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211 Cards in this Set
- Front
- Back
Define pharmacodynamic
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Study of drug effects on the body. Interactions of the drug with its receptors and the dose response relationship.
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define pharmacokinetics
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Study of the effects of the body on the drug and itss travels through the organism. Time-action relationship for each drug.
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Define affinity, efficacy, signal transduction.
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Affinity- A measure of the strength of chemical interaction betwen the drug and its receptor
Efficacy- Measure of the ability of the drug to activate the receptor Signal transduction- linking activation of the receptor to a change in cell physiology involves second messengers. |
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Definition of agonist, competitive antagonist, partial agonist
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agonist = affinity and full efficacy
competitive antagonist = affinity but no efficacy partial agonist= affinity and partial efficacy |
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What does an agonist's effect depend on?
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Concentration of the drug and affinity of the receptor for the drug.
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What are "spare receptors"?
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Extra receptors that are unoccupied despite the cell having full physiological effect due to other receptors of the same type being occupied. This is due to amplification.
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What is EC50?
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The agonist concentration when E/Emax is .5 or half the maximal response.
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Define potency.
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How much drug it takes to cause the effect. Highest affinity for the receptor = smallest Kd
Can be expressed by comparing differences in EC50 values. |
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Define efficacy
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Intrinsic activity of a drug at its receptor and is defined in the concentration-response relationship by the maximum effect that can be obtained.
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What is an allosteric interaction?
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Binding of a noncompetitive antagonist to a DIFFERENT site than the agonist to prevent the agonist from binding.
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What is the incidence of acute drug reactions in the US?
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6.7%
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What is the incidence of fatal drug reactions in the US?
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0.3%
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Define therapeutic Index
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TD50/ED50 bigger = better
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What is the effect of a competitive antagonist on a log concentration response curve?
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Decrease in potency, no change in efficacy
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What is the effect of a non competitive antagonist on the log concentration response curve of an agonist?
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Decrease in efficacy (maximal effect), potency remains the same.
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What are some factors that can cause the dose-response curve to change?
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sensitization and desensitization
tolerance changing disease states/physiology altering pharmokinetics of drug |
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Describe the morphology of Tyrosine kinase receptor family members. How are they different and how so?
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General morphology include a single transmembrane alpha helix which divides receptors into extracellular domains containing a ligand binding site and and intracellular domain containing tyrosine kinase activity.
Tyrosine kinase family includes Epidermal growth factor (cysteine rich domain extracellularly) Nerve growth factor Platelet derived growth factor Colony Stimulating factor Fibroblast growth factor Vascular endothelium growth factor (all have immunoglobulin like extracellular domain) Insulin receptor- 2 beta and 2 alpha chains. Alpha chains are binding site. Beta chains cross membrane and have Tyrosine Kinase. |
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Diagram and describe the insulin receptor pathway signalling.
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Ligand binding to receptor induces autophosphorylation on the tyrosine residues on the intracellular domain. Two ligands of insulin peptide are required for full activation.
Autophosphorylation stimulates: Tyrosine phosphyrlation of IRS-1 leading to two pathways 1) Growth pathway = IRS-1 phosphylates Shp leading to activtion of Ras. Ras activates the mitogen activate protein (MAP kinase) and activates transcription factors that control growth promoting genes. (Myc and Elk) 2) Glucose uptake pathway. IRS-1 phosphorylates PI3K initiating a phosphorylation cascade that leads to placement of glucose receptors (GLUT4) in the plasma membrane. |
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Describe aberrant growth factor signalling in chronic myelogenous leukemia. What drug acts on this pathway and in what way?
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Aberrant fusion gene (philadelphia translocation) protein Bcr-Abl. Bcr-Abl is normally regulated by tyrosine kinase but altered product is always active and thus always phosphorylates Shp. and turns on Ras activating the rest of the cascade. Bcr-Abl is inactivated by Gleevec supressing aberrant growth.
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Give some examples of ligands that act via G protein linked receptors.
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Catecholamines
Neurotransmitters Peptide hormones |
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Give some examples of second messengers.
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cAMP
DAG IP3 Ca2+ cGMP |
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What are the 3 major classes of G Protein linked receptors? Describe their mechanism of action.
