Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
314 Cards in this Set
- Front
- Back
|
define hypersensitivity
|
reaction of the immune response is inappropriate or exaggerated
|
|
|
incidence of hypersensitivity
|
6-10% of observed ADRs in patients
|
|
|
risk for allergic reactions among hypersensitivity reactions
|
1-3%
|
|
|
incidence of fatal allergic reactions
|
1/10,000
|
|
|
define drug allergy
|
an immunologically mediated reaction characterized by specificity, transferability by antibodies (Ab) or lymphocytes and recurrence on re-exposure
|
|
|
define pseudoallergic reaction
|
a reaction with the same clinical manifestations as allergic reaction (e.g. histamine release, complement activation) but lacking immunological specificity
|
|
|
8 features of an allergic reaction
|
-occurs in small %
-rxn does not follow pharmacology -typical syndrome (anaphylaxis, rash, etc) -lag between 1st exposure and event -independent of dose (smaller doses may decrease response) -reproduced with similar agents -eosinophilia -resolves on discontinuation |
|
|
type I reaction
|
-immediate hypersensitivity
-IgE mediated |
|
|
type II reaction
|
cytotoxic (anemia, thrombocytopenia)
|
|
|
type III reaction
|
immune complex
|
|
|
type IV reaction
|
cell-mediated (delayed)
majority of rashes |
|
|
describe immediate hypersensitivity (known mechanism)
|
(upon 2nd exposure)
-occurs within 30 minutes -requires pre-exposure of IgE antibodies -IgE cross-links -activation of cells / preformed mediators (histamine, proteases, LTs, PGs, PAF) |
|
|
hazy mechanisms of type I reactions
|
skin manifestation
-rashes -targeted skin lesions -Stevens-Johnson -toxic epidermal necrosis drug fever others |
|
|
describe anaphylactoid reactions
|
-release inflammatory mediators, but not immunologically through IgE
opiates contrast dye vanco (red man syndrome) |
|
|
incidence of anaphylaxis
|
10-20 / 100,000 ppl/year
|
|
|
# of deaths of anaphylaxis / year in the US
|
1500 of deaths of anaphylaxis / year in the US
|
|
|
4 common anaphylactic agents
|
ASA
NSAIDs penicillins insulin |
|
|
Panel Definition of Anaphylaxis
|
Any 3
1) acute onset with skin or mucosa, plus a) respiratory compromise OR b) reduced BP or organ dysfunction 2) 2+ after allergen exposure -skin/mucosa -respiratory compromise -low BP -GI symptoms 3) low BP after allergen exposure |
|
|
5 mediators in bronchospasm
|
histamine
PG LT bradykinin PAF |
|
|
4 mediators in mucus secretion
|
histamine
PG LG HETE |
|
|
4 mediators in mucosal edema
|
histamin
PG LT bradykinin |
|
|
4 mediators in airway inflammation
|
-neutrophil chemotactic factor
-eosinophil chemotactic factor -PAF -LT |
|
|
describe serum sickness
|
Type II - cytotoxic reaction
-soluble immune complexes -7-14 days post exposure -fever malaise, arthralgias -drug causes |
|
|
4 common drugs that cause serum sickness
|
sulfa
hydantoins penicillins cephalosporins |
|
|
describe drug fever
|
-diagnosed by exclusion, no other causes
-2-5% of hospital ADRs -fever (>100.4) with no pattern, but is dose dependent -w/ rash (18%) or eosinophilia (22%) |
|
|
4 common drugs that cause drug fever
|
cardiac
antimocrobial antineoplastic CNS |
|
|
4 types of drug-induced autoimmunity
|
SLE
hemolytic anemias interstitial nephritis drug-induced hepatitis |
|
|
4 Sx of SLE
|
arthralgias
rash polyarthritis renal/pulmonary |
|
|
3 common drugs that cause SLE
|
hydralazine
INH procainamide |
|
|
1 common drug that causes interstitial nephritis
|
nafcillin
|
|
|
describe vasculitis
|
-inflammation of the blood vessels
-cutaneous or organ systems |
|
|
5 common drugs that cause vasculitis
|
allopurinol
beta-lactams sulfas thiazides phenytoin |
|
|
top 10 drugs that cause skin reactions
|
amoxicillin
SMX/TMP ampicillin iodopate blood cephalosporin erythromycin hydralazine penicililn G cyanacobalamin |
|
|
most common type of rash
|
maculopapular
|
|
|
describe maculopapular rashes
|
-start on trunk, areas of pressure
-flat or raised, may have vesicles -mild fever, involvement of mucus membranes, possible |
|
|
time course of maculopapular rashes
|
early: within hours or up to 3 days in a previously sensitized patient
late: 9 days after exposure |
|
|
pathogensis of maculopapular rashes
|
Type IV - cell-mediated
usually fade after D/Cing drug |
|
|
3 Tx for maculpapular drug reactions
|
-cool water baths/compresses
-systemic antihistamines for pruritis -short course of steroids not hugely concerning |
|
|
describe urticaria/angioedema
|
concerning
raised well-definied pruritic erythematous wheals fever, lymphadenopathy, joint swelling, arthralgias possible time course: 12-36 hours |
|
|
pathogenesis of urticaria, angioedema
|
Type I: IgE immune complexes
pseudoallergic reaction |
|
|
2 Tx of urticaria, angioedema
|
antihistamines
doxepin (affinity for H1 and H2) topicals not recommended: contact sensitization |
|
|
