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328 Cards in this Set
- Front
- Back
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What are the two components of the extracellular buffer system |
bicarbonate buffer system & proteins |
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What are the two components of the Intracellular buffer system |
phosphate buffer system & proteins |
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Define Hydrophilic |
water loving |
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Define Hydrophobic
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water–fearing
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Define Amphipathic
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molecules having both phobic and philic portions (cell membranes)
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Predict the movement of water across membranes with a Hypotonic extracellular fluid
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Higher water to solute ratio than the cell, floods the cell. The Cell will expand and eventually rupture
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Predict the movement of water across membranes with a Hypertonic extracellular fluid
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lower water to solute ratio than cell, transfer H2O from cell into solution causing shrinkage
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Predict the movement of water across membranes with a Isotonic extracellular fluid
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same water to solute ratio as cell, no net change = neutral situation
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Describe Henderson–Hasselbalch equation for acids
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pH – pKA = log of [ionized & unprotonated acids] / [protonated & unionized acids]
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Describe the Henderson–Hasselbalch situation where a acid’s pKa is higher than the pH
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the equilibrium will force more of the substance towards the fully protonated, unionized right side of the equation. A–+H+ > AH
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Describe the Henderson–Hasselbalch situation where a acid’s pKa is lower than the pH
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the equilibrium will force more of the substance towards the unprotonated, ionized left side of the equation. A–+H+ > AH
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Describe with the Henderson–Hasselbalch: the differences in ionization/protonation between acids and bases
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pH – pKA = log of [unionized base] / [protonated & ionized acids]
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Name the steps in protein expression [general]
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DNA located in the nucleus are transcribed into mRNA which are transported to the Endoplasmic Reticulum where they are translated into polypeptides
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Describe the important pieces of the Amino Acid Structure [general]
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Amino Acid – H3N+
Carboxyl Group – COO– alpha–Carbon – center carbon attached to the Carboxyl group Functional Group – R–group |
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Explain how the properties of amino acids determine protein structure/function
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Folding provides the overall shape which determines the affinity/fitting of the receptor sites
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Describe the characteristics of polar proteins
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typically hydrophilic, water–soluble, and require active transport across membranes
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Describe the characteristics of non–polar proteins
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typically hydrophobic, lipid–soluble, and utilize passive diffusion across membranes |
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Describe the characteristics of the Primary protein structure
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Sequence of the Amino Acid chain
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Describe the characteristics of the Secondary protein structure
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relationship of H–Bonding between the R–groups that cause alpha–helices and beta–sheets
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Describe the importance of the cysteine amino acid
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the cysteine amino acid contains an SH on the R–group that creates Disulfide (covalent) bonds with other cysteine molecules that are very strong.
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Describe the characteristics of the Tertiary protein structure
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overall/3–D structure of a single protein
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Describe the bonding associated with the Tertiary protein structure
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h–bonding, ionic bonding, disulfide bonds, Hydrophobic reactions
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Describe the bonding associated with the Quaternary protein structure
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h–bonding, ionic bonding, disulfide bonds, Hydrophobic reactions
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Describe the characteristics of the Quaternary protein structure
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combination of multiple protein monomers together
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Define protein: Homodimer
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2+ polypeptide chains, identical order, number, & kind of A.A. Residues
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Define protein: Heterodimer
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2+ polypeptide chains, differ in order, number, & kind of A.A. Residues
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Define term: Isoform with regards to HbF & HbA
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different structures, same function, slight alteration of specificity, activity, binding efficiency. Fetal Hemoglobin has 2–alpha globins + 2 gamma–globins while the Adult hemoglobin has 2–alpha globins + 2–beta–globins
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Define polymorphic
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Genetic Diversity, slight variations in a population
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Describe various ways [general] that a protein structure can be disrupted
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alterations in folding
temperature, pH, ionic detergents, heavy metal ions, organic solvents such as alcohol molecules that alter bonding post–translational modifications [specific] – phosphorylation and glycosylation Glycation [non–specific] Proteases |
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Define the function of proteases
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break the amino acid backbone, a part of the protein half–life regulatory system
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Describe the Proteasome
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protein chopping factor in the cell, maintains cellular homeostasis through removing unwanted or dangerous proteins
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Describe Ubiquitination
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enzymatic addition of lysine residue to proteins that are targeted for proteolysis by the proteasome |
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Describe the equilibrium dissociation constant Kd
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Kd is a measurement of the binding Strength/Affinity between a protein and a ligand
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Describe the result of a low Kd value
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lower Kd values reflect a high affinity or a more tightly bond between the ligand and the protein
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Describe the result of a high Kd value
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Higher Kd values reflect a low affinity or a loose bond between the ligand and the protein |
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Define the term Saturable in regards to Protein–Ligand Data
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Saturable refers to the percent of the substrate that is bound to a ligand. When 100% of the substrate is bound, any excess ligand is extraneous and ineffective |
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Describe Allosteric behavior
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change in protein activity by binding of effector|Enzyme NOT at the active site |
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Describe Cooperativity
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assists in reaction rates based on changes within the molecule. Binding of first O2 on Hgb increases likelihood of #2 binding etc. [unloading also cooperative] |
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What are the two CoEnzymes involved in Redox Reactions
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FADH – flavin adenine dinucleotide
NADH2 – nicotinamide adenine dinucleotide |
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Define the mnemonic OIL RIG
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Oxidizing is Losing e–, Reducing is Gaining e–
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Define Reducing Agent
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The reducing agent is the molecule that is donating/losing the electron. The reducing agent is ultimately oxidized (lost electron) |
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Define Oxidizing Agent
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The oxidizing agent is the molecule that is accepting/gaining the electron. The oxidizing agent is ultimately reduced (gained electron) |
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What vitamin is NAD derived from
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niacin
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What vitamin is FAD derived from
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riboflavin
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What vitamin is TPP derived from
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Thiamine (B1)
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What vitamin is CoA derived from
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Pantothenate (B5)
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What vitamin is Tetrahydrofolate derived from
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Folic Acid
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What vitamin is Pyridoxal phosphate derived from
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Pyridoxine (B6)
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Define Michaelis–Menton’s Km
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kM is the substrate concentration that is required for the reaction to occur at ½ of the maximum (Vmax) reaction rate
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Define Michaelis–Menton’s Vmax
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Vmax is the maximum reaction rate |
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What does a low Michaelis–Menton Km mean
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lower Km values show a higher affinity for the substrate, requires less [s] to achieve Vmax
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Describe the graph of a Lineweaver–Burk plot with regards to the changes in the graph caused by a competitive inhibitor
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The Km of the graph changes which changes the slope of the line and the point where it intercepts the X–Axis while the Y–Intercept stays the same |
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Describe the graph of a Lineweaver–Burk plot with regards to the changes in the graph caused by a noncompetitive inhibitor
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The Vmax of the graph changes which Y–intercept point but the slope of the line and the X–intercept remain relatively unchanged.
