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47 Cards in this Set
- Front
- Back
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Lipid diffusion
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movement of molecules thru membranes and other lipid structures
-governed by Fick's Law |
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What does the pH of the medium determine?
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the fraction of molecules that are charged or uncharged
-consequently the absorption of the drug across a lipid membrane |
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Electrostatic charge
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-HH eq.--> predicts teh propensity of a drug to carray a charge (Ionized = charged) under different physio conditons
-eq is important to understanding both drug absorption and excretion |
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Ionized drugs vs non-ionized drugs
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Ionized are more water soluble, while non-ionized are lipid soluble
since membranes are composed of lipids, non-ionized drugs are absorbed and ionized are excreted -most drugs are racemic--> stereoisomers, R/S |
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Acid
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non-ionized, "protonated" molecule that can reversibly dissociate into an anion and a proton
*proton donor |
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Remember AAA
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-an ACID in an ACIDIC environment favors ABSORPTION (more uncharged molecules)
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Remember BAE
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-a BASE in an ACIDIC environment favors EXCRETION (more charged molecules)
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Where are most drugs freely filtered?
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At the glomerulus, but lipid-sol drugs can be rapidly reabsorbed from the tubular urine
*if a pt takes an overdose of aspirin (weak acid) the excretion of this drug can be accelerated by alkalinizing the urine (***AAA***) |
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General rule for weak acids
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-excreted faster in basic urine
-reabsorbed faster in acidic urine |
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General rule for weak bases
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-excreted faster in acidic urine
-reabsorbed faster in basic urine |
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Acidify urine vs alkalinize urine
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-give ammonium chloride vs. sodium bicarbonate
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Fick's law of diffusion
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-predicts the rate of movement of molecules across a barrier
-the concentration gradient (C1-C2) and permeability coefficient for the drug and the area and thickness of the barrier membrane are used to compute rate as follows |
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Fick's Law of Diffusion Equation
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Write here:
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Interpretation of Fick's Law
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-drugs are absorbed faster from organs with/ large SAs and thinner membranes
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Aqueous Diffusion
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movement of molecules through the watery EC and IC spaces
-the membranes of capillaries have small water-filled pores that allow aqueous diffusion of molecules in the blood and extravascular space |
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Aqueous Solubility is a function of ?
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-electrostatic charge
-water molecules are attracted to charged drug molecules forming an aqueous shell around them |
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Transport by special carriers
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-drugs can be actively transported by mechanisms involving transporters, specialized molecules, usually proteins
-important in the mvmt of drugs and can be the target of drug action (ex: SSRI drugs) |
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Carrier transport is governed by?
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Capacity limited NOT Fick's Law
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Endocytosis/pinocytosis
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-contents released into the cytoplasm of the cell
-allows very large or lipid-insoluble chemicals to enter cells |
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In determining route of administration, what must be considered?
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1. Drug properties and profile
2. Drugs site of action 3. Condition and age of patient 4. Rapidity and duration of drug effect required 5. Convenience, cost, availability |
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Oral ingestion/route
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-usually the safest, most convenient, and economical
-can be used for local or general treatment |
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Disadvantages to the oral route
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1. limited absorption
2. vomiting as a result of irritation to GI 3. destruction of drug by dig enzymes or low pH 4. variation of absorption in the presence of food or drugs 5. pt compliance |
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Oral route: Local treatment
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can be used as a GI protectant of the dig tract
-treatment of an intestinal infx or a parasitosis -in these cases the ideal drug will not be absorbed or only poorly absorbed |
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Oral route: General treatment
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-common route of administration of many drugs
-digestive absorption is followed by drug diffusion throughout the body |
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Digestive absorption: Mouth
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-absorption of the drug by the oral mucosa allows a fast absorption and avoids the hepatic transfer
***sublingual route -venous drainage from the mouth is superior vena cava which protects the drug from rapid hepatic first-pass metabolism |
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Digestive absorption, oral route: Stomach
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-area of the stomach is approx 1 meter squared, pH ranges from 1-4, flow rate of blood drainage is low, ~.2L/min
-neutral molecules and acids not ionized in an acid pH are absorbed from the stomach |
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Which molecules are secreted into the gastric fluid from the blood?
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many molecules, but in particular bases which are ionized by protonation int eh acidic gastric fluid
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Digestive absorption, oral route: Intestine
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-area of intestine is large 200-300 m2
-pH is alkaline 6-8 -blood irrigation is important, 1L/minute -majority of drugs are absorbed at this level |
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First-pass metabolism
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-the drug, absorbed from the dig tract passes through the liver, reaches the right heart and after pulmonary transfer is distributed by the left heart to the whole body
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First-pass metabolism continued
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-in the intestinal mucosa and liver, the drug meets enzymes able to transform it into one or more metabolites, sometimes active but generally inactive
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What explains the low efficacy of certain drugs?
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-first pass metabolism
-especially when they are given in low doses because they are mainly metabolized before arriving into systemically circulated blood to reach target organs |
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Form or presentation of the drug:
Drops vs tablets |
-not necessarily the same kinetics of absorption, nor the same bioavailability
drops, are immediately available for absorption whereas tablets must be first disintegrated so as to release the powder which is emulsified |
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Advantages to controlled release (sustained released) drugs
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-reduction in the frequency of administration
-maintenance of a therapeutic effect overnight -decreased incidence or frequency of undesirable effects **particularly beneficial for antidepressant therapy b/c slow uniform absorption avoids peaks and troughs in drug [plasma] |
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Effects of food: reduced
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-it is the case of tetracyclines, ioniazid, penicillamine, captropril
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Effects of food: unchanged
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-or little modified, it is he case of amoxicillin
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Effects of food: Increased
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-it is the case of propanolol
-increase in its bioavailablity comes from a decrease of first pass intestinal and hepatic metabolism |
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Drug interaction in the digestive tract: Cholestyramine
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-an anion exchanging resin, able to bind drugs such as diuretics and reduce their absorption
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Drug interaction in the digestive tract: Metals
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-iron and aluminum can reduce the bioavailablility of certain antibiotics by forming arganometallic complexes
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Drug interaction in the digestive tract: Activated charcoal
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-known for its capacity to absorbed a great number of molecules, in particular drugs
-activated charcoal must be given as soon as possible after ingestion of the poison |
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What are the principle routes of parenteral administration?
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1. intravenous
2. subcutaneous 3. intramuscular -a drug to be injected by this route must be sterile and non-irritant |
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Paraenteral Route: Subcutaneous
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-suitable for some poorly soluble suspensions and for instillation of slow-release implants
-vol of fluid injected is limited with possible pain or necrosis from irritating substances -rate of absorption is prompt from aqueous solution, however sclerosis and circulatory state influence absorption Ex. heparin and insulin |
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Paraenteral Route: Intramuscular route
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-gradual releasing drugs
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Intraarterial route
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-localize its effect in a particular tissue or organ
-no first pass and cleansing effect of lungs -rarely used |
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Intrathecal route
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-rapid effects on the meninges or CS axis
-injected directly into the spinal subarachnoid space |
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Nasal route
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-both local and general treatment
-avoids first pass metabolism |
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Advantages of Pulmonary Absorption (inhalation)
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1. instantaneous absorption
2. advoidance of hepatic 1st pass metabolism 3. w/ pulmonary disease, local application of the durg at desired site of action |
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Disadvantages of Pulmonary Absorption (inhalation)
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toxicity due to systemic absorption
rapid dissipation of effects |
