Term
| All receptors have the ability to recognize _______________________________________ |
|
Definition
| endogenous chemical messengers (or endogenous ligands) |
|
|
Term
| true or false: receptors are most commonly proteins? |
|
Definition
|
|
Term
| Ligand binding produces a ________________ transformation of the receptor that alters _____________ |
|
Definition
| physiochemical, subsequent cellular events |
|
|
Term
| true or false: receptors can only have one binding site? |
|
Definition
| false, some receptors have multiple binding sites for different ligands |
|
|
Term
| name four types of ligand-receptor binding. order them from most to least common. |
|
Definition
| Van der waal's interactions/hydrogen bonds (most common), ionic bonds, covalent bonds (very rare) |
|
|
Term
| An (agonist/antagonist) is a ligand that activates a series of cellular events while an (agonist/antagonist) deactivates cellular events |
|
Definition
|
|
Term
| What are factors affecting drug-receptor interactions at the binding site? |
|
Definition
1. local chemical environment
2. pKa of aa's and drug
3. hydrophobicity and hydrophilicity of drug and receptor
4. the steriochemistry of the drug (sometimes one isomer fits where another does not, not superimposable) |
|
|
Term
| true or false: specific drugs have more side effects than non-specific drugs |
|
Definition
| false. non-specific drugs have more side effects because they bind to many different types of cells/receptors. their effect, however, is going to be weaker than a more specific drug. |
|
|
Term
| what do the classifications D/L, R/S and +/- tell you about a drug? |
|
Definition
| how strong the interaction/binding and specificity of a drug to receptor will be |
|
|
Term
| chemical interactions determine ______________, ____________ and _______________ |
|
Definition
| affinity, specificity and selectivity |
|
|
Term
| what are 4 major types of receptors? |
|
Definition
1. ion channels
2. G-protein coupled receptors
3. Tyrosine-kinases
4. Internal receptors |
|
|
Term
| (hydrophilic/hydrophobic) drugs are able to pass through cell membranes without a receptor. |
|
Definition
|
|
Term
| hydrophilic drugs generally act on _______________ receptors, which affect ___________________ |
|
Definition
| internal (intracellular), transcription/translation |
|
|
Term
| what are two main effects of a drug binding to a receptor? |
|
Definition
1. blocks access of endogenous (natural) ligand to binding site
2. induces a conformational change of the receptor |
|
|
Term
| what are a few possible outcomes of a conformational change of a receptor? |
|
Definition
1. an active (enzymatic) site could be exposed
2. could change the active site of a natural ligand so it can no longer bind
3. could open ion-channels
4. could create an induced fit (increased ligand-receptor affinity) |
|
|
Term
|
Definition
| what drugs do to the body (ie. receptor biding affinity, potency, etc.) |
|
|
Term
| what is the law of mass action |
|
Definition
|
|
Term
| what is the purpose of competition curves? |
|
Definition
| used to help determine the specific binding of a drug (affinity) and measure the effectiveness of a compound at inhibiting binding of a known drug |
|
|
Term
| what is the purpose of drug-receptor binding curves? |
|
Definition
| to describe receptor binding across drug concentrations. can also use to determine specificity of a binding. |
|
|
Term
| graded dose-response relationships tell us about the _______________ and ________________ of a drug on a system |
|
Definition
|
|
Term
| quantal dose-response relationships tell us about the ______________ of a drug |
|
Definition
|
|
Term
| polar compounds are (hydrophilic/hydrophobic) |
|
Definition
|
|
Term
| a ________________ binds to a receptor and can initiate a maximal effect but regardless of dose a _____________ can only ever initiate a partial effect |
|
Definition
| full agonist, partial agonist |
|
|
Term
| a (full/partial) agonist can can at as both an agonist and an antagonist |
|
Definition
| partial. at first acts as an agonist but because it blocks natural ligand and never produces a maximal effect it eventually becomes an antagonist. |
|
|
Term
| what does a competitive antagonist do? |
|
Definition
| binds at the same site as an agonist |
|
|
Term
