Term
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Definition
| Drug that binds receptor and stimulates cellular activity |
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Term
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Definition
| Drug that binds receptor and inhibits action of agonists (drugs or endogenous agonists) |
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Term
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Definition
| Exogenous substance that binds to a receptor or has biological action |
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Term
| Why is it useful for a drug to be small? |
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Definition
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Term
| Why is it bad if a drug is too big? |
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Definition
| LIMITED MOVEMENT WITHIN THE BODY |
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Term
| What is the relationship between Kd and the affinity of a drug for its receptor? |
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Definition
Lower Kd has higher affinity;
Higher Kd has lower affinity |
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Term
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Definition
| A measure of drug affinity for receptor |
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Term
| In a stereoselective enzyme, what is an example of a difference in the action of the two possible enantiomers? |
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Definition
Most obvious is duration of action- one enantiomer will have higher affinity
Stereoselectivity also affects efficacy |
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Term
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Definition
| An inactive substance that is converted to an active drug by conditions or enzymes within the body |
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Term
| Name 5 possible targets of drug action: |
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Definition
Receptors- mediate action
Enzymes- can break a drug into active or inactive forms
Carrier Molecules- like albumin
Ion Channels- like GABA receptor
Structural Proteins- |
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Term
| What is the mechanism of action of colchicine? |
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Definition
| Binds to tubulin and inhibits mitosis |
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Term
| What is a chemical antagonist? |
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Definition
| A chemical or drug that interacts with other drugs: Protamine binds to heparin anticoagulants in the case of overdose to reduce blood thinning effects of heparin |
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Term
| What is an osmotic agent? |
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Definition
| A passive substance that acts osmotically on tissues: like giving mannitol to reduce pressure from subarachnoid hemmorhage |
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Term
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Definition
| It is an osmotic agent- given for subarachnoid hemmorhage |
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Term
| What is pharmacodynamics? |
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Definition
| The actions of a drug on the body |
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Term
| What is pharmacokinetics? |
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Definition
| The actions of the body on a drug |
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Term
| What is a drugs Indication? |
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Definition
| The basis for initiation of treatment; FDA establishes approved use of drug |
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Term
| What is a drugs mechanism of action? |
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Definition
| How a drug works- includes the site where the drug acts and the mechanism by which it produces effects |
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Term
| What does propranolol do? |
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Definition
Blocks Beta Adrenergic Receptors in heart myocardium to reduce contractile force
ANTIHYPERTENSIVE |
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Term
| What is a side effect, and give an example? |
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Definition
UNDESIRED or ADVERSE effects of drug-
Beta blockers used to lower blood pressure cause bronchoconstriction that can be fatal in asthmatics or patients with COPD |
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Term
| What is a contraindication and give an example? |
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Definition
Conditions that preclude the safe use of the drug
Propranolol is contraindicated in asthmatics |
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Term
| What are 4 special considerations of administering drugs in geriatric patients? |
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Definition
Reduced blood supply (decreased absorption and distribution)
Reduced renal function (prolonged half-life; reduced excretion)
Reduced liver function (decrease in plasma protein binding and volume of distribution)
Greater likelihood of debilitating diseases |
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Term
| What is pharmacogenetics? |
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Definition
| When drug effects are altered by hereditary factors |
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Term
| What is a rapid acetylator? |
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Definition
| Increased synthesis of n-acetyltransferase- genetic |
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Term
| What is a slow acetylator? |
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Definition
| Decreased synthesis of n-acetyltransferase |
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Term
| What is the problem with slow acetylators? |
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Definition
| 4-6 times the blood concentration of a given dose compared to fast acetylators; LONGER HALF LIFE |
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Term
| The fast acetylator phenotype can be found expressed in what racial population? |
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Definition
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Term
| What are 4 modifying factors due to gender? |
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Definition
| Metabolism; fat content; blood volume; hormonal differences |
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Term
| What are the two conditions under which a drug may be administered to a pregnant woman? |
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Definition
1) there is a clear need and it is known to be safe for the fetus
2) the mother is so ill that it is justified even if the fetus might be harmed |
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Term
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Definition
| The science of drug prep and medicinal use |
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Term
| Who is considered the father of modern experimental physiology and pharmacology, and who was his student? |
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Definition
| Francois Magendie; Claude Bernard |
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Term
| What is an orphan receptor? |
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Definition
| A receptor for which no ligand has yet been discovered- function is unknown |
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Term
| What is a crucial point about supplements and alternative therapies? |
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Definition
| That ALL SUPPLEMENTS AND ALTERNATIVE THERAPIES SHOULD MEET THE SAME STANDARDS AS DRUGS |
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Term
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Definition
| Insertion of an appropriate healthy gene into somatic cells |
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Term
