31 Anti-allergics Flashcards
Histamine
Derivation: histidine
Storage: mast cells
Inc vasodilation, capillary permeability, smooth muscle contraction, mucus secretion, PANS
Physiologic antagonist: Epi
Pharmacologic antagonist: antihistamine
CNS effects of histamine
Control sleep-wake cycle Inc BBB permeability Neuroendocrine control (behavior, biological rhythms, energy metab, thermoreg, fluid bal, stress, repro) Thyroid function Cognition
H1 antihistamines mechanism of action
Dec production of proinflammatory products
Dec granule products, cytokine release, superoxide radicals release, chemotaxis of eosinophils
Dec CAM expression
First gen antihistamines
Use: urticaria, rash, pruritus, bronchoconstriction
Faster acting, more potent in short term
Mechanism: inverse agonists (stabilize inactive H1 receptor)
Side effect: drowsiness and sedation
Ethanolamines = most sedating (diphenhydramine, dimenhydrinate)
Second gen antihistamines
Less sedation, longer duration
Mechanism: bind noncompetitively to H1 receptor for longer duration
Weaker sedation: Cetirizine, acrivastine,
True non-sedating: loratadine
Third gen antihistamines
Increased efficacy, less side effects
Levocetirizine = does not cross BBB
Desloratadine
Cortisol
Hypothalamus: corticotropin-releasing hormone
Pituitary: secreted adrenocorticoropic hormone
Adrenals: cortisol
Regulators: CRH = pituitary, ACTH = adrenal gland, negative feedback
Stimulator: stress, circadian rhythm (high in daytime 7am, low in night time)
Adrenal gland
Adrenal cortex
Zona glomerulosa = mineralocorticoids (aldosterone)
Zona fasciculata = glucocorticoids (cortisol)
Zona reticularis = androgens (estradiol, estrone, testosterone)
Adrenal medulla = catecholamines
Pathways of steroids
Androgens: progesterone -> estrone, estradiol, testosterone
Glucocorticoids: cholesterol -> cortisol/corticosterone
Mineralocorticoids: cholesterol -> mineralocorticoids
Adverse side effects = give steroids 1-2 weeks only
Glucocorticoid inhibitory effects
B cell: inc apoptosis, dec BAFF, dec Ig Neut: inc apoptosis, inc annessin A1 Macro: dec cell activity DC: dec proliferation, dec cytokines, inc reg T-cell induction Eos: inc apoptosis Bas: dec histamine, dec basophils Mast: dec mast, dec mediators Th17: inc Th2: dec cytokines, TCR signal Th1: dec IL2, dec TCR
Glucocorticoid stimulatory effects
Treg: inc cells, inc IL2 receptors, inc IL10
Macrophages: low dose increases cell activity
Hypertension, peptic ulcer, hyperglycemia
Cataracts
Corticosteroid effects
Dec eosinophils, cytokines (t-lymph, macro, epithelial cells), mast cells, DCs
Dec leakiness, mucus secretion
Inc B2 receptors
Side effects of steroid use
Bones: inhibit osteoblasts, osteopenia, osteoporosis
CNS: mental status changes
Growth stunting: dec GH
GIT, pancreas: peptic ulcer, pancreatitis
Endo: Thyroid suppression, adrenal suppression, secondary sex charac
Indications for steroids
Collagen/MSK: SLE, rheumatoid arthritis Allergic rhinitis Immunosuppression: organ transplant Ocular disease Skin disease: contact dermatitis Pulmo: bronchial asthma Renal: glomerulonephritis, nephrotic syndrome Cerebral edema Endotoxic shock Hema diseases
Corticosteroid excess: Cushing’s syndrome
ACTH secreting pituitary edema -> bilateral adrenal hyperplasia
Manifestations: (Hey Suck His Cock For HellA Coin) Hyperglycemia Skin (striae/bruising) Hypertension Central/truncal obesity Facial edema Hirsutism, Amenorrhea Closure of epiphyseal plate
Secondary cushingoid syndrome: excess cortisol