describe fixed drug reactions
|
-an erythematous or hyperpigmented round/oval lesion
-color change from pale red - dusky red - gray brown that may not go away -recurrence of eruption in the exact location as the previous reaction -pruritis, painful burning sensation |
|
|
pathogenesis of fixed drug reactions
|
T-cell attack on epidermal cells
|
|
|
3 Tx of fixed drug reactions
|
-stop drug
-cool water compresses -bleaching creams corticosteroids and antihistamines have no effect because the pathogenesis is T cell mediation |
|
|
describe erythema multiforme
|
-acute cutaneous reaction on hands, feet, face, limbs, and mucous membranes
-round erythematous macule becomes edematous and papular -they enlarge to plaques to form an erythematous periphery with a clear center, aka a iris/target lesion -resolves in 4-5 days -postinflammatory hyperpigmentation occurs without healing |
|
|
describe Stevens Johnson Syndrome
|
-extensive mucosal and conjunctival edema
-high fever -myalgias -vomiting/diarrhea -arthralgias |
|
|
Pathogenesis of Stevens Johnson Syndrome
|
immune complex and/or cell mediated immunity
|
|
|
4 Tx for Stevens Johnson Syndrome
|
-supportive
-antihistamines for pruritis -cool water compresses -hydrogen peroxide for oral lesions -steroids?? |
|
|
3 common drugs that cause SJS
|
sulfonamides
SMX/TMP oxicam |
|
|
age RF for SJS
|
young, middle aged adults
because they have really good immune systems |
|
|
gender RF for SJS
|
twice as common in females
|
|
|
genetic RF for SJS
|
-HLA types predispose allergies to ASA and insulin
-slow acetylators: sulfonamide reactions (esp with HIV) |
|
|
drug related RF for SJS
|
-macromolecular size (complete antigens)
-bivalence (can crosslink receptors) -haptens (small MW substances that become immunogenic when conjugated with a carrier molecule) -route of therapy worse with topical>IV>PO |
|
|
2 aggravating factors for SJS
|
pregnancy
asthma |
|
|
hypersensitivity incidence in beta-lactam use
|
<1 - 8%
|
|
|
severity of beta-lactam hypersensitivity
|
severity varies
from rash to anaphylaxis |
|
|
allergic components of beta-lactams
|
major determinants
minor determinants (most common) |
|
|
cross-reactivity of cephalosporins and beta-lactams
|
3-18%
penicillin allergics may tolerate cephalosporins, but not usually v.v. |
|
|
cross-reactivity of carbapenems and beta-lactams
|
20%?
|
|
|
incidence of hypersensitivity to radiocontrast media?
|
1-3%
0.01% - 0.04% anaphylaxis |
|
|
Sx of hypersensitivity to radiocontrast media
|
delayed skin reactions are most common
|
|
|
mechanism behind hypersensitivity to radiocontrast media
|
cloudy
|
|
|
4 RF for hypersensitivity to radiocontrast media
|
-female
-Hx of atopy (e.g., contact dermatitis) -Hx of asthma -allergy, cardiac disease, beta-blockers |
|
|
5 Other common classes of drugs that cause hypersensitivity
|
-ASA, NSAIDs
-Sulfas (esp in HIV) -dyes/additives (tartrazine, sulfites, parabens) -chemotherapy -anticonvulsants |
|
|
7 components of detailed drug history
|
-prior allergy and medication Hx
-nature/severity of rxn -temporal relationships (IgE rxns are fast) -prior exposure to similar agents -effect of discontinuation (half-life x 5) -route of administration (preservatives?) -other medical problems |
|
|
describe skin testing
|
-best defined with Abx
-intradermal or percutaneous ---no commercial major determinants ---misses minor determinants ---tried w/ commercial drugs, effect not known negative tests are helpful ---unlikely Type I ---no predictive value for delayed skin |
|
|
Tx of anaphylaxis
|
-stop offending agent
-EPI -fluid (maintain BP) -diphenhydramine -corticosteroids |
|
|
describe desensitization
|
-used for IgE reactions only
-PO route preferred -close supervision 5-20% will have cutaneous reaction -transient, lasts only 48 h after last dose -keeps mast cells from accumulating histamine |
|
|
Type I Osteoporosis
|
postmenopausal osteoporosis
|
|
|
Describe Type I Osteoporosis
|
-increased trabecular bone loss
-occurs mainly during 1st 3-6 years -bone loss can continue for 20 years |
|
|
common fractures in Type I osteoporosis
|
vertebral
distal radius (wrist) tooth loss |
|
|
Type II Osteoporosis
|
senile osteoporosis
|
|
|
age of onset for senile osteoporosis
|
over 70 years old
|
|
|
gender differences in senile osteoporosis
|
F:M 2:1
|
|
|
bone loss in senile osteoporosis
|
trabceular bone loss
|
|
|
common fractures in Type II osteoporosis
|
hip
pelvic vertebral |
|
|
Type III osteoporosis
|
secondary osteoporosis
|
|
|
age of onset for secondary osteoporosis
|
any age
|
|
|
gender differences between secondary osteoporosis
|
women = men
|
|
|
10 disease states that can cause type III osteoporosis
|
chronic liver failure
chronic kidney failure hyperthyroidism 1' hyperparathyroidism Cushing's GI resection malabsorption Ankylosing spondylitis lupus RA |
|
|
