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201 Cards in this Set
- Front
- Back
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How is the drug usually distributed?
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Passive diffusion
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What is the formula for diffusing of everything?
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Ficks
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What other stuff goes by ficks?
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O2, drugs, O2 in ocean, everything because everything has cells
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Draw lipophillic drug going from blood to cell
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(picture) easy, for some drugs
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Draw arestheia going through
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(picture) blood, will do some work on membrane. It hits a receptor on the sit of the cell
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What is pharmacokmetic phase?
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(picture) Human system acts on drug. Effects of liver, lungs, kidneys, fat, bloodstream on the drug
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What stuff in the body effects the drug?
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The fate of the drug
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Describe first order kinetics
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(picture) The rate of elimination is directly related to drug concentration. When there is 206g/cc, only lowering by a rate of 5. When there is 50meg/cc, lowering by a rate of 17(meg/cc/hr). (regarding picture) -look @ 10. Concentration is higher, body is eliminating @10g/L. -look @5. Concentration is less, body is eliminating @5g/L.
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What is pharmacodynamic phase?
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(picture) The effects of the drug on the organism (body, cell)
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Describe zero order kinetics
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(picture) The same amount is eliminated over time. The rate of elimination does not change - looks like this (refer to picture) -elimination @ x g/hr, not changing
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With blood and inside cell, which has a larger concentration?
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Blood stream. Stuff passively diffuses
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With drawing of blood, interstit, cell, according to Ficks law, which way is everything going?
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Blood -> iss -> cell
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Chemically, what characteristics does a lipophillic drug have?
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Lipid soluble. Non polar. Non charged. Non-ionic
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The 3 types of plasma proteins:
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Albumins, globulins, fibronogins
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Why liver pt's have less protein?
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They cannot produce as much albumin and globulins in their livers
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How big are PP?
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100,000. They are larger MW substances they create higher oncoxic pressure
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ASA and cum given together?
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They compete for the same PP bonding sites. Given together, S.C. will higher of cumodin. Higher % of free concentrations
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Drug conc, pH, osmo, buffers
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-Drug concent; -%; -osmolarity; -solution; -water; -pH; -buffers; water dissociating; Need 1. Diagrams of (a) water, hydrolysis, (b) water dissociating, (c) buffer, (d) pneumonic
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Is an acid a Ht donor or acceptor?
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Donor. It donates a Ht to another compound. After the protein is donated, the acid is dissociated
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Is a base a Ht donor or acceptor?
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Acceptor. It accepts a Ht from another compound
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To do:
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Clarify drawing the buffer reations
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What are the 3 body compartments?
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Intervascular (blood, plasma), Interstitial, Intercellular
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Where do drugs fall on pH?
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Most drugs are either weak acids or weak bases
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Describe the movement of ionized drugs
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Restricted. They are water solube (non pda)
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Describe the movement of non-ionized drugs
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Easy. Cross barriers more easily
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How does pH affect drugs?
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pH in the body can make drugs more or less ionized
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1M of glucose =
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180g
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10 to the -3 M of glucose =
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.18g (move the . To the left for every -p10
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How do you make a molar solution
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Take MW of substance, expressiting, then dilute it in 1 Liter of solution
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Describe a 1 molar solution of glucose
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180 grams in 1000cc water
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Describe a .1 molar sol. of glucose
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18 grams of glucose in 100 cc
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With %, express % solution of something
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1g per 100cc, or .1g per 10cc
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If drugs always trave by PD, what do all other transport phenomenon apply to?
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Pharmacodynamics. Ex: FD, CT, AT. These are not drug moving through membrane
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How do you make a 1% solution?
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Add 1g to 100cc, or, .1g per 10cc, or, .01g to 1cc
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Why is % not best?
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If substance is light, it might be a huge pile added to the solution and the # of molecules in this huge pile will be different
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How can you compare drugs?
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By molarity
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What is molarity?
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The # of moles of a given substance (expressed in grams) per liter of solution
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What is a substance dissolved in liquid?
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Solute
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What is the liquid?
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Solvent
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How many molecules does one mole of any substance contain?
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6 x 10 to the 23rd
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How is osmolarity expressed?
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Osmoles
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What does one osmole =?
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1 mole for the solutes which do not dissociate
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What is 1 osmole of glucose?
