Adrenal Pharm
ADRENAL GLANDS
three zones
zona glomerulosa makes mineralocorticoids (aldosterone)(pharm: fludrocortisone)
zona fasciculata makes glucocorticoids (cortisol)
zone reticularis makes sex steroids (DHEA)
MINERALOCORTICOIDS
endogenous produced by zona glomerulosa
aldosterone and others reg intravascular volume and BP
aldosterone works on renal tubule
aldosterone-->Na+, bicarb and H2O retention, decreasing resorption of potassium
pts with Addison's dz have low minieralocorticoid production
so far we can't synthesize aldosterone
aldosterone levels are incr in Conn's syndrome
Conn's: tx is aldosterone antagonist: spironolactone & surgery if adrenal adenoma is etio
GLUCOCORTICOIDS: MOA
endogenous released on diurnal cycle from zona fasciculata
exogenous are most potent anti-inflam medications available
synthetic drugs mb 20-100x more potent than endogenous cortisol
cortisol is principle endogenous one
binds to cell receptors-->changes gene transcription and behavior of cells
promotes gluconeogenesis-->incr blood sugar to deal with stressor (trauma, infx, disease)
regulates metab of prots, carbs, lipids
causes mild incr in BP mbdt vasoconstrx dt andrenergics in BVs
incr circ of neuts, HGB, RBC's
decr circ of lymphs incl T cells, eos, basos, monos, macrophages
pharmacologic doses dramatically reduce accumulation of leukocytes and inhbits chemotactic signalling
also inhibits access of leuks to inflam sites, intereferes with fx of leuks, ECs and fibroblasts
inhibition of phospholipase A2-->blocks release of arachadonic acid--///-->no new PGs or LKs
anti-inflam effect dt decr production of prostaglandins & leukotrienes
also suppresses histamine release and kinin activity
metabolized by liver microsomal oxidizing enzymes
drug characterized by duration of actions, potency and mineralocorticoid effects
short acting: hydrocortisone, cortisone (8-12 hours)
intermediate acting: prednisone, prednisolone, methylprednisiolone, triamcinolone (18-36 hours)
long acting: paramethasone, dexamethasone, betamethasone
RELATIVE ANTI-INFLAMMATORY EFFECTS
the stronger the corticosteroid effect, the weaker the mineralocorticoid effect
reverse is also true, so all the meds with a 5 or less may have some aldosterone effect-->Na retention
Cortisone .8
Hydrocortisone 1
Prednisone 4
Prednisilone, Methylprednisilone, Triamcinalone 5
Paramethasone 10
Dexamethasone 30
Betamethasone 35
INDICATIONS
(be SURE there's no infection!!!!)
inflammatory or allergic conditions
reactive airways disease
allergies: rhinitis, hay fever, drug allergy
"itises" (tonsilitis, bursitis, etc), IBD
organ transplant
autoimmune: rheumatoid arthritis
Addison's disease (replacement therapy to begin here, do not give thyroid when cortisol is low)
SE OF SYSTEMIC DOSES
adrenals suppressed within a week at any dose over 20mg
insomnia, mental status changes: jitters, hyperness, euphoria
reduced resistance to infections
hyperglycemia-->diabetes mellitus
weight gain: increased appetite, salt and water retention-->bloating
severe bone loss, avascular necrosis (femoral head)
cataracts
myopathy
thinning of the skin, easy bruising
diminished wound healing
chronic use-->iatrogenic Cushings: moon facies, buffalo hump, striae, telangiectasias, acne, incr body hair
kids with nephrotic syndrome often put on steroids and have moon facies and telangiectasias soon after
DOSING
oral, inhaled or topical preparations
prednisone 5-10mg dose to start
bitter, take with food
take in the morning only
can take as much as 60-100mg in am for temporal arteritis
WITHDRAWAL
must be carefully monitored
can lead to exacerbation of underlying disease or worse-->
abrupt discontinuation-->acute adrenal insufficiency syndrome-->Addisonian crisis-->death
some docs stop dosage at 20mg but DrM ramps down gradually to 10 or even 5mg
wean by 10mg/day over 10-14 days
if pts adrenal condition in question wean last day(s) by 5mg/day
ADDISONIAN CRISIS
severe lethargy
severe V, D-->dehydration
low BP esp orthostatic
hyponatremia, hypoglycemia
confusion, loss of consciousness, convulsions
INHALED GLUCOCORTICOIDS
not for acutes (need bronchodilator like coffee)
usu used to tx asthma but sometimes also prescribed for emphysema and chronic bronchitis
inhaled favored to work directly on airways, lower systemic dose means less SEs