ratio of people who have an osteoporosis related fracture in their life time
|
1:2 women
1:5 men |
|
|
osteoporosis is responsible for how many fractures annually
|
1.5 million
hips vertebral wrist other |
|
|
3 functions of bone
|
-structural support
-depot for Ca, P, Mg, Na, CO3 -provides homeostasis of above ions and buffers |
|
|
2 types of bone
|
cortical (compact)
cancellous (trabecular) |
|
|
describe cortical bone
|
-located on midshafts and outer surfaces of long and flat bones
-75% of skeletal mass -low porosity and S:V -decreased metabolic activity -provides structural support |
|
|
describe cancellous bone
|
-found in inner aspects of the metaphysis of long bones and between the cortical surfaces of vertebra, ribs, and pelvis
-25% of skeletal mass -high porosity and S:V -increased metabolic activity |
|
|
function of a bone multicellular unit (BMU)
|
repair damage and calcium homeostasis
|
|
|
5 phases of bone remodeling
|
-resting/quiescence
-activation -resporption -reversal -formation |
|
|
2 types of cells involved in bone remodeling
|
osteoblasts
osteoclasts |
|
|
function of osteoclasts
|
bone resorption
|
|
|
osteoclasts are activated by (8)
|
PTH
vitamin D osteoblasts IL-1 lymphotoxin **glucocorticoids thyroid hormone TNF |
|
|
osteoclasts are inhibited by (3)
|
calcitonin
estrogen transforming growth factor-beta |
|
|
function of osteoblasts
|
bone formation
|
|
|
osteoblast activity is regulated by (6)
|
-PTH
-Vitamin D -insulin -growth factor -transforming growth factor-beta -platelet derived growth factor |
|
|
osteoblasts are inhibited by (1)
|
glucocorticoids
|
|
|
6 nonmodifiable RFs for osteoporosis
|
-advanced age
-female gender -whites > hispanics > blacks (based on bone mass) -FH -small stature -early menopause or oophorectomy |
|
|
9 modifiable RFs for osteoporosis
|
-sedentary lifestyle
-decreased mobility -excessive EtOH use -low body weight -drugs -medical disorders -low calcium intake -low vitamin D intake |
|
|
in women, describe changes in cortical bone
|
peaks around 30
-3% per decade to menopause -9% per decade menopause to 75 -3% per decade from 75-90 -6% per decade thereafter |
|
|
in women, describe changes in trabecular bone
|
6% per decade
|
|
|
in men, describe changes in cortical bone
|
3-4% per decade
|
|
|
in men, describe changes in trabecular bone
|
2% per decade
|
|
|
WHO T scores
|
normal: >-1.0
osteopenia: -1.0 to -.25 osteoporosis: <-2.5 |
|
|
who should be treated for osteoporosis?
|
-F (pm) and M age 50+
AND ONE of the following -hip or vertebral fracture -T < -2.5 at femur, neck, or spine -osteopenia + 10 y probabilities (>3% hip, >20 other) |
|
|
7 nonpharm for osteoporosis
|
-exercise
-increased muscle strengh -minimize or eliminate alcohol and smoking -fall safe environment -adequate Ca and VitD -proper diet -minimize/eliminate medications that can increase fall risk or increase bone loss (***BZDs) |
|
|
MOA of bisphosphonates
|
inhibits osteoclast activity
|
|
|
administration of bisphosphonates (PO)
|
-empty stomach
-take with 8 oz water, upright -stay upright x 30-60 minutes w/ no food |
|
|
Px dosing of alendronate
|
5 mg po QD
35 mg po QW |
|
|
Tx dosing of alendronate
|
10 mg po QD
70 mg po QW |
|
|
dosing of risedronate
|
5 mg QD
35 mg QW 150 mg QM (or 75 mg x 2) |
|
|
dosing of ibandronate
|
2.5 mg QD
150 mg QM |
|
|
dosing of zolendronic acid
|
5 mg/100 mL IV over 15 minutes Q YEAR
|
|
|
differences between alendronate/risedronate and ibandronate/zolendronic acid
|
alendronate/risendronate
----M/F ----dec all Fx ibandronate/zolendrenic acid ----F only ----decreases vertebral Fx only |
|
|
use of teriparatide
|
type I
type III - men who have hypogonadal osteoporosis |
|
|
MOA of teriparatide
|
PTH recombinant
increases osteoblast activity |
|
|
dosing of teriparatide
|
20 mcg SC thigh/abdomen
|
|
|
ADR of teriparatide
|
Nausea
dizziness leg cramps inc HR/ orthostatic hypotension possible hypercalcemia osteosarcoma |
|
|
DI of teriparatide
|
-bisphosphonates
-hypercalcemia can cause digoxin toxicity |
|
|
MOA of estrogen replacement therapy
|
inc bone mass
dec bone loss |
|
|
dosing of estrogen replacement therapy
|
0.625 mg conjugated estrogens QD
|
|
|
ADR of estrogen replacement therapy
|
-vag bleeding
-breast tenderness -CA, TE, CVD -pedal edema -weight gain |
|
|
clinical benefit of estrogen therapy
|
all fractures
lipid metabolism |
|
|
MOA of raloxiphene
|
estrogen R agonist/antagonist
antagonist in uterus, breast agonist in bone, lipids |
|
|
dosing of raloxiphene
|
60 mg QD
|
|
|
ADR of raloxiphene
|
hot flashes
CP, TE weight gain GI |
|
|
calcitonin MOA
|
inhibits osteoclasts
|
|
|
dosing of calcitonin
|
200 IU in 1 nostril, alternating every day
|
|
|
place in therapy of calcitonin
|
bone pain
NO EVIDENCE FOR FRACTURE REDUCTION |
|
|
ADR of calcitonin
|
inhibits osteoclasts
|
|
|
what is the MOA of GC induced OP?
