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62 Cards in this Set
- Front
- Back
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What are the two functions of receptors?
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1. recognition of molecules
2. transduction of information |
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What are some xenobiotics?
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chemicals not synthesized in the body.
examples: medications, inorganic poisons(lead, arsenic), organic poisons(parathion), toxins. |
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List 5 chemical forces involved in drug-receptor interactions.
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1. covalent bonds: often cause toxic effects, require synthesis of new receptors. ex: cholinesterase and its inhibitors, alkylating agents(chemo therapy).
2. van der waals-london forces: weaker bonds bind more selectively 3. ionic bonds 4. H bonds 5. hydrophobic interactions: lack structural specificity. ex: lipid soluble drugs |
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What is the most important limitation in drug-receptor binding?
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Steric hindrance: need at least 3-point attachment, all binding groups should be different and attached to either a center or plane of asymmetry.
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T/F: Optimal isomers have vastly different pharmacological actions.
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T.
Steric hinderance |
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T/F: Only a few surface receptors have to be occupied to produce maximal effects.
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T.
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T/F: For drugs with high efficacy, only a few receptors are needed to be occupied to produce a maximal effect.
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T.
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What is intensity of a drug?
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The result of number of receptors stimulated and efficacy of drug.
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What are the two terms used to describe a drug dose-response curve?
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1. potency
2. intrinsic activity: relative maxima achieved |
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What is the efficacy for a full agonist?
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1
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What is the efficacy for a partial agonist?
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0<efficacy<1
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What is the efficacy for an antagonist?
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0
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T/F: The failure of a partial agonist to produce a maximal response is because of decreased affinity for binding receptors.
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F.
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What is an inverse agonist?
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It acts to abolish the intrinsic activity("tone") of the unoccupied receptor.
Ex. effect of atropine on S.A node |
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What are some differences between competitive antagonist and irreversible antagonist?
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Competitive antagonist: reversible, can be overcome by increasing the agonist. Efficacy stays the same, lower potency, lower affinity.
Irreversible antagonist: can not be overcome, lower efficacy, same potency and affinity. |
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What are the three types of nonreceptor antagonist?
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1. bind to a downstream molecule
2. inhibit agonist directly 3. activate an opposing pathway |
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If drug A has lower affinity than drug B for the receptor, and both are agonist, then the drug A is called the ______.
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mixed agonist-antagonist
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When two drugs interact to chemically neutralize each other, it is called____.
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chemical antagonism.
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When two drugs influence a physiological system in opposite direction, it is called____.
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Nonreceptor antagonism.
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What is pharmacological antagonism?
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interactions of agonists and antagonists at receptor sites.
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What are congeners?
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drugs with closely related chemical structures.
SAR of congeners indicate interaction at a specific receptor site. |
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What are the three ways for a drug-receptor complex to propagate a signal?
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1. direct intracellular effect
2. interact with closely associated cellular protein (receptor-effector systems) 3. second messengers |
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What is the action of Gs?
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activate Ca2+ channels, activate adenylyl cyclase.
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What is the action of Gi?
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activate K+ channels, inhibit adenylyl cyclase
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What is the action of G0?
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inhibit Ca2+ channels
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What is the action of Gq?
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activate PLC
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What is the action of G12/13?
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diverse ion transporter interactions
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Give an example for each of the following receptors.
1. Tyrosine kinase transmembrane receptors with enzymatic cytosolic domains. 2. Tyrosine kinase receptors act as tyrosine phosphatases. 3. Tyrosine kinase-associated receptors lack a definitive enzyme domian. 4. Serine/Threonine kinases on certain cytosolic proteins. 5. Guanylyl cyclase receptor |
1. insulin receptor, BCR-Abl receptor
2. cells of the immune system 3. cytokine receptors 4. TGF-β receptors 5. nitric oxide receptors |
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action of β-1 receptor
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SA node
cardiac muscle adipose tissue |
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action of β-2 receptor
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bronchial smooth muscle
GI smooth muscle uterus bladder liver pancreas |
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action of β-3 receptor
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adipose tissue
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Which two of the following act on adipose tissue?
A. β-1 receptor B. β-2 receptor C. β-3 receptor |
A.C.
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Drug absorption: list some types of membrane transfer mechanisms.
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1. Passive transfer: most common and important
2. Active transport 3. Facilitated diffusion 4. Pinocytosis |
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Drug absorption-Passive diffusion:
1. What molecules are passively transported? 2. The rate of transfer is depedent on ____. |
1. non-ionized, lipid soluble drugs.
