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36 Cards in this Set
- Front
- Back
Name 4 Body compartments drugs can distribute to |
1. Total Body Water: (includes blood plasma, interstitial space, and intracellular fluid) 2. Adipose tissue: Fat 3. Muscle 4. Bone: Some drugs absorb to the surface of bones and become absorbed in the crystal lattice. Bones can also be a reservoir for the slow release of drugs |
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If a drug is given parenterally, where does it go first and where could it distribute to next? |
A parenterally administered drug will be absorbed in the plasma first. If the drug is absorbed as a free drug, it can distribute to bone, muscle, interstitium, fat, kidney (for excretion) or liver (for metabolism). If the drug is absorbed as a protein bound drug, it will stay in the plasma. |
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If a drug is given orally, where does it go first and where could it distribute to next? |
First the drug will go to the liver for metabolism, then either the drug or the metabolite will go into the plasma. If the drug is a free drug, it can go to the muscle, bone, fat, interstitium, or kidney/liver for excretion. If the drug is protein bound it will remain in the plasma |
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What are the three factors that affect drug distribution |
1. Blood flow to tissues 2. Ability of drug to move out of capillaries 3. Ability of drug to move into cells
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Name 3 tissues that are highly perfused/have high blood flow |
Brain, Kidney, Liver |
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Name 3 tissues that are not highly perfused/have lower blood flow |
Skin, Fat, Bone |
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T/F poor blood flow rarely limits drug distribution in humans |
False. Poor blood flow rarely limits drug distribution in adults, however is a limiter of drug distribution in neonates. |
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What are 3 examples where poor blood flow can limit drug distribution? |
1. Patients experiencing heart failure or shock 2. Solid tumours. They have low regional blood flow, even though they have high external blood flow. It is difficult to attain high drug concentrations in tumours. 3. Abcesses (infections filled with pus) have no blood supply. |
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A drug has successfully exited the vasculature and is attempting to enter a cell. Name 2 barriers to entry. |
1. Chemical nature. It must be either lipophilic or able to be taken by an uptake transporter.
2. Efflux transporters
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What is P-glycoprotein? |
The most widely studied efflux transporter. Promotes drug excretion from cells and protects the body from exposure to drugs. |
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What does PGP need to function and why does it need this? |
PGP actively pumps out drugs, so it needs ATP. It needs ATP because it effluxes these drugs against a concentration gradient. |
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Name 4 areas PGP is expressed/localized, and to where it pumps drugs to. |
1. Liver: PGP is expressed in hepatocytes and actively pumps drugs into the bile canalicular membrane, where they become eliminated 2. Intestine. PGP is expressed on enterocytes on the apical membrane (facing the lumen). It actively pumps drugs into the lumen, preventing absorption. 3. Kidney: PGP is expressed in the proximal tubule on the apical membrane, preventing reabsorption 4. Brain: PGP is expressed in the brain, facing capillary endothelial cells, pumping drugs from the brain back into the blood, limiting the brains exposure to drugs. |
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T/F Only the free drug can elicit a pharmacological response |
True |
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Explain the equilibrium of free and protein-bound drugs |
Free drugs and protein bound drugs are in equilibrium. Since binding is reversible, if some of the free drug is removed, protein bound drugs will dissassociate from their proteins and become free drugs |
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You have a condition where the kidney overactively eliminates all drugs in the body. What will happen to levels of protein bound drugs? |
They will decrease, because p-bound drugs and free drugs are in equilibrium, if the levels of free drugs decreases, p-bound drugs will dissassociate from their constituent proteins and become free drugs |
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Name and describe the two major plasma proteins |
1. Albumin. The most common one. Binds lipophilic, and anionic/weakly acidic drugs. Think: Albumin --> Fat Albert --> probably has acid reflux 2. Alpha 1 acid glycoprotein: Binds hydrophilic and cationic/weakly basic drugs |
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What factors affect albumin concentrations in the blood, and what are the effects of these changes? |
Malnutrition, trauma, aging, liver disease and kidney disease decrease albumin concentrations in the blood. This Causes an increase in free drug concentration, which could lead to increased therapeutic and toxic effects. |
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What factors affect alpha 1 acidic glycoprotein concentrations in the blood, and what are the effects of these changes? |
Aging, trauma, and hepatitis increase alpha 1 acidic glycoprotein concentrations in the blood. This leads to decreased free drug concentration and so ineffective therapy. |
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Define Volume of Distribution |
Apparent volume that a drug distributes into. Ratio of the total amount of drug in the body to the plasma concentration of the drug |
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Why can the VD sometimes be larger than the actual volume of water in the body |
The drugs can extensively bind to tissues, giving a large numerator and small denominator |
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For a 70kg person, how much total body water is there? |
42 L |
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for a 70kg person, how much intracellular fluid is there? |
28L |
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For a 70kg person, how much interstitial fluid is there? |
10L |
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For a 70kg person, how much plasma is there? |
4L |
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What are 2 characteristics of a drug with a small VD. Where do these drugs distribute primarily? |
1. It is bound to plasma proteins 2. It is large and cannot pass through capillary fenestrations
For these reasons the drug stays in the plasma |
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What is volume of plasma per kg in a 70 kg patient? |
4/70 = 0.057 L/kg |
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Name 3 characteristics of drugs with an intermediate VD. Where do these drugs distribute to primarily? |
1. Low molecular weight. Can pass through capillary fenestrations. 2. Hydrophilic, can't directly penetrate cell membranes 3. Intermediate protein binding: some are free some are bound in plasma
Since these drugs can leave the vasculature, but can't enter cells, these drugs will distribute in the extracellular space, comprised of the interstitium and the plasma |
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What is volume of extracellular fluid per kg in a 70 kg patient? |
14/70 = 0.2 L/kg |
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What are 3 characteristics of drugs with a high VD? Where do they distribute to? |
1. Low molecular weight (can pass through capillary fenestrations) 2. Lipophilic (can directly penetrate cell membranes) 3. Minimal plasma protein binding
These drugs can leave the vasculature AND enter cells (due to their lipophilicity). They can distribute into the total body water. This includes extracellular AND intracellular fluids, cells of which include fat, muscle and bone |
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A plasma protein bound drug with a small VD is displaced by another drug. What happens to the free drug concentration, and the apparent VD of the drug? |
Free drug concentration increases, because the drug cant leave the vasculature so it stays in the plasma. Apparent VD, however, stays the same, due to the amount and plasma concentration of the drug remaining the same |
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A plasma protein bound drug with a large VD is displaced by another drug. What happens to the free drug concentration, and the apparent VD of the drug? |
The free drug concentration will decrease as the displaced drug will leave the vasculature and enter cells. The apparent VD of the drug will also increase because, although the amount of the drug in the body stays the same, the plasma concentration decreases. |
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Decreasingly order water as % of body weight between infants, healthy adults, obese, and elderly |
baby --> healthy adult --> obese --> elderly |
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Decreasingly order fat as % of body weight between infants, healthy adults, obese, and elderly |
obese --> elderly --> healthy adults --> baby |
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Decreasingly order muscle as % of body weight between infants, healthy adults, obese, and elderly |
healthy adult --> obese, --> elderly --> infant |
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T/F as we get older drugs that distribute in fat will have a lower VD |
False. higher VD. |
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T/F as we get older drugs that distribute in muscle will have a lower VD |
True. |