Term
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Definition
Rate of drug metabolism is directly proportional to free drug concentration
A FRACTION of the drug is metabolized per unit time |
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Term
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Definition
the rate of drug metabolism remains constant
A CONSTANT amount of drug is metabolized per unit time
Ex: alcohol. only a shot metabolized per hour |
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Term
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Definition
changes the parent drug by adding O, N, or S to make it more water soluble.
These drugs are then usually excreted by the kidney |
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Term
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Definition
Takes water soluble chemical and links it to the parent drug to make it more water soluble
Does NOT use cytochrome system |
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Term
| Drugs that stimulate the MFO system do so via.. |
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Definition
Induction, which means an increase in enzyme synthesis
Include sedatives, tranquilizers, analgesics, some antihistamines |
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Term
| Drugs that inhibit the MFO system do so via.. |
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Definition
a decrease in the activity of existing enzyme
Include: the antihistamine cimetidine (tagamet); secobarbital (seconal; suicide inactivator) |
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Term
| Name the 6 Conjugation Reactionsin Phase II of drug metabolism |
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Definition
| Glucouronidation, Glutathione, Amino Acid, Sulfate, Acetylation, and Methylation |
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Term
| What four steps are involved in acetaminophen metabolism? |
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Definition
1. oxidation
2. reactive intermediate
3. Glutathione Conjugation
4. Hepatic Cell Death |
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Term
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Definition
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Term
| The First-Pass Effect occurs when there is a .... |
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Definition
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Term
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Definition
Elimination of a large fraction of drug during first passage through the gut wall and then through the liver
Examples: nitroglycerin, propranolol, imipramine, acetylsalicylic acid |
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Term
| What two steps are involved in the elimination of drugs and what organ(s) are included in each step? |
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Definition
1. Metabolism: liver
2. Excretion: kidney, liver (bile), lungs |
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Term
| What are the three parts of renal excretion of drugs? |
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Definition
filtration, reabsorption, and secretion
reabsorption is through passive transport (tubule)
secretion involves active transport and is also in the tubule |
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Term
| Glomerular Filtration Rate (GFR) |
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Definition
the percentage of blood cleared per unit of time (always labeled as something per minute)
Represents a clearance (Cl) of plasma |
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Term
| What prevents drug filtration in the kidneys? |
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Definition
plasma protein binding and large molecular size
Ex: thyroxine is 99% bound |
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Term
| Protein binding has no effect on what process that takes place in the kidneys? |
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Definition
| Proximal Tubular Secretion (this involves active transport) |
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Term
| In order to prevent the excretion of a weak acid (aka want to reabsorb it in the distal tubule) what should you do to the urine? |
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Definition
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Term
| In order to excrete a weak base, what should you do to the urine? |
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Definition
make the urine more acidic.
This will cause ionization of the weak base, it will not be passively reabsorbed, and will be secreted. |
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Term
| What 5 things affect the transport of a drug in distal tubular reabsorption? |
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Definition
pH, concentration, size, lipid solubility, and ionization.
Distal Tubular Reabsorption involves passive transport |
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Term
| Equation to determine the amount of blood cleared of a drug per minute? |
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Definition
| GFR = 125 ml/min = clearance |
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Term
| What is the normal renal blood flow? |
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Definition
650-700 ml/min
rate of urinary excretion depends on the renal blood flow |
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Term
| What is the equation to determine clearance? |
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Definition
| Cl (ml/min) = (drug in urine x Urinary Blood flow) / plasma drug concentration |
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Term
| 4 steps in the enterohepatic cycle |
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Definition
| portal vein, liver, common bile duct, and small intestine |
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Term
| What factors affect pulmonary excretion? |
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Definition
plasma solubility, cardiac output, respiration
The more cardiac output, the more blood is going through the lungs at a time |
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Term
| Factors that affect increased toxicity and/or decreased effectiveness of a normal dose |
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Definition
age (renal and hepatic metabolism), renal disease, liver disease, drug interactions
liver makes the drugs more water soluble when it metabolizes them. The older you get, the less efficient your liver is at metabolizing. |
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Term
| factors that indicate renal disease |
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Definition
1. excretion of an active drug is less than or equal to 50%
2. renal function drops below 50% normal adult value
3. drug has low therapeutic value |
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Term
| clinical importance of liver disease |
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Definition
parenchymal liver disease, heptatic perfusion (cardiac failure, cirrhosis)
affects mainly those drugs with high extraction ratio |
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Term
| Drugs that enhance liver metabolism via induction |
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Definition
| *pheobarbital, phenytoin, phenylbutazone |
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Term
| drugs that directly inhibit liver metabolism |
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Definition
| *Cimetidine, carbidopa, MAOI, disulfiram |
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Term
| Drugs that inhibit the renal tubular secretion of weak acids |
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Definition
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Term
| Drugs that inhibit the renal tubular secretion of weak bases |
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Definition
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Term
| What affect does grapefruit juice have on certain drugs? |
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Definition
it inhibits first-pass elimination of drugs metabolized by certain CYP P450s
It inhibits cytochromes which causes drug potency to be accentuated
include CYP 34A, 1A2, and 2A6 |
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Term
| Drugs that have interactions with grapefruit juice |
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Definition
| Dihydropyridine Ca2+ channel blockers, cyclosporine, midazolam, estrogens, and caffeine |
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Term
| Plavix is metabolized by which cytochrome in the P450 cycle |
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Definition
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