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With regards to the Lineweaver–Burk plot, what does a larger or smaller X–Intercept value mean
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a larger X–intercept means a higher Km and a lower affinity for the substrate while a lower X–intercept means a lower Km and a stronger affinity for the substrate
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Which of the inhibitors can be overcome by increasing the concentration of substrate
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The competitive inhibitors
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Define Allosteric inhibitors
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binds at somewhere other than the active site to alter function
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Define Reversible inhibitors
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bind non–covalently to the enzyme, do not change it, and are able to be separated |
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Define Irreversible inhibitors
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bind covalently to the enzyme, change it chemically, permanently
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Explain the difference between a receptor agonist and a receptor antagonist
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A receptor agonist binds & fully activates the receptor while the receptor antagonist binds but does not activate the receptor
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Describe the methods by which enzyme activity are regulated
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non–specific inhibition of enzymes such as overall temperature and pH, any proteolytic behavior
Specific inhibition of enzymes such as intentional substrates, products, drugs etc. Phosphorylation and dephosphorylation post–translational modifications such as the addition of objects to the protein structure or specific folding sequences protein–protein interactions expression level – what is needed at that point in the cellular life and function proteolysis – ubiquitination of unneeded or harmful proteins |
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define accuracy
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closeness to the known standard
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Define Precision
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reproducibility |
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Define Sensitivity
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the smallest amount of detectable analyte
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Define Specificity | Selectivity
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ability of a method to measure one analyte vs another. How well a ligand will bind to Substrate A vs Substrate B
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Describe the general method and clinical uses for electrophoresis
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electrophoresis is the process of separating proteins based on size and molecular weight. Clinical Significance is the ability to detect amounts of expressed proteins.
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Describe the clinical uses for Enzyme Assays
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The examination of expressed enzymes and proteins such as the glucose oxidase test that measures the light–scattering effect of light shone through a sample of a sample
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Describe the clinical uses for Mass Spectrometry
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able to tell the amount and sequence of proteins |
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Describe the clinical uses for Immunoassays
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utilizes detection antibodies labelled with radioactive, fluorescent, or colorimetric parts that allow the examination of expressed mRNA and proteins. This is useful with cancer patients. A subset of this is the ELISA test.
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Describe the general method and clinical uses for DNA sequencing
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allows for the sequencing by synthesis of DNA by tagging the bases in various methods, able to explore a patient’s genome
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Describe the general method and clinical uses for DNA fingerprinting
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DNA fingerprinting allows for the examination by fragment length, variations in the genome due to RFLP, STR, and VNTR alterations.
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Define RFLP with regards to genetic structure
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Restriction fragment length polymorphism, enzymatic digestion of the genome at known points resulting in varying fragment lengths due to polymorphisms or small sequential differences in the populous
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Define STR with regards to the genetic structure
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Short Tandem Repeats, alterations in the genetic code 2–7 base pairs long |
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Define VNTR with regards to the genetic structure |
Variable Number Tandem Repeats – alterations in the genetic code > 8 base pairs long
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Define SNP with regards to the genetic structure |
Single Nucleotide Polymorphisms – alterations in the genetic code only 1 base pair long |
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Describe the PCR
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PCR is polymerase chain reaction and is the process of generating large amounts of DNA from a small initial sample. This allows specific regions of DNA to be examined and tested
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Explain the difference between Northern, Southern, and Western Blotting
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Northern – studies RNA, the North is Really Cold
Southern – studies DNA, the Dukes of Hazard were in the South Western – studies proteins, the Pacific ocean is on the West Coast |
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What information can Proteomic studies provide
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proteomics refer to the investigation of all the proteins expressed by the cell. This is not examining the genome itself but rather the proteins expressed by it which are susceptible to many alteration |
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What information can DNA microarray studies provide
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DNA Microarray or DNA Chip detects specific genetic mutations and determines which mRNAs are being expressed in the patient
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Define Physical Diagnosis
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determine nature of disease by physical measures that include inspection, palpation, percussion and auscultation
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History provides what percent of the diagnosis?
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90%
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What are the 4 intellectual processes involved in arriving at a diagnosis?
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Pattern Recognition
Sampling the Universe Algorithms Hypothesis |
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Define using pattern recognition to arrive at a diagnosis:
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If it look likes a Duck, quacks like a duck..... |
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Define using Sampling of the Universe to arrive at a diagnosis:
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Sampling the Universe involves an exhaustive method of performing copious tests in order to slowly limit the probability of the disease process. Useful in situations where limited information is available (ER/Trauma)
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Define using Algorithms to arrive at a diagnosis:
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Algorithms provide a distinct, tried, tested pathway of following s/sx to a diagnosis and subsequent treatment plan
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Define using hypotheses to arrive at a diagnosis:
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Gather information
Assessment of the information Form hypothesis most likely to fit assessment Assess the probability and utility of various ways to test the hypothesis |
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Define Baye's Theorem
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use sensitivity and specificity of disease in the patient's population to determine if a certain course of action should be taken. Probability and utility enter the process to allow the physician to decide how probable a patient is to have a disease and the utility determines whether certain procedures have worth to the patient.
