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Pharm chapter 4

The intensity of the response to a drug is directly related to what? It's related to the concentration of the drug at its site of action
How do you maximize beneficial effects of a drug and minimize harm? -achieve conc that are high enough to elicit desired responses but avoid concentrations that are too high
How is this balance achieved between maximal benefit of a drug and minimizing harm? -by selecting: 1) appropriate route, dosage, and dosing schedule -we need to consider pharmcokintetics
True or False drug must leave vascular system to reach their sites of action TRUE
True or False drug usually passes in between the cells False -since the cells are close together, the drug usually passes through the cell instead of in between them and so the ability of a drug to cross a membrane is determined by the drugs ability to cross through the single cells.
What is the cytoplasmic membrane? -the membrane that surrounds the cell -it is the major barrier to passage through a cell
what is a phospholipid molecule? -it's the basic structure of a cell membrane -it's a double layer molecule -are composed of lipids that contain atoms of phosphate -has a phosphate head and two long-chain hydrocarbon tail
What are the three ways a drug crosses a cell membrane? 1)through channels or pores 2) with the help of a transport system 3) direct penetration of the membrane (most common)
True or False Drugs commonly travel through channels and pores ANS: FALSE -very few drugs cross this way since channels are particularly small
True or False -compounds of MW of below 200 can only pass through the channels ANS: TRUE -it also has to be the right channel
What are transport systems? -they move drugs from one side of cell membrane to the other -may require expenditure of energy -selective -depends of drug structure
T/F All transport systems require the expenditure of energy ANS: F -some require it others don't.
T/F Renal excretion of many drugs would be extremely slow were it not for transport systems in the kidney that can pump drugs from the blood into the renal tubules. T
T/F P-Glycoprotein transports drugs into the cell F -P-glycoprotein is a transmembrane protein that transports a wide variety of drugs out of cells -type of transporter -present in cells at sites: liver, kidney, placenta, intestine, and capp of the brain
what is the function of the P-glycoprotein in the following sites: 1)liver 2)kidney 3)placenta 4)intestine 5)capp of brain 1)t drugs into bile for elimination 2)pumps drug into urine for excretion 3) t drug back to maternal blood - minimize fetal drug exposure 4) t drug into intestinal lumen to reduce absorption of drug into blood 5 p drug into blood-limit access to brain
why do most durgs directly penetrate membranes directly? 1) most drugs are too large to pass through channels or pores 2) most drugs lack transport systems to help them cross all of the membranes that separate them from their sites of action, metabolism, and excretion.
why must a drug be a soluble lipid (lipophilic) in order to directly penetrate membrane? B/C membranes are mostly composed of lipids so the drug must be able to dissolve into the lipid that makes the membrane
T/F -polar molecules and ions can directly penetrate the membrane -F - these are no lipid soluble so they cant penetrate membrane
what are polar molecules? -molecules w/ uneven distribution of electrical charges + and - congregate separately -have NO net charge --> have P=E-->balance eachother out
what are ions? -have an overall +/- net electrical charge
T/F -Quaternary Ammonium Compounds are polar molecules that carry no net charge -F -they carry at least one atom of nitrogen and carry a positive charge at all times -I.E.: Tubocurarine
How is a weak acid or weak base carrying a charge determined? -by the pH of the surrounding medium
T/F -aspirin is a base and will accept protons in an acidic media and become ionized F -aspirin is an acid and therefore will be non-ionized in an acidic media -however in a basic media it will give up its protons and become ionized
T/F -since the stomach is an acidic environment, aspirin will remain non-ionized T -and b/c of this, they can be absorbed across the membranes that sep stomach from bloodstream. pass from the stomach into the small intestine--> environment is relatively alkaline, they change to their ionized form, so cant absorb A from intestine
What causes ionization of drugs? -the pH -ionization is pH dependent and drug molecules will accumulate on side of cell that will cause ionization
T/F basic drugs will accumulate on alkaline side F -basic drugs will accumulate on acidic side and the acidic d will accumulate on the alkaline side
what is pH partitioning aka ion trapping a drug accumulates on the side of a membrane where the pH most favors its ionization -helps with movement of drugs
The rate of absorption determines ______________ The amount of absorption __________________ how soon effects will begin. helps determine how intense effects will be.
What are the 5 factors that affect drug absorption 1) Rate of Dissolution 2) Surface Area 3) Blood Flow 4) Lipid Solubility 5) pH partitioning
Before a drug can be absorbed it must first be _______ dissolved the rate of dissolution helps determine the rate of absorption.
What is the major determinant of the rate of absorption? Surface area that is available for absorption -larger SA faster absorption
T/F orally administered drugs are absorbed quickly from the stomach instead of the small intestine F the small intestine, because of its lining of microvilli, has an extremely large surface area, whereas the surface area of the stomach is relatively small.
Why are drugs absorbed more rapidly from sites where blood flow is high? b/c blood that has newly absorbed drug is replaced quickly w/ drug free blood so ther is a large gradient of conc of drug in the blood and out of the blood -The greater the concentration gradient, the more rapid absorption will be.
why are highly lipid-soluble drugs absorbed more quickly? -lipid-soluble drugs can readily cross the membrane while low lipid solubility cannot
T/F Abosrption of drug will be enhanced if there is a difference between the pH of plasma vs. pH at site of admission T -ion partition--> ionization-->drugs like this
What are the 2 major groups of administration? Enteral (GI tract--> oral PO) Parenteral (injection-->intravenous, subcutaneous, and intramuscular)
Why are there no barriers when you administer via IV? b/c the the drug is directly put into the blood so all barriers are bypassed -absorption is instantaneous since it enters the blood and all of the dose gets into the blood -rapid onset -need precise control over dose since all goes in blood
-which route allows the administration of large fluid volumes? -the IV route -only parenteral route -Some drugs that require parenteral administration are poorly soluble in water, and must be dissolved in a large volume.
