Pharmacokinetics: Metabolism and excretion Flashcards
Metabolism
The liver contains enzymes that mediate chemical reactions. If a molecule is ionized, the body can get rid of it (because it is not lipid soluble).
Active metabolites
metabolites that produce an effect that is the same or greater than the drug and prolong the effect
First pass metabolism
Drugs absorbed from the intestine go directly to the liver, which metabolized the drug molecules. Parental routes bypass first pass metabolism in the liver. First pass metabolism also occurs in the stomach and intestines.
Excretion
Kidney: filters 1 L of plasma permute and produces 1 mL of urine per min. Filters everything out of the blood and then selectively reabsorbs. The blood passes into a nephron (tube), Bowman’s capsule (contains a clump of capillaries), and the nephron connects with tubes to the bladder.
Glomerular filtration
everything other than proteins, red and white blood cells, and drugs bound to proteins pass through pores in capillaries into the nephron
Distal reabsorption
non-ionized drug molecules (lipid soluble) are reabsorbed into capillaries. Ionized molecules required by the body (glucose) are actively transported back into the capillaries. Ionized drub molecules/metabolites pass into the bladder
Excretion through the urine for drugs that are more acidic or basic
The kidney can make urine more based to increase the secretion of barbiturate (weak acid). Bicarbonate or ammonium can make using more basic or acidic, respectively to help secrete weak acids or bases, respectively.
Rate of excretion/elimination
Halflife = time to reduce the concentration of the drug in the blood plasma by one half. First order kinetics: rate of metabolism is proportional to the concentration of the due in the blood and so T1/2 varies with does. Zero-order kinetics: drug cleared at a constant rate (independent of dose - alcohol) - not described in terms of T1/2
Factors that affect rate of metabolism (3)
1) stimulation of enzyme systems
2) inhibition of enzyme systems
3) age
Stimulation of enzyme systems
Enzyme induction: drug exposure increases levels of enzymes that metabolize that drug. This is the bassi of metabolic tolerance (repeated administration lessens all effects of that drug due to enhanced metabolism).
Inhibition of enzyme activity (a and b)
A) Competition (administer 2 drugs that use the same enzymes, lower the metabolic rate of both drugs)
B) drug-food interaction (grapefruit juice blocks cytochrome enzyme in intestine and blocks 1st pass metabolism of drugs, elevates blood levels of drug.
Age
Infants lack fully developed enzyme systems (metabolize tea differently and slowly), liver metabolism is slow in the elderly, children utter 2 have less metabolic capacity
Time course for blood levels in the blood is made up of…
the absorption curve (time course for the absorption of the drug into the blood) and the excretion curve (time course for the elimination of the drug from the blood). This changes as a function of the route of administration. Look at graphs
Therapeutic window
The range of drug levels that produce a therapeutic effect. Doses given at regular windows to keep blood levels in the therapeutic window. The dose and the frequency depends on how fast the drug is absorbed and eliminated.