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Define Rapport
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Seriously.... treat your patient like he was your Mom, or... rather, how you should have treated your Mom. |
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Describe the aspects of history taking
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history taking includes the Chief Complaint, HPI, PMH, Social History, the Review of Systems
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Define HPI and the associated mnemonic
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OLD CARTS: Onset, Location, Duration, Character, Associated & Aggravating factors, Relieving Factors, Temporal factors, Severity of Symptoms
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Define PMH & the associated mnemonic
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MIIFMASH: Medical Illness, Injuries, Immunization, Family History, Medications, Allergies, Surgeries, Hospitalization |
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Describe when you would include first and second degree relatives in family history
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Always include first degree relatives but only include second degree relatives when situationally appropriate |
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Detail the mnemonic used for history taking–
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history taking includes the Chief Complaint, HPI, PMH, Social History, the Review of Systems |
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Explain when to do a complete history
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On every new patient
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Explain when a focused history is appropriate
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on returning patients or emergent/trauma patients |
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What are the cardinal principles of the physical exam |
Inspection |
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Physical Exam: provide details regarding
Inspection |
yields the most # of diagnoses, generalized, localized
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Physical Exam: provide details regarding
Auscultation |
is performed from the moment you walk in the door |
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Physical Exam: provide details regarding
Percussion |
helps to locate organs and map out sizes, tests for density in tissue & air/fluid filled cavities
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What three aspects are important re: Percussion
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Tympany
Resonance Flatness |
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Define Tympany
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air filled stomach
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Define Resonance
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air filled lungs
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Define Flatness
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solid muscle e.g. thigh
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Physical Exam: provide details regarding
Palpation |
Tenderness
Texture Temperature Tone Masses Consistency Location Mobility Pulsation |
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What is the most important part of palpation during the physical exam?
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Keep the patient at ease
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Define Ballottement
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solid structure suspended in fluid e.g. patella
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What is important regarding the sequencing of the various parts of the physical exam?
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the sequence should be divided by system but adjusted to minimize the amount of changing positions the patient will have to do.
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Describe parts of the physical exam to be performed while the patient is in the seated position
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general appearance
vital signs extremities parts of the neurological & musculoskeletal systems |
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Describe subjective vs. objective information
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Subjective – information given to you, what the patient tells you.
Objective – measurable information such as vital signs & head to toe exam |
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Describe the difference between Autocrine, Paracrine, and Endocrine action
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Autocrine – target sites are on the same cell that produces the messenger |
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Describe the general characteristics of signal transduction systems
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signal/ligand released due to stimulus |
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Regarding signal transduction, describe small messenger molecules
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steroids – cortisol, estrogen, testosterone
lipid–soluble, able to diffuse across membranes |
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Regarding signal transduction, describe peptide messenger molecules
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proteins
cytokines growth factors Hormones require active/facilitated transport |
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List the main types of plasma membrane receptors
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Ligand–gated ion channels |
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Describe intracellular receptors
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act primarily as transcription factors which regulate gene expression in the response signals being released
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Describe Protein Kinases
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Protein Kinases transfer a phosphate group from ATP to the –OH group of a specific Amino Acid side chain on a protein |
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Describe Protein Phosphatases
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Protein Phosphatases catalyze the dephosphorylation & modulate the phosphorylation cascade process |
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Describe Co–Repressors / Co–Activators
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modulate signaling through intracellular receptors that are transcription factors
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Explain the general mechanisms through which signal termination & desensitization occur
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Uncoupling – GPCRs uncoupling from G–proteins after the ligand binds
Endocytosis – internalization and degradation of protein receptors Modifications by other proteins decreasing signal activity Altered expression of the proteins |
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Describe the process by which a Tyrosine Kinase Receptor connects to an adaptor protein in general terms:
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Ligand binding
Dimerization Autophosphorylation Connection to Adaptor protein on activated receptor site |
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Describe the process by which Tyrosine Kinase Receptors activate the Ras pathway
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Ligand binding
Dimerization Autophosphorylation binding of Adapter protein binding of GEF protein attachment & activation of Ras to Ras–GTP Ras–GTP activates Raf Raf continues on into the MAP–K pathway |
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What type of receptor initiates the MAP–K pathway through Ras
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Tyrosine–Kinase Receptors
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Define GEF proteins
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Guanine Nucleotide Exchange Factors
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Define GAP proteins
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GTPase Activating Protein
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Define the function of GTPase
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replace GTP with GDP
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What is the domain on the Adaptor Protein that binds to the phosphorylated region of the Tyrosine Kinase Receptor
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SH2 domain
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What is the domain on the Adaptor Protein that binds to the GEF protein
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SH3
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What is the function of the GEF protein?
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Catalyzes the exchange of GDP to GTP on Ras
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In Signal Transduction:
Define PI |
Phosphotidylinositol
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Define the importance of phosphatidylinositol
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membrane bound structure that through phosphorylation becomes PIP2 and PIP3
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What processes work on PIP2 leading to the release of Calcium intracellularly
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Phospholipase C + PIP2 creates IP3 and DAG
IP3 stimulates the release of Calcium from the Endoplasmic Reticulum |
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What molecule is needed to change PIP2 to PIP3?
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Phosphatidylinositol 3–Kinase |
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Define DAG
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Diacylglycerol
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What is the function of DAG
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DAG interacts with Protein Kinase C
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Describe the Jak–STAT pathway
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Receptor binds cytokines, dimerizes, and binds 2 Jaks which phosphorylate each other and the receptor. The receptor binds & phosphorylates 2 STATs which dissociate from the receptor, dimerize, and translocate to the nucleus
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Describe the Serine–Threonine Kinase Pathway
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TGF–beta binds to Type 2 receptor which phosphorylates the type 1 receptor.
