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Elimination of the
drugs
Drug Biotransformation
Metabolism or
biotransformation -
complex of processes which provide
decreasing of toxicity and accelerate
excreting of the molecule of a drug or
other foreign substance after its
incoming into the organism
(Chemical alteration of the drug in the body )
Metabolism of Drugs
Aim: to convert non-polar lipid soluble
compounds to polar lipid insoluble
compounds to avoid reabsorption in renal
tubules
Most hydrophilic drugs are less
biotransformed and excreted unchanged
streptomycin, neostigmine and pancuronium
etc.
Biotransformation is required for protection
of body from toxic metabolites
Results of Biotransformation
Active drug and its metabolite to inactive
metabolites most drugs (ibuprofen,
paracetamol, chlormphenicol etc.)
Active drug to active product (phenacetin
acetminophen or paracetamol, morphine to
morphine-6-glucoronide, digitoxin to digoxin
etc.)
Inactive drug to active/enhanced activity
(prodrug) levodopa - carbidopa,
prednisone prednisolone and enalapril
enalaprilat)
No toxic or less toxic drug to toxic
metabolites (Isonizide to Acetyl isoniazide)
Biotransformation of drugs into active (or
more active) metabolites
Initial drug Active metabolite
Allopurinol Aloxantin
Amitriptilin Nortriptilin
Acetylsalicylic acid Salicylic acid
Butadion Oxyfenbutazon
Diazepam Dismethyldiazepam
Digitoxin Digoxin
Codein Morphine
Cortizol Hydrocortizon
Methyldopa Methylnoradrenalin
Prednison Prednisolon
Novocainamid N-acetylnovocainamid
Propranolol N-oxypropranolol
ORGANS OF DRUGS METABOLISM
liver
kidneys
muscle tissue
intestinal wall
lungs
skin
blood
Reactions of biotransformation
Nonsynthetic - phase metabolite may be
active or inactive
1) microsomal reactions
2) nonmicrosomal reactions
Reactions of phase - transformation in
molecule with formation of functional groups
with active hydrogen atom
Phase I - Oxidation
Oxydoreductases, esterases,
enzymes of proteins, lipids,
glycerophosphatides, lipo- and
glycoproteids, bile acids,
cholesterol, prostaglandins
biosynthesis, enzyme systems
of biosynthesis of couple
compounds, ethers of
glucuronic and sulfur acids
Oxydoreductases of microsomes (oxygenases of
microsomes, microsomal hydroxydating system, NADPH-
hydroxylase system,
monooxygenases of mixed functions)
these are enzymes which activate molecular oxygen and
catalize including of one (monooxygenase) or two
(dioxygenases) atoms of oxygen into molecule of substrate
(R) Reaction is presented as follows:
R + O2 + D = ROH + H2O + D
One atom of 2 is included into molecule of the substrate,
other is reduced to 2, therefore enzyme performs
oxygenase and oxydase functions simultaneously. Thats
why monooxygenases ate also called oxydases of mixed
function. Along with this hydroxyl group (-) forms in
molecule of substrate, thats why monooxygenase is also
calles hydroxylating system, and reaction of oxydation
oxydating hydroxylation
Nonmicrosomal Enzyme
Oxidation
Absolutely contraindicated
Antibacterial: tetracyclins, levomycetin, fluoroquinolones,
sulfonamides, nalidixic acid, metronidazole
Antiviral: amantadin, gancyclovir, zidovudin, remantadin
Cytostatics
Drugs effecting CNS: difenin, sodium valproate, lithium
preparations, barbiturates, reserpin, opioid analgesics (regularly)
Drugs of other groups: iodides, antithyroid drugs, undirect
anticoagulants, radiopharmaceutical drugs (radioactive iodine
etc.), Ergot alkaloids, chlorpropramid, cyclosporin
USING DRUGS DURING LACTATION
(continuation)
Undesirable
Bromides, meprobamat, derivatives of benzodiazepine
(diazepam, chlozepid, oxazepam etc.), aminazin,
ethosuximid;
M-cholinoblockers, glucocorticosteroids (if dosage is over
100 mg per day), indometacin, salycylates (large doses),
derivatives of sulfonilurea, theophyllin, chloroquin,
nitrofuran derivatives (furazolidon etc.), isoniazid,
cymetidin, aluminum containing antacids, estrogens,
gold medications, retinoids
Enzyme Inhibition