The sum of chemical reactions in which an endogenous or exogenous substrate is converted into a larger molecule or a smaller molecule.
Metabolism plays an important role in the ________ and ________ of drugs.
Kidneys provide a concentration gradient which favors...
passive resorption of lipid-soluble molecules back into the blood.
The development of metabolic pathways renders lipid-soluble materials that would normally be resorbed back into the blood at the kidneys...
less lipid soluble and less likely to be resorbed, thus eliminated more quickly.
The primary site for drug metabolism.
The system of enzymes located on the smooth endoplasmic reticulum that is the primary site for drug metabolism and endogenous steroid metabolism.
hepatic microsomal system
A hyperbolic curve that provides estimates of maximal reaction velocity (Vmax) and the apparent Km.
What is phase I of drug metabolism?
oxidations, reduction, hydrolysis, deaminations
Phase of drug metabolism that transforms the molecule to a more polar product which then may be excreted.
What are phase II reactions of drug metabolism?
conjugated of glucronic acid, glycine, etc. are added
The phase of drug metabolism in which the addition of a conjugate increased the polarity of the drug molecule and the size, making is much less likely to be resorbed at the kidney.
Phase ___ products sometimes retain biological activity, but Phase ___ products are rarely active.
The primary phase I reactions, _________ and __________, are carrier out by the __________, which requires... (3)
oxidation and reduction; electron transport system; molecular oxygen, reduced NADPH, and cytochrome P450
The phase II reactions are _______ in nature; they can be limited in their rate or capacity by... (2)
synthetic; limited amounts of transferase enzyme, limited amounts of conjugate substrate
Metabolic transformation can result in... (3)
inactivation of an active drug, activation of an inactive drug (prodrug), and conversion of one form of an active drug to another active form.
Acetominophenis a(n) ________ that is metabolized to a(n) ____________, which leads to ____________.
active drug; reactive intermediate; hepatic necrosis
Benzo[a]pyrene is a(n) ___________ that is metabolized to a(n) ____________, which is ___________.
active drug; reactive intermediate; carcinogenic
Two important properties of drug metabolism are...
enzyme induction and enzyme inhibition.
When one drug stimulates or induces enzymes for its own metabolism and the metabolism of the other.
With enzyme induction, the dosage of the second drug will need ____________.
to be adjusted
When one drug competitively or non-competitively inhibits the metabolism of another drug.
The u=inhibited drug may require that its dosage rate be __________ to __________.
lowered; avoid toxicity
With enzyme induction, when an active drug is metabolized to an inactive molecule, you need ________ drug.
With enzyme inhibition, when an active drug is metabolized to an inactive molecule, you need ________ drug.
With enzyme induction, when an inactive drug is metabolized to an active molecule, you need ________ drug.
With enzyme inhibition, when an inactive drug is metabolized to an active molecule, you need ________ drug.
The ________ is principally responsible for drug excretion.
Many polar drugs depend on excretion of the ________, __________ form of the drug as the main means of elimination.
There is significant _____________ in herbivores.
There is significant __________ in the lactating female.
The kidney functions ___________ to maintain body fluid composition and balance.
What are the steps of filtration in the kidney? (5)
systemic circulation--> glomerular filtration --> active tubular secretion <--> passive and active tubular resorption --> excretion
The glomerular membrane acts as a filter, allowing _________ and _________ of the plasma to enter the nephron, while excluding ________ and ________.
water; solutes; blood solutes; large proteins
Filtration through the glomerulus is driven by _____________.
The processes of _________ and ________ modify the tubular fluid in the tubule.
Active transport mechanisms occur primarily in the _________ of the kidney.
Most ________ solutes diffuse passively from higher concentration within the tubular fluid back to the blood via peritubular capillaries.
Drugs that are _____________ are not filtered at the glomerulus but are secreted by active transport.b
bound to protein
__________ accounts for the retention of many lipid-soluble substances, but substances that do not easily diffuse across membranes can be resorbed by _____________.
Passive reabsorption; active reabsorption
The rate of renal excretion of a substance is summarized by what 3 processes?
filtration, secretion, and reabsorption
The volume of blood which would be required to contain the amount drug which is removed per unit of time; the rate of removal from thhe total body or from a specific organ.
Changes in ___________ or _____________ will affect a drug dosage schedule.
elimination rate; volume of distribution
Two clearance mechanisms that are related to renal drug elimination.
GFR and effective renal plasma flow (ERPF)
A substance which is almost completely removed in one passage through the kidney can be used to measure ________.
As clearance increases, half-life _______.
As volume of distribution increases, half-life ________.
Inulin is only cleared by _________.
If clearance ratio is <1, _________ has taken place.
If clearance ratio = 1, then ___________.
filtration removes the drug or filtration= secretion
If clearance ratio > 1, __________ has taken place.
Drugs that are weak acids or bases will ____________ from the ___________ to the __________.
passively diffuse; tubular fluid; blood (based on their degree of ionization)
If the concentration of drug exceeds the capacity of the transport system, then __________ occurs and the rate of _________ becomes limited.
saturation; secretion or reabsorption
If a drug is excreted by filtration but not secretion, then only ___________ is available for filtration and excretion. If a second drug competes with the first for protein binding so that more drug is _______________, the rate of excretion of the first drug will _________.
free, unbound drug; free to be filtered; increase
If a drug is protein bound and also actively secreted so that not only free drug but also bound drug become cleared as it passes through the kidney, if you cause less drug to be bound, excretion can be ________.
Diuretic drugs __________ drug excretion by.... (2)
increase; decreasing the conc gradient that drives passive reabsorption and by decreasing contact time resorption in the tubules by increased flow.
Drugs which are extensively and rapidly removed by the liver following oral administration undergo ____________.
Drugs enter the bile by a ____________.
active transport secretory mechanism
The proportion of drug in the bile compared to the urine increases as ____________ increases.
Dogs, rats, and chickens are classified as _______ excreters; cats and sheep are ___________ excreters; rabbits, guinea pigs, and primates are ________ excreters.
good; moderate; poor
Unmetabolized drug secreted in the bile to the intestine ill undergo reabsorption according to its ______________; drug that are __________ at the pH of the intestine will not be reabsorbed; ___________ drugs will largely be reabsorbed back into circulation.
lipid-solubility; polar/mostly ionized; less polar/more unionized
The major difference b/w renal and hepatic excretion is that...
intestinal contents, unlike urine, are capable of altering/degrading the drug molecule through chemical or enzymatic processes.
Extraction ratio (E) > 0.7 refers to those drugs which are __________ (i.e most drugs undergoing ____________); E <0.3 refers to drugs with ___________.
highly extracted significant first-pass effect; low extraction [BY THE LIVER]
Drugs with low extraction ratios are referred to as ____________ and depend on the _______________.