The activated Type 1 receptor phosphorylates R–Smad. R–Smad complexes with Co–Smad & migrates to nucleus |
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Define the term GPCR
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G–Protein coupled Receptor
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Describe the G–protein structure [general]
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Subunits – alpha, beta, gamma
Alpha subunit is activated with the exchange of GDP to GTP, leaves the beta/gamma to go off intracellularly to create a cell response |
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Describe the three types of G–alpha sub proteins that are relative to [general] signal transduction as covered in the directed study
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G–alpha–S
G–alpha–i G–alpha–q |
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What is the general function of G–alpha–S protein
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G–alpha–S is attached to GTP, detaches from gamma & beta components of the G–protein. |
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Describe the function of G–alpha–I protein
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G–alpha–i protein inhibits Adenylyl Cyclase and thus the production of cAMP and the phosphorylation cascade
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What structure degrades cAMP
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cAMP phosphodiesterase
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What is the general function of G–alpha–Q protein
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G–Alpha–Q activates phospholipase C which ultimately stimulates DAG and IP3 release
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State the function of GAPs
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GTPase activating proteins – terminate reactions that utilize GTP
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What [DS] signal transduction reactions are inhibited by GAPs
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G–alpha–S
G–alpha–Q Ras |
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State the function of cAMP phosphodiesterase
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turns off cAMP which goes on to stimulate the phosphorylation cascade through Protein Kinase A |
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What [DS] signal transduction reactions are inhibited by cAMP phosphodiesterase |
G–alpha–S due to the reliance on Adenylyl cyclase which catalyzes ATP to cAMP which travels on–wards to stimulate PKA and the phosphorylation cascade. |
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What [DS] signal transduction reactions are inhibited by protein phosphodiesterase |
all phosphorylations
kinases–TK, JakSTAT, PI3–K |
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State the function of protein phosphatase |
dephosphorylates proteins |
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Describe receptor internalization and degradation and the effect
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tendency of cells to internalize structures and recycle the components. The reduction in the number of receptors bound to the membrane can decrease the overall sensitivity of the cell to outside messaging unless it maintains spare receptors and the fluctuation is negligible.
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Describe chemical chirality
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tendency for substances to have a combination right & left handed enantiomers
e.g. Mirror Images |
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Describe chirality and the effect on pharmaceutical action
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chemical chirality influences pharmaceutical action because different isomers may be +/– effective or inactive
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Describe chirality and the effect on pharmaceutical toxicity
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chemical chirality influences toxicity because one isomer may have a therapeutic effect while the other may be toxic
ex: lamivudine. L–form tx HIV, R–form toxic |
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Describe chirality and the effect on pharmaceutical metabolism
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chemical chirality influences drug–metabolism because if a dose is 50/50 racemic mixture of R–L handed structures and only half is absorbed via the GI or if one undergoes faster processing via the Renal/Liver systems, the overall effective dose is lessened than a purely 100% functional isomer
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Describe Drug Selectivity
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ability to affect one tissue, cell type, or organ while not others
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Describe determinants of drug selectivity
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Drug Dose
Drug Distribution Receptor Distribution Receptor Specificity & Selectivity |
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What is the significance of a drugs selectivity
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a drug is given to stimulate/inhibit an effect in a specific target tissue, the drug's selectivity determines whether that drug will inhibit/stimulate ancillary tissues/processes causing side–effects not beneficial to the original cause of the administration.
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Describe the term pharmaceutical Agonist
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a drug that has an affinity to the receptor and also has intrinsic activity
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Define Intrinsic activity [pharm]
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able to produce a measurable effect
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Define the term pharmaceutical Antagonist
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a drug that has an affinity for a receptor but does not have intrinsic activity
receptor is activated but no measurable effect is produced |
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Define the term pharmaceutical partial agonist
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a drug that interacts with the same receptors but cannot produce the same maximal effect as a full agonist
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Define the term Affinity [pharm]
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how strong an attraction that the drug has for the receptor.
measure of binding |
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Define the term Potency [pharm]
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related to the drug binding affinity (Kd)
related to the amount of drug needed to produce a given intensity of effect Higher binding reduces the overall drug needed to produce a specific effect |
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Define the term Efficacy [pharm]
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the largest response or maximal effect – Emax
that a drug can produce |
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Describe the [pharm] term Intrinsic Activity
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extent to which a bound Ligand activates a receptor
Agonist: IA=1 Antagonist: IA=0 |
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Describe the graph of two drugs, an agonist & a partial agonist
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The agonist will have a E–max of 100 while the partial agonist will partial agonist will have a reduced E–max.
The ED–50 value will be identical between the two. |
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Define the [pharm] term E50
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The drug dose needed to reach 50% of the maximal drug effect (Emax) |
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Describe the [pharm] term clinical efficacy
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depends on maximal efficacy & the drugs ability to reach the relevant receptors
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[pharm] Describe the relationship between ED–50, potency, binding affinity, and Kd
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The higher the binding affinity(lower Kd), the lower the drug concentration needed to reach 1/2 Emax (ED–50)
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Describe the graded log–dose response curve
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the curve looks like a vertically stretched S with the maximum point being the Emax of the drug with the lowest point being the threshold dose. |
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[pharm] Define threshold dose
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the lowest drug dose that will produce a therapeutic effect or an effect first appears
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[pharm] Describe the change to a graded log–dose response curve graph of agonists that differ in potency
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potency = drug concentration vs. effect
graph will shift R or L there will be no change in E–Max |
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[pharm] Describe the change to a graded log–dose response curve graph of agonists that differ in efficacy |
E–max will have a vertical shift (up/down)
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Describe [pharm] graphically the effect of a competitive antagonist on an agonist drug's action
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the antagonist binds to the same receptor site as the agonist, preventing it from binding while producing no intrinsic activity.
potency of drug is reduced, graph shifts right because the antagonist can be overcome with more a higher agonist concentration No change to E–Max |
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Describe [pharm] graphically the effect of a non–competitive antagonist on an agonist drug's action
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the antagonist binds to a non–active site on the receptor causing a conformational change in the receptor shape, eliminating the agonists ability to bind. IA=0.
increasing the agonist conc. has zero effect Graph will show a downward shift in E–max |
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Describe [pharm] graphically the effect of an irreversible antagonist on an agonist drug's action
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the antagonist covalently binds to receptor first, eliminating the agonists ability to bind. IA=0.
increasing the agonist conc. has zero effect Graph will show a downward shift in E–max |
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What are the advantages & disadvantages to irreversible inhibitors?
