetigo
typical topical azoles
miconazole
clotrimazole
ciclopirox is good for what
in lotion its good for tinea
in nail polish its good for onychomycosis
what is oral terbinifine used for
how long is the treatment
what must be monitored
onychomycosis
3-6mo
can be liver toxic
types of drugs used for acne
retinoids
benzoyl peroxide
azelaic acid
ABx
what are retinoids made of
what are they used for
vitamin A derivatives
acne and psoriasis
general guidelines for retinoid use in acne
8-12 weeks to max benefit
may make acne look worse to start
avoid mucous membranes and eyes
use sunscreen after treatment ↑risk of skin cancer
100% necessity for retinoid therapy
must be on oral contraceptives because they cause birth defects
ADRs related to isoretinoin
chapped lips
dry skin
nose bleeds
dry eyes
action of bezoyl peroxide for acne
what is it tpically paired with
opening skin pores with some intrinsic antibiotic effect
clindamycin or erythromycin
what is the mode of action of azelaic acid
common side effect
antibacterial and may ↓test conversion ot DHT
erythema and dryness
Abx for acne treatment
systemic: tetracycline or erythromycin
topical: clindamycin, erythromycin, metronidazole
anti itching drugs
steroids
doxepin
pramoxine
doxepin is a what?
what is its method of action
ADRs?
tricyclic antidepressant
not sure, possible antihistamine effect
drowsiness, exacerbate narrow angle glaucoma
pramoxine for dermal itching
topical anesthetic, not going to fix the issue!
can be used with hydrocortisone
may cause burning
psoriasis defined
females <>=males?
symptoms
chronic relapsing skin disorder
no bias
itching, joint inflammation, depression
wht causes psoriasis
rapid turnover of skin cells
psoriasis treatment options
high potency topical steroids and tar
acitretin
tazarotene
calcipotriene
ADRs of acitretin
no blood donation, requires 3 years to clear system
no alcohol (liver toxic)
ADRs with tazarotene
<20% of body surface is treated
can be teratogenic
also photosensitizing
ADRs with calcipotriene
hypercalcemia, but rare
general causes of anemia
nutritional deficiency (folate, iron, B12)
EPO ↓ (CKD)
hemolysis (genetic, drug induced, autoimmune)
bone marrow suppression (drugs, cancer, aplastic anemia)
typical causes of iron deficient anemia
poor diet
increased need
chronch blood loss
treatment for iron deficient anemia
ferrous sulfate
ferrous glucaonate
IM or IV iron
compliance issues with iron supplements
GI upset very common
black stools
might need a creative dosing schedule
what is the role of vitamin C in iron therapy
500mg taken with iron sulfate can help absorption
what is the last resort for iron deficient anemia
why should you refer
parenteral
anaphylaxsis risk warrants refereal
chronic hemochromatosis can come from what
iron toxicity leading to organ failure
iron toxicity in pediatrics can becaused by how many pills
what is the risk
>10
neocrotizing enteritis
when should iron supplements be avoided
men with normal diets
non-menstruating women with normal diets
causes of vitamin b 12 deficient anemia
diet deficient
loss of intrisic factor
why is dietary deficiency of vitamin B 12 rare
small daily needs with large stores
what might cause loss of intrinsic factor leading to anemia
pernicious anemia, gastric surgery, gastric atophy
what causes pernicious anemia
DX by what
treatment consideration
intrinsic factor autoantibodes that ↓folate absorption
megaloblastic anemia and progressively declining neurologic function
treating the folate ↓ will fix anemia but not the the neuro issues
usual treatment for Vit B 12 deficienct
IM injections daily, then weekly, then monthly
OR massive oral doses
what is folate used for
what will low folate do to a fetus
essential cofactor for AAs, purines, DNA
↑ risk for ancephaly and spina bifida
folate deficiency is caused by what
diet (↓ fruits and veg)
↓absorption (sprue, drugs)
↑increased need (pregnancy, hemolytic anemia)
important safety rule regarding folate and B12 for anemia
NEVER prescribe folate for megaloblastic anemia UNLESS you are sure the patient’s B-12 level is normal
EPO toxicity issues
increase viscosity can cause HTN or DVT
↑risk of CVA or MI with chronic don’t come
can ↓cancer surviability
describe the chemical process of a clot
fibrinogen is convered to thrombin by prothombin and then is converted to fibrin
plasmin starts to break the clot down into d-dimer and spllit fiborin products
natural anticoagulants
antithrombin III
protein s and c