| What is a knockout animal? |
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Definition
| An animal (mouse) in which the function of a specific receptor is suppressed to isolate the role of the missing gene |
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Term
| What is a knockdown animal? |
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Definition
| If all knockout animals die at birth, it is possible to make knockdown animals with LIMITED suppression of the gene in question to see what it does |
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Term
| What is covalent bonding of a drug to a receptor, and give an example? |
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Definition
Very strong, usually irreversible binding- long lasting- action usually only goes away with synthesis of new receptor
e.g. acetyl of aspirin to cyclooxygenase |
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Term
| What is electrostatic bonding of a drug to a receptor? |
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Definition
| Common- relatively strong- uses hydrogen bonds, dipoles, and Van Der Waals forces |
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Term
| What is hydrophobic binding of a drug to a receptor? |
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Definition
| Quite Weak- most important with LIPID SOLUBLE drugs and receptor pockets |
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Term
| Are drugs more selective if they bond weakly or strongly? |
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Definition
| Drugs with weaker bonds are more selective because they require a more precise fit |
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Term
| Describe the role of chirality in the action of Carvedilol: |
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Definition
The S enantiomer is a 100-fold stronger beta blocker than the R enantiomer;
both are equipotent as alpha blockers |
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Term
| What is the relationship between chirality and metabolizing enzymes of the drug? |
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Definition
| One enantiomer is usually more susceptible to metabolism, so the duration of action will be shorter |
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Term
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Definition
| Predicting a drugs molecular structure based on the structure of its receptor |
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Term
| How does an antagonist work? |
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Definition
| It inhibits the receptor- specifically, it STABILIZES THE INACTIVE STATE |
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Term
| What is allosteric binding? |
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Definition
| Binding to a receptor, but not at the active site, so does not prevent agonist binding- can enhance or inhibit, and IS NOT EFFECTED BY INCREASING DOSE OF AGONIST |
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Term
| How do Acetylcholinesterase Inhibitors mimic agonist action even though they are inhibitory? |
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Definition
| They slow the destruction of acetylcholine, the endogenous agonist, so that it has a longer duration of action |
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Term
| What is Constitutive Activity? |
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Definition
| Due to thermodynamics, some receptors are in the active form even in the absence of ligand |
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Term
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Definition
| If the receptor pool is flooded, we get maximum effect- majority of receptors in the Ra-D form |
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Term
| What is a partial agonist? |
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Definition
| Not as great a response as a full agonist regardless of the concentration- Ra form of receptor is not as stabilized- LOW INTRINSIC EFFICACY regardless of receptor affinity |
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Term
| What is a conventional antagonist? |
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Definition
| A drug that fixes the fractions of Ri and Ra in the same amounts as if no drug was present- no change is observed, so it looks like no drug is present, but the action of the agonist is blocked= NEUTRAL ANTAGONISM |
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Term
| What is an inverse agonist? |
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Definition
| If a drug has higher affinity for and stabilizes the Ri state there is a reduction in constitutive activity, so the effects are opposite conventional agonists |
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Term
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Definition
| Drug binds but causes no effect- as in carriers like albumin- affects drug distribution and free drug in circulation without having biological activity |
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Term
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Definition
| How a drug gets into the blood stream |
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Term
| PK- what is distribution? |
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Definition
| How a drug is distributed to the site of action and to other tissues- crossing of barriers |
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Term
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Definition
| How, and if, a drug is degraded |
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Term
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Definition
| How a drug is removed from the body |
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Term
| What is the difference between free vs. bound drug? |
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Definition
Usually only free drug is available to tissues because bound drug is stuck to proteins that cannot penetrate-
Free drug goes to site of action |
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Term
| What is the problem with having more drug in reservoirs? |
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Definition
| More drug in reservoirs (away from the site of action) greatly increases the likelihood of side effects |
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Term
| What drives the movement of free drug in and out of cells? |
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Definition
CONCENTRATION- more free drug in the plasma means more tissue penetration
-as free drug concentration in plasma decreases, drug returns from tissue to bloodstream |
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Term
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Definition
| Minimum Effective Concentration- the bottom end of the desired therapeutic range |
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Term
| What are the 4 primary mechanisms of drug permeation? |
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Definition
| Aqueous diffusion; Lipid Diffusion; Transporters; Endo and Exocytosis |
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Term
| How does aqueous diffusion work and what is the driving force? |
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Definition
Drug moves through epithelial junctions, aqueous pores-
Driving force is CONCENTRATION GRADIENT |
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Term
| How does lipid diffusion work and what is its significance? |
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Definition
Lipid-soluble drugs can permeate compartments separated by lipid barriers-
MOST IMPORTANT LIMITING FACTOR OF DRUG PERMEATION |
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Term
| What is the most important factor of drug permeation? |
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Definition
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Term
| How does drug distribution via transporters work and what is unique about this pathway? |
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Definition
ENERGY IS REQUIRED- VERY SPECIFIC
