Receptors | PHAR - Pharmacology, Quizzes of Pharmacology

Download Receptors | PHAR - Pharmacology and more Quizzes Pharmacology in PDF only on Docsity! TERM 1 Receptor definition DEFINITION 1 (a) receptors determine the dose-response relationship(b) are responsible for drug selectivity(c) they mediate the actions of drug agonists and drug antagonists TERM 2 Types of receptors DEFINITION 2 regulatory proteins,enzymes,transport proteinsstructural proteinsLipid soluble drug directly on intracellular target.Activate intracellular enzyme domain.Activate intracellular tyrosine kinase.Ion gated channel.G Protein coupled receptor. TERM 3 Dose-response relationship (drug binds to receptor and produces biological effect) = hyperbolic curve DEFINITION 3 at higher doses the curve flattens out and additional drug produces no further biological response Kd =drug concentration at which receptor occupancy is half maximalEC50 = drug concentration at which biological effect is half maximalDose response plots (Fig 2-2): drug effect (ordinate) against log dose concentration (abscissa) TERM 4 Spare receptor concept DEFINITION 4 maximal biological response provided by a drug dose that does not result in all available receptors being occupied.4 receptors + 4 drug molecules = no spare receptors Kd is 50% max response Kd caused when 2 drug molecules bind40 receptors + 4 drug molecules = Kd is still 50% max response Kd still caused by 2 drug molecules bindingmany spare receptorschanges in receptor concentrations (numbers) changes the sensitivity of the tissues to the drug concentration TERM 5 Reversible Competitive Antagonistis DEFINITION 5 propranolol (beta blocker antagonist) pushed off the receptor byincreasing concentrations of the endogenous ligand (epinephrine)propranolol at daily dose X works well to lower blood pressurewhen patient is under stress or exercises too much the increasedoutput of epinephrine replaces the drug and produces a biologicalresponse (increase blood pressure) TERM 6 Irreversible Antagonists DEFINITION 6 May bind to receptor through covalent attachmentendogenous ligand can not knock off the drugphenoxybenzamine binds to alpha receptors and blocks the binding of excess epinephrine produced by a tumor of the adrenal gland (a pheochromocytoma). TERM 7 Partial Agonist DEFINITION 7 drug produces lower response even when all receptors are occupied compared to a full agonistbuprenorphine safer analgesic compared to morphine because itproduces less respiratory depression even at high doses (lessdanger of overdose). TERM 8 Chemical antagonism DEFINITION 8 drug A binds to Drug B and neutralizes the effects protamine binds to heparin and reverses heparin overdose (bleeding) TERM 9 Physiological antagonism DEFINITION 9 drug actions at one receptor type neutralizes(counteracts) the effects of an endogenous ligand at other receptor typesinsulin (the drug) counteracts the increase in blood glucose due to the actions of endogenous glucocorticoid hormones (natural andsynthetic, drug, glucocorticoids increase glucose levels) TERM 10 Intracellular Receptors DEFINITION 10 (lipid soluble drug passes into cell and binds to cytoplasmic and/or nuclear receptors). also called gene-active receptorsmost drugs that use this type of receptor initiate transcription factors through release of inhibitory factors on the gene (regulators of gene expression) Ex: steroids (cortisol etc), thyroid hormones, vitamin Dresult is protein synthesis which takes 30 min to hourslag time characterizes the dose and the effectbiological effect can remain for days after the drug has left the system, the protein produced remains until it is removed from the body and its the protein which is producing the biological effectEx: corticosteroids for relieving joint pain an inflammation TERM 21 Variation in endogenous receptor ligands DEFINITION 21 (epinephrine levels between patients and within the same patient at different times) saralsan blocks angiotensin II receptors, angio II can not bind, blood pressure is lowered but only in patients whose angioII levels are elevated. Saralsan raises blood pressure if angio II levels are normal. TERM 22 Alterations in receptor number or function DEFINITION 22 thyroid hormone excess increases beta receptor number, thismakes patient more sensitive to endogenous catecholamines, blood pressure increases, treat with a beta blocker drug (propranolol). Note: down- regulation = reduced receptor number densensitization = reduced drug coupling efficiency up-regulation = increased number of receptorsGenetic factors (pharmacogenomics) can cause alterations in receptor number and function. Changes in components of response distal to the receptor (the most important and largest of all the reasons) cause is most often wrong drug for the condition, wrong diagnosis. TERM 23 Up-regulation DEFINITION 23 a drug causes increase in the number of receptors,when the drug is stopped, the endogenous ligand causesa dramatic increase in the response (exaggerated response to a normal endogenous ligand conentration) TERM 24 Down-regulation DEFINITION 24 a drug can induce reduced number of receptors, when drug is discontinued the number of receptors is too low for the endogenous ligand to produce a normal response.Clonidine an alpha2 receptor binder lowers blood pressure by blocking the outflow of norepinephrine (NE) in the CNS. The drug also reduces receptor number. When the drug is abruptly stopped a hypertensive crisis can occur because the resumption of NE outflow has reduced number of receptors to bind to, all receptors are filled with NE and blood pressure increases dramatically. TERM 25 Drug Selectivity DEFINITION 25 most drugs will not bind to only one specific