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cAMP pathway (Gs + Gi)
increase or decrease cAMP via activation or inhibition of Adenyl cyclase Phospholipase C pathway (DAG, IP3) Receptor activates Gq/Gp which causes PLC to cleave PIP2. IP3 goes on to increase Ca while DAG activates PKC. Rhodopsin pathway. Light activates transducin to cause phosphodiesterase to decrease cGMP. |
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What hormone uses the cAMP pathway to effect its activity?
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Epinepherine
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Diagram cAMP mediated cellular
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See notes p.15
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Diagram Epinepherine induced breakdown of liver and muscle Glycogen
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See notes p.16
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Diagram how adenylate cyclase can be inhibited by an inhibitory protein. Be sure to show the various receptors/ligands.
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See notes p. 16
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Diagram the Ca2+/PIP pathway
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See notes p. 17
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List the adrenergic receptors, the effect, and the G protein involved.
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Notes p.20
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List the muscarinic cholinergic receptors, the effect and the Gprotein.
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Notes p.20
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Diagram NO signaling
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Notes page 21
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From what types of are steroids derived?
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Cholesterol, aromatic amino acids, or fatty acids
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What are the 3 domains of a steroid hormone receptor? What do they do?
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TAF= Transcription Activation Domain (responsible for interaction promoting activity by DNA polymerase)
DBD= DNA binding domain (site of direct interaction of DNA) LBD= Ligand binding domain (Site of high selectivity binding by steroid hormones) |
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Describe the two step receptor activation of gene transcription.
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1) Ligand receptor recruits the steroid receptor co activator complex (CoA) SRC which contains histone acetyl transferase (HAT) activity leading to acetylation of histones.
2) Acetylation leads to unwinding of chromatin allowing binding by general transcription factors (Pol II) |
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What is reverse endocrinology?
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Using genes to determine receptor, hormone, and the predicted physiology response.
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What is an orphan nuclear receptor?
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Receptor for which the steroid is unknown.
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What is an adopted orphan receptor?
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Receptor that has a low affinity for dietary lipids and most likely control lipid metabolism.
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Describe some newly discovered orphan receptor ligands and their receptors.
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Peroxisome proliferative activated receptor (activated by fatty acids) and TZDs (thiazolidinedione)
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Diagram how insulin mediates glucose-lipid crosstalk
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Page 27
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What are the locations of activity of peroxisome proliferator activated receptors? What are they activated by? What do they do?
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p. 27
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What tissues are Peroxisome Proliferator Activating Receptor alpha found in? What are they activated by? What do they do?
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PPAR-alpha are expressed in liver and muscle
They are activated by fatty acids and fibrate drugs They have hypolipidemic actions and promote FFA uptake, and Beta oxidation of FA |
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What tissues are Peroxisome Proliferator Activating Receptor beta found in? What are they activated by? What do they do?
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PPAR-beta are expressed in liver, muscle, adipose and bone
They are activated by fatty acids, arachidonic acid derivatives, and antidiabetic drugs (thiazolidinediones TZDs) They have insulin sensitizing actions and promote adipocyte differentiation, lipogenesis, and storage. They promote glucose uptake in adipose and muscle. |
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What tissues are Peroxisome Proliferator Activating Receptor gamma found in? What are they activated by? What do they do?
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Ubiquitous expression.
Involved in Fatty acid oxidation, and energy uncoupling. |
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What is the activity of TZDs on adipose, muscle and liver?
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Adipose = promote glucose uptake, lipid uptake and storage, and increased energy expenditure
Liver = increased lipid uptake and storage as well as increased energy expenditure leading to decreased gluconeogenesis Muscle = increased glucose oxidation |
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Where is LXR expressed and what does it do?
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LXR is the liver x receptor and is a cholesterol sensor. It is expressed in liver, adipose, kidney, intestine and macrophages.
It is activated by cholesterol metabolites and controls cholesterol homeostasis |
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Where is FXR expressed and what does it do?
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FXR is the Farnesoid X Receptor or bile acid sensor.
It is expressed in liver and intestine and is activated by bile acids. It controls bile efflux from the liver that serve to solubilize lipids and vitamins for excretion. |
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Diagram how LXR and FXR work together.
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p. 30
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What is the partition coefficient?
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PC= (concentration of drug in oil) / (concentration of drug in water)
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What are the 3 acid/base properties of drugs?