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180g
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What if solute dissociates into 2 ions?
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The 1gm MW = 2 osmoles
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How many osmoles is 58.5g of NACl? (MW of Nacl is 58.5)
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2 osmoles
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How do we measure the amount of osmoles in a solution?
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Sum up all the osmoles. 1 osmoles + 2 osmoles + 3 osmoles
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What are the 2 buffering systems in the body?
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Chemical and physical
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Divide them up, tell how fast they work
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Chemical <1 sec. Chemical buffering sys. in blood. Physical lungs minutes. Kidneys (most powerful) hours to days excrets acid/alkaline in urine
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What are chemical buffers composed of?
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A weak acid and a weak base
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What do chemical buffers do?
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Respond, and regulate pH
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Which buffer is the body fluids buffer?
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Bicarbonate buffer - bristol jet on the sheet
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Which buffer is the intra/extra cellular buffer?
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Phosphate buffer - giving to 3rd sp pt to the 5th
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Which buffer is the intra cell/urinary buffer?
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Proteins buffer - kidney pts protein
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Which buffer works as the primary buffer against carbonic acid B's?
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Hemoglobin buffer
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What is a buffer solution?
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A solution that resists change in Ht ion and OH ion concentration upon addition of sm. amt. of acids or bases, or upon dilution
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What does a buffer solution consist of?
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A weak acid + its conjugate base, or a weak base and its conjugal acid
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Water and its 7 attributes
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T - temp stab; S - solvent; H - hydrolysis; R - reactant; R - radiation (absorbs); C - cush on mg; D - density is maxed @ 4 degrees C
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How may g will 10 to the -2 molar sol. of glucose be?
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1.8g
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How bout 10 to the -3?
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.18g
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Why is this unit of measure so important?
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Allows you to compare all drugs
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How is water unique?
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Is a universal solvent. High stabilizer. High BP
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What is stronger, covalent o-H bonds or H bonds?
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Covalent. H bonds are weak
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Re: drug bonding with P.P., how does drug have its effect?
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In its free form - not bonded
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Ex?
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95% bonded, 5% free. High PP = low am + free drug
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How would you dose liver dis or elderly?
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Lower dose. Will be more free drug
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Log of 100=
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2 if the base is 10
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Log of 1000=
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3 if the base is 10
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What is pH?
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A negative logarithm of the concentration of H protons
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What is the decimal of pH?
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.00000001 moles per liter
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Water has a pH of 4, so; it has (blank) moles per liter of H ions?
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.00000004 moles per liter
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Why is pH so important and so strictly regulated?
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Ex: typical liver cell. 3000 enzymes are operating, affecting reactions. Enzymes are T and pH sensitive
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What happens when an acidic drug gets entrapped in a high pH compartment?
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Entrapped, can't get out because it became more ionized
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In which environment does an acidic drug operate fastest in?
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An acidic one. Travels fastest, operates fastest
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What happens to weak acids in low pH (charge wise)?
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They are non-ionized. Thus, permiability of membrane will increase. They are more effective
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What happens to an acidic drug on a high pH?
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Permiability is lowerd. Drug is not as effective because it cannot travel because it has become more charged (ionized, polar, hydrophillic)
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What buffers do when there is an abrupt change in pH?
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Work to help stablize H
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Ex. of buffer pair:
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Carbonic acid and Lactic acid
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Is a buffering more powerful?
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Yes. pH will shift rapidly
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Which line of defence is all this?
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1st
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Draw graph with reaction rate and pH with pepsin (pH 1,000), pancreatic (pH8) anylase
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(picture)
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Does lower pH make dopamre and levo more polar, more ionized, more H2O sol?
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When there is a charge of the molecule of a drug, movement is
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Impaired
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pH is different in diff. compartments: (re movement of drugs)
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Vascular 7.4, interstit 7.1, cell 6.8
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What happens to a drug that is a base when pH falls?
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The drug becomes more ionized. Cellular permiability is decreased (dd to cell lowered)
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Rises?
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More drug is non-ionized, higher permiability cellular wall, higher travel in and out. (higher dd to cell
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Where does regulation of peripheral blood flow occur?
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In the arterioles, by smooth muscle elements
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So where do vasodialatory and vasoconstrictive agents work on?
