Term
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Definition
| =the study of the actions of drugs & their effects on a living organism |
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Definition
=the specific molecular changes produced by a drug when it binds to a particular target site or receptor
--> leads to more widespread alterations: drug effects |
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Definition
| =widespread alterations in physiological or psychological functions caused by molecular changes caused by drug action |
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Term
| site of drug action= site of drug effect? |
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Definition
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Term
| drugs have multiple effects because? |
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Definition
| they act at a variety of target sites |
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Definition
| =drug-receptor interaction produces desired physical or behavioral changes |
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Definition
=any other effect caused by drug that is not a therapeutic effect
-mildly annoying-> distressing -> dangerous |
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Definition
| =effects based on physical & biochemical interactions of a drug with a target site in living tissue |
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Definition
=effects not based on the chemical activity of a drug-receptor interaction but on certain unique characteristics of the individual
ie) mood, expectations, perception of drug-taking situation, attitude towards administrator of drug, etc.
ex) placebo effect |
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Term
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Definition
=the amount of drug in the blood that is free to bind at specific targets to elicit drug action
-determined by pharmacokinetic component of drug action |
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Term
| 5 factors of pharmacokinetics |
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Definition
1. Adminstration
2. Absorption
3. Distribution
4. Biotransformation/Inactivation
5. Elimination/Excretion |
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Term
| when a drug binds to plasma proteins in blood or is stored temporarily in bone or fat (where it is inactive) |
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Definition
depot binding
-causes biotransformation |
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Term
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Definition
=per os
=oral administration
-most popular route for taking drugs
--safe, self-administered, economical, avoids complication/discomfort of injections
--form: capsules, pills, tablets, liquids
--must dissolve in stomach fluids & pass through stomach wall to reach blood capillaries
--drug: must be resistant to destruction by stomach acid & enzymes |
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Term
| can insulin be administered orally? |
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Definition
| No, it is destroyed by digestive processes |
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Term
| 4 properties of drugs absorbed by gastrointestinal tract? |
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Definition
1. water soluble
2. gastric resistant
3. lipid soluble
4. first pass metabolism |
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Term
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Definition
=movement of drug from site of administration to blood circulation
-most drugs are not fully absorbed until they reach the small intestines |
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Term
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Definition
| -lined by tightly apposed epithelial cells |
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Term
| factors affecting how quickly GI tract empties contents into small intestine? |
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Definition
1. fatty foods in stomach slow movement of drug (aka slows absorption)
2. amt of food
3. amt of physical activity of individual
etc.. |
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Term
| reduces amt of available drug molecule before reaching circulation? |
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Definition
first-pass effect
-by liver metabolism of some of the drug |
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Term
| has irregular & unpredictable drug plasma levels? |
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Definition
Oral administration
-also has more slowly rising drug plasma |
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Term
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Definition
=intravenous injection
=most rapid & accurate method of drug administration
-precise quantity of agent placed directly into blood (eliminates passage through cell membranes ie stomach wall) |
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Term
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Definition
quick onset of drug effect is potential hazard
-overdose or allergy to drug leaves little time for corrective measure
--drug can not be removed from body (ie stomach pumping)
-needle sharing of drug abusers |
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Term
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Definition
-slower, more even absorption than IV (10-30 min)
-can be further slowed by combining drug with 2nd drug that constricts blood vessels
-disadvantages: injection solution can be irritating or cause muscle discomfort
-inserted at 15 degree angle |
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Term
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Definition
=intraperiotoneal injection
=drug injected through abdominal wall into peritoneal cavity (space that surrounds abdominal organs)
--rarely used with humans->danger of peritoneal infection
-produce rapid effects (not as rapid as IV)
-variability depeding on where within peritoneum the drug is injected |
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Term
| biotransformation is primarily a result of? |
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Definition
| metabolic processes in the liver |
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Term
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Definition
=subcutaneous administration
=drug is injected 45 degrees just below skin
-absorption: depends on blood flow to site; usually slow & steady
-drug + nonaqueous solution = slows rate
-silastic capsules (produces time rls effect) |
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Term
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Definition
=drugs absorbed into blood by passing through lungs
ex. smoking, inhalers
absorption: very rapid because are of pulmonary absorbing surfaces is large & rich with capillaries
-effect brain rapidly because lung capillaries go straight to brain (w/o returning to heart)
disadvantages: damage to nasal & lungs bye small particles |
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Term
| 2nd preferred method of self-administration? |
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Definition
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Term
| effect of nicotine inhalation? |
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Definition
rlsd from tabacco by heat
-rapid rise in blood level & CNS effects
-peak: minutes |
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Term
| intracoelomic administration |
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Definition
=i.c.