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adv – a bound inhibitor stays bound until replaced. Eliminates the need to repeatedly dose a patient to maintain therapy
dis–the body must replace the receptor before any other action can be taken (tetanus) |
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Describe the concept of Spare receptors
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A cell maintains more receptors than strictly necessary to produce the maximal internal response. This increases cellular sensitivity to messengers such as hormones that are typically in low serum concentrations
effect: lower dose to provide a result |
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Detail how spare receptors will interact with agonist and antagonistic drugs in a graph
|
The graph of a drugs response will shift to the right without changing E–max if there are spare receptors present as there is no initial competition for sites between the agonist–antagonists.
Once all receptors are occupied, the antagonist will force the E–max downwards as they fight for an increased % of total receptors. |
|
|
[Pharm] describe chemical antagonists
|
chemical interaction of two substances where a receptor is NOT involved
overall effect of the active substance is lost IA = 0 |
|
|
Name examples of chemical antagonists
|
Metal chelators (EDTA) vs. toxic metals (lead)
Antiseptics |
|
|
[Pharm] describe pharmacologic antagonists
|
a drug that has an intrinsic activity of 0
prevents action from happening |
|
|
[Pharm] describe physiological antagonists
|
when there are opposing effects by 2 agonists
Biceps vs. Triceps = no movement of the arm |
|
|
Define ED50, LD50, TD50
|
ED50 – Effective Dose in 50% of the populous
LD50 – lethal dose in 50% of the populous TD50 – Toxic dose in 50% of the populous |
|
|
Define therapeutic index
|
the ratio of Lethal dose (50%) to Effective dose (50%) that provides a measure of the safety of a drug
higher value = safer drug |
|
|
Describe the purpose of the cellular membrane
|
structure/rigidity
transportation of substances in/out |
|
|
Describe why substrate transport across the cell membrane is necessary for cellular function
|
cellular homeostasis
metabolism cellular signaling |
|
|
Describe [bio] selectively permeable
|
the ability of the cellular membrane to allow only desired substances to pass
|
|
|
Cellular Membrane, describe the movement of Gases, Water, Ions, metabolic substrates, and proteins across the cellular membrane
|
Gases & water(maybe) – simple diffusion
Ions & metabolic substrates – facilitated diff proteins – facilitated diffusion if not necessary for cellular function |
|
|
Name the factors that determine substances membrane permeability
|
size & charge – smaller = better
larger area = larger diffusion rate |
|
|
Describe the two forces in molecular movement in physiological systems
|
Diffusion – randomized movement, movement from a higher to lower gradient
Bulk Flow – concerted manner, driving pressure |
|
|
List two systems that utilize bulk flow to function
|
Circulation
Respiration |
|
|
Describe the term Concentration Gradient
|
the concentration/charge/forces on a molecule on one side of a membrane versus those applied to the other side of the membrane.
Movement always from higher conc. gradients to lower if possible |
|
|
Describe the difference between simple & facilitated diffusion
|
Simple diffusion – transfer of a molecule across a membrane without help
Facilitated diffusion – carrier molecules (transport proteins or ion channels) are needed for the molecule to move across the membrane |
|
|
Name the two types of proteins that facilitate diffusion
|
transport proteins
ion–channel proteins |
|
|
list the factors that determine the rate of diffusion across the membrane
|
concentration gradient lipid solubility, size, charge |
|
|
Describe the graphic relationship between the rate of diffusion & concentration gradient across a membrane for a freely permeable molecule |
straight line with slope dependent on permeability coefficient vs concentration gradient |
|
|
Describe the effect of saturation on the graph of the rate of molecular facilitated diffusion & concentration gradient across a membrane
|
the graph will appear roughly straight with a slope depending on the permeability coefficient and concentration gradient until all of the facilitating proteins are occupied at 100% capacity where the graph will level off to a maximum rate |
|
|
Explain the role and selectivity of gating channels in controlling membrane permeability to ions
|
Channels assist with membrane permeability in allowing specific ions to pass. Channels maintain different shapes.
Some require a ligand binding or specific voltage charge in order to allow passage to ions |
|
|
Describe the difference between voltage & ligand gating
|
voltage – motivated by the net difference in charge across the channel
ligand – opens only when ligand–bound |
|
|
Define Active transport & its purpose
|
Active transport refers to the process in which a solute is moved up a concentration gradient with an energy input (ATP)
|
|
|
Explain secondary active transport
|
utilizes the passage of another molecule (usually Na+) to facilitate the movement of a 2nd
|
|
|
What is the functional importance of Secondary Active Transport
|
move other substances into the cell by using the already existing process of sodium ion transport moving into the cell
|
|
|
List the two types of secondary active transport proteins
|
Symport – co–transport system, usually with glucose
Antiport – sodium in, another molecule out |
|
|
Name the secondary active transport mechanism that prevents glucose from appearing in the urine under the normal glycemic conditions
|
glucose is reabsorbed via symports in the proximal renal tubules in conjunction with sodium ions
|
|
|
Explain why glucose might be present in urine
|
glucose will be found in the urine when the concentration of glucose exceeds the available symports, any excess glucose that is unable to be reabsorbed will be excreted in the urine (glycosuria)
|
|
|
Give the Professional definition of osteopathic medicine
|
Osteopathic medicine is a complete system of medical care practiced by physicians with an unlimited license that is represented by a philosophy that combines the needs of the patient with the current practices of medicine, surgery, and obstetrics. It emphasizes the interrelationship between structure and function, and that has an appreciation of the body's innate ability to heal itself.