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Arterioles
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What else about arterioles and regulation?
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They are the target of a high # of regulations
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What are the three types of capillaries?
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Continuous, fenesivated, sinusoid
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What layers do capillaries lack?
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Tunica media and externa
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What do all other blood vessels have that epithelial tissue does not?
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All 3 layers, intima, media, externa
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Why are endothelial cells so important?
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Endothelial cells help regulate everything. It is huge. It is practically its own organ
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10 meds given intervascularly meet
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Meet different kinds of endothelial cells in different vasculatives
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Draw the structure of a typical blood vessel: (cross section)
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(picture) outside = tunica externa (elastic elements); middle = tunica medig (smooth muscle); inside = tunica intima (consists of endothelial cells)
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Hydrogen bonds are only found in
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Water and living things
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What type of bond is neat?
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Covalent. Strong. Stays together
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When Na and Cl are dissocated in water, what is their relationship?
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They are attracted, but not bonded. There is a hydration shell
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What is the force of attraction between Na and Cl in water?
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30 - almost as strong as ionic. Pretty strong
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Explain vanderwaals
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Weakest. Not sharing - just induction of opposite charge in adjacent atom. They "pretend" to bond
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Draw a description of Amplification with G-receptor protein
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(pictures) 1 - receptor; 100 - G protein; 10,000 - AC; 1,000,000 - CAMP; 10,000,000 - phospho-kinase
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Talk about relationship between CAMP and phosphodiasterase
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CAMP is normally removed by phosphodiasterase. When you add a phosphodiasterase inhibitor, cyclic AMP will go up, and heart muscle will be stimulated. Phosphodiasterase inhibited = high CAMP, high CO, Cl
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Talk about CAMP as second messanger and drugs
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The system can be activated at step 6 through CAMP. Example: Aminone used to stimulate heart musle. Phosphodiasterase inhibitors will inhibit phosphodiasterase, thus causing CAMP to high, thus stimulating cardiac muscle
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What is the difference between potency and efficacy?
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Potency is the range of doses over which a drug produces increasing response. Efficacy is the limit of the dose response relationship on the response axis
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What is LD?
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When the response is death. Ex: LD 50 = 50 mice died
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What is ED?
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When 50% of the people got a response
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What is TD?
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When there is a toxic effect other than death
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What is TI?
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LD50/ED50 or TD50/ED50
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Draw the picture only of G protein receptor model. Label.
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(picture) receptor; alpha, beta, gamma (all in G protein); Adenylicle cyclase; channel (can be either opened or closed)
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What is the primary challenge to acid/base balance
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Organisms produce a significant amount of Ht as a result of metabolism
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What are the sources of Ht, causing acidity in organisms?
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Carbonic acid formation; inorganic acids (lactic acid); organic acids (phosphoric acid) - look up all on wiki
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Does facilitated diff apply to drugs?
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No. Carriers are only for natural occurring substances. You see this only with biological processes (except insulin)
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Draw the 2 models of F.D.
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(picture) -glu <- specific substance for a specific receptor
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What is Aragados #?
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The number of molecules that any one substance has. 6 x 10 to the 23rd
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Carbonic acid
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Carbonic acid - CO2 + H2O = H2CO3
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pH and decimals, explain:
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pH7 is .0000001 or, 1 x 10 to the -7 (less zeros because you have to cross the 1 first -> 8 places)
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What are the 7 characteristics of water?
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T stabilizer (higher bp, higher evaporation point); Is a universal solvent; Is an important reactant; It is important in hydrolysis (almost all reactions involve water); It helps with cushioning; It helps absorb radiation; Maximum density @ 4 degrees C (not @ freezing point and expands upon freezing)
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Formula for pH
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pH = 10g(1/[Ht])
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pH of the following: (a) Gastric sec; (b) vaginal sec; (c) urine; (d) blood; (e) saliva; (f) semen; (g) CSF; (h) pancreatic juice; (sem, csf, blood same)
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(a) 1-2; (b) 3-4 [4]; (c) 4-8 [6]; (d) 7.36(v)-7.4(A); (e) 6.5; (f) 7.4; (g) 7.4; (h) 8
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1000
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What is the osmolarity of blood?
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300 milliosmos (MillI!)
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What is the osmolarity of N/S?