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Neutral
Weak acid/base and salts strong acid/bases and salts |
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What is the most important physicochemical property of a drug?
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Partition coefficient
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What does the term "weak" mean as far as acids and bases in solution?
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Weak indicates that both ionized and unionized forms of the drug are present in equilibrium in the aqueous solution
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What is the key difference between acids and bases as far as drug delivery?
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Which is the uncharged species.
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Give the equilibrium constant for the acid form of a drug.
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Ka = [Base][H+]/[Acid]
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Give the Henderson Hasselbach equation
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pH - pKa = log [base]/[acid] or
[base]/[acid] = 10 ^ (pH-pKa) |
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pH = ?
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pH = -log [H+]
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What special properties do tertiary ammonium have?
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Always charged and never donate or accept a charge
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What are the three major transport mechanisms of drugs?
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1)Diffusion across a lipid bilayer
2)Active or passive transport by specialized transport systems 3)Filtration through pores |
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What properties to cross a lipid bilayer must a drug have? What types of effects is this important for?
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Must be uncharged and have a favorable partition coefficient
Important for Absorption from GI Entering cells (especially if receptor is intracellular) Entering the CNS (if inside blood-brain barrier) |
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What is the Rate of passive diffusion?
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Rate = k (C1-C2)
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What is the relationship between partition coefficient and constant of diffusion?
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k depends on the partition coefficient. The higher the concentration in the membrane, the faster it will be transported.
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What does passive diffusion of a weak acid/base depend on?
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Concentration of the uncharged form (amount of drug, its pKa and the pH), as well as the partition coefficient of the uncharged form.
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Suppose a drug has a Ka of 10^-9
If the pH is 7 on the left of a barrier and 2 on the right, what will be the concentration of the base on each side of the barrier? |
100 on the left
100000 on the right Note that the acid in the case of a weak base is the uncharged species. |
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What is ion trapping?
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Accumulation of an acid or base on one side or another of a barrier due to a difference in pH
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What is required for active transport to occur?
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A transporter and ATP.
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Give approximate pH of:
Stomach Vaginal secretions Prostratic secretions Urine Breast Milk Jejunum, Ileum |
Stomach 2
Vaginal secretions 3.4-3.2 Prostratic secretions 6.4 Urine 5-8 Breast Milk 6.4 Jejunum, Ileum 7.5-8.0 |
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What are the two families of transporters?
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One transports positively charged species
One transports negatively charged species |
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Where in the body does active transport take place?
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Proximal tubule of nephron (excretion of drugs)
Hepatocytes (transport into cells for biotransphormation or transport out into bile or blood) Choroid plexus (protects brain by pumping drugs out of the CSF into the blood) |
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What type of transporter is required for quaternary ammonium drugs? (always charged)
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Pores
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What is the major determinant of the ability of something to cross a pore?
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Its size
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Where are pores found in the body? Where are pores not found?
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Pores are found in most capillaries except for in brain capillaries
Kidney glomerular capillaries contain large pores Also liver and spleen hepatocytes contain pores |
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What stage of administration of drugs do IV drugs avoid?
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Absorption
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Define Absorption
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Process by which the drug gets from the site of administration into the blood stream
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What does the rate of absorption depend on?
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Area of surface exposed to the drug
Thickness of the barrier How well perfused the area is with blood |
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Name some of the major sites for absorption of drugs
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GI
Lungs Injection site Skin |
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In what manner are drugs absorped in the GI? What do different drugs depend on for their absorption rate?
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Via passive non-ionic diffusion
Neutral drugs are absorbed at a rate dependent on their partition coefficient Weak acids and bases are absorbed at rates dependent on their PC, their pK and the pH of the GI tract Drugs with fixed charges are very poorly absorbed |
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Can weak bases be absorbed in the stomach?
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NO
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What is the best place for absorption of drugs?
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Small intestine
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What is the problem with the small intestine being used as a place for the absorption of drugs?
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All stuff absorbed goes through the liver via the hepatic portal vein before entering the blood stream. Hence can be metabolized.
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Define first pass effect.
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Fraction of an orally administered drug that is metabolized by the liver and GI tract before reaching the systemic circulation.
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Name some drugs that have a high first pass effect.
