Term
| What type of drugs may be reabsorbed in the glomerulus? |
|
Definition
|
|
Term
| What types of conditions decrease excretion in the kidney? |
|
Definition
| Age, renal disease, enzyme deficiencies |
|
|
Term
|
Definition
| The volume of blood cleared per unit time |
|
|
Term
| What are the 3 drugs that undergo zero-order clearance? |
|
Definition
| Phenytoin, Ethanol, Aspirin (PEA) |
|
|
Term
| What characterizes zero-order clearance? |
|
Definition
| CONSTANT AMOUNT OF DRUG ELIMINATED OVER TIME- enzymes are SATURABLE and the CAPACITY IS LIMITED |
|
|
Term
| What does the regular graph of zero order kinetics look like? What does the log graph of zero order kinetics look like? |
|
Definition
Regular- straight line
Log- Curve |
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|
Term
| In what type of kinetics is the amount of drug eliminated in a given time constant and independent of the amount of drug present? |
|
Definition
| Zero-order kinetics (clearance) |
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|
Term
| In what type of kinetics is the clearance constant over the concentration range? |
|
Definition
| First-order Kinetics (clearance) |
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|
Term
| What does first-order kinetics depend on? |
|
Definition
| Concentration of drug achieved |
|
|
Term
| In what type of clearance kinetics is elimination NOT saturable? |
|
Definition
|
|
Term
| In first order kinetics, the rate of drug elimination is directly proportional to what? |
|
Definition
|
|
Term
| What does a normal graph of First-order kinetics look like? What does a log graph of First-order kinetics look like? |
|
Definition
Normal- Curve
Log- Straight line |
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|
Term
| In what type of kinetics is the FRACTION of total drug eliminated in a given time always constant, regardless of the amount present? |
|
Definition
|
|
Term
|
Definition
| The amount of time required to reduce the amount of drug in the body by one half during elimination |
|
|
Term
| What is the most important factor in reaching steady state? |
|
Definition
| The elimination half-life- it is independent of the dose size or frequency of administration |
|
|
Term
| What defines steady state? |
|
Definition
| The amount of drug eliminated is equal to the amount of drug being administered |
|
|
Term
| How many half-lives does it take to reach steady state? |
|
Definition
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|
Term
| When considering steady state, increasing the dose given changes the steady state drug level, but does not change what? |
|
Definition
| The amount of time it takes to get there |
|
|
Term
| What is target concentration? |
|
Definition
| The dose that produces the desired therapeutic effect- the IDEAL concentration for treatment |
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|
Term
| What is the MOST important pharmacokinetic factor in determining rational steady state? |
|
Definition
| Clearance- the decision is made based on how the drug is eliminated from the body |
|
|
Term
|
Definition
| If the time to reach steady state is prolonged, give the patient a large dose to start them out at target concentration, then continue dosing |
|
|
Term
| What determines the most appropriate drug for a given disease? |
|
Definition
|
|
Term
| What are the two important factors in the mechanism of a drug action? |
|
Definition
1- must cause conformational change of the receptor
2- must activate, or produce an effect, on an effector |
|
|
Term
| What are 4 properties of drug receptors? |
|
Definition
-selectivity
-capability to achieve multiple conformations
-dynamism
-mediation of drug action |
|
|
Term
|
Definition
| The ability of a receptor to change it numbers depending on need- upregulation and downregulation |
|
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Term
| Give an example of an autacoid regulatory protein receptor and the drug that binds it: |
|
Definition
| 5HT1 Receptor- Sumatriptan |
|
|
Term
| Give an example of a hormone regulatory protein receptor and the drug that binds it: |