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300 milliosmos - it is isotonic
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What is better than an isotonic sol?
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An isoionic sol.
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15mo in milliosmos:
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One thousand
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Does glucose dissolate in water?
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No. It remains 1osmo
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Does Nacl?
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Yes. It dissoliates for 2 milliosmos
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Draw a picture of water dissociating in a solution and explain:
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(picture that kind of looks like following) H2O + H2O <=> H3O(positive) + OH(negative). This is reversible
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Draw a picture of water when an acid is added to the solution:
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(picture that kind of looks like following) (donor) HCL + H2O -> H3O(positive) + Cl(negative). A proton is donated when HCL is dissolved in water. This raises the Ht concentration and lowers pH
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Draw a picture of water when a base is added:
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(picture that kind of looks like following) NH3 + H2O <=> NH4 (acceptor) + OH(negative). A base is a protein acceptor. This results in an increased OH concentration and higher pH
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The liver, through hepatic bio-transformation, inactivates drugs. Are there exceptions to this?
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Yes. Pro-drugs - Drug: some drugs can become activated by metabolism. This can result in toxicity
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Of the 2 phases of Hep-biotransformation, where does 1 occur?
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SER, mitochondria, cytosol
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Where does phase 2 occur?
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Cytosol only
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Describe key and lock theory with protein band receptors
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Cygand bonds, channel opens or allows substance in
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Describe competition
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No drug or substance is an exact fit, but may compete anyway
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What are the 4 types of receptors (on protein channels)?
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Recepts, ion channel (L. Gated), enzymes, carrier proteins (RIEC)
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What are the 4 types of bonds between drugs and their receptors? Name their strength
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Van-der Waals attration <1; Hydrogen bond 1; Ionic bonds 30; Covalent bonds 300
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Draw a picture of the capillary. Label everything. Where does exchange of drugs occur?
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(picture) (labels in circle beginning with left) Artery; arteriole; pre-capillary; post capillary; venule; exchange of drugs
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Name the 3 types of capillary wall and the distance between cells
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Continuous - smallest. Fenestrated - med. Sinusoid - big gap
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Can RBC pass sinusoid?
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Yes
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What stuff goes right through the sinus and capillary cell and reaches all compartments?
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Lipid soluble
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What stuff is lipid sol?
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Anestetic gas, O2, CO2, lipids
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What are some water sol substances?
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Clucose, AA, ions (Na, Kt)
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How do WSS pass the capillary wall?
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sinus only
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How bout PP and capillary wall?
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They pretty much stay within capillary wall. (A little bit leaks in reality from sinusoid)
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What is capillary in brain?
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Continuous. Tighter than most other continuous. Also, surrounded by Astrocyte
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What about LSS and brain cap?
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Passes easily
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From where does blood drain into the liver?
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Every organ. Everywhere
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What is bio-transformation (Hepatic)?
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The drug is converted
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How does it work?
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It is enzymatic. Enz are stored in liver (P450). Results in inactivation
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What happens during phase II of hepatic bio-transformation?
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Conjugation. Inactive and readily excreted products are usually formed
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What are the fixed phasocytic cells in the liver?
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Kupfer cells
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Can PP make it through GF?
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No
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Explain reabsorption in the tubule:
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99 of 100cc get reabsorbed. This is active. ATP is utilized. Polor substances (drugs that have been converted to polar and bad guys) leave in urine (1cc/minute)
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In which instance will drugs not make it through glomerulus in GF?
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When they are bonded to PP. Only free drug will go through
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Reabsorption is active, except for which instance?
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LS, which gets re-absorbed by PD
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If you give repeated doses before 4.5 half lives, what will happen to SC?
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It will go up, up, up
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What does magic bullet theory state?
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Drug has to work on the cell cecptor, either on surface or inside. Drug will not work unless it is bonded to a receptor
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What are the 3 types of drug antagonism?
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phisiological antagonism (opposing responses) (nipricle neo); (Neutralization of compounds) Antagonism (forms an inactive compound); pharmacological antagonism, competitive vs non competitive
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Describe competitive pharmacological antagonism
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There is reversible binding for the same receptor site. There is a precise parallel shift of the curve. ED50 increases (in tabs). There is no change in max response. Ex: add nitro to dobute comp for receptors, will need more dobute
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Describe non competitive antagonism
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There is irreversible binding. Occurs at a different receptor site. ED50 stays the same, but max response decreases. There is a non-parallel shift
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Draw ion-channel linked receptor. Explain
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(picture) Lygand opens or closes the channel. Ex: Na, Ca blocker
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What does GP transduction do in body (processes it contributes to)
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cell gravin and differentiation
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What are the 4 types of signal transduction with drugs binding to receptors?