type of receptor (side effects)any one single type of receptor is coupled in biological function to a wide (unknown number) of other biological processes TERM 26 Beneficial and toxic effects mediated by same receptor-effector mechanisms DEFINITION 26 insulin in high dose cause hypoglycemia excess heparin causes lethal bleeding (all drugs are poisons, its the dose that differentiates toxic frombeneficial) TERM 27 Beneficial and toxic effects mediated by identical receptors but in different tissues or by different effector pathways DEFINITION 27 drug binds to same receptor in different tissues but causes a difference in response among those tissues digoxin inhibits the sodum-potassium ATPase pump in a wide variety of tissues which causes a wide variation in the types of drug response Ways to avoid these multiple different response with somewhat non-selective drugs TERM 28 Ways To Increase Drug Selectivity DEFINITION 28 (1) use the lowest possible dose (2) use a second type of drug which can often allow lower doses of the first drug (add an immunosuppressive agent to cortisol an immunosuppressive agent) (3) keep the first drug at the site of action (use the drug as an inhalant instead of as a po pill). TERM 29 Beneficial and toxic effects mediated by different types of receptors DEFINITION 29 Rational drug design is directed toward developing drugs that bind with a high degree of selectivity to only one type of receptor.Cimetidine a specific H2 receptor blocker used to reduce acidrelease by parietal cells in the stomach. Drug design was so specific for these receptors that after 7 years of prescription only the drug converted to OTC (Tagamet). TERM 30 RECEPTORS: DEFINITION 30 Receptors exist in two main forms Active = Ra Inactive = RiReceptors exist in a pool (balance) of Ra and Ri formsDrugs can shift the balance of these pools.Spare receptors describes when drug binds and the maximum biological response is achieved but not all the receptors have drug on them. TERM 31 AGONIST DEFINITION 31 drug binds and activates the receptorhave high affinity for the Ra form of a receptor TERM 32 Full agonist DEFINITION 32 drug binds and converts most of the receptors to the Ra form TERM 33 Partial agonist DEFINITION 33 drug binds but can not shift the pool to mostlyRa form no matter how much drug is given themaximum response (in the patient) cannot be obtained TERM 34 Inverse agonist DEFINITION 34 drug binds with greater affinity to the Ri form ofthe receptor the Ri pool is stabilized TERM 35 Pharmacologic antagonist DEFINITION 35 drug binds to a receptor and prevents (blocks) other molecules from binding TERM 46 Ligand DEFINITION 46 molecule that binds to receptor TERM 47 Specificity DEFINITION 47 Atropine binds to Ach receptor only TERM 48 Affinity DEFINITION 48 Strength of drug binding TERM 49 Selectivity DEFINITION 49 Atropine binds to Ach receptors in exocrine glands and smooth muscle but not on skeletal muscle TERM 50 Five mechanisms of Drug Action DEFINITION 50 Lipid soluble drug crosses membrane. Drug binds to outside face, allosteric enzyme activation. As in (2), enzyme is tyrosine kinase. Drug binds to outside face, alters ion channel. Drug binds outside stimulates intracellular message through G-Protein TERM 51 Potency & Efficacy DEFINITION 51 Potency is a comparative measure of the two doses of two different drugs required to produce the same effect.Efficacy is the maximum effect of a drug andClinically more important than potency when selecting patient drugpotency determines patient dose TERM 52 Therapeutic Range (Window) DEFINITION 52 Therapeutic Range or Window is also sometimes called the Therapeutic Index but is different.Therapeutic Range is the range of Cp within which the drug will have maximum effect. Theophylline 10 - 20 ug/mL Digoxin 0.8 - 1.2 ng/mL TERM 53 Therapeutic Index DEFINITION 53 The Therapeutic Index (TI) of a drug is a measure of the drugs toxicity.The TD50 = dose that is toxic in 50% of the animals that receive it. (Death is the ultimate toxicity)TI = LD50/ED50 TERM 54 Quantal Dose Response -2 DEFINITION 54 ED50 now means the median effective dose at which 50% of patients exhibit the quantal effect.TD50 the median toxic dose, the dose that produces toxicity in 50% of the patients TERM 55 Quantal Dose Response -1 DEFINITION 55 Used when response is digital instead of sigmoid dose-effect curves. Digital involves Yes/No response to drugs (headache gone, infection gone, seizures, increase in heart rate by 20 beats/minute etc.Used for population response.Population Gaussian distribution produced.ED50 and LD50 calculated.Margin of SafetyTherapeutic Index TERM 56 Efficacy DEFINITION 56 the maximal response a drug can produce TERM 57 Potency DEFINITION 57 a measure of the dose that is required to produce a response. EC50 or dose required to produce a 50% response compared to max response TERM 58 Receptor Concepts DEFINITION 58 Receptors help explain drug selectivity and endogenous ligand variety of actions.NE binds to all of the following receptors Beta increase heart rate Alpha1 vasoconstriction Alpha2 opens potassium channel, K+ flows into cell, inhibition.Beta blocker drugs bind to beta receptors only and increase heart rate with no vasoconsctriction. TERM 59 Receptor Desensitization DEFINITION 59 pharmacological response diminishes even when drug continues to attach to receptor. Mechanism may involve reversible phosphorylation of signal proteinsDesentization.failed response after repeated exposure to the drug agonist TERM 60 Receptor down regulation DEFINITION 60 where actual number of receptors decrease after repeated drug administration.Down Regulation.number of receptors are reduced, new synthesis required