-aka intraperitoneal |
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Term
| topical application of drugs |
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Definition
=application to mucous membranes (conjunctiva of eye, nasopharyns, vagina, colon, urethra)
->local drug effects
ex) snorting coke
-transdermal: drug admin through skin, can penetrate if lipid-soluble |
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Term
| in order to penetrate skin? |
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Definition
-must be lipid-soluble substance (dissolve fat)
-skin is an effective barrier to the diffusion of water-soluble drugs |
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Term
| transdermal administration |
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Definition
-type of topical application
=with skin patches (polymer matrix embedded with the drug in high conc)
-provides controlled & sustained delivery of drug at preprogrammed rate
-common: prevent motion sickness, reduce cigarette cravings |
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Term
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Definition
| transdermal medicine to prevent motion sickness |
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Term
| administration for some drugs that act on nerve cells |
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Definition
special injections
-because BBB (cellular barrier)prevents/slows passage of drugs into neural tissue
ex. epidural, intracranial, intracerbroventricular |
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Term
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Definition
-a special injection used when spinal anesthetics are administered directly into CSF surrounding SC
-bypasses BBB
ex) during childbirth |
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Term
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Definition
-special injection
-only in animals
-microsyringe or cannula employed
-injection into discrete area of brain tissues
-bypasses BBB |
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Term
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Definition
-special injection
-animals
-injection into cerbrospinal fluid-filled chambers aka ventricles |
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Term
| how scientists study electrophysiological, biochemical, or behavioral effects of drugs on particular nerve groups? |
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Definition
| -special injections: intracranial &/or intracerebroventricular |
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Term
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Definition
| =absorption rate + liver metabolism |
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Term
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Definition
1. Dura
2. Arachnoid
3. Sub-arachnoid
4. Pia |
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Term
| Intrathecal Administration |
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Definition
-lumbar puncture (spnal needle inserted between 3rd & 4th lumbar vertebrae)
-into sub-arachnoid space into CSF |
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Term
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Definition
-cloudy
-trtment: anesthetics, analgestics, antibiotics |
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Term
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Definition
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Term
| sensory nerves found where? |
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Definition
| DRG- dorsal root ganglion |
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Term
| most rapid, most accurate blood concentration administration method |
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Definition
IV
-OD
-need sterile needles |
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Term
| slow & even absorption from? |
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Definition
IM
-but need sterile equipment |
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Term
| slow & prolonged absorption from |
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Definition
SC
-but variable depending on blood flow |
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Term
| localized action & effects |
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Definition
topical
-but may be absorbed into general circulation |
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Term
| controlled & prolonged absorption? |
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Definition
transdermal
-but local irritation
-only useful for lipid soluble drugs |
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Term
| longest threshold for effectiveness? |
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Definition
| IM-oil > SC > IM > PO > IV |
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Term
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Definition
| IV > IM > IM-oil > SC >PO |
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Term
| primary target site for psychoactive drugs? |
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Definition
brain
-site of admin-> blood -> circulated throughout body -> brain |
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Term
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Definition
1. route of administration (bc of area, # of cell layers, amt of drug destroyed, extent of binding to inert complexes)
2. Drug concentration (determined by age, sex, size)
3. solubility & ionization of drug |
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Term
| most important factor in determining drug plasma levels? |
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Definition
| rate of passage of the drug through various cell layers (& membranes) between site of admin and blood |
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Term
| cell membranes made up of? |
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Definition
phospholipids
=complex lipid (fat) molecules which have a negatively charged region at one end & two uncharged lip tails
-arranged into bilayer with phosphate ends forming 2 almost continuous sheets filled with fatty material |
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Term
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Definition
=charged heads in contact both aqueous intracellular fluid and extracellular fluid.
=phosphate ends forms sheets filled with fatty material
-have proteins inserted into bilayer
-prevent passing unless soluble in fat |
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Term
| what can pass through phospholipid bilayer?? |
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Definition
molecules soluble in fat
-by passive diffusion |
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Term
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Definition
| drugs leaving water in blood/stomach juice & entering lipid layers of membran |
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Term
| cells with high lipid solubility move through cells by? |
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Definition
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Term
| larger concentration difference means? |
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Definition
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Term
| which is more lipid soluble? heroin or morphine? |
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Definition
heroin is more lipid soluble.
