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| The study of substances that interact with living systems through chemical processes |
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| Deals with the undesirable effects of chemicals on living systems |
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- Study of the biochemical and physiologic effect of drugs and their mechanism of action
- The actions of the drug on the body |
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- The actions of the body on the drug
- Involves absorption, distribution, metabolism and elimination (ADME) |
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| The study of genetic variations that cause differences in response among individuals or populations |
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- The component of a cell or organism that interacts with a drug
- Initiates the chain of biochemical events leading to the drug’s observed effect
- Plays a regulatory role in the drug molecule interaction with specific molecules in the biological system |
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- Molecule that binds to a receptor
- Involved in chemical signaling
- Ex: Neurotransmitter, hormone, drug, messenger molecule. |
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| - Drug that is synthesized within the body |
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| - Drug that is made of chemicals outside of the body |
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- Poisons of biologic origin
- causes harmful effects |
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- Drugs bind to and activate the receptor
- Directly or indirectly brings about the effect
- elicits response and gives enhanced activity of a cell |
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| Binds to the receptor and prevents binding by other molecules |
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The penetration of a permeate (such as a liquid, gas or vapor) through a solid.
- Ex: Aqueous diffusion([high] -> [low])
Lipid diffusion, Transport by special carriers, Endocytosis and exocytosis |
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| Aqueous Diffusion(permeation) |
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Definition
- Occurs within the larger aqueous compartments of the body
- Across epithelial membrane junctions
Through aqueous pores of the endothelial lining of blood vessels(ex. b/w the blood & extravascular space)
- determined by Ficks Law(high ->low) |
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| Lipid Diffusion(permeation) |
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Definition
- MOST important limiting factor for drug permeation is the lipid barriers
- The ability to move from aqueous to lipid (or lipid to aqueous) varies on the pH of the medium
- determined by Fick’s Law(high->low) |
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| Special Carriers(permeation) |
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Definition
- Exist for certain substances that are important for cell function
- Amino acid carriers in the blood-brain barrier
- Weak acid carriers in the renal tubules
- May be too large to diffuse passively through the membrane
- NOT Ficks law and is capacity-limited |
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| Special Carriers(permeation) |
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Definition
- Multidrug-resistance type 1 (MDR1) transporter
- Also known as P-glycoprotein
- Found in the brain, testes, many neoplastic cells and other tissues
- Cancer drug resistance in GI tract epithelium |
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| Multidrug resistance-associated protein (MRP1 – MRP5) transporters [special carrier permeation] |
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Definition
- Important role in excretion of some drugs/metabolites into the urine and bile
- Uptake of neurotransmitters across nerve ending membranes |
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Endocytosis(permeation)
"engulfed by the cell" |
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Definition
- Substance is too large, lipid-insoluble or impermeant to the cell
- The process by which the substance is engulfed by the cell membrane and carried into the cell by pinching off of the newly formed vesicle inside the membrane |
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The process by which a cell directs the contents of secretory vesicles out of the cell membrane, RELEASING a substances from the cell.
Ex. calcium into the bloodstream, enzymes from pancreatic cells, hormones from endocrine glands |
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- passive diffusion from [high] -> [low]
- drug absorption occurs faster in organs with large surface area(large intestine)
- organs with thin membranes(lungs) absorb the drug faster than thicker membranes(skin) |
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Definition
- H2O molec. are attracted to charged drug molec. (more charged = more H2O soluble)
- Lipid solubility of a drug is inversely proportional to its charge
- more charged => less lipid solubility
- uncharged => more lipid soluble |
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Definition
HA + H2O <-> H3O+ + A- or HA <-> H+ + A-
- HA is uncharged and lipid-soluble |
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Definition
- when a protonated weak base dissociates, it results in an unprotonated weak base (RNH2) and a proton (H+)
RNH3+ <-> RNH2 + H+
- RNH3+ is charged and more water soluble
- RNH2 is uncharged and more lipid soluble |
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Definition
- protonation(combining w/ a proton)
- Weak acids: Protonated form is neutral
- Weak bases: Unprotonated form is neutral |
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| Uncharged form is more soluble: |
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Definition
- Uncharged form is protonated for acids
- Uncharged form is unprotonated for bases
- More WA will be lipid soluble at acidic pH
- More WB will be lipid soluble at alkaline pH |
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| Excretion of acidic drugs |
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Definition
- weak acids are excreted faster in alkaline urine
- lipid soluble drugs are rapidly reabsorbed in glomerulus |
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| A drug in an acidic solution? Alkaline solution? |
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Definition
- would be in neutral, lipid-soluble form
- would be in polar, charged form (H+)
*** This charged form is more water-soluble and less lipid-soluble, making it not able to diffuse back into the bloodstream |
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| - excreted faster in acidic urine |