what accelerates the action of antithrombin III
heparin
most common genetic cause of hypercoagulability
what does it do
abnormal factor V (Leiden)
factor V Leiden cannot be inactivated by protein C
most common presentation of thrombosis
MI, ischemic stroke, DVT
treatment of an acute thrombic event
thrombolysis
anticoagulation
thrombectomy
anticoagulation strategies
block platelet function
inhibit thrombin directly
inhibit thrombin indirectly (vit K or ↑antithrombin III)
inhibit factor X
antiplatelet approaches for anticoagulation
block prostaglandin
inhibit ADP pathway
block IIb/IIIa platelet receptors
antiprostaglandin approach to anticoagulation
asipirin to prevent CVD
can cause GI bleeds
Anti-ADP approach to anticoagulation
drugs
primary use
side effects
plavix
adjunct to stent, used chronically to prevent MI or CVA
nausea, diarrhea, leukopenia
what is action of coumadin drugs
why is it still used today
interferes with the action of Vitamin K in clot formation
cheap, welll understood, reversible
how long does it take for warfarin to have an effect
how should it be monitored
8-12 hours with no loading dose
prothrombin time ratio (INR)
what two things will cause megaloblastic anemia
vit B and folic acid deficiency
what is the target INR for warfarin
2-3.5
ADRs with coumadin
hemorrhage
fetotoxic
multiple drug interactions
dietary restrictions
what should be done when prescribing warfarin or with a patient who is on warfarin
check for drug interactions
what is the action of heparin
enhances the action of antithrombin III (inhibits activation of factor X)
two types of heparin
unfractionated and LMW
what is the choke point between the intrinsic and extrinsic pathways for clotting
factor x or thrombin
how is heparin therapy monitored
what is the goal
activated protamine titration (PTT)
goal is 2-2.5 x control
indications for heparin use
prophylaxis (surgery, ICU)
theraputic (DVT, PE)
Heparin Toxicity
hemorrhage
thrombocytopenia
osteopenia
heparin induced thrombocytopenia type II
what is the reactive measure for this
Two types, Type II is an immunte related drop in platelets that leads to thombosis
immediately stop thrombin and start something else
why does HIT cause thrombosis with thrombocytopenia
because all the platelets are being take up by clots
what is the advantage of LMW heparin
↓risk of thrombocytopenia or osteopenia
usually no monitoring needed
can be used at home
LMW heparin preparations
enoxaprin (lovenox)
when can a patient be switched from lovenox to warfarin
INR > 2 for two consecutive days
what is the advantage of arixta over lovenox
daily dosing
better at DVT prevention with equal prevention of thrombosis
common treatment for the prevention of MI
clipidogrel (plavix) + aspirin (↑risk for GI bleeds, but relatively small)
what is dabigatran (predexa) used for
what is the advantage over other drugs
issues
thombin inhibitor
better at preventing stroke and afib, no monitoring
non-reversible, more GI upset, expense
two factor X inhibitors
rivaroxaban (xarelto) and apixaban(eliquis)
what is the advange to factor X inhibitors in anticoagulation
what are the drawbacks
oral, no monitoring, no diet restriction
expensive, not easily reverible
treatment strategy for an acute thrombus
thombolysis
anticoagulation
thrombectomy
rules for thrombolytic therapy
sooner is better
its not always effective
can cause hemorrhage
what is the action of thrombolytic drugs
activates plasminogen to become plasmin
indications for thrombolytics
DVT, PE, ischemic stroke, clotted shunts/catheters
examples of thromblytic agents
what is their universal method of adminstration
streptokinase, urokinase, etc
all given IV
what is the cheapest thrombolytic drug
streptokinase
contraindications for thrombolytics
<10days post op
serious GI bleed
HTN (diastolic >110)
pregnant
reversal agents for fibrinolytics (streptokinase)
aminocaproic acid (amicar)
what is used to reverse heparin
protamine sulfate
three methods for reversing warfarin
vitamin K, FFP, prothrombin concentrats
what is the risk with treatment for refludan
since it comes from leechs it can cause an allergic reaction
multistep theory of oncogensis
there must be an activated oncogene and a deactivated or overwhelmed tumor suppressor gene
driver mutations
oncogenic mutations that drive the cancer process, tend to be the same in the same types of cancer
hitchhiker mutation
mutations found in cancerous cells that don’t necessarily contribute to the disease
four pillars of cancer treatment