| what does a non-competitive antagonist do? |
|
Definition
| binds at sites outside the primary binding site for the agonist thereby disrupting binding (generally by inducing a conformational change of the protein) |
|
|
Term
| what does an inverse agonist do? |
|
Definition
| binds to the receptor and inhibits the intrinsic activity of that receptor (ie turns something OFF that is usually ON) |
|
|
Term
| what do allosteric modulators do? |
|
Definition
| bind to a receptor at a site distinct from the active site and induce a conformational change that alters the affinity of the receptor for the endogenous ligand |
|
|
Term
| ______________ allosteric modulators increase the affinity of the agonist for the modulator and ____________ allosteric modulators decrease it. |
|
Definition
|
|
Term
| what is a suicide substrate? |
|
Definition
| a substrate that binds to a receptor irreversibly (via a covalent bond) and turns on or off the receptor until it is recycled by the cell |
|
|
Term
| what are three types of drug-drug interactions (drugs acting on different systems that in turn interact)? |
|
Definition
1. physiological antagonism
2. additive effects
3. potentiation |
|
|
Term
|
Definition
| what the body is doing to/with the drug (ie where does it go? how long until it takes effect, gets excreted etc.) |
|
|
Term
| name the nine routes of drug administration used on humans |
|
Definition
| oral, sublingual, topical, transdermal, intramuscular, subcutaneous, intravenous, intrathecal, epidural |
|
|
Term
| name the three routes of administration used exclusively on animals |
|
Definition
| intraperitoneal (i.p), intracraneal, intracerebroventricular (i.c.v.) |
|
|
Term
| which three routes of drug administration are used for lipid soluble drugs? |
|
Definition
| transdermal, intramuscular, subcutaneous |
|
|
Term
| what are the three most common types of injections? |
|
Definition
| subcutaneous, intramuscular and intravenous |
|
|
Term
| put these three types of injections in order of speed of effect (from fastest to slowest: intramuscular, subcutaneous, intravenous |
|
Definition
| subcutaneous, intramuscular, intravenous |
|
|
Term
| why does oral administration take so much longer than other types of admin? |
|
Definition
| because a lot of the drug is metabolized by enzymes in the stomach and liver before it reaches the circulatory system (plasma) where it takes effect |
|
|
Term
| non-polar drugs such as ______________ and ______________ can easily pass through cell membranes via ______________________________ |
|
Definition
| steroids, hormones, passive diffusion |
|
|
Term
| ______________ and ______________ diffusion require a transporter |
|
Definition
|
|
Term
| (facilitated/active) diffusion is energy-dependent. (facilitated/active) diffusion is energy-independent. |
|
Definition
|
|
Term
| what are organic anion and organic cation transporters? |
|
Definition
| large families of proteins that transport ions and are often hijacked and used by drugs |
|
|
Term
| what are three factors that affect the rate of transport of a drug? |
|
Definition
| concentration gradient, electrical gradient, pH |
|
|
Term
| true or false: most drugs are weak acids or weak bases |
|
Definition
| true. this means that they can ionize or deionize in certain situations. |
|
|
Term
|
Definition
| a mechanism for the body to keep a substance from entering or leaving a certain part of the body by changing the pH of tat substance (different parts of the body have different pH's). |
|
|
Term
| what is one example of pH trapping that was used in class? |
|
Definition
| asprin (salicylic acid) is deionized in the stomach (where there is a low pH). it then enters the blood stream where it is re-ionized (due to a higher pH) keeping it from reentering the stomach |
|
|
Term
| true or false: drugs travelling in typical capillaries use the same mechanisms to get to the target organ as drugs traveling in brain capillaries |
|
Definition
| false. at the end of typical capillaries the drugs are released via intercellular clefts and fenestration. due to the blood-brain barrier drugs traveling in brain capillaries need transporters to reach their target organ |
|
|
Term
| how does sex affect the absorption of drugs? |
|
Definition
