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25 Cards in this Set
- Front
- Back
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Main mechanisms by which drugs cross membranes:
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1. Simple diffusion
2. facilitated diffusion 3. active transport 4. diffusion thru pores 5. pinocytosis. - 2 and 3 are examples of carrier mediated transport. |
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Diffusion through water pores
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- aqueous pores are very small in diameter (0.4 nm)
- allow small water-soluble drugs less than 150-200 Da to pass. - Movement occurs down a concentration gradient. - therapeutic ions such as radioactive iodine may pass through water pores. |
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Passive diffusion
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- nonpolar, lipophilic molecules readily diffuse through the lipid bilayer
- e.g. steroids - polar molecules and charged molecules do not use passive diffusion |
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Ficks Law
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dC/dt = -k(C2-C1)
- K = (Area X Permeability)/Thickness ; aka partition coefficient - governs passive diffusion |
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Major physiochemical determinants of permeability
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- lipid solubility
- size of the drug - pH of meduim - pK of chemical |
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Lipid partition coefficient
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- the lipid solubility of a drug
- lipid solubility is directly proportional to absortion rate across lipid bilayer - drugs must also be water soluble enough to disolve in aqueous fluids, therefore, administered as weak electrolytes - |
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Pinocytosis
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- drugs larger than 1000 Da can only be absorbed by pinocytosis
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Henderson-Hasselbach Equation
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pH = pKa + log[A-]/[HA]
pH = pKa + log[B]/[BH+] |
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Characteristics of absorption through passive diffusion
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- cannot cross membranes from a lower to higher concentration
- increases as the partition coefficient increases - only uncharged form of the drug crosses membranes - increases with surface area - non saturable - increases with increasing concentration of drug |
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Sites where carrier mediated transport is important
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- renal tubule
- blood-brain barrier - GI tract |
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Characteristics of facilitated transport
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- independent of surface area
- proportional to the number of carriers - cannot transport from a lower to a higher concentration - dependent on concentration of drug. Can become independent of drug concentration when the carriers are saturated. |
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Differences between carrier mediated transport and passive diffusion
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- rate of permeation is faster with mediated transport than passive diffusion
- carrier mediated transport is saturable - carrier mediated transport has a high degree of specificity, structural analogues can competitively inhibit carrier proteins. |
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differences between facilitated transport and active transport
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- facilitated transport obeys Fick's law, active transport does not
- Facilitated transport is not sensitive to ATP levels, Active transport is. |
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Characteristics of Active Transport
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- independent of surface area
- proportional to the number of carriers - Can transport from a lower to a higher concentration - dependent on energy - dependent on concentration of drug, but saturable. |
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Factors affecting absorption of orally given drugs in the gut
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- surface area - most drugs absorbed in the small intestine
- Presence or absence of food - drugs delivered to small intestines through gastric emptying - pH affects on acids and bases, ion trapping - drug formulation |
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Hematocrit
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- measure of the proportion of the plasma volume and cell volume
- found by centrifuging heparinized blood - PCV (packed cell volume) is a measure of the pellet (mostly RBCs) |
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equation for concentration of a drug in plasma or blood
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Cb = (Sf x Sw x Cp) + (CELLf x CELLw x Ci)
- Cb = total concentration in blood - Sf = fraction of blood that is serum - Sw = serum water content (100%, ignoring 2% that is proteins) - Cp = concentration of drug in plasma - CELLf = fraction of blood that is cells - CELLw = cell water content (70%) - Cc = concentration of drug in cells |
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factors affecting drug distribution
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- exit from circulation
- rate of distribution; blood perfusion - extent of distribution; lipid solubility, pH & pKa, plasma protein binding, intracellular binding |
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Factors that affect the rate of drug distribution
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- Capillary permeability
- blood perfusion |
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Factors that affect the extent of drug distribution
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- Capillary permeability
- plasma protein binding - intracellular binding - pH in kidney |
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Relative order of rates of transport through capillaries in various organs
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liver > kidney > muscle >>> brain
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Areas where the Blood-Brain-Barrier is missing
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- pineal body
- pituitary gland - area postrema - median eminence |
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areas with continuous endothelium
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- skeletal, cardiac and smooth muscles
- lung - skin - central nervous system - mucous membranes |
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Areas with fenestrated endothelium
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- kidney
- intestine - endocrine glands |
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areas with discontinuous endothelium
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- liver
- bone marrow - spleen |