|
Definition
| NR3C2 Receptor (Aldosterone)- Spironolactone |
|
|
Term
| Give an example of a neurotransmitter regulatory protein receptor and a drug that binds to it: |
|
Definition
| Alpha1 receptor- Terazosin |
|
|
Term
| What receptor does Edrophonium bind to? |
|
Definition
|
|
Term
| What receptor does warfarin bind to? |
|
Definition
| Vitamin K Epoxide Reductase |
|
|
Term
| What receptor does Zalcitabine bind to? |
|
Definition
|
|
Term
| Give an example of a drug that binds to Ca2+ channel: |
|
Definition
|
|
Term
| All anti-arrythmic drugs bind to what? |
|
Definition
|
|
Term
| What dose Colchicine bind to? |
|
Definition
|
|
Term
| What are the two most important contributors to the drug-receptor interaction? |
|
Definition
| Selectivity of the ligand; Stability of the Drug-Receptor complex |
|
|
Term
| List the 5 types of Drug-receptor bonds in order of strongest to weakest: |
|
Definition
| Covalent, ionic, hydrogen, hydrophobic, van der Waals |
|
|
Term
| What is the relationship between Kd and affinity? |
|
Definition
| Kd is INVERSELY proportional to affinity |
|
|
Term
| What is the relationship between the number of receptors bound and the concentration of the drug? |
|
Definition
| It is a direct proportion but is NON-LINEAR |
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|
Term
| What is the relationship between EC50 and potency? |
|
Definition
EC50 is INVERSELY proportional to potency
-A larger EC50 means less potent |
|
|
Term
| What characterizes a full agonist? |
|
Definition
| High affinity for the active form of the receptor- STABILIZES RECEPTORS IN ACTIVE CONFORMATION |
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|
Term
| Give an example of a full agonist and the receptor it acts on: |
|
Definition
|
|
Term
| What characterizes a partial agonist? |
|
Definition
| Stabilizes receptors equally in active and inactive conformation- has equal affinity for both active and inactive conformation |
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|
Term
| Give an example of a partial agonist and the receptor it binds to: |
|
Definition
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|
Term
| What characterizes a competitive antagonist? Can max drug effect still be reached? |
|
Definition
A competitive antagonist prevents the agonist from binding to the receptor, but if more agonist is added it can outcompete with the antagonist
MAX EFFECT CAN STILL BE REACHED |
|
|
Term
| What characterizes a non-competitive antagonist? Can max drug effect still be reached? |
|
Definition
COVALENT or HIGH-AFFINITY BONDING
Drug and receptor binding is permanent
Max effect is decreased and flooding the receptor does nothing |
|
|
Term
| Give an example of a competitive antagonist: |
|
Definition
|
|
Term
| Give an example of a non-competitive antagonist: |
|
Definition
|
|
Term
| What is an allosteric agonist? |
|
Definition
| Affects the action of the ligand by binding to the enzyme at a location other than the binding site- can either potentiate OR antagonize the action of the agonist |
|
|
Term
| What is an inverse agonist? |
|
Definition
| When a receptor has intrinsic activity (constitutive), an inverse agonist shuts it off. Therefore, compared to the normal state, there is LESS activity |
|
|
Term
| Give an example of an allosteric agonist: |
|
Definition
|
|
Term
| Give an example of an inverse agonist |
|
Definition
Fexofenadine
Many H1 blocking allergy medications |
|
|
Term
| What is a chemical antagonist? |
|
Definition
| Another drug/xenobiotic that neutralizes the agonist |
|
|
Term
| Give an example of a chemical anatagonist: |
|
Definition
| Protamine- binds with and neutralizes heparin in the event of overdose |
|
|
Term
| What is a physiologic antagonist? |
|
Definition
| Produces physiologically opposing effects |
|
|
Term
| Give an example of physiological antagonism: |
|
Definition
| Insulin and cortisol- both endogenous, and have opposite effects |
|
|
Term
| What is significant about spare receptors? |
|
Definition