| there is a difference in the distribution of adipose and muscular tissue between men and women. the drug dosage is going to be different for men and women based on whether it is a fat-soluble or water-soluble drug |
|
|
Term
| ____________ binding is nonspecific binding that occurs at inactive sites where drugs have no measurable biological effect |
|
Definition
|
|
Term
| what are some examples of where depot binding occurs? |
|
Definition
| bone, fat, muscle and plasma proteins (such as albumin) |
|
|
Term
| what does depot binding do? |
|
Definition
| delays the onset of drug action, can lead to drug toxicity (other drugs and/or endogenous ligands cant bind to receptor, too many remain in circulation |
|
|
Term
| what is one example of depot binding given in class? |
|
Definition
| Phenytoin (anti-seizure medication), shares receptor with aspirin, aspirin has higher affinity, if take aspirin after taking phenytoin, aspirin will kick out phenytoin into blood stream which can lead to toxic effects. |
|
|
Term
| how do you calculate bioavailability? |
|
Definition
| quantity of drug reaching systemic circulation/quantity of drug administered |
|
|
Term
| true or false: oral administration is much more predictable in terms of bioavailability than intravenous |
|
Definition
| false. it is much less predictable because so much is metabolized along the way. |
|
|
Term
| what are the two types of biotransformation? |
|
Definition
| phase I metabolism and phase II metabolism |
|
|
Term
| what happens in phase I metabolism? |
|
Definition
oxidation and reduction reactions occur
-generally make drugs more hydrophilic by adding small functional groups |
|
|
Term
| phase I metabolism takes place in the ____________ |
|
Definition
|
|
Term
| what three enzymes generally perform phase I metabolism reactions? |
|
Definition
| cytochrome P450, monoamine oxidase and alcohol dehydrogenase |
|
|
Term
| what happens in phase II metabolism? |
|
Definition
| the conjugation of a drug with small molecules, creates non-polar molecules that can be easily excreted |
|
|
Term
| true or false: hydrolysis reactions may be either phase I or phase II metabolism |
|
Definition
|
|
Term
| true or false: the metabolism of drugs can lead to activation |
|
Definition
|
|
Term
| what are some factors in the number of enzyme numbers available for drug metabolism? |
|
Definition
| sex, age and past drug history |
|
|
Term
|
Definition
| the time it take for the plasma drug concentration to fall to half its peak level |
|
|
Term
| what is the difference between zero-order kinetics and first-order kinetics? |
|
Definition
| in zero-order kinetics a set amount of drug is eliminated at each interval, in first-order kinetics half of the drug previously present is eliminated at each time interval |
|
|
Term
| what does ADME stand for? |
|
Definition
| absorption, distribution, metabolism, excretion (clinical application of pharmacokinetics) |
|
|
Term
| what is the value of the resting membrane potential (RMP)? |
|
Definition
|
|
Term
| How do you calculate the RMP? |
|
Definition
| using the Nernst equation |
|
|
Term
| How is the RMP maintained? |
|
Definition
| the Na+/K+ pump maintains concentration gradients across the cell membrane by pumping 2 K+ molecules out of the cell and 3 Na+ molecules into the cell with the use of ATP |
|
|
Term
| what activates the Na+/K+ pump? |
|
Definition
| high intracellular concentrations of Na+ |
|
|
Term
| ____________ are local (graded) potentials that make it more difficult for the neuron to fire |
|
Definition
| inhibitory postsynaptic potential (IPSP) |
|
|
Term
| ______________ are local (graded) potentials that make the neuron more likely to fire |
|
Definition
| excitatory postsynaptic potentials (EPSP) |
|
|
Term
| what are some major differences between electrical and chemical synapses? |
|
Definition
-electrical synapses are bidirectional, chemical synapses are typically unidirectional
-elec syn's are fast, chem syn's are slow
-elec syn's send messages via gap junctions (direct connection of 2 cells), chem synapses use nt's which travel in synaptic vesicles
-elec syn's not very common in mammals |
|
|
Term
| describe what happens when an AP reaches the axon terminal |
|
Definition