asthma: 20% cough instead of wheezing
infection to watch for: candida, thrush, if undetected before med may have dramatic onset with med
ALTERNATIVE: Cromolyn from Kella stabilizes mast cells
NASAL INHALED GLUCOCORTICOIDS
indications: allergic rhinitis, vasomotor rhinitis,
rhinitis medicosum (rebound from alpha agonist ie afrin)
nasal polyps
TOPICAL GLUCOCORTICOIDS
indications: atopic or contact dermatitis, eczema, seborrhea, psoriasis, lichen planus, lichen simplex chronicus, poison oak/ivy, severe insect bite reactions, discoid lupus
limit use and avoid on eyelids, genitalia, thin skin, in folds, on broken skin, face, groin, perineum
weaker topicals used in thin skinned areas
mod topicals for: atopic, nummular eczema, lichen sclerosis of the vulva, scabies and severe dermatitis
strong used for: psoriasis (may use occlusive dressing), lichen planus, discoid lupus,
lichen simplex chronicus, severe PI, alopecia areata (patchy AI esp in female), nummular eczema,
severe atopic dermatitis
can use with antifungal
can drive into joint with iontophoresis
dosing: to prevent tolerance or tachyphylaxis: topical mb prescribed for week on/week off routine
or 3 days on, 4 days off
tachyphylaxis = fast developing tolerance mc with neurotransmitter tx
rectal preparations for itch of hemorrhoids, UL
(active ingredient in some Preparation H is Phenylephrine in 0.25% concentration,
Prep H with hydrocortisone contains a 1% concentration)
OCULAR GLUCOCORTICOIDS
indications: allergic conjunctivitis, corneal ulcers & other injuries, iritis, uveitis, keratitis, optic neuritis, and after ophthalmic procedures such as keratoplasty
can use for zoster in combination with antiviral
IV GLUCOCORTICOIDS
indic: severe acute allergic response, reactive airways dz,
spinal cord trauma, shock, addisonian crisis, ITP, CVA
bacterial meningitis, cerebral edema, septic shock, blood transfusion reactions
SPECIFIC DRUGS FOR FINAL EXAM
HYDROCORTISONE/CORTEF
class: glucocorticoid/corticosteroid
indic: preferred drug for cortisol replacement therapy, potency: 1
MOA: change gene transcription
char: po/IV/IM/topical. Chemically identical to naturally occurring cortisol. Short duration of action.
SE: oh lordy
PREDNISONE/DELTASONE
class: glucocorticoid/corticosteroid
indic: preferred drug for reactive airways disease or mod-sev allergic rxn. also imp for leukemic rxns.
potency relative to hydrocortisone: 4
MOA: change gene transcriptn
char: po. intermediate duration of action
aside about chemo: pts say "I'm on chop" or "lip" and the "P" means prednisone
SE: see list of systemic effects above
DEXAMETHASONE/DECADRONE
class: fluorinated glucocorticoid/corticosteroid
indic: IV form useful for reducing intracranial pressure
extremely potent anti-inflammatory(30x hydrocortisone)
MOA: change gene transscription
char: po/IV/topical/inhaled. long acting. minimal mineralocorticoid effects.
SE: oh please
TRIAMCINOLONE INHALER/AZMACORT
class: synthetic corticosteroid
indic: asthma, COPD (not for acutes)
MOA: decr inflam in bronchi, 5x stronger anti-inflam than hydrocortisone)
char: oral inhaler, 1-2 inhalations (75-150mcg) or 3-4 inhalations 1-2x/day
max: if need more call doc
SE: thrush, sore throat, nosebleed, coughing, headache, runny nose, plus systemic effects with long/heavy use
FLUDROCORTISONE/FLORINEF
class: halogenated glucocorticoid/mineralocorticoid agonist
indications: to maintain BP in pts with Addison's and other hyponatremia
MOA: sodium retention in renal tubules-->less urine
char: PO, potent mineralocorticoid effects, long duration of action, minimal glucocorticoid effects
(not indicated as anti-inflammatory agent)
SE: edema, HTN, rash, N/V, and systemic glucocort effects
DEHYDROEPIANDROSTERONE/DHEA
endogenous from zona reticularis
DHEA converted to testosterone and estrogen
exact indications not well established
clinical trials show variable results
indic: osteoporosis, depression, SLE, skin grafting
anti-aging drug? because levels normally decrease throughout life
levels fluctuate throughout day
use should be decreased or discontinued if pts develop acne or hirsutism
CI: pts with hx of hormone-responsive CA incl breast, uterine, ovarian, prostate, and also BPH
also consider carefully if there's a FHx of any of these
***just created chemo tag, all prior references not tagged