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Nitroglycerin
Morphine Lidocaine Estradiol |
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Define Bioavailability
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The fraction of uncharged drug that reaches the system circulation.
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What factors reduce bioavailability?
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GI tract metabolism especially CYP 3A4
Liver metabolism |
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If a drug has 0 oral bioavailability is it useless?
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NO! If its metabolite is active then it may still be useful.
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What does bioavailability have to do with drug interactions?
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Some drugs when combined may increase bioavailability of one of the drugs. This may produce a toxic effect.
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What are two enteral routes that avoid the liver? What are the positives and negatives of each?
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Sublingual
Drug enters circulation before the liver Rectal Administration Usefor when patient is unconscious or vomiting but absorption tends to be incomplete and unpredictable 50% enters circulation before the liver |
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What are the advantages and disadvantages of IV administered drugs?
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Advantage:
Very rapid no absorption Best control over blood concentration Disadvantage Blood concentration rises rapidly leading to adverse effects (inject slowly) Problems with repeat dosing leading to vein damage Drug must be in aqueous solution Cannot be reversed |
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What are the advantages and disadvantages of intramuscular administered drugs?
How are they absorped? |
Absorption occurs via capillary pores or lymphatic system for larger molecules.
Advantage Fairly rapid absorption from aqueous solution Absoprtion rate depends on blood flow, fat content of tissue (ergo deltoid > gluts, men > women) Slow but sustained absorption of water soluble drugs in oil Disadvantages do not use during anti coagulant therapy Painful! |
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What are the advantages and disadvantages of subcutaneous administered drugs?
How are they absorped? |
Absorption occurs via capillary pores or via lymphatic system for larger molecules
Advantages: Rapid absorption from aqueous (rate depents on blood flow, fat content) Slower absorption of insoluble drugs Solid pellets can be inserted for release over months or years. Disadvantages: Cannot be used with drugs that irritate the tissue |
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What are the advantages and disadvantages of topically administered drugs?
How are they absorped? What does the rate of absorption depend upon? |
Drug needs to be potent and have a very favorable partition coefficient to be absorbed through the epidermis.
Absorption depends on site of administration (foot = very slow, scrotum = very fast) Blood flow in skin Inflammation of the skin greatly increases absorption |
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Define Distribution. What does it depend on?
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Distribution is the process by which the drug moves from the blood to the various tissues and organs of the body.
Rate of distribution depends on 1) permeability of the capillaries to the drug, and the 2) rate of blood flow to the tissue. Rate of distribution therefore differs for different organs. |
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Name some of the organs which reach maximum concentration in minutes.
Name some of the organs where drugs may take minutes to hours? |
Fast = Heart, liver, kidneys, brain
Slow = Muscle, Skin, viscera, Fat |
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What is the equation that describes the concentration of a drug in the blood?
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[x]blood = x (added) / (Vblood+Vextracellularfluid)
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At what point does Cmax occur for most drugs? What is the exception?
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Cmax occurs when drug absorption = drug distribution + elimination
For food bolus drugs, when given they are at Cmax |
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What is the primary factor tending to decrease plasma drug concentration early on?
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Distribution
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When does elimination become the dominant factor controlling plasma drug concentration?
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After absorption and distribution are complete.
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What determines the maintenance dosage regimen?
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The rate of drug elimination.
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Define minimum effective concentration
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Concentration above which there is reasonable expectation of achieving the desired effect.
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Define Minimum toxic concentration
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Concentration above which there is reasonable expectation of apperance of adverse toxic effects.
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Define therapeutic range
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Concentrations between MEC and MTC
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Define lag time
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Time between administration and first apperance of drug action
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Define duration of action
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Time plasma concentration is above MEC
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What are the three most important pharmacokinetic variables? Define them.
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Bioavilabilty (f)
Fraction of dose which reaches the systemic circulation unchanged Apparent volume of distribution (Vd) A measure of the apparent space in the body throughout which the drug appears to be distributed. Clearance (Cl) measure of the body's ability to eliminate a drug |
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Define F (bioavailability) as a function of the time curve (AUC) for iv and x (any other method of delivering the drug)
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f = AUGx/AUGiv
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Can the bioavailability of a drug be affected by the manner in which it is adminstered?