| depolarization causes opening of Ca2+ channels, influx of Ca2+ causes vesicles to fuse with presynaptic membrane, nt is released into synaptic cleft via exocytosis, nt binds to receptors on postsynaptic membrane and opens channels, vesicular membranes are retrieved from plasma membrane |
|
|
Term
| true or false: neurotransmitters are released in quantal units |
|
Definition
| true. the smallest unit = 1 synaptic vesicle |
|
|
Term
| what are the names of the two places nt's are stored in a cell? |
|
Definition
| the readily releasable pool and the reserve pool |
|
|
Term
| where are the reserve pool nt's located in the cell? |
|
Definition
| they are anchored to the cytoskeleton (actin) by a protein call synapsin |
|
|
Term
| how are nt's released from the reserve pool? |
|
Definition
| the synapsin must be phosphorylated by CamKII (Ca2+/Calmodulin-dependent kinase II) which then releases the vesicle allowing it to travel to the presynaptic density |
|
|
Term
| ______________ positions vesicles in the active zone using Vesicle (V-) Snares and Target (T-) Snares |
|
Definition
|
|
Term
| _______________ is an example of a V-Snare |
|
Definition
|
|
Term
| Syntaxin and SNAP-25 are examples of ____________ |
|
Definition
|
|
Term
| what happens during the priming step of nt release preparation? |
|
Definition
| SNARE proteins (ie SNAP and NSF) on the vesicular and extracellular membranes bind to form SNARE complexes and pull the two membranes together (uses ATP). |
|
|
Term
| Ca2+ entering the cell binds to _______________ which catalyzes the fusion of the vesicle and cellular membranes |
|
Definition
|
|
Term
| what are two examples of toxins that can interfere with nt release? and how? |
|
Definition
1. Butulinum toxin: prevents exocytosis by cleaving SNAP-25 and/or synaptobrevin (T-snares)
2. Tatanus: prevents exocytosis by cleaving synaptobrevin in GABA and motor neurons |
|
|
Term
| what is one important experiment that illustrates the importance of Ca2+ in NT release? |
|
Definition
1. When Ca2+ was injected artificially into presynaptic neuron of a giant squid shown that a response occurs (change in membrane potential) in the postsynaptic cell, indicating Ca2+ induced release of NT. SAme study showed that if a Ca2+ buffer is injected into the synaptic cleft no postsynaptic response is observed
Other studies have shown that the amount of NT released is proportional to the amount of Ca2+ that enters the cell (varying extracellular [Ca2+] alters postsynaptic response). |
|
|
Term
| What are three types of chemical synapses? |
|
Definition
1. axoaxonic
2. axodendritic
3. axosomatic |
|
|
Term
| describe the experiment conducted by Heuser and Reese that demonstrated synaptic vesicle recycling |
|
Definition
| Injected horseradish peroxidase (HRP), ,which can be visualized, into synaptic cleft and stimulated neuron to induce NT release. Viewed the position of HRP over a short serious of time intervals. Found that immediately following NT release the HRP was in "coated vesicles" (special endocytotic organelles). A few minutes later it was in an endosome and finally ended up in synaptic vesicles. |
|
|
Term
|
Definition
| a triskeleton molecule that binds to the plasma membrane (via adaptor proteins) and to other clathrins to create clathrin-coated pits which then beome clathrin-caoted vesicles with the aide of dynamin |
|
|
Term
| ________________ is a protein that forms a ring around newly formed clathrin-coated pits and piches them off from the plasma membrane, making them free moving clathrin-coated vesicles |
|
Definition
|
|
Term
| what are two functions of membrane recycling? |
|
Definition
1. keeps the terminal bouton from exploding
2. keeps cell from having to make new membrane (which costs energy) |
|
|
Term
| _____________ and its cofactor ______________ remove clathrin coating from vesicle |
|
Definition
|
|
Term
| what are three ways that nt's are inactivated? |
|
Definition
1. reuptake into neurons (via transporters)
2. reuptake into glia cells
3. degredation by enzymes in the membrane or synaptic cleft |
|
|
Term
| what are two ways NT release is modulated? |
|
Definition
1. terminal autoreceptors
2. somatodendritic receptors |
|
|
Term
| terminal autoreceptors inhibit the ___________ and ________________ of NT's |
|
Definition
|
|
Term
| somatodendritic autoreceptors inhibit _________________ |
|
Definition
|
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