what are some of the disadvantages of IV look at table 4-1 on pg 32 (46) -costly -inconvenient-->tethered to IV line and bottles-->difficulty moving -pt, cant self administer -dangerous, irreversible--> once in the blood no way turning back -oral-->easy, convenient and cheap
why should IV drugs be injected slowly around 1 minute or more? by injecting a drug over a 1-minute interval, it causes the blood to be diluted in the largest volume of blood possible and so we avoid high concentrations of the drug -also reduces the risk of toxicity to CNS
how does IV injection cause embolism (em) 1) IV needle can injure the venous wall--> formation of a thrombus (clot); embolism can result if clot breaks loose & lodges in another vessel. 2) injection of hypo or hypertonic fluids can destroy red blood cells; the debris from the cells can cause em
How can injections of drugs that are not fully dissolved cause embolism? particles of undissolved drugs can embedd in blood vessels and cause blockage, so you should check IV soln b4 administration to make sure drugs are in soln
T/F All types of insulin med can be given as IV F some can be given as IV such as regular insulin while others such as NPH insuln cannot since its formulated as a particulate insuline
what is the only barrier for IM injection the capillary wall
the rate of absorption for IM injection is determined by what two factors 1) water solubility of drug 2) blood flow to the site of injection - water sol drugs absorbed more quickly -less water sol drugs absorbed more slowly
why cant IV be used for poor sol compounds while the IM route can be used for that? -b/c for IV the drugs must be dissolved first b4 administration and since little harm will come from depositing a suspension of undissolved drug in the interstitial space of muscle tissue, IM route is acceptable for drugs whose water solubility is poor
what is a depot preperation and give an example used for IM route -drug is deposited and is absorbed slowly Ex: benzathine penicillin G advantage --> reduce number of injections during long-term therapy
why can't patients on anticoagulant therapy receive IM injections? because IM injections can cause local tissue injru and maybe nerve damage
subQ similiar to IM look at table4.1
what are the barriers for oral medication (1) the layer of epithelial cells that lines the GI tract, and (2) the capillary wall -the major barrier is (1) also unlike IM, sub Q the cells have to pass through the cells instead of in between the cells
what are the 5 factors that determine absorption rate? (1) solubility and stability of the drug, (2) gastric and intestinal pH, (3) gastric emptying time, (4) food in the gut, (5) coadministration of other drugs, and (6) special coatings on the drug preparation.
why cant all drugs be taken orally? Some will become inactivated because they will get destroyed by the stomach acid such as pencillin G and others will get destroyed by digestive enzymes such as insulin and there are other causes as well
what are the different types of oral medications? -tablets -enteric-coated preparations -sustained-release preparation
what is the purpose of enteric-coated preparations? -these are used for fatty acids, waxes, and shellac -and the reason why their content is released in the intestine and not the stomach is b/c 1. to protect drugs from acid and pepsin in the sto 2. to protect stomach from drugs that cause discomfort
what are the three determinants for distribution? -blood flow to tissue -ability of a drug to exit the vascular sys -ability of drug to enter cells
why is it important for drugs to leave the vascular system and at how do they leave it? - it is necessary for it to leave the blood for metabolism and excretion and it leaves it at the capillary beds and they pass in between the cells.
T/F drugs that are water soluble can pass through the BBB false -the bbb is composed of tight junctions in between the cappilaries and the only thing that can pass are lipid soluble drugs or drugs that have a transport sys that allows them to pass the BBB
what is the function of P-glycoprotein in the BBB -it pumps drug back into the blood, thus limiting its access to the brain
what drugs readily and non-readily pass from the maternal bloodstream into the blood of the fetus? readily: lipid sol and noionized drugs excluded: ionized, highly polar, or protein bound (to plasma albumin) or drugs that are substrates for P-glycoprotein, a transporter that can pump a variety of drugs out of placental cells into the maternal blood
T/F Albumin is a small protein that is able to leave the vasculature system through capillary walls F -it has a MW of 69,000 and b/c of its big size it can pass through the pores in the capp walls and so no transport sys exists for it to leave the blood
what system causes drug metabolism in the liver? -the hepatic microsomal enzyme system aka P450
what are the two types of metabolic transformations that enhance excretion? 1A: the addition of a hydroxyl group converts the pentobarbital into a more polar, less lipid-soluble form 1B: uses the process of glucuronidation to convert a highly lipophilic drug such as phenytoin into a H20 sol form and is excreted from the kidneys
define prodrugs and give an example it is a compound that is pharmacologically inactive when administered but undergoes conversion to its active form w/in the body Ex: prazepam-->desmethyldiazepam
t/f drug metabolism can only cause an increase in drug toxicity -reread page 39 f -since one of the functions of drug metabolism is converting a drug to its inactive form it can also cause a decrease in toxicity
why are drugs that have a rapid hepatic metabolism usually administered parenterally? to allow the medication to bypass the liver and be able to reach therapeutic levels in the systemic blood. if given orally, the first-pass effect will inactivate the med when it passes through the liver (look at pg 39) ex: nitroglycerin
why is nitroglycerin administered sublingually instead of orally -if given sublingually, it is very active and is able to be absorbed directly into the systemic circulation and is able to reach its site of action b4 passing through the liver
t/f the most important organ for excretion is the liver f -it's the kidneys
what are the three net results of the urinary excretion process? pg.41 glomerular filtration->drug moves from blood into tubular urine. drugs attached to big proteins cant pass through passive tubular reabsorption-> lipid sol drugs move back into the blood & polar and onized drugs remain in urine 3. active tubular secretion
Created by: Jaspritk



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