|
|
|
Give the 4 Principles of Osteopathic Medicine
|
the body is a unit: body, mind & spirit
the body is capable of self–regulation, self–healing, and health maintenance Structure & function are reciprocally interdependent Rational treatment is based upon an understanding of these principles |
|
|
Define somatic dysfunction
|
a somatic dysfunction is the impaired or altered function of related components of the somatic (body framework) system
|
|
|
Describe the diagnosis of a Somatic Dysfunction
|
1) Can treat with OMT
2) TART |
|
|
Define the mnemonic TART
|
Tissue texture abnormalities
Asymmetry Restriction of Motion Tenderness |
|
|
Describe the concept of Joint Play
|
movement of the synovial joint that is independent of & cannot be reproduced by a voluntary movement
essential for maximal pain free movement can be restored by OMT |
|
|
What are the absolute contraindications of OMT
|
The patient refuses to have OMT performed
Absence of a somatic dysfunction |
|
|
What are the relative contraindications of OMT
|
When the potential benefits outweigh the risk of harm to the patient
Acute muscle spasms or muscle soreness or treatment reactions |
|
|
Describe direct OMT techniques [general]
|
technique in which the restricted tissue is initially taken in the direction of the restriction of motion
|
|
|
Describe indirect OMT techniques [general]
|
techniques that initially position the restricted tissue toward the relative ease or freedom of motion
Less risk for the patient |
|
|
Discuss the range of motion diagram
|
Depicts the RoM of any particular joint |
|
|
Define soft tissue techniques
|
a direct osteopathic technique that usually involves lateral & linear stretching, deep pressure, traction and/or separation of muscle origin & insertions while monitoring tissue response & muscle changes by palpation
|
|
|
Define the differences between OMT:
Traction |
Traction – Longitudinal Muscle Stretch |
|
|
Define the differences between OMT:
Kneading |
Kneading – Lateral Muscle Pressure |
|
|
Define the differences between OMT: |
Effleurage – Stroking pressure to move fluid |
|
|
Define the differences between OMT: |
Petrissage – Squeezing pressure to move fluid |
|
|
Define the differences between OMT:
Tapotement |
Striking with the side of the hand
|
|
|
Define the differences between OMT:
Skin Rolling |
Lifting the skin away from the deeper structures & rolling the skin fold along the body
|
|
|
List the physiological mechanisms of action & therapeutic effects of soft tissue techniques
|
Relax hypertonic muscles and reduce spasm
Stretch and increase the elasticity of shortened fascial structures Enhance circulation to local myofascial structures Improve local tissue nutrition, oxygenation, and removal of metabolic wastes Improve abnormal neurological reflexes Identify areas of restricted motion, tissue texture changes and sensitivity Improve local systemic immune responses Observe tissue response to the application of manipulative technique Provide a general state of relaxation Provide a general state of tonic stimulation Optimize overall autonomic tone |
|
|
What are indications for soft tissue techniques
|
any somatic dysfunction
|
|
|
What are contraindications of soft tissue techniques
|
local infection,
open wounds lack of skin soft tissue integrity anti–coagulated patients with bruising |
|
|
Define OMT Treatment Reaction
|
24–48 hours after OMT
muscle soreness relieved by rest, warm bath, mild anti–inflammatory/analgesic medication Somatoemotional release |
|
|
Define Somatoemotional release
|
if an emotion is connected in some way to a somatic dysfunction and this dysfunction later receives OMT has the risk of the unexpected recurrence of the emotion
Think: Doc's shoulder |
|
|
Where and when does replication occur?
|
In the Nucleus
During S–Phase |
|
|
What is the role of helicase in DNA replication?
|
separates the parental DNA strands
Hint: Zipper |
|
|
What is the role of topoisomerase in DNA replication
|
relieves the supercoiling after helicase uncoils the strands
single–stranded binding proteins then keep the strands from binding back together hint: Legs |
|
|
What is the role of single–stranded binding proteins in DNA replication
|
prevents the parental strands from pairing back up after topoisomerase splits the strands and helicase uncoils the strand
|
|
|
Describe the role of primase in DNA replication
|
adds RNA primer once topoisomerase splits open the strands of DNA.
this is followed by DNA polymerase adding in the daughter strands |
|
|
What is the role of processivity factors in DNA replication?
|
helps hold DNA polymerase onto the substrate as it creates the daughter strands
|
|
|
Describe the role of RNAse in DNA replication?
|
RNAse removes the RNA primers
after RNAse: ends are then joined by the ligase |
|
|
Which polymerase synthesizes the leading strand?
|
DNA Polymerase E (epsilon)
|
|
|
Which polymerase synthesizes the lagging strand?
|
DNA Polymerase d (delta)
|
|
|
Describe the function of Telomerase
|
Edits the end of the lagging strand in order to get a segment containing the hydroxyl group that a ligase can use to bind the Okazaki fragments together
|
|
|
What are Okazaki fragments?
|
the segments of the lagging strand that are written by DNA polymerase delta and are joined by the DNA ligase
|
|
|
What are the 3 types of RNA
|
rRNA
mRNA tRNA |
|
|
Describe the function of tRNA
|
transport RNA moves amino acids for use in protein translation
|
|
|
Describe the function of mRNA
|
messenger RNA that is transcripted from DNA and it transported out of the nucleus and translated into proteins
|
|
|
Describe the function of rRNA
|
ribosomal RNA is a component of Ribosomes which are used to translate mRNA into proteins
|
|
|
What is the importance of the TATA box?