|
-increased activity of osteoclasts
-decreased activity of osteoblasts MEN - decreased testosterone -increased excretion of Ca -decreased absorption of Ca |
|
|
when does GC induced OP occur?
|
right away in the first 6-12 months of therapy
|
|
|
which bone loss is greater with GC induced OP?
|
trabecular bone loss is greater
|
|
|
Px of GC induced OP
|
-D/C GC if possible
-use lowest effective dose (<5 mg/d) -alternate day therapy -supplement Ca and Vit D -HRT |
|
|
monitoring for GC-induced OP
|
-BMD before starting
-DEXA of femoral neck or lumbar spine -repeat BMD q 6-12 months with chronic use |
|
|
Tx of GC-induced OP
|
-Ca (1200 mg/d)
-vitamin D (800-1000 IU) -bisphosphonate (alen/rise) -HRT (esp testosterone) |
|
|
when should OP in men be evaluated?
|
-over 70 yo
-pts with conditions assocaited with low bone loss -pts with fragility fractures |
|
|
Px of OP in men
|
-peak bone mass
-physical exercise -hormones -risk factor modification |
|
|
Tx of OP in men
|
-Ca and vitamin D
-testosterone if low -alendronate -teriparatide |
|
|
3 layers of adrenal cortex
|
zona glomerulsa
zona fasciculata zona reticularis |
|
|
zona glomerulosa secretes
|
aldosterone
|
|
|
zona fasiculata secretes
|
cortisol
|
|
|
zona reticularis secretes
|
testosterone
estradial (from cholesterol) |
|
|
adrenal medulla secretes
|
catecholamines
|
|
|
describe corticosteroid physiology
|
-hypothalamus secretes corticotropin releasing factor
-pituitary gland secretes corticotropin/ACTH -adrenals secrete cortisol and aldosterone |
|
|
how much cortisol do the adrenals usually secrete each day?
|
12-25 mg
|
|
|
ACTH peaks at
|
2 AM
|
|
|
cortisol peaks at
|
6 - 8 AM
but varies with sleep cycle |
|
|
cortisol can also increase due to
|
STRESS
-surgery -trauma -sepsis -hypoglycemia -mediators -----CNS releases CRF) -----cytokines: IL-1, IL-2, IL-6, TNF, PAF |
|
|
in cell membrane destruction, cell membranes are converted to
|
arachidonic acid by phospholipase A2
|
|
|
arachadonic acid is converted to LTs by
|
lipooxygenase
|
|
|
LTs cause (2)
|
inflammation
bronchospasm |
|
|
arachadonic acid is converted to PGs by
|
cyclooxygenase
|
|
|
PGs affect (4)
|
PGE
prostacyclin (vascular) thromboxane (platelets) PGF |
|
|
steroidal antiinflammatories act at which part of the arachadonic acid cascade?
|
phospholipase A2
the top, nearly after cell membrane destruction |
|
|
ASA, NSAIDs act at which part of the arachadonic acid cascade?
