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31 Cards in this Set

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Aminophylline
a methyl xanthine

80% theophylline
20% ethylene diamine
Theophylline
a methyl xanthine
methyl xanthines help with...
broncho-spasms

Nocturnal asthma
Theophylline inhibits...
phosphodiesterase

remember: phosphodiesterase breaks down cyclic amp...so if I inhibit PDE, i increase cAMP...this will lead to things that will help bronchodilate
Theophylline antagonizes...
the adenosine receptor on adenylate cyclase...therefore PDE can't do it's thing...(I think)
Pharmacodynamics of methyl xanthines
*relaxes smooth muscle (vasodilates/bronchodilates)
*CNS: increases stimulation
*CVS: increases myocardial contractility, vasodilates, and reduces PVR
*Skeletal muscle: reduces fatigue
*Kidneys: diuresis

Increased pepsin and gastric acid

Metabolism: increases basal metabolic rate and FFA
Theophylline toxicity
Early CNS: anxiety, tremor, insomnia

GI: nausea, vomiting

CVS: tachycardia, palpitations, arrhythmias, hypotension

CNS effects: twitching, seizures

Metabolic
Theophylline therapeutic monitoring
poor clinical indicators of efficacy/toxicity

narrow therapeutic range

action proportional to concentration

variable phamacokinetics

reasonable half-life

relatively rapid easy HPLC assay
Cromokalin derivatives
anti-inflammatory drugs:

sodium cromoglycate

Nedocromil
Glucocorticosteroids
Anti-inflammatory drugs

2 types inhaled and systemic
Inhaled steroids
anti-inflammatory:

Beclomethasone
Systemic steroids
Anti-inflammatory:

hydrocortisone, prednisone, prednisolone, methylprednisolone
Sodium cromoglycate and Nedocromil
anti-inflammatory drugs:

cromokalim
Uses of Sodium Cromoglycate
(Cromolyn)
prophylaxis in antigen and exercise induced asthma

allergic rhinitis and conjunctivitis
Mechanism of sodium chromoglycate
*not a direct bronchodilator

*inhibits the release of inflammatory mediators from mast cells in particular

*suppresses effects of kinins on inflammatory cells

*inhibits sensory C-fiber endings? (reduced cough?)
Side effects of Sodium cromoglycate
VERY SAFE!!!

he says it's one of the safest drugs on the market

cough and wheeze

headache, nausea
Uses of corticosteroids:

SYSTEMIC THERAPY
acute severe asthma (status asthmaticus)

chronic maintenance therapy
Use of corticosteroids:

INHALED THERAPY
prophylaxis in mild/moderate asthma

can be combined with systemic steroids in chronic severe asthma to reduce systemic steroid requirements

use when people have worsening of their noctural syndromes
Which enzymes do glucocorticosteroids inhibit?
enzymes producing PGs, LTs, and TX, eg. PLA2 via lipocortin, COX-2
Glucocorticosteroids inhibit the transcription of...
pro-inflammatory cytokines eg. IL-1, TNF-alpha, G-MCSF, IL-3, and IL-4, 5, and 6
Glucocorticosteroids directly counteract...
the positive effects of several cytokines on transcription factors AP-1 and NF-KB
Glucocorticoids induce the enzymes...
ACE and NEP which degrade bradykinin and tachykinin

(bradykinin is a bronchoconstrictor)
Glucocorticosteroids increase...
beta 2 and NK1 receptor transcription
Glucocorticosteroids reduce cell trafficking by...
inhibiting effects of TNF etc and reduces the expression of cell adhesion molecules...
Glucocorticoids induce apoptosis in...
eosinophils
Vasocortin!!!!
the antipermeability factor that glucocorticoids stimulate the synthesis of...this inhibits plasma exudation from venules
Pharmacokinetics of the inhaled steroids
inhaled route:

about 10% of dose reaches bronchi

90% of dose is swallowed

metabolism: hepatic CYP3A

low systemic circulations
Side effects/toxicity of inhaled glucocorticoids

(just local effects)
Thrush - C. Albicans (10-15% of patients)

Dysphonia - hoarse voice (causes a local myopathy)
Side effects/toxicity of inhaled glucocorticoids

(systemic effect: at doses of about 1600 mcg/day Beclomethasone)
HPA axis suppression

Bruising/Purpura

Cataracts

Inhibits bone growth (?children?)

Hypercholesterolemia

Hyperglycemia

Behavioral disturbances
Side effects of systemic glucocorticoids

(Acute)
CNS- insomnia/psychosis

Metabolic- 1) hyperglycemia and 2) Na and H20 retention

Proximal myopathy

Suppress signs of infection
Side effects of systemic glucocorticoids

(chronic)
HPA axis suppression
(adrenal suppression)

Cushing's appearance

Peptic ulcer

Opportunistic infection

Osteoporosis

Growth suppression (kids)

Pancreatitis

Aspetic necrosis of the femoral head