|
TATA binding protein must find the TATA box to begin transcription
|
|
|
What is the role of the TATA binding protein
|
TATA binding proteins locate the TATA box
|
|
|
What is the role of transcription factors
|
transcription factors recruit RNA polymerase which is used to synthesize RNA
|
|
|
What is the function of RNA polymerase
|
RNA polymerase synthesizes RNA during transcription
|
|
|
What is the importance of the 5'–cap on RNA
|
the 5'–cap increases the half–life of the transcripted RNA & is important in binding the transcript to the ribosome
|
|
|
What is the part of RNA that increases the half–life & assists in binding the mRNA to the ribosome?
|
5'–cap
|
|
|
What is the polyA–tail and what does it do?
|
the polyA–tail protects the transcribed mRNA from degradation
|
|
|
Describe the composition of ribosomes in Eukaryotes vs. Prokaryotes
|
ribosomes = rRNA + ribosomal proteins
Eukaryotes: 60s + 40s = 80s Prokaryotes: 50s + 30s = 70s |
|
|
What are the two types of ribosomal subunits in Eukaryotes
|
60s + 40s
combine into a 80s |
|
|
What are the two types of ribosomal subunits in prokaryotes
|
50s + 30s
combine into a 70s |
|
|
Describe the process of transcription [general]
|
TATA binding proteins find TATA box
Transcription factors recruit RNA polymerase RNA polymerase synthesizes new RNA into mRNA mRNA travels to the ribosomes for processing |
|
|
List the three steps of RNA translation [general]
|
Initiation
Elongation Termination |
|
|
Describe RNA translation Initiation
|
tRNA gets charged by Aminoacyl tRNA synthetase
initiation factors bind – initiate translation charged tRNA finds 80s[40s/60s] ribosomal subunit elongation begins |
|
|
Describe RNA translation elongation
|
tRNA+Amino Acid are picked up by the elongation factors
complex enters ribosomal A site Anticodon matched against mRNA at A–site chain is shifted to the P–site where peptide bond formed between the amino acid in P–site with the incoming amino acid in A–site proofreading via the elongation factors |
|
|
What is the function of peptidyl transferase?
|
formation of the peptide bonds between the amino acids in P–site and A–site
|
|
|
What is the importance of chaperones & heat shock proteins?
|
these are required to overcome kinetic barriers
force the protein into the correct desired protein folding |
|
|
Define Free ribosomes
|
ribosomes not attached to the endoplasmic reticulum
|
|
|
Compare the processing of proteins that are synthesized on free ribosomes vs those on the rough ER
|
free ribosomes – may stay in the cytoplasm or certain organelles
ER – enter golgi apparatus and are subjected to exocytosis |
|
|
What is the translation function of aminoacyl tRNA synthetase
|
charges the tRNA before synthesis
|
|
|
What is the function of initiation factors in RNA translation
|
required to find the start codon & thus initiate translation
|
|
|
What is the role of histones?
|
chromatin remodeling is needed to unwind the chromatin that are tightly bound around the histone protein. Histones are proteins that wind DNA very tightly so as to compact it into a very small area. These combine into a 4–protein octamer within the nucleus.
|
|
|
What is the function of HATs
|
Histone acetyltransferase – responsible for turning ON gene expression. HATs transfer an acetyl group to the chromatin to neutralize the charge–attraction between the DNA strand and the histone resulting in the DNA unwinding
Recruited by activator proteins |
|
|
What is the function of HDACs
|
Histone deacetylases turn OFF gene expression by removing the acetyl group & allowing the recondensing of the histone octamer.
Recruited by repressor proteins |
|
|
Describe methylation and the effect on DNA
|
methylation of genes results in them being less readily transcribed. Problems are encountered when the STOP codon is methylated.
|
|
|
What is the function of methyltransferases
|
maintain methylation by adding methyl groups to the daughter strands and performing maintenance methylation
|
|
|
What is name for the process by which new methyl groups are added?
|
De Novo Methylation
|
|
|
By what mechanisms are transcription factors regulated?
|
their own expression level
expression of coactivators & corepressors presence of inhibitors phosphorylation |
|
|
Describe alternative RNA processing & RNA editing
|
RNA editing – bases are altered chemically, using different exons
by alternative splicing to allow different protein sequencing from the same gene |
|
|
Which stays with the protein: Intron or Exons?
|
Exons, they exit with the protein
|
|
|
Describe 3 mechanisms affecting RNA stability
|
regulatory proteins
5'–cap poly–A tail |
|
|
Describe the effect of MicroRNA on gene expression
|
induce transcript degradation
block translation |
|
|
Define cell "resting membrane potential"
|
The resting membrane potential of a cell is the point at which there is zero net movement of ions across the cell membrane.
|
|
|
What are the two uses the resting membrane potential for a cell? |
Excitability – ability to signal electrically |
|
|
What is the voltage of a cell at the typical resting membrane potential?
|
-60 to -85 mV |
|
|
Describe why the cellular resting membrane potential is maintained at a specific value?
|
the cell membrane overs around 60–85 mV because the membrane is fully permeable to K+ ions that have a Nernst potential of –88 mV but some Na+ ions (NP=+70) leak through forcing the membrane more positive
|
|
|
What is the extracellular membrane potential in mV?
|
always 0 mV
|
|
|
What are two types of cells that utilize membrane potential?
|
Nerve cells
muscle cells |
|
|
What are the two forces that control movement of ions across the membrane
|
Concentration gradient
Electrical Gradient |
|
|
Define concentration gradient
|
directs the flow of ions based on the concentration of solutes on the outside of the membrane versus those on the inside of the membrane. Solutes always move from high to low concentration if permitted
|
|
|
Define electrical gradient
|
difference in the electrical charges in vs outside the membrane. net flow will move to equalize the difference between negative & positive sides.