|
cyclooxygenase component
|
|
|
3 main GC actions
|
-decrease inflammatory response
-increase neutrophils -decrease lymphocytes, eosinophils, and basophils |
|
|
how do GCs decrease inflammatory response
5 |
-inhibit PLA2, dec AA, indirect inhibition of PGs and LTs
-inhibit activity of T cells (esp TH2) -suppress IL-1,3,4,5 - decrease chemotraction of EOSINOPHILS and macrophages -vasoconstrict, dec edema, dec fever -stabilize neutrophilic (granulocyte) lysosomes to decrease lysosomal enzyme release |
|
|
how do GCs increase neutrophils
|
WITHOUT SHIFT TO LEFT
-demargination (dec adherence to vascular endothelium) -dec neutrophil egress from intravascular space -stimulate marrow release of MATURE WBCs (not immature band cells as in infection) |
|
|
how do GCs decrease lymphocytes, eosinophils, and basophils
|
-decrease B and T cell function
-basis for role in Tx of lymphomas and lymphocytic leukemia |
|
|
4 other GC effects
|
-dec protein synthesis and protein movement out of vessels (not good, muscle wasting)
-inc gluconeogenesis (hyperglycemia) -fat redistribution: suppress lipolysis and lipogenesis via insulin inhibition -inc beta adrenergic responses (value in asthma, but are not themselves bronchodilators) |
|
|
2 mineralocorticoid effects of GCs
|
Na retention
K loss |
|
|
6 considerations in choosing an agent
|
-relative GC/MC potency
-relative duration of action -organ specificity -lack of systemic absorption, if topical -cost -who sponsored the original clinical trials |
|
|
methylprednisolone is preferred in
|
acute asthma
|
|
|
dexamethasone is preferred in
|
cerebral edemia
|
|
|
equivalent doses of
cortisol prednisone methylprednisone dexamethasone |
cortisol 20-25 mg
prednisone 5 mg methylprednisone 4 mg dexamethasone 0.75 mg |
|
|
relative antiinflammatory potencies of
cortisol prednisone methylprednisone dexamethasone |
cortisol 1
prednisone 3.5 methylprednisone 5 dexamethasone 30 |
|
|
relative sodium retention
cortisol prednisone methylprednisone dexamethasone fludrocortisone |
cortisol 2+
prednisone 1+ methylprednisone 0.5+ dexamethasone 0 fludrocortisone 125 |
|
|
durations of
cortisol prednisone methylprednisone dexamethasone fludrocortisone |
cortisol 8-12 h
prednisone 18-36 h methylprednisone 18-36 h dexamethasone 36-54 |
|
|
unique application of fludrocortisone
|
-chronic hypotension
-no adrenal glands -Addison's 0.1-0.2 mg/d |
|
|
dosing strategy for acute GC insufficiency
|
moderate to high dose for rapid resolution of symptoms
high dose "bursts" x 7-14 days, QID dosing |
|
|
dosing strategy for chronic GC insufficiency
|
minimum dose for shortest duration possible
avoid if possible morning doses to mimic physiology |
|
|
what is the theory behind QOD dosing of GCs?
|
-use prednisone / methylprednisolone QOD to allow HPA to function every other night
-fewer side effects? but concern over loss of effect late day 2 |
|
|
tapering GCs when patient has had no prior exposure
|
rapid taper is possible
|
|
|
concerns during rapid tapering
|
disease exacerbation
mild flu like Sx depression |
|
|
strategy in tapering when pt has long term GC exposure
|
slow taper is mandatory
taper back to pt's baseline dose |
|
|
concern during slow tapering
|
physiologic withdrawal may occur
|
|
|
7 withdrawal Sx of GC weaning
|
-time and dose dependent
-CNS depression -flu like Sx -muscle and joint pain -tremor -hypotension (not necessarily hyponatremic) -hyperkalemia, arrhythmias |
|
|
how long does withdrawal from GC take?
|
7-14 days
|
|
|
after prolonged dosing, how long does it take the HPA to recover?
|
9-12 months
|
|
|
which glands recover first in the HPA axis?
|
pituitary response
may need to cover with prednisone bursts during times of stress after complete withdrawal |
|
|
6 acute ADRs of GCs
|
-dose dependent, low risk
-endocrine: hyperglycemia -elevated white count -GI: bleeding, stress ulcers (mucous production, local vasoconstriction) -Na retention (caution in edema, HTN, CHF) -hypokalemia, acidosis -jitteriness, euphoria, confusion |
|
|
8 chronic ADRs of GC
|
-short term ADRs
-HPA axis suppression after 2 weeks -Cushingoid features -muscle weakness, myopathy, protein wasting -thinking skin, capillary fragility, bruising, acne -OP in adults with compression fracturs, necrosis of hip, growth retardation in children -cataracts glaucoma -decreased immune response, TB activation, poor wound healing |
|
|
steroid and ASA interaction
|
steroids increase ASA clearance
risk of ASA toxicity when steroids are stopped |
|
|
4 drugs that increase steroid clearance/metabolism
|
barbiturates
phenytoin rifampin cimetidine |
|
|
DI between steroids and ketoconazole
|
ketoconazole decreases cortisol production
|
|
|
DI between steroids and hypoglycemics
|
steroid induced glucose increase
|
|
|
DI between steroids and some diuretics
|
K wasting
|
|
|
DI between steroids and NSAIDs
|
ulcerogenic
|
|
|
precautions to take with GC use
|
-Na retention in pts with HTN or HF
-effects of electrolytes in arrhythmias or renal disease -hepatic failure? lack of conversion between predinson to prednisolone |
|
|
describe Cushing's disease
|
1' - overactive pituitary
2' - overactive hypothalamus causes excess ACTH production with 2' bilateral adrenal hyperplasia |
|
|
3 types of Cushing's syndrome
|
adrenal adenoma
adrenal carcinoma ectopic ACTH syndrome |
|
|
Iatrogenic Cushing's syndrome
|
overuse of exogenous corticosteroids
mimics hyperfunctioning gland, but actually an UNDERactive gland |
|
|
clinical features of Cushing's disease
|
-central obesity/moon facies/buffalo hump
-HTN via hyperNa -glucose intolerance -menstrual dysfunction, hirsutism -abdominal striae -muscle weakness/myopathy, compression fractures -anxiety, tremor, mood elevation, psychosis |
|
|
workup of a suspected Cushing's patient
|
-screening serum or urine cortisol level
----should be high unless another disease, or is taking exogenous steroids -if cortisol is high, measure ACTH level to differentiate pituitary or adrenal origin |
|
|
findings of 24 hour urine cortisol
|
