Term
| What is pharmacokinetics? |
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Definition
| What the body does to the drug (how handled) |
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Term
| What is pharmacodynamics? |
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Definition
| What the drug does to the body (effects) |
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Term
| Drugs must bind to macromolecules/ receptors/ proteins (all these are other names for drug receptors) to produce an effect, an exception to this is? |
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Definition
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Term
| What are the other drug receptors? |
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Definition
Physiological receptors
Enzymes
Transporters
Ion channels
Structural proteins |
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Term
| So we know that drugs act on mainly protein receptors but the exception to that are DNA receptors. Now there are drugs that done need a receptor to have an effect, these are? |
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Definition
Antacids;
Mesna - reacts w/ acroleine (a cyclophosphamide metabolite which can cause hemorrhagic cystitis) in the bladder;
Mannitol - a diuritic via increasing osmolarity;
Cholestyramine, colestipol & colesevelam - bind to bile acids to prevent reabsorption and thus Tx hyperlipidemia;
Dimercaprol - chelates heavy metals;
Structural analogs of pyrimidines & purines |
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Term
| There are two ways to illustrate dose-response relationships, which are? |
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Definition
| Graded curve which shows the maximal efficacy of a drug & Quantal curve which shows the variability of responsiveness amoung individuals |
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Term
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Definition
| B-max (the max drug bound to receptor). Both curves are hyperbolic when the x-axis is linear but when its logged then it becomes a sigmoid curve. Also important to note are the notations: EC-50 (conc. that causes 50% of effect & K-D which the conc. of drug that occupies 50% of binding receptors) |
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Term
| Efficacy vs Potency (NB that both are independent of each other)? |
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Definition
| Maximal effect vs EC-50 being more to the left (more potent) or right along the x-axis |
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Term
| Antagonism is organized as? |
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Definition
A) Receptor Antagonism: Competitive, Noncompetitive, Uncompetitive
B) Nonreceptor antagonsism: Chemical, Functional, Pharmacokinetic |
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Term
| Competitive antagonism is? |
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Definition
| Either reversible (same E-max but surmountable with more drug - thus almost like less potent) or irreversible (which has a lower E-max and is insurmountable) |
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Term
| What are the few irreversible competitive antagonist? |
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Definition
Phenoxybenzamine - alpha adrenoceptor blocker to Tx pheochromocytoma
Enzyme inhibitors - aspirin, omeprazole, MAO inhibitors |
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Term
| Noncompetitive antagonism is? |
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Definition
| Same curve as irreversible competitive but has allosteric binding |
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Term
| Uncompetitive antagonism is? |
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Definition
Binding to agonist-receptor complex. Eg: Memantine - an antagonist at NMDA receptors used in Alzheimer's Dz;
Lithium - an inhibitor of inositol monophosphatase |
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Term
| Functional antagonism is? |
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Definition
A) Indirect - where drug acts on a downstream protein
B) Physiological - one agonist opposes another agonist but via different receptors (like ying and yang), eg. muscarinic agonist inhibits beta-adrenoceptor-stimulated adenylyl cyclase activity in the heart |
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Term
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Definition
| One drug binding an inactivating another drugs (think antidote such as in the case of Heparin OD use Protamine - which is positively charged) |
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Term
| Pharmacokinetic antagonism is? |
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Definition
| What the body does to maintain homestatsis such as increasing metabolism, reducing the rate of absorption and increasing the rate of renal excretion |
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Term
| Graded property tells us? |
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Definition
| If the agonist is full or partial (two-state model i.e Ra vs Ri) response |
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Term
| When no ligand is present on a receptor which state is preferred? |
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Definition
| 99% Ri at equilibrium. Now NB that the equilibrium is shifted depending on the affinity of the ligand. If affinity is equal for either Ra & Ri then its known as a competitive antagoinist but if it shows more affinity to Ra then its an agonist and finally a drug/ ligand that has a high affinity for Ri is known as inverse agonist |
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Term
| What are other names for Desensitization & Tachyphylaxis? |
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Definition
| Tolerance, Refractoriness & Drug resistance |
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Term
| What are the different mechanisms of Desensitization & Tachyphylaxis? |
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Definition
A) Change in receptors: activation of ion channels lead to rapid desensitization; or in the case of G-protein couple receptors they become phosphorylated
B) Loss of receptor: w/ prolonged exposure there is endocytosis of the receptor
C) Exhaustion of mediators: drugs such as amphetamines work by releasing NE stores at nerve terminals and thus show tachyphylaxis
D) Increased metabolic degradation: P450
E)Physiological Adaptation: nullification by homeostatic response |
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Term
| Quantal Dose-effect curves show? |
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Definition
| The fraction of the pop. that respond (works or not - no inbtw) to a given dose of the drug |
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Term
| What is ED-50 (median effective dose)? |
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Definition
| The dose at which 50% of the pop. show drug effect |
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Term
| What is TD-50 (median toxic dose)? |
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Definition
| The dose at which 50% of animals show toxicity |
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Term
| What is LD-50 (median lethal dose)? |
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Definition
| The dose at which 50% of animals die |
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Term
| What is common btw the graded and quantal curves? |
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Definition
| They both show info regarding potency & selectivity of drugs |
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Term
| What is therapeutic index (TI)? |
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Definition
| Is TD-50 or LD-50/ ED-50 (The bigger the TI the better). NB that although TI is interesting to know it really cant give us a real value as to the therapeutic index in humans. Instead more clinical is the Therapeutic window which shows the range btw the minimum ED and TD |
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