-transporters exist for substances that are important to cell function but too large or insoluble to pass through membranes
SATURABLE AND INHIBITABLE |
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Term
| What types of drugs utilize transporters for distribution? |
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Definition
| Large drugs resembling peptides, amino acids, or glucose molecules |
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Term
| What types of drugs utilize endocytosis and exocytosis? |
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Definition
Polar substances too large to enter cells by other means
i.e.- Iron, Vitamin B12, Steroids |
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Term
| What is Fick's Law of Diffusion? |
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Definition
Rate of diffusion=
(surface area *concentration gradient)/
(membrane resistance*thickness of membrane)
Sorry its not pretty- see powerpoint |
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Term
| What is the lipid:aqueous partition coefficient? |
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Definition
Determines how readily a drug moves between lipid and aqueous media-
-varies with charge and pH |
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Term
| What types of tissues have no pores for aqueous diffusion, and what happens to drugs in these sites? |
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Definition
| Brain, testes, etc.- they act as sanctuaries for circulating drugs (drugs can't go anywhere) |
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Term
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Definition
| Solute Carrier- specialized carrier for uptake of neurotransmitters across nerve ending membranes |
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Term
| What is a requirement for endocytosis of drugs? |
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Definition
Must have RECEPTORS FOR TRANSPORT PROTEINS-
i.e. Iron+ Transferrin, there must be a receptor for transferrin for the complext to enter the cell |
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Term
| At lower pH, what state is a weak acid in? |
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Definition
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Term
| At lower pH, what state is a weak base in? |
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Definition
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Term
| At higher pH, what state is a weak base in? |
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Definition
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Term
| Why is ammonium chloride given to patients that overdose on crystal meth? |
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Definition
| Because meth is a weak base, ammonium chloride is given to acidify the urine and keep the meth ionized for removal |
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Term
| What is the goal of clinical therapeutics? |
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Definition
| Clinician administers a drug to MAXIMIZE THERAPEUTIC VALUE and MINIMIZE SIDE EFFECTS |
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Term
| What is the typical pH range of the stomach? |
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Definition
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Term
| What is the typical pH of blood plasma? |
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Definition
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Term
| What is a typical urine pH range? |
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Definition
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Term
| Le Chattliers principle only applies to what scenario? |
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Definition
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Term
| Weak acids always dissociate: |
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Definition
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Term
| Weak bases always ionize: |
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Definition
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Term
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Definition
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Term
| The malaria drug Pyrimethamine is a weak...? |
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Definition
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Term
| What must we do to the pH to get more of a weak acid to dissociate? |
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Definition
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Term
| What must we do to the pH to get more of a weak base to ionize? |
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Definition
| Increase [H+], DECREASE pH |
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Term
| In a highly acidic medium, a weak acid will be.... |
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Definition
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Term
| In a highly acidic medium, a weak base will be... |
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Definition
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Term
| For a weak acid or weak base to be lipid soluble, it must be in what form? |
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Definition
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Term
| To increase lipid solubility of a weak acid, what must we do? |
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Definition
| Decrease pH, driving more of the weak acid into its neutral state |
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Term
| To increase lipid solubility of a weak base, what must we do? |
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Definition
| Increase pH, driving more of the weak base into its neutral state |
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Term
| The response of a drug to pH is ALWAYS relative to what feature of that drug? |
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Definition
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Term
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Definition
| The pH at which 50% of the drug is ionized |
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Term
| In the stomach (acidic medium) most acetaminophen is in what form? (pKa=9.5, weak acid) |
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Definition
| HA, or NEUTRAL form- it is ABSORBED in the stomach |
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Term
| What happens to a drug that is a weak base when it hits the stomach? |
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Definition
| Complete ionization- NOT PERMEABLE |
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Term
| Why do first generation histamine (H1) blockers cause sedation and drowsiness but second generation histamine blockers do not? |
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Definition
| First generation H1 blockers like Diphenhydramine are neutral in blood and cross the Blood Brain Barrier; second generation H1 blockers are ionized at physiologic pH and remain trapped |
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Term
| If a patient overdoses or is poisoned by a weak acid, what can be done to increase urine excretion and decrease toxicity? |
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Definition
| Increasing the pH will promote the ionized form, thus increasing excretion and decreasing toxicity |
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Term
| For aspirin (weak acid) to be reabsorbed in the glomeruli and into the blood stream it must be in what state, and what can be done to promote its excretion? |
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Definition
| NEUTRAL; increase the pH to ionize the aspirin and cause excretion |
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Term
| What can be done to increase the duration of action of a drug that is a weak base? |
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Definition
| Increase the pH to keep the drug in its neutral form, thereby decreasing urine excretion and promoting drug retention |
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