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YES
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Define apparent volume of distribution
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The total amount of drug in the after absorption and distribution are complete prior to any elimination.
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Define volume of distribution
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Apparent volume that a drug occupies after absorption and distribution are complete.
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What sorts of drugs will fail to cross the placenta?
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Large, multiple charges, extremely low lipid soubility, assume all drugs cross to the baby
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What exports blood from the placenta?
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P-glycoprotein
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Is the baby's blood pH different from the mother's?
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Yes, it is more acidic
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What transports drugs in the blood? How do the two proteins differ?
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albumin carries acidic drugs
alpha-1 acid glycoprotein carries basic drugs |
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What sorts of diseases will reduce plasma protein levels? What sort of diseases will increase them?
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Liver disease decrease albumin
Renal disease can lead to loss of plasma protiens in the urine. Some diseases that induce an acute phase response will stimulate protein synthesis. |
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Define biotransformation.
Where does it occur? |
Chemical alteration of drugs in the body.
It occurs primarily in the liver. |
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Describe Phase I (non-synthetic) biotransformation.
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Oxidation, reduction and hydrolysis
Products have unpredictable biological activity |
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Describe Phase II (synthetic transformation)
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Addition of metabolites to the drug
Usually less active and toxic in the conjugated drug Highly polar conjugate is formed. |
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What is the majore chytochrome P450 enzyme of the liver?
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CYP3A4
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What structurs are recognized by P450 enzymes?
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Benzene
Alkyls Amines |
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Where does glucuronidation occur?
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in the ER
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What sort of compounds does glucuronidation work on?
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Weak acid bases
RNH2 RCOOH RSH |
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What compound does glucuronidation require?
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Uridine diphosphat lucuronic acid.
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What pathway/enzyme removes epoxides?
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Glutathiokinase
Glutathione conjugation pathway |
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What enzyme is involved in methylation?
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SAM
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What enzyme is involved in amino acid conjugation?
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CoASH (ATP)
Glycine |
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What enzyme is involved in acetylation?
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Acetyl SCoA
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What enzyme is involved in sulfonation?
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PAPS
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What are the four characteristics of a drug that allow prediction of its renal handleing?
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Its size or MW
extent of plasma protien binding Its electric charge Its partition coefficient |
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What is inulin?
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a polymer of fructose
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How does inulin enter the urine?
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Does not bind to plama proteins so fraction filtered = 20%
No charge so not actively secreted in proximal CT. Partition coefficeint = 0 so not readsorped. Therefore amount in urine only dependent on the glomerular filtration rate. |
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Describe Glomerular filtration rate and urinary filtration rate as a function of inulin concentration in the blood and plasma.
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GFR x [inulin]plasma = UFR x [inulin]urine
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What type of molecule is penicillin?
What is its partition coefficient? What percentage of it binds to albumin? |
Weak acid
PC = 0 60% binds to albumin so 0.4 * 20% (filtration) = 8% filtration factor |
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What is the half life of penicillin?
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30 min
|
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What is the purpose of probenecid?
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Prolong activity of penicillin
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What percentage of Probenecid is bound to albumin?
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90%
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What type of molecule is probenecid? Where is mostly readsorbed?
|
It is an anion
mostly readsorbed in distal convoluted tubule. It competes with penicillin. |
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Describe the flow of blood in the Liver
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Blood from the GI brought via the hepatic portal vein and from the rest of the body via the hepatic artery. Blood leaves through central vein
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What are the two pathways in which drugs can go after they are metabolized in the liver?
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1) Back into systemic circulation
2) Into the bile canaliculus and on to the gall bladder for release into the small intestine. (biliary excretion) |
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What type of drugs are eliminated via biliary excretion?
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Those with a poor partition coefficient
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What is enterohepatic cycling?
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When a drug that has been conjugated with glucuronic acid has an unfavorable partition coefficient. However bacteria in the colon can remove the glucuronic acid and release the drug. If the released drug has a favorable partition coefficient it can be resorbed and the process can be repeated.
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How are most drugs that undergo enterohepatic cycling eventually excreted?
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Kidney
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What is isotretinoin?
|
A vitamin A analog used for acne tratement that can be a teratogen
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What are the characteristics of newborns nad elderly that effect their response to drugs?
|
Poor blood brain barrier in children
Limited microsomal biotransformation in liver Increased gastric emptying and decreased peristalsis. Decreased GFR and decreased renal tubular secretion. |
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What are some diseases state sthat may alter responses to drugs?