morphine is parent molecule. |
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Term
| weak acids and weak bases may become ionized when dissolved in what? |
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Definition
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Term
| extent of ionization depends on? |
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Definition
1. relative acidity/alkalinity (pH) of the solution
2. pKa (an intrinsic property of the molecule) |
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Term
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Definition
| =represents the pH of the aqueous solution in which the drug would be 50& ionized |
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Term
| weak acids ionize most in what type of solution? |
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Definition
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Term
| weak acids ionize least in what type of solution? |
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Definition
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Term
| If aspirin (was) placed in stomach? |
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Definition
| would remain primarily non-ionized -> more lipid soluble -> readily absorbed from stomach to blood |
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Term
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Definition
| absorption decreased compared to stomach because pH of intestine is higher and causes aspirin to ionize |
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Term
| why would aspirin not move to stomach and back? |
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Definition
once aspirin is in the blood (pH 7), it becomes trapped because it becomes more ionized
-also circulation moves it away from concentrated site to maintain concentration gradient |
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Term
| if a drug is highly charged in both acidic and basic environments? |
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Definition
| can not be administered orally |
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Term
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Definition
small intestine
-greater SA
-slower movement
--> rate at which stomach empties into small intestine can be rate-limiting |
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Term
| negative part of a phospholipid molecule? |
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Definition
the negatively charged PO4- group head
-is attracted to water |
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Term
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Definition
-reflects both size & weight
--> better basis for determining drug dose |
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Term
| why does sex affect drug dosage? |
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Definition
-females contain more adipose tissue (relative to water)
-->represents a laterger prportion of the total body weight
--> total fluid volume is smaller in women |
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Term
| time it takes to carry a drug throughout the body once in the blood stream? |
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Definition
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Term
| highest blow flow will have |
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Definition
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Term
| most drugs can move from blood and enter body tissues regardless of lipid solubility because? |
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Definition
blood capillaries have numerous pores
-unless the drugs are bound to proteins in depot binding |
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Term
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Definition
fills subarachnoid space that surrounds entire bulk of brain & sc
-also fills ventricles & interconnecting channels (aqueducts |
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Term
| choroid plexus of lateral ventricle |
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Definition
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Term
| walls of typical capillaries made of? |
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Definition
endothelial cells that have small gaps (intercellular clefts) & larger openings (fenestrations)
-job of blood vessels: deliver nutrients to cell & remove waste |
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Term
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Definition
-contained in typical capillaries
-envelop & transport larger moleucules through capillary wall |
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Term
| intercellular clefts of brain capillaries |
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Definition
-are closed because adjoining edges of enothelial cells are fused
--> forms tight junctions |
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Term
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Definition
fenestrations & intercellular clefts are absent
-pinocytotic vesicles are rare
-most material (if not lipid-soluble) is moved through walls by special transporters |
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Term
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Definition
-close interface with nerve cells & brain capillaries
-glial feet surround brain capillaries
-->modify neuron function |
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Term
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Definition
-selectively permeable
-does not diffuse water-soluble or ionized molecules
-lipid soluble molecules can diffuse |
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Term
| areas where BBB is not complete? |
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Definition
1. area postrema
2. median eminence
3. subfornical origin |
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Term
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Definition
aka CTZ (chemical trigger zone)
-located in medulla of brain stem
-"vomiting center"
--causes vomiting when toxic substances are detected in blood
---> lifesaving response! |
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Term
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Definition
-in hypothalamus
-caillary fenestrations allow neurohormones (rlsing factors) manufacted by hypothalamus to move into the blood traveling to the pituitary gland
--regulate anterior pituitary hormone secretion |
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Term
| second barrier only in women? |
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Definition
-placental barrier
-between blood circulation of pregnant woman and fetus |
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Term
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Definition
agents that induce developmental abnormalities in the fetus
-dependent on timing of exposure
-most suceptible during first trimester because organs are forming
ex. accutane |
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Term
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Definition
=drug binding can occur at inactive sites where no measurable biological effect is initiated
ex. plasma protein (albumin), muscles, fat
-unbinds when blood level drops
-effects magnitude and duration of drug action |
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Term
| binding to albumin, fat, and muscles is? |
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Definition
nonselective
-> drugs with similar physiochemical characteristics compete with each other for these sites which can lead to higher than expected free drug blood level of displaced drug
--> can cause OD |
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Term
| many psychoactive drugs have extensive? |
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Definition
90% plasma protein binding
-may contribute to drug interaction |
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Term
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Definition
-usually occurs exponentially (a constant fraction of the free blood is removed in each time interval)
-first-order kinetics |
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Term
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Definition
-not as common as first order clearance
- drug molecules are cleared at a constant rate regardless of concentration
ex) ethyl alcohol |
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Term