NI: 20-90 mcg/d
-Cushing's: 2-3x -low if taking exogenous steroids |
|
|
findings of plasma cortisol
|
NI: 12-20 mcg/100 ml @ 8AM
4-8 mcg/100 ml @ 11 PM -Cushings: higher (up to 50 mcg/100 mL) and not circadian -low if taking exogenous steroids |
|
|
findings of plasma ACTH
|
NI: 150 pcg/mL
high (up to 500 pcg/mL) if pituitary or hypothalamic origin low (<50 pcg/mL) if adrenal adenoma or carcinoma |
|
|
findings of dexamethasone suppression test
|
1 mg dexamethasone @ 11 PM
NI: suppressed plasma cortisol at 8 AM, < 5 mcg/100 mL (can repeat in 2 days with higher doses) Cushings: fails to suppress |
|
|
other tests for adrenal
|
nuclear scanning
CT scans MRI |
|
|
Tx of Cushing's
|
surgical removal or radiation of adrenal, pituitary, or hypothalamus
-replace cortisol and fludrocortisone QD (x 6-12 months if one adrenal only is involved) -replace other pituitary hormones as indicated |
|
|
other rare Tx of Cushing's
|
ketoconazole - refractory
metapyrone and/or glutethamide - ectopic ACTH syndrome mitotane for adrenal carcinoma RU 486 |
|
|
define Addison's disease
|
hypofunctioning adrenal gland
|
|
|
1' Addison's disease
|
autoimmune (most common, 70%)
-may involve other organs: thyroid, ovary, pancrease -TB, AIDS, other infections -vascular obstruction, bleeds |
|
|
2' Addison's disease
|
low ACTH
-hypopituitarism -corticosteroid administration |
|
|
clinical features of Addison's disease
|
-weakness 100%
-weight loss 100% -increased pigmentation (via ACTH stimulation of melanocyte stimulating hormone, absent in 2') -hypotension -vitiligo (depigmentation) -diuresis -hyponatremia/hyperkalemia (maybe not in 2') |
|
|
workup of suspected Addison's patient
|
-screen serum or urine cortisol level (should be low)
-if cortisol level is low, measure ACTH level to differentiate pituitary v. adrenal cause -to differentiate, conduct ACTH or Cosyntropin stimulation test |
|
|
2 lab tests for adrenal insufficiency
|
-serum cortisol low in both 1' and 2' Addison's disease
-serum ACTH above normal in 1' Addison's, but low or absent in 2' Addison's |
|
|
describe ACTH stimulation test
|
-administer ACTH or Cosyntropin in early AM
-measure serum cortisol 30 minutes later -cortisol level should double -a lack of response = Addison's |
|
|
what is the difference between ACTH and Cosyntropin
|
1 mg cosyntropin = 100 mg ACTH
in stimulation test use 25-40 U ACTH OR 0.25 mg Cosyntropin |
|
|
describe metyrapone test
|
-to verify 2' Addison's (hypopituitarism)
-metyrapone blocks conversion of desoxycortisol to cortisol -as cortisol levels fall, there should bea reflex increase in ACTH production -ACTH levels DON'T RISE if pituitary is hypofuncitoning |
|
|
Tx of Addison's
|
-prednisone or hydrocortisone to mimic diurnal rhythm
prednisone 5 mg AM prednisone 2.5 mg PM cortisone 25 mg AM cortisone 12.5 mg PM hydrocortisone 20 mg AM hydrocortisone 10 mg PM extra for stress fludrocortisone 0.05 - 0.2 mg QAM |
|
|
monitoring of Addison's
|
hyperpigmentation with fludrocortisone
|
|
|
incidence of acne
|
affects 17 million americans
90% of all adolescents 10% of PCP encounters 4.8 million visits/year |
|
|
onset of acne in males
|
10-17 years
|
|
|
onset of acne in females
|
14-19 years
|
|
|
prevalence of acne by ethnicity
|
asians 10%
african americans 25% (ass'd with hyperpigmentation) caucasions 29% |
|
|
4 MOAs of acne
|
-retnation hyperkeratosis
-increased sebum production -bacterial growth and colonization -inflammation |
|
|
3 types of exogenous factors that can contribute to acne
|
occupational
environmental cosmetics |
|
|
3 types of occupational factors that can contribute to acne
|
-halogenated compounds
-UV light -dioxin |
|
|
2 types of environmental factors that can contribute to acne
|
-hot humid weather sitmulates sweating which worsens acne
-dry sunny weather improves acne appearance |
|
|
2 types of cosmetics that can contribute to acne
|
pomades
moisturizers individual response |
|
|
pathophysiology of acne
|
-common, self-limiting disease
-characterized by the appearance of lesions on the face, back, and/or upper arms -noninflammatory follicular comedones -inflammatory papules, pustules, and nodules |
|
|
blackheads v. whiteheads
|
blackheads - open comedos with oxidized sebum and melanin
whiteheads - closed comedos |
|
|
describe inflammatory acne
|
usually involves a large portion of the body
|
|
|
describe acne fulminans
|
acute febrile ulcerative acne
req's inpatient Tx initially |
|
|
describe acne conglobata
|
keloidal and atrophic interconnecting abscesses and scars
|
|
|
describe acne mechanica
|
repetitive mechanical trauma
culprits: headbands, chin straps, backpacks, or should straps, tight synthetic fabrics, orthopedic casts |
|
|
3 complications of acne
|
scarring
-pitting w/ disfigurement -exacerbated by picking/squeezing psychological distress -anxiety/depression -increased unemployment |
|
|
blackheads v. whiteheads
|
blackheads - open comedos with oxidized sebum and melanin
whiteheads - closed comedos |
|
|
describe inflammatory acne
|
usually involves a large portion of the body
|
|
|
describe acne fulminans
|
acute febrile ulcerative acne
req's inpatient Tx initially |
|
|
describe acne conglobata
|
keloidal and atrophic interconnecting abscesses and scars
|
|
|
describe acne mechanica
|
repetitive mechanical trauma
culprits: headbands, chin straps, backpacks, or should straps, tight synthetic fabrics, orthopedic casts |
|
|
3 complications of acne
|
scarring
-pitting w/ disfigurement -exacerbated by picking/squeezing psychological distress -anxiety/depression -increased unemployment |
|
|
4 goals of acne therapy
|
relieve discomfort
improve skin appearance prevent pitting or scarring alleviate psychological distress |
|
|
differentiate acne from 6 other diseases
|
-PCOS
-tumor: adrenal or ovarian -Cushing's disease -folliculitis -rosacea -acne aestivalis (UV light dermatosis) |
|
|
resolution of acne lesions can be expected when
|
20% in 2 months
60% in 6 months 80% in 8 months |
|
|
how frequently should acne therapy be modified?