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Heart disease
Kidney disease Severe liver disease |
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What drug will fast and slow acetylators have altered metabolism for?
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Isoniazid
|
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What drug will people with atypical plama cholinesterase have?
|
Slow recovery from succynlcholine.
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What does Cyp2D6 defieciency result in?
|
Codeine oxidation reduction.
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How do esomeprazole and lanoprazole effect penicillin G absorption?
|
By inhibiting stomach pH more penicillin is absorbed.
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What sort of things can affect tetracycline production?
|
Antacids combine with them and form an insoluble complex.
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What cytochrome does ketoconazole inhibit?
|
2C19
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What cytochrome does itraconazole inhibit?
|
3A4
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What cytochrome does ritonavir inhibit?
|
2D6 and 3A4
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What cytochrome does erythromycine inhibit?
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34A
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What cytochrome does terfenadine inhibit?
|
3A4
|
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What does tyramine inhibit?
|
MAO, tyramine is found in cheeses, beer, wine
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What enzyme is tolbutamide metabolized by?
|
Alcohol dehydrogenase
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What do HIV protease inhibitors doe to CYPs? What do HIV antivirals do to CYPs?
|
Protease inhibitors Inhibit
Antivirals induce |
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What drug induces CYP 2B6, 2C19, 2C9, 2D6, 3A4?
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Rifampin
|
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What sort of things induce CYP1A2?
|
Broccoli
Char-grilled meat Tobacco Methychol-anthrene |
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What does Amphotericin B have as a side effect?
|
Severe nephretic damage resulting in alteration of glomerular filtration rate.
|
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What does Sodium bicarbonate have as a side effect?
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Will make the urine more basic and will increase renal loss of aspirin.
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What does Penecillin G have as a side effect?
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COmpetes with probenecid for renal tubular excretion.
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What is the order of passive diffusion of a drug in the absorption phase?
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First order
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When might there be instantaneous absorption?
|
When a drug is given IV
|
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What dictates the maintenance dosage regimen?
|
Rate of drug elimination
|
|
Define bioavialablity
|
Fraction of the dose which reaches the systemic circulation unchanged.
|
|
Define Apparent volume of distribution.
|
A measure of the apparent space in the body throughout which the drug appears to be distributed.
|
|
Defien Clearance
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A measure of the body's ability to eliminate a drug. Rate of eliminiation of the drug from the body relative to its concentration in the plasma. It is the volume of the biological fluid that must be removed inorder to account for the observed rate of drug elimination.
|
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Will binding to plama proteins increase or decrease Apparent volume of distribution of a drug?
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It will tend to reduce it.
|
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What is an intrincsic factor?
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A factor that effects the capacity of the eliminating organ to metabolize or excrete the drug
|
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What is an extrinsic factor?
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Affect presentation to drug to eliminating organ.
a) blood flow to the organ b) extent of distribution of the drug |
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Css or plasma steady state concentration = ?
|
D/CL
Dosage/ Clearance |
|
First order vs. zero order
Amount eliminated per unit time conc. independent or dependent? Fraction eliminated per unit time conc. independent or dependent? |
First order
Amount Dependent Fraction Independent Zero order Amount Independent Fraction Dependent |
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What is the half life of a drug in relation to the elimination constant?
T1/2 = ? |
T1/2 = 0.693/Kel
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How do you determine the plasma drug concentration prior to any elimination?
|
AVd = Dose/ Co
|
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Relate CL, AVd and Kel
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CL= AVd x Kel
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T1/2beta = ?
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T1/2beta = 0.693 AVd/ CL
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What is AUC? (area under the plasma concentration vs. time curve)
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AUC = Dose/CL
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Css = ?
Relate to 1.44 Dose (D) Bioavialbility (f) (T1/2 beta) AVd and Dose interval (i) |
Css= 1.44 *D *f *T1/2beta
--------------------------------- AVd *i |
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Dose (mg)/ Dose interval (hr) = ?
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Dose (mg)/ Dose interval (hr) = Css (mg/L) * Cl (L/hr) / f
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Loading dose = ?