| They increase a patients sensitivity to the drug- the maximum effect is achievable without occupying all available receptors |
|
|
Term
|
Definition
| The drug concentration at which half of the receptors are bound |
|
|
Term
| How do spare receptors effect the EC50 of a drug? |
|
Definition
If spare receptors are present, EC50 decreases, thereby INCREASING POTENCY
(Kd stays the same) |
|
|
Term
| Give 3 examples of non-receptor drugs: |
|
Definition
Sucralfate- forms a protective coating on ulcers to prevent erosion by stomach
Osmotic Diuretics- increase osmotic pressure in kidney
Antacids- |
|
|
Term
| What is most important about non-receptor drugs? |
|
Definition
|
|
Term
| On a dose response curve, if the graph is shifted further to the right, how does this effect the potency of the drug? |
|
Definition
| Further to the right= LESS POTENT |
|
|
Term
| What effect does a high first pass extraction ratio have on bioavailability? |
|
Definition
| High first pass extraction ratio decreases bioavailability |
|
|
Term
| How dose Vd effect pharmacokinetics? |
|
Definition
| Drugs with a high Vd will be more spread out in the body, further from the site of action, and generally less efficacious (sequestered in other tissues so unavailable to produce effect) |
|
|
Term
| What intrinsic quality does a partial agonist have with regard to pharmacokinetics? |
|
Definition
| Lower efficacy by its very nature- cannot achieve maximum effect |
|
|
Term
| What happens if there is underlying renal insufficiency in a patient? |
|
Definition
| Drug cannot be excreted fast enough, so it makes the drug look more powerful but INCREASES SIDE EFFECTS AND TOXICITY |
|
|
Term
| What is the relationship between body size and Vd? |
|
Definition
| Body size is directly proportional to Vd |
|
|
Term
| What is the relationship between body size and efficacy? |
|
Definition
| Body size is inversely proportional to efficacy |
|
|
Term
| Why do water soluble drugs have more of an effect on women than on men? |
|
Definition
| Men have more water, women have more fat- men can distribute water soluble drugs over a wider range of tissue reservoirs |
|
|
Term
| What is the most useful clinical application of a graded dose response curve? |
|
Definition
| Choosing the most appropriate drug |
|
|
Term
| If a drug shows a very steep line on a GRADED dose response curve, what is most important to know? |
|
Definition
| The drug is DANGEROUS because a small dose increase creates a huge effect |
|
|
Term
|
Definition
| The effective dose for 50% of patients on a quantal dose response curve |
|
|
Term
|
Definition
| The lethal dose for 50% of patients on a quantal dose response curve |
|
|
Term
| How do we determine therapeutic index? |
|
Definition
| LD50/ED50= Margin of Safety |
|
|
Term
| On a dose response curve of two different drugs, if one drug graphs further to the left and the other graphs further to the right, what do we know about the first drug? |
|
Definition
|
|
Term
| What is an idiosyncratic drug response? |
|
Definition
| An unusual and unexpected adverse drug response, neither related to dose or to allergy |
|
|
Term
| Give an example of a symptom of idiosyncratic drug response: |
|
Definition
|
|
Term
|
Definition
| The intensity of response to a drug decreases with continual (prolonged) use |
|
|
Term
| Give an example of a drug that achieves tolerance? |
|
Definition
| Nitroglycerine for Angina- after a while it doesn't work anymore |
|
|
Term
|
Definition
| Depletion of the neurotransmitter involved in drug action |
|
|
Term
| What are the 3 types of metabolizers? |
|
Definition
Poor metabolizer; Extensive metabolizer (normal); Ultra-rapid metabolizer
(Polymorphism in drug metabolizing enzyme CYP2D6) |
|
|
Term
| What effect does a partial agonist have on a full agonist? |
|
Definition
| It acts as an ANTAGONIST in the presence of a full agonist |
|
|
Term
| What effect does a partial agonist have in the absence of a full agonist? |
|
Definition
| It acts as an AGONIST in the absence of a full agonist |
|
|
Term
| Give an example of a partial agonist: |
|
Definition
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