surgery
chemo
radiation
immunetherapy
what types of cells are most susceptible to cytotoxic chemo
rapidly dividing cells
what is the rationale of chemotherapy in cancer treatment
because cancer cells are genetically fragile and rapidly dividing they are susceptble to chemo, allowing therapy to kill the tumor without killing the patient
weaknesses on cancer cells that can be exploited by chemo
outgrows blood supply
decreased ability to repair themselves
multiple mutations
most cancers have unique antigens
factors affecting prognosis of cancer
cancer type
differentiation
staging at Dx
age
quality of medical care
how does a clinician know when to stop chemotreatment
Biochemical markers (HCG, CEA, PSA)
clinical markers (palpable nodes, imaging)
how can cancer cells develop resistance to treatment
what can be done to prevent this
genetic mutations continue after malignant transformation
use the correct amount of the correct drug
what is the action of alkylating agents
three examples
what are three ADRs
damages the DNA in dividing cells
cyclophosphamide, ifosfamide
nausea, germ cell destructon, bone marrow suppression
types of antimetabolite chemo drugs
folic acid analogs (methotrexate)
purine analogs (mercaptopurine)
pyrimidine (flurouracil)
typical ADR of methotrexate
bone marrow suppression, mucosal ulcers, hepatotoxic
what is the action of antibiotic chemo
one example
Three ADRs
disrupt DNA
dactinomycin
bone marrow suppression, cardiac toxicicity (adriamycin), pulmonary toxicity (blenoxane)
action of microtubule inhibitors
ADRs
interrupts mitotic spindle
bone marrow suppression, hypersensitivity
common uses for tyrosine kinase inhibitors
ADRs
leukemia, lung cancer, renal cell carcinoma
drug interactions, bone marrow suppression
what is the action of topoisomerase
commonly used for what?
ADR
blocks enzyme for DNA supercoiling
lung, ovarian, colorectal
bone marrow suppression
two types of platinum corrdination complexes used in chemo
ADRs
cisplatin, carboplatin
severe nausea, ototoxicity
how is predinosne used in chemo
acute leukemia and lymphoma
how is tamoxifen used in chemo
reduced risk of breast cancer recurrenct
how is letrozole or armidex used in chemo
anti aromatases, used to prevent breast cancer
how is estrogen used in chemo
prostate cancer
how is lupron used in chemo
down regulation of FSH receptors produces low androgen levesl
how is dexamethasone used in chemo
anti emesis, blocks hypersentivity reactions
what is the advantage of immune therapy
it has targeted treatment against specific mutations in cancer cells that uses that patients own immune system
specific tactics of immune cancer therapy
prevent evasion of apoptosis
increased immune response
monoclonal antibodes against specific targets
what is the use of PD-1 blockade in cancer patients
allow cytotoxic t cells to recognize cancer cells and kil them
what is the advantage of PD-1 blockade
20-25 durable response rate, especially useful in difficult to treat cancers (renal cell, melanoma)
what is the action of interferon therapy in cancer treatment
notable ADRs
stimulation of NK cells
neuropsyciatric
describe in vitro immune enhancement
in cancers with a specific antigen, lymphocytes can be cultured with that antigen and reinfused to target those cells
what is the issue with in vitro lymphcyte training
it doesn’t add much to life span an costs a lot
describe lymphocyte gene therapy
lymphocytes are removed and exposed to a retrovirus that will force expression of CD19nreceptors (b cells)
reinfused T cells will then go kill b cells (used for B cell leukemia/lymphoma)
what is the most important determinant of cancer biology
cancer genomics, not organ of origin
what is HER2 therapy for breast cancer
monoclonal antibodies (herceptin) with or without (herceptin + mertansine) will attack cells with mutated human endothelial growth receptor, improving prognosis for HER2 cancer
ADRs related to HER2 therapy
cardiac toxicity, especially between trastuzumab and doxorubicin
describe VEGF therayo for cancer therapy
inhibits the BRAF gene, improves outcomes in melanoma, colon, lung cancer
why is prevention of bone marrow suppression important to chemotherapy
better bone marrow function increased tolerance to additional chemotherapy
how is EPO used in cancer treatment
helps prevent anemia in the presence of bone marrow suppression
what is the action of granulocyte colony stimulating factors
one notable ADR
helps prevent neutropenia
can cause bone pain