Слайд 2Theophylline
Adenosine receptors blockers
Phosphodiestheraze inhibitor
stabilizes cAMP
Decreases intracellular calcium concentration
Dilates smooth
muscles
Supresses degranulation of mast cells
Increases tonus of respiratory muscles (intercostal
and diaphragm)
Dilates pulmonary vessels, improves oxygenations
Suppresses platelet aggregation factor and PGE2alpha, improves stability of RBC to deformation
Coronary arteries dilation
Слайд 3Bioavaolability > 90%
Cmax 2 hrs (non-retard) and 6 hrs (retard)
Excreted by kidneys
and partially breast milk
Слайд 4Indications
Asthma (including status)
COPD
Sleep apnoe
Слайд 5Contraindications
Hypersensitivity including to other xantines (coffein, pentoxyphyllin, theobromin)
Hemorrhagic stroke,
retinal bleeding, MI, recent bleeding, peptic ulcer,
Marked coronary arteries
atherosclerosis
Epilepsy
Hypotension, hypertension, severe tachyarrhytmia
Слайд 6Accurately
Marked coronary insufficiency (unstable angina)
Advanced atherosclerosis
Obstructive CMP
Heart failure
Trend to convulsions
Porphyria
Hypothyrosis
Peptic ulcer
GERD
Prolonged hyerthermia
Prostatic gland hyperplasia
Hepatic or renal failure
Age >60 ore
children
Слайд 7Side actions
Anxiety, conscious disorders, cramps, vision disorders, scotoma
angina, arhhythmias,
tachycardia, hypotension or hypertension
flu like syndrome, laryngitis and pharyngitis,
nasal obstruction
xerostomia, anorexia, vomiting, nausea, heartburn, exacerbation of cholecystitis, cholestatic hepatitis, increase of ALAT ASAT ALcPH, intestinal atony
decrease of WBC, platelets, pancytopeny
allergy
Слайд 8Interactions
Cimetidin, allopurinol, cyclosporin, macrolides, oral contraceptives – decrease clearance
Phenobarbital,
phentoin, xantines, smoking increase biotransformation (induce microsomal enzymes)
Beta-blockers decrease broncholytic
activity
Adsorbents and antacides decrease bioavailability
Theophyllin increases effect of diuretics and decrease – NSAIDS, probenecid, beta blockers
Слайд 9Teotard
200 and 350 mg
After meals, 350 mg once daily (evening)
– start dose, then 350 mg 2 times daily
Body mass
<40 kg – 200 mg initially, then 200 mg 2 times daily
Theophyllin blood levels should be 10–20 mg/ml.
Слайд 10Afonilum® SR
Retard forte 375 mg
Retard 250 mg
Prolinged action 125 mg
Prolonged action 500 mg
2-3 capsels a day
Слайд 11Agrylin
Decrease of platelets formation
Dose dependent heart rate increase and QTc
increase
Cmax 1 hr, H1/2 1,3 hrs
Indications: high risk essential
thrombocytemia (age more than 60, platelets > 1000 х 109/l; thrombotic and hemorrhagic complications in history)
Слайд 12Roflumilast Daxas®
Phosphodiestherase 4 inhibitor
PDE4 is the enzyme which metabolises cAMP
located in inflammatory cells
Mostly PDE4A, B,D
Main metabolite – N-oxide –
has same properties
Increased cAMP due to PDE block leads to decrease of excretion of LTB4, RPS, TNFalpha, IFN gamma, granzymB
In COPD decreases number of neutrophils in sputum
In healthy decreases neutrophils and Eos influx in airways after endotoxin use
Слайд 13Bioavailability 80%
Cmax 1 hr; for N-oxide - 8 hrs (
4 – 13 hrs).
No influence of food intake
P450 metabolism
(CYP1A2 and 3A4)
T1/2 17 for roflumilast, 30 hrs for N-oxide
In aged – activity is increased
No serious changes in kidneys failure
In renal failure the inhibiting activity increases 20% for A class Clhild Peugh, 90% - in B class
Слайд 14Contraindications
B,C class liver failure
Systemic autoimmunities (not studied), tb, cancer, HIV
Use
of biologics (no experience)
Depression with suicide trend
Galactose metabolism impairment
Слайд 15Accurately
Cytochrome
Fluvoxamin treatment (CYP1A2 inhibitor)
Enoxacin or cimetidin treatment
( CYP3A4/1A2)
Class A liver failure
Слайд 16Side effects
Angioedema, gynecomastia, decreased body masse, decreased appetite
Insomnia, anxiety, several
reports inluded suicidal trend or suicide
Headache, tremor, vertigo, dizziness
Tachycardia
GGTP
increase, ASAT incrase, diarrhea, nausea, GERD, gastritis
Rash, urticaria
Myalgia, weakness, rare – CK increase
Слайд 17Use
0,5 mg once daily
No dose corrections for aged and mild
liver failure
Слайд 18Sildenafil Revatio™ (20 mg)
Inhibits cGMPdependent PDE-5
This enzyme is
present not only in male reproductive system but in pulmonary
vessels also
Слайд 19Small BP decrease (about 9 mm), less marked in PH
patients (2 mm)
No influence on ECG
Improves life expectancy in
patients with pulmonary hypertension
Слайд 20Rapidely absorbed
Cmax 30-120 min
Р450: CYP3A4 and CYP2C9
T1/2 – 4-5 hrs
80% - intestinal
excretion
Слайд 21Contraindications
Venoocclusive pulmonary disease
Use of nitric oxide donators
Use of CYP3A4 inhibitors
Anterior ishemic
optic neuropathy with one eye vision loss (not vasculitic nature)
Pigment
retinintis
Liver failure >9 points
MI or stroke in case history
SBP<90, DBP<50
Lactose intoleranse
age <18
Слайд 22Accurately
III and IV classes of PH
Lecukemia, sickle cell anemia
Severe cardiac and pulmonary diseases
Слайд 24Bosentan
Antagonist of ЕТА and ЕТВ receptors
Decreases pulmonary and systemic vascular resistance
Слайд 25Prolonged treatment (12 and 16 weeks) treatment III–IV functional class
lead to significant improvement
Слайд 2662,5 mg и 125 mg
62,5 mg 2 time daily –
4 wks, then 125 mg 2 times