| combined action of biotransformation + excretion of metabolites |
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Definition
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Term
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Definition
-chemical changes aka drug metabolism
-most common in liver
-2 types:type I & II |
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Term
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Definition
-often first, not always
-involves nonsynthetic modification
ex. hydrolysis, oxidation, reduction
--oxidation is most common |
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Term
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Definition
-most common phase 1 reaction
-produces metabolite that is less lipid soluble & less active usually |
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Term
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Definition
-biotransformation
-synthetic reactions that require conjugations of drug with small molecule
ex. glucuronide, sulfate, methyl groups
-metabolites are usually less lipid soluble & almost always biologically inactive |
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Term
| inactivates psychoactive drugs? |
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Definition
| glucuronide (phase 2 rxn) |
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Term
| liver enzymes responsible for metabolizing psychoactive drugs are located? |
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Definition
on smooth ER
-a network of tubules within liver cell cytoplasm
aka microsomal enzymes
-lack specificity & can metabolize wide bariety of compounds
-cytochrome P450 |
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Term
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Definition
-most important microsomal enzyme
-responsible for oxidizing a majority of psychoactive drugs
-contribute to cross tolerance
-Phase 1 reaction
-can be inducible (by exposure to some drugs) |
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Term
| factors produced by enzymes of liber that influence rate of biotransformation |
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Definition
1. enzyme induction
2. enzyme inhibition
3. drug competition
4. differences in age, sex, genetics |
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Term
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Definition
=when psychoactive drugs are used repeatedly, can increase amount of liver enzymes
-can cause cross tolerance (ex. smoking cigarettes means you'll need higher does because of increased P450 |
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Term
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Definition
-drugs that directly inhibit the action of enzymes which reduces metabolism of other drugs taken at the same time
->impaired metabolism -> higher blood levels
ex. food toxicity |
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Term
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Definition
occurs when drugs share a metabolic system
ex. 450 metabolism of alcohol leads to higher than normal brain levels of other sedatives (eg valium) |
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Definition
-most important route
-liver biotransformation of drugs into ionized (water-soluble) molecules traps the metabolites in the kidney tubules so they can be excreted with wastes in urine |
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Term
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Definition
| =the study of the physiological and biochemical interaction of drug molecules with target tissues that is responsible for ultimate drug effeccts |
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Term
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Definition
=large protein molecules located either on surface or within the cell
-the initial sites of action of a biologically active agent like a nts, hormone, or drug |
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Term
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Definition
| =molecule that binds to a receptor with some selectivity |
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Term
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Definition
-lock and key
-intrinsic
-highest affinity
-can cause down regulation |
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Term
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Definition
=fits in lock, but no action
-antagonists
-prevent binding of active ligand
-block
-can lead to up-regulation of receptors |
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Term
| changes in sensitivity of receptor caused by? |
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Definition
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Term
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Definition
| =drug receptor proteins may have different characteristics in different target tissue |
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Term
| important method to evaluate receptor activity? |
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Definition
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Term
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Definition
=evauluates receptor activity
-describes amt of biological or behavioral effect (response) for a given drug (dose)
-classic S shape |
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Term
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Definition
| =smallest dose that produces measurable effect |
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Term
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Definition
50% effective dose
=the dose that produces half the maximal effect (ED100-when all receptors are occupied) |
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Term
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Definition
=the absolute amt of drug necessary to produce a specific effect
-differences in potency can be seen by comparing ED50 |
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Term
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Definition
-calculates drug safety
TI=TD50/ED50
-low TI->dangerous |
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Term
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Definition
50& toxic dose
-50% of population experiences a particular toxic dose |
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Term
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Definition
| -can be displaced from sites by an excess of agonist because an increaded conc of active drug can compete more effectively fo the fixed number of receptors |
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Term
| addition of competetive agonist |
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Definition
| causes decrease in potency of drug |
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Term
| non competetive antagonst |
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Definition
=drugsthat reduce the effect of agonist in ways other than competing for receptor
ex. impair agonist action by bind to a portion of the receptor, disturbing cell membrane supporting receptor, interfering with intracellular processes that were initiared by the anoist |
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Term
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Definition
| rate which drug associtates with receptor |
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Term
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Definition
| rate which drug dissociates from receptor |
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Term
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Definition
aka dissociation constant (not same as rate of dissocation from receptor, k2)
-determines drug affinity. the conc of radioligand that labels 50% of total receptors in sample
Kd= k2/k1 |
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Definition
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Term
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Definition
low Kd=higher affinity
so you'd need less of the drug to label receptors |
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Term
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Definition
| conc of competitor drug that inhibits 50% of radioligand binding |
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Term
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Definition
| high affinity, would need more competitor drug thus IC50 would be higher |
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