Professional Documents
Culture Documents
Arvesu, RPh
Albumin
- at least 6 binding sites, 2 very tightly and
specifically bind long chain FA, 1 for acidic
drugs
- 50-60% of plasma proteins
- 1 agent responsible for maintaining osmotic
pressure of the blood, and for transport of
FA, hormones, enzymes and drugs.
- Drugs which bind at the same site can
displace each other respectively
- decreased concentration in liver and renal
diseases
1-acid glycoprotein
- 1 binding site selective for basic drugs
- increased concentration in RA and post MI
bad cholesterol
- HDL High Density Lipoproteins
good cholesterol
Metabolism
Metabolism
- e.g., Phenacetin from Acetaminophen;
Oxazepam from Diazepam
Presystemic Metabolism
(First Pass Effect)
MOUTH
Enzymes and normal oral flora
STOMACH
Acidic pH
Small Intestine
Enzymes and Intestinal flora
Presystemic Metabolism
(First Pass Effect)
Gut wall and blood
leading to the liver
enzymes
Liver microsomes
bioavailability for
systemic circulation
Hepatic Biotransformation
PHASE I REACTIONS
- Convert lipophilic molecules into more
polar molecules by introducing or
unmasking a polar functional group
- catalyzed by the cytochrome P450
system (microsomal mixed function
oxidase)
Phase I reactions
OXIDATION
- addition of O2 or removal of H
REDUCTION
- addition of H or removal of O2
Hydrolysis
- addition of H2O and break down of the
molecule
Phase II reactions
- Occur when the metabolites from Phase I are
too lipophilic to be retained in the kidney
tubules
- Result to polar, more water-soluble
compounds that are most often
therapeutically inactive
Glucuronidation
- MAIN conjugation reaction
- natural substrates are bilirubin and thyroxine
Phase II reactions
Acylation
- with acetyl group
Glycine
- glycine addition
Sulfate
- sulfate addition
Pharmacogenetics
Type
Genetic
Alteration
Selected
Examples
Clinical
Manifestation
N- acetyl
transferase
INH,
Hydralazine,
Procainamide
Toxicity
Pseudocholin
Esterase
Succinylchloride
Toxicity
Glucose-6phosphate
dehydrogenase
(G6PD)
G6PD
Primaquine,
Aspirin, Fava
beans
Hemolysis
Uncontolled
Calcium release
heterogenous
General
Anesthetics,
Neuromuscular
blocking agents
Malignant
Hyperthermia
Excretion
Excretion
1.
Glomerular Filtration
- ALL low MW molecules are filtered out of
the blood
- normal filtration rate (GFR) = 100-130
ml/min
- often measured by the RENAL CLEARANCE
of INULIN
- Inulin is readily filtered in the glomerulus
and is NOT subject to tubular secretion or
reabsorption
Hemodialysis
Hemodialysis
Biliary Excretion
Jaundice
Pulmonary Excretion
Salivary Excretion