|
no more often than 1-2 months
unless significant ADRS it takes 8 weeks for comedos to form |
|
|
acne treatment failure is when
|
no response in 3+ months
|
|
|
2 nonpharmcologic acne Tx
|
-nonmoisturizing mild soap BID
-mechanical comedo extraction -Pre-Tx with tretinoin cream x 4-6 weeks -EMLA cream 1.5-2 hours prior to procedure |
|
|
describe mild acne (grade I)
|
comedones
-few lesions located on face -little or no inflammation -no likelihood of scarring |
|
|
Tx of mild acne
|
topical therapy
|
|
|
describe moderate acne (grade II-III)
|
comedones + papules
pustules -many lesions with presence of papules and pustules -significant inflammation -scarring potential |
|
|
Tx of moderate acne
|
-topical therapy if localized to face
-if Tx resistant, consider combo Tx -if covering face, back, chest, arms, use systemic therapy |
|
|
describe severe (grade IV) acne
|
nodulocystic acne
numerous lesions or nodulocystic, extreme inflammation and/or cysts, presence of scarring |
|
|
Tx of severe acne
|
systemic therapy
|
|
|
algorithm for Tx mild acne
|
topical retinoid
may also consider BPO, AA, or SS |
|
|
3 topical retinoids
|
tretinoin
adaptalene tazarotene |
|
|
MOA of topical retinoids
|
Vitamin A analogs
normalize keratinization prevent formation of new comedo |
|
|
dosing of topical retinoids
|
daily at bedtime
|
|
|
relative efficacy between topical retinoids
|
similarly effective
tazarotene QD > tretinoin QD tazarotene QOD = tretinoin QOD adapalene QD > tretinoin QD |
|
|
MOA of benzoyl peroxide
|
antibacterial and comedolytic properties
|
|
|
dosing of benzoyl peroxide
|
monotherapy: BID
dual Tx: qAM |
|
|
efficacy of benzoyl peroxide
|
-decreases P acnes by 98%
-decreases inflammatory lesions by 50-75% in 8-12 weeks |
|
|
ADRs of benzoyl peroxide
|
erythema
pruritis phototoxicity skin bleaching (clothing, linens)**specific to BO |
|
|
MOA of azelaic acid
|
dicarboxylic acid structure
reduced bacterial colonization comedolytic |
|
|
dosing of azelaic acid
|
mono Tx: BID
dual Tx: qAM |
|
|
efficacy of azelaic acid
|
equally effective as oral Abx or topical tretinoin
|
|
|
ADR of azelaic acid
|
erythema
burning pruritis no bleaching - useful in people of color |
|
|
MOA of salicylic acid
|
follicular activity, inc skin turnover
|
|
|
dosing of salicylic acid
|
mono Tx: BID
dual Tx: qAM |
|
|
efficacy of salicylic acid
|
possibly less effective than BO or tretinoin
|
|
|
CI of salicylic acid
|
salicylism
-tinnitus, very rare seen with increasing BSA |
|
|
ADRs of salicylic acid
|
pruritis tinnitus
|
|
|
mild-mod comedo-papule (Grade II) Tx algorithm
|
TR + BPO
TA AA |
|
|
2 topical antibiotics
|
erythromycin
clindamycin |
|
|
MOA of topical antibiotics
|
decrease P. acnes, indirectly decreasing inflammatory rxns
|
|
|
dosing of topical Abx
|
BID to clean/dry skin
|
|
|
efficacy of topical Abx
|
-BP + erythromycin = PO minocycline = PO tetracycline
-BP + erythromycin > erythromycin -TA + TR > monotherapy |
|
|
ADR of topical Abx
|
erythema
pruritis drying decrease use if browning of skin occurs |
|
|
Tx algorithm for severe papulo-pustular (grade III) acne
|
1) SA + TR, BPO, or AA
OR 2) TR + BPO + TA if no response: add oral contraception or antiandrogen then, PO isotretinoin |
|
|
5 systemic Abx
|
doxycycline
azithromycin clindamycin tetracycline minocycline |
|
|
MOA of systemic antibiotics
|
decrease P. acnes, indirectly decreasing inflammatory rxns
|
|
|
resistance among systemic antibiotics
|
erythromycin 60%>
tetracycline > minocycline ~1 % |
|
|
in tetracycline resistant acne, use __2___ instead
|
minocycline - most ADRs
doxycycline |
|
|
tetracycline is CIed with
|
pregnancy
|
|
|
MOA of oral contraceptives in acne
|
estrogen decreases free endogenous testosterone
decreases sebum and bacteria |
|
|
onset of oral contraception in acne
|
3-6 months
|
|
|
drospirenone in acne
|