2. concentration gradient. (may be influenced by other factors) |
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What type of absorption mechanism is associated with epithelial lining of cornea, gut, bladder?
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Simple diffusion.
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In what areas of the brain does simple diffusion occur?
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Capillaries in pituitary gland, pineal gland, median eminence, area postrema, and choroid plexus.
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Drug absorption: faciltated diffusion:
1. What is the driving force? 2. The rate is dependent on ____. |
1. concentration gradient
2. binding capacity of solute and carrier. (limited by carrier availability) |
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Does amino acid cross BBB? If not, how does the brain absorb it?
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No.
Using facilitated diffusion. |
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Give some examples where absorption is done by facilitated diffusion.
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1. amino acids through BBB
2. weak acids through proximal convoluted tubule of kidney 3. glucose (glucose-Na symport, Ca2+-Na antiport) |
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What type of drugs are not suitable for intravenous administration?
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oily solutions and insoluble substances
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What are some types of parental drug administration?
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1. IV
2. Intramuscular 3. subcutaneous 4. intradermal 5. intraperitoneal 6. intrathecal 7. inhalation 8. transdermal |
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What is the most important disadvantage of enteral drug adminstration?
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Variability in bioavailability due to first pass effect.
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How to adminster a drug to CNS that does not cross BBB? What are some disadvantages?
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Intrathcal.
Infection, complication of procedure. |
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List the following route of adminstrations in decreasing speed order.
IV Intramuscular-Subcutaneous Intradermal Intraperitoneal topical oral inhalation |
IV
Inhalation Intraperitoneal Intramuscular-Subcutaneous Intradermal Oral Topical |
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In general, ___ drugs are absorbed in the stomache, whereas ___ drugs are not.
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Acidic
Basic |
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What is the pKa range of the drugs that allow absorption in the GI tract?
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3-7.8
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Describe first pass effect.
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1. drugs are metabolized by liver before reaching systemic circulation.
2. enterohepatic recirculation: Drugs that are metabolized by liver enzymes may reenter the intestine via bile secretion. |
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What are some sites of absorption that avoid first pass elimination?
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1. Sublingual
2. Rectal suppository |
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What is the effect of grape fruit juice on P450?
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inhibiting CYP3A4
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List factors that determine the duration of drug effect.
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1. nature of drug (affinity for receptors)
2. rate of metabolism 3. lipid solubility 4. rate of excretion 5. dosing schedule 6. pharmaceutical preparation |
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Drug adminstation-Oral delivery:
What are some techniques to extend release formulations? |
1. solubility modified with inert excipients
2. enteric coating that dissolves at alkaline pH 3. osmotic pump 4. lipophilic liposomes taken up by M cells via Peyers patches. 5. microspheres adhere to different aegments of intestinal mucosa. |
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What is an ideal site for administering protein and peptide drugs?
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pulmonary delivery: large surface area, thin tissue lining, limited number of proteolytic enzymes.
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What is the best way to adminster drugs through pulmonary system?
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incorporating drugs into large, highly porous aerosol particles with very low densities:
1. large size: not cleared by macrophages 2. low density: can reach deep parts of the lung |
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What are some practices of transdermal delivery?
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1. patches
2. ionophoresis: charged low MW molecules, low voltage 3. electronporation: large charged molecules, temporary pores, high voltage 4. sonophoresis: temporary air-filled cavitations in lipid bilayers of stratum corneum |
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What are some uses of sonophoresis?
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1. insulin, interferon, erythropoietin administration.
2. remove diagnostic samples from extracellular area through skin. |
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List types of polymer based delivery systems.
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1. diffusion
2. chemical reaction 3. solvent activation 4. osmotic pressure |
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Drug adminstration:
Compare passive and active targeting. |
Passive targeting: target tissue by expoiting vascular differences.
Active targeting: polymer-drug is linked to molecules recognized by cell surface receptors in tissue of interest. |
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What does sub therapeutic dosing mean?
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Dosage is too low or interval is too long. (want peak concentration and trough concetration in therapeutic range)
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Steady state concentration is achieved after ____ elimination half lives.
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4-5
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How to calculate the loading dose?
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LD = Vd x Css
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How to calculate the maintanence dose?
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MD = CL x Css
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What are some factors determining drug absorption?
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1. concentration gradient
2. permeability: DMSO, long term slow absorption 3. bioavailability: AUC 4. competing substances 5. surface area 6. duration of exposure 7. blood flow 8. ionization constant and lipid solubility: drugs with quaternary ammonium are not lipid soluble thus will be poorly absorbed (not pass BBB) |