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Loading dose = (Targe Css) (AVd)/ f
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What are the contraindications for syrup of ipecac?
|
Regurgitation will cause damage
Risk of aspiration Vomiting is dangerous for the patient |
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What are the complications of gastric lavage?
|
Aspiration pneumonitis
Laryngospasm Mechanical injury to throat Hypothermia Fluid electroyte imbalance |
|
What are the contraindications for gastric lavage?
|
Risk of pulmonary aspiration
Regurgitation could be harmful Process of gastric lavage may have adverse effects (GI performation) |
|
What sorts of things is single dose activate charcoal NOT useful for?
|
Li, Fe, Pb, methonal, ethanol, sorbitol
strong acids/bases |
|
What are the contraindications to charcoal use?
|
Petroleum
Corrosive agent Process (may cause GI perforation) |
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What are the complications of laxatives (sorbitol)?
|
Nausea, vomiting
Transient hypotension Dehydration Hyernatremia (Na) Hypermagnesemia (Mg salts) |
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What are the contraindications of sorbitol?
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Ingestion of corrosive agent
Lack of Gi motility damaged gi tract Hypotension or elecytrolyte imbalance |
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What is unique about whole bowel irrigation compared to the other methods?
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Entire GI tract is decontaminated
Solution is neither absorbed nor secreted. |
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What are the contraindications of Whole bowel irrigation?
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Pulmonary aspiration
Toxicity of agent can be increased due to regurgitation Process can have adverse effects |
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What is the most commonly used GI decontaminant?
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Activated charcoal
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How might what increase the excretion of a weak acid by altering urine pH? What sort of drugs is it used for?
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Alkanize the urine with NaHCO3
Used for Salicylic acid and phenobarbitol |
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Describe the pKa, partition coefficient, MW, and binding to plasma proteins of salicylic acid.
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MW = small
80% bound to plasma proteins weak acid Partition coefficient is very good |
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Describe the pKa, partition coefficient, MW, and binding to plasma proteins of phenobarbitol
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MW = small
50% bound weak acid Partiton coefficient very favorable |
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What drug to you give to promote acidification of the urine?
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NH4Cl
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When can hemodialysis be used?
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Drug has low MW
Drug is water soluble Large propriton of drug is in blood (not tissues) Drug has significant fraction not bound to plasma proteins Useful for alcohol, salicylates, Li |
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When can hemoperfusion be used?
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Drug has high MW
poor water solubility Most of drug bound to plasma proteins Drug has a high volume of distribution. |
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What signs are hallmark of reversible injury?
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Cell swelling
Fatty change |
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What signs are halmark of irreversible injury?
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Amorphous or flocculent densities.
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What is dystrophic calcification?
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A normal process of calcification in necrotic tissues
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What is metastatic calcificaiton
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calcification that occurs due to hyper calcemia
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What accumulates in cells as they age?
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lipfuscin pigment which is indicative of lipid peroxidationl
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What is anascara?
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Severe generalized edema
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What causes elephantiasis?
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Filariasis or inflammation and fibrosis obstructing lymph.
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What is hyperemia?
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Increased blood in a tissue
Blood is oxygenated. Active |
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What is congestion?
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Blue venous blood in a tissue due to long standing tissue damage. Passive.
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Put these in order of size
Ecchymoses Petichial hemmorage Purpura |
Petichial hemmorage
Purpura Ecchymoses |
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What is the primary genetic cause of hypercoagubility?
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Factor V leiden mutaiton which leads to resistance to Protein C
Prothrombin gene mutation (usually prevents thrombosis) Methyltetrahydrofolate gene mutation Leads to homocysteinemia. |
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Where do arterial thrombi usually propegate?
Where do venous thrombi usually propegate? What color are they? |
Arterial = heart or aorta (pale)
Venous = lower extrematies (red) |
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What causes cells to swell in ischemia?
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Decreased action of the Na pump
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What causes lipid deposition in ischemia?
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Detached ribosomes leading to decreased protein synthesi
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What causes clumping of nuclear chromatin?
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Increased glycolysis leading to decreased pH
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What type of necrosis is caused by ischemia?
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Coagulation necrosis
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What type of necrosis is associated with the brain?
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liquefactive necrosis
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What type of dye, dyes amyloid protiens?
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Congo red shows them as an apple green birefringence
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