|
|
|
Define Driving Force [cell membrane]
|
force that dictates which direction the molecules move. Combines electrical & concentration gradients.
|
|
|
Define equilibrium in terms of membrane ion movement
|
No driving force for ion movement. It is established when the conc. & electrical gradient are equal but opposite
|
|
|
What is the Nernst equilibrium potential
|
is the membrane potential at which the concentration gradient + electrical gradient are equal but opposite e.g. balanced |
|
|
What is the NP of Sodium?
|
+70 mV
|
|
|
What is the NP of Potassium?
|
–88 mV
|
|
|
What is the NP of Chlorine?
|
–47 mV
|
|
|
What is the NP of Calcium?
|
+122 mV
|
|
|
What are the concentrations of Sodium?
|
in: 10 mM
out: 140 mM |
|
|
What are the concentrations of Potassium?
|
in: 140 mM
out: 5 mM |
|
|
What are the concentrations of Chlorine?
|
in: 20 mM |
|
|
What are the concentrations of Calcium?
|
in: 0.0001 mM
out: 1 mM |
|
|
Describe the factors that make a membrane selectively permeable to an ion
|
membrane permeability to an ion depends on the # of open channels selective for that ion present in the membrane
|
|
|
Describe the graphic relationship between [K+]o, Ek, and the membrane potential
|
[K+]o is the concentration of K+ ions outside
Ek is the NP for potassium Membrane potential is the membrane response to balance the gradients |
|
|
If the membrane is solely permeable to Sodium ions, what is the membrane potential?
|
+70 mV
|
|
|
Explain why membrane potential is different from Ek at very negative membrane potentials
|
there will be slight movement of Na+ into the cell from Na+ leak channels
|
|
|
What is the ratio between Na+/K+ ions in a typical resting permeability
|
1 Na+ to 100 K+
in : out 10 : 140 Na 140 : 5 K |
|
|
Describe the influence of Ca2+ & Cl– ions on the resting membrane potential in nerves and in the muscle cell
|
Calcium = zero influence on membrane potential |
|
|
What is the membrane potential for Skeletal muscle cells?
|
–85 mV
|
|
|
Define depolarization
|
a situation where the membrane or Nernst potential become less negative
|
|
|
Define hyperpolarization
|
Nernst or membrane potential becomes more negative
|
|
|
Describe the 7 basic elements of Healthcare communication
|
Open the discussion
Build a relationship Gather information Understanding the patients perspective Sharing Information Reaching agreement of problems/plans Providing closure |
|
|
List the methods drug administration
|
Oral
|
|
|
Describe the benefits & disadvantages of:
Oral administration |
most common route, generally the safest, GI irritation, First–pass effect
|
|
|
Define First–Pass metabolism
|
metabolism of the drug by the GI bacterial enzymes, the GI tissue enzymes, and by the Liver enzymes prior to the drugs insertion into the systemic circulation
|
|
|
Describe the benefits & disadvantages of:
Rectal administration |
potentially avoids first pass, absorption is slow and possibly erratic
|
|
|
Describe the benefits & disadvantages of:
transdermal administration |
must be lipid–soluble, slow absorption, varying bioavailability
|
|
|
Describe the benefits & disadvantages of:
sublingual administration |
direct absorption into the systemic circulation, higher bioavailability, rapid absorption
|
|
|
Describe the benefits & disadvantages of:
Buccal administration |
direct absorption into the systemic circulation, higher bioavailability, rapid absorption
|
|
|
Describe the benefits & disadvantages of:
topical administration |
no systemic exposure, localized effect
should be lipid–insoluble |
|
|
Describe the benefits & disadvantages of:
subcutaneous administration |
absorption is constant, complete, and slow
depends on blood flow for absorption rate bypass First Pass effect |
|
|
Describe the benefits & disadvantages of:
intramuscular administration |
absorption by simple diffusion, generally rapidly, higher bioavailability |
|
|
Describe the benefits & disadvantages of:
intravenous administration |
avoids first–pass effect, fastest route, complete bioavailability, rapid effect, toxicity and occur with rapid drug administration
|
|
|
Describe the benefits & disadvantages of:
inhalation administration |
local effect & systemic effect
absorption is rapid avoids first–pass effect |
|
|
Describe the benefits & disadvantages of:
Intrathecal administration |
administration into the cerebrospinal fluid
used for local, rapid effect on the meninges & CS axis avoids blood–brain barrier |
|
|
Describe the graph of the IV drug concentration over Time
|
The IV dosage avoids the first pass effect and is placed directly into the systemic circulation at full concentration with subsequent elimination by the liver & kidneys |
|
|
Describe the graph of a PO drug concentration over time
|
The PO dosage undergoes delivery through the GI system after undergoing First Pass metabolism prior to delivery into the systemic circulation where it subsequently undergoes elimination. |
|
|
Describe primary process by which drugs cross the membrane
|
First Order process: rate is dependent on concentration (high to low)
|
|
|
Describe the importance of lipid–solubility on drugs membrane permeability
|
higher lipophilic = higher solubility = faster diffusion across the membrane |
|
|
Describe the relationship between pH & ionization of a drug which is either a weak organic acid or base.
|
the drug must be administered so that the pH of the delivery system pushes the drug to unionized structure in order to pass through the membrane |
|
|
Define Strong vs. Weak Acids & bases.
|
Strong Acid & Bases: fully ionized in all solutions |
|
|
Define pKa
|
pH where the substance is 50% ionized & 50% unionized
|
|
|
Provide the equation for a weak acid
(think Log) |
pH–pKa = log [ionized / unionized]
|
|
|
Provide the equation for a weak base
(think Log) |
pH–pKa = log [unionized / ionized]
|
|
|
List the factors that affect the rate & extent of oral absorption
|
drug solubility |
|
|
What determines bio–availability |
% of drug in systemic circulation after: |