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Intracellular receptor; trans-membrane receptor protein; on channel-linked receptors; and the biggy, G-Protein-coupled receptors
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Draw intracellular receptor
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(picture)
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What kind of drug does this?
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Lipid-soluble
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Draw dose response curve. Label: (a) ED50; (b) what happens when you keep going up in tablets
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(picture)
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Dig has a narrow theraputic range. Explain
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There is little difference between the effective and toxic dose
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Do benzos have a narrow theraputic range?
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No. TI is >1000
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What are the 4 types of drug interactions?
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Antagonism, addiction, synergism, potentration
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Antagonism=
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1 + 1 = 0
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Addiction=
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1 + 1 = 2
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Synergism=
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1 + 1 = 72 much larger than 2. Stronger
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Potentration=
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0 + 1 >1 ex: non drug + drug, maoI
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Name the 7 (8) steps to G protein receptor, labeling the picture.
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(picture) 1. Lygand hits receptor; 2. Conformation changes in receptor struct.; 3. Activation of G protein; 4. Alpha part of G-protein slides over to AC; 5. Activation of AC; 6. ATP is converted to CAMP; 7. Activation of Phosphokinase - e-given to protein
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How is CAMP removed?
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By phosphodiasterase
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Draw trans-membrane receptor
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(picture)
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What is an example of a drug that uses transmembrane receptor?
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Insulin - the x -> y lets glucose in at some other channel in the cell membrane
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What are the 2 curses of Pharmacology?
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(a) Drugs are not lazer guided; (b) Down regulation of receptors
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Explain down regualtion of receptors:
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The receptors literally move down into the cell
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What can the response of the cell be (in signal transduction)?
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Physical (muscle cont.) Hormonal (release)
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What does Ficks apply to?
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Everything. It is universal
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What is an advntage of facilitated?
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More biological substances can go into the cell
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An example of facilitated
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Insulin latching to the cell, activating a specific transporter, that lets glucose into the cell
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Draw a graph comparing facilitated and passive diffusion
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(picture) Spikes big time, until receptors get taken up. With passive diff, rate of transport only increase when change p does
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What stuff can move by simple passive?
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Anything
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What level of energy is required to get stuff from sm. intest. to blood stream?
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Expenditure of ATP
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Transport occurs through epithelial cells. Where in the body are they usually found?
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Sm. intestine, lg intesting, tubules of kidney
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Blood (gluc) in intestine 20, bs 100. How does glucose get into bloodstream?
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Through epithelial, by coupled, then through baso-lateral space -> blood. (by passive diff)
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How will Na get into blood through epith?
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Through the bl space, by active transport
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Who provides energy for soduim getting in through basolateral space?
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NAK atdase pumps
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In transport, what size is glucose, comparibly?
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Bulky
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Where is para-cellular?
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Between cells
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What can go para-cellular?
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Water
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When water gets to bl space, how does it get into blood?
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By mech. pressure. Nu + water = high inter-cellular pressure - forced through
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Majority of drugs metabolized by which order kinetics?
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1st
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Which capillaries are found where? (a) Continuous; (b) Fenestrated; (c) Sinusoid
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(a) cont - brain, skeletal muscle, lungs; (b) fen - S1, L1, kidneys; (c) sinusoid - liver (because "conjugated" stuff goes through maybe?), BM <-wss (glu, AA, ions) get by only in the junction
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Substances to remember for weight:
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Water, glucose, drug, PP
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Their weights, respectively
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18g, 180g, 200-1kg, 100,000g
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Substances/things to remember for size?
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Cell, CM, drug
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Their respective size
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10,000 NM (= 10 micrometers), 10NM, 1NM
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What are the 4 types of transport?
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Passive diffusion, primary active transport, secondary active transport, endocyrosis
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What are the 3 types of passive diffusion?
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Simply diffusion, facilitated diffusion, osmosis
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