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| drugs are excreted faster: |
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Definition
| - Leaves urine faster in more basic environment b/c it is more lipid soluble |
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Definition
area of a cell/organism that interacts with a drug & initiates the chain of biochemical events leading to the drug’s observed effect
- determines quantitative relationship b/w dose/concentration & pharmacological effects |
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| 3 properties responsible for selectivity of a drug |
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Definition
- Size
- Shape
- Electrical charge |
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| Receptors(regulatory proteins) |
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Definition
- Mediate the action of both pharmacologic agonists and antagonists
a)Mediates the actions of endogenous chemical signals
b)Mediates the effects of many of the most useful therapeutic agents |
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Definition
| - receptors that lack its own ligand(ion/molecule that binds to the central atom to form a complex) and its function can only be surmised based on predicted structure/likeness of already known structures. |
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| - may be inhibited or activated by binding to a drug |
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| Receptors(transport proteins) |
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| A protein involved in the movement of a chemical across a biological membrane |
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| Receptors(structural proteins) |
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Definition
| Those proteins with the primary purpose of producing the essential structural components of the cell |
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| Drug Concentration & response |
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Definition
E = Emax x C/C + EC50
a) E is effect observed at [C]
b) Emax is the maximal response that can be produced by the drug
c) EC50 is the concentration of drug that produces 50% of maximal effect |
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| Max is usually when all of the receptors are bound |
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| Drug Receptor & effect relationship |
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Definition
B = Bmax x C/C + Kd
a) B is drug bound to receptors
b) Bmax indicates the total concentration of receptor sites
c) C(antagonist) is concentration of free, unbound drug
d) Kd is the equilibrium constant; concentration of free drug at which half maximal binding is observed |
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| Drug response produced by an agonist depends on 2 factors: |
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Definition
1. Affinity: how well does it bind to the receptor
2. Efficacy: how well does it cause a response once bound |
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| Which provides information about the largest response a drug can produce, regardless of dose? |
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| Produces a full response at full receptor occupancy |
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- Produces a lower response at full receptor occupancy
- Response similar to that when a competitive antagonist irreversibly blocks some of the receptor sites |
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Definition
| readily dissociate from their receptor |
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Definition
| form a permanent, irreversible (or nearly irreversible) chemical bond with their receptor |
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| - binds to the receptor and prevents binding of the agonist at that site (does NOT activate it) |
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| Noncompetitive Antagonist |
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Definition
| can be bound simultaneously with agonist but reduces/prevents action of agonist |
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Definition
| Ionically binds to a DRUG to make it unavailable for interaction with receptors or other substances |
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| Pharmacological Antagonist |
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Definition
| Produces action at the same site as agonist |
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| Produces the opposite effect of the agonist through a different receptor |
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| Transmembrane Signaling(lipid-soluble) |
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Definition
| Chemical signal crosses the plasma membrane and acts on intracellular receptor |
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| Transmembrane Signaling(extracellular) |
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Definition
signal binds to extracellular domain which initiates enzymatic activity of intracellular domain
(substrate A -> product B) |
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| Transmembrane Signaling(extracellular domain) |
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Definition
- Signal binds to an extracellular domain of a transmembrane receptor
- the receptor is bound to tyrosine kinase(protein) which is then activated |
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| Transmembrane signaling(direct binding) |
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Definition
| The signal binds directly to the ion channel, channel opens and is directly regulated by signal |
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| Transmembrane Signaling(G proteins) |
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Definition
| signal -> cell surface receptor -> linked to G protein -> effector enzyme -> converts substrate into product |
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| - due to the concentration of the agonist, not all receptor sites are used, but maximal biological response is reached |
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| Process when normal cell receptor degradation exceeds the synthesis of new receptors (less receptors to activate) |
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| Process by which the amount of active drug in the body is reduced after absorption into systemic circulation |
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| Process by which drug in the body is reduced after administration but before entering the systemic circulation |
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| Kinetics that are characteristic of the excretion of ethanol, high dose phenytoin and ASA |
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