antiandrogenic properties
|
|
|
1 antiandrogen used in acne
|
spironolactone
|
|
|
MOA of spironolactone
|
inhibits 5alpha-reductase
decreases sebum production |
|
|
dose of spironolactone in acne
|
50 mg QD
|
|
|
use of antiandrogens in females for acne
|
-often in combo with estrogens to prevent menstrual irregularities
|
|
|
ADRs of antiandrogens
|
dose dependent
-hyperkalemia -irregular menses -breast tenderness -HA -fatigue |
|
|
Tx algorithm for grade IV severe nodulocystic acne
|
1) SA + TR + BPO +/- OC
2) oral isotretinoin |
|
|
MOA of isotretinoin
|
blocks all 4 factors
|
|
|
dosing of isotretinoin
|
0.5 mg/kg/d
|
|
|
ADR of isotretinoin
|
teratogenicity
relapse |
|
|
13 drugs that can induce acne
|
ACTH
androgens azathioprine barbiturates bromides cyclosporin disulfiram phenytoin lithium psoralens corticosteroids thiourea vitamins (B2, B6, B12) |
|
|
3 products that normalize follicular activity
|
retinoids
azelaic acid BPO |
|
|
2 products that decrease sebum production
|
isotretinoin
hormones |
|
|
4 products that suppress bacterial flora
|
Abx
BPO Azelaic acid Isotretinoin |
|
|
2 products that prevent inflammatory response
|
Abx
Retinoids |
|
|
2 drugs to be avoided in pregnancy
|
isotretinoin
tazarotene |
|
|
3 acne drugs to consider during pregnancy
|
-topical oral erythromycin
-topical clindamycin -topical azelaic acid |
|
|
4 things that worsen psoriasis
|
cold weather
stress URI medications |
|
|
1 thing that improves psoriasis
|
warm weather
|
|
|
3 things that affect progression of psoriasis
|
EtOH - men
smoking - women obesity |
|
|
2 things that affect onset of psoriasis
|
infection
injury - Koebner response (psoriasis at the exact location of a previous injury) |
|
|
4 epidermal changes that cause psoriasis
|
-increased # cells under going DNA synthesis
-shortened cell cycle time for keratinocytes -epidermal cell proliferation -dermal vasculature changes - angiogenesis |
|
|
5 components of the autoimmune mechanism behind psoriasis
|
-cause and effect relationship
-cellular infiltrates (neutrophils, T cells) -activation of growth factors in psoriatic skin -cytokine overexpression -T cell activation |
|
|
3 genetic factors in the etiology of psoriasis
|
-family history
-MHC (PSORS1 on chromozome 6, PSORS2 on chromozome 17q) -histocompatability antigens (B, C, D loci - HLA-Cw6 esp) |
|
|
5 clinical features of psoriasis
|
-sharply demarcated erythematous plaques with a silvery scale
-Auspitz sign: scraping scales reveals bleeding points -ears, elbows, knees, umbilicus, gluteal cleft, genetalia - nails -Itching is the most common symptom -lifelong relapsing and remitting disease -rare mortality |
|
|
5 types of psoriasis
|
plaque-type
guttate (tear drops on trunk, children) pustular, localized (pain) pustular, generalized (fever) erythrodermic (severe, intense, fatal) |
|
|
type I psoriasis
|
-early onset (F 16 yo, M 21 yo)
-family history -strong HLA Cw6 involvement -larger BSA involvemnet |
|
|
Type II psoriasis
|
-onset in 50s
-no FH -small BSA involvement |
|
|
3 Goals of Psoriasis therapy
|
-skin normalization, reduction, or clearing
-improve psychological/social QoL -minimize toxicity |
|
|
3 considerations in selecting therapy for psoriasis
|
-psoriasis subtype and severity
-co-morbid conditions (EtOH, hepatitis, pregnancy) -cost |
|
|
describe PASI
|
psoriasis assessment and severity index
1 palm area = 1% BSA assess psoriasis over body before and after Tx |
|
|
mild psoriasis
|
PASI <12
|
|
|
moderate psoriasis
|
PASI 12-18
|
|
|
severe psoriasis
|
PASI >18
|
|
|
Tx algorithm for psoriasis + psoriatic arthritis
|
anti-TNF +/- MTX
|
|
|
Tx algorithm for psoriasis w/out arthritis
|
-topicals
-targeted photo therapy if no effect or in extensive disease -UVB/PUVA -systemic -biologic |
|
|
1st line topical agents for psoriasis
|
emollients
salicylic acid corticosteroids calcipotriene |
