Biopharm Exam 1

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Systemic Route is classified into two classes:
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Terms in this set (97)
Systemic Route is classified into two classes:
Enteral routes: drug is placed in the gastrointestinal tract (see figure on next page) where it is absorbed into the blood

Parenteral Routes: drug does not pass through the gastrointestinal tract.
Oral Route (Enteral):
drug is placed in the mouth and swallowed
Sublingual Route (Enteral):
the dosage form is placed under the tongue and it is taken without the use of water.
Buccal Route (Enteral):
dosage form is kept in the buccal cavity (i.e. between the cheek and the teeth or gum) where it disintegrates and the drug is absorbed through the cheek
Rectal Route (Enteral):
administered rectally as a suppository (cannot take a drug orally because they have nausea, cannot swallow, or have restrictions on eating, which is commonly required after many surgical operations)
First-pass effect:
the hepatic metabolism of a pharmacological agent when it is absorbed from the gastrointestinal tract and carried to the liver via the portal circulation (drug taken orally, liver metabolizes drug first so bioavailbility decreases)
Rectal Route:
only avoids 2/3 of bypass effect; portal vein goes to vein

2/3 systemic (avoids liver)

1/3 hepatic (through liver)
Intravenous (IV) (Parenteral):
the drug is directly taken into the blood with the help of injection; absorption phase is bypassed; 100% bioavailability
Intramuscular (IM) (Parenteral):
the drug is given into the muscles with the help of injection; vaccines are often administered this way
Image: Intramuscular (IM) (Parenteral):
Subcutaneous (SQ or SC) (Parenteral):
the drug is given into the subcutaneous layer under the skin with the help of injection; Some vaccines such as Measles, mumps, and rubella (MMR) and Live Zoster (ZVL) are given by subcutaneous injection.
Local or Topical Routethe dosage form is applied on the skin and/or mucous membrane for local actionIn acute or emergency situation, the route used must allow sufficiently fast absorption to ensure a prompt onset of action:he parenteral injection (intravenous, intramuscular or subcutaneous) is often the route of choicePlasma Concentration Time Curve Oralgraph depicts the typical concentration vs. time plot for a fast and slow release oral dosage formsWhich of the following routes administration are best suited for acute care (especially in an emergency situation? oral transmucousal intravenous buccalIntravenous (IV)Which of the following routes of administration is best suited for the treatment of chronic illness (considering patent convenience and complication of administration)? Rectal Oral Intramuscular (IM) IntravenousOralThe following routes of administration bypass the first-pass effect, EXCEPT: Inhalation Sublingual Oral TransdermalOralWhen the same amount of a drug is administered by each of the following routes, which one has the highest initial plasma drug concentration on the plasma drug concentration-time curve? Oral Intravenous Intramuscular TransdermalIntravenous (IV)The bioavailability of a drug given by the intravenous route of administration is considered to be: 150% 0% 50% 100%100%The site of drug absorption for sublingual and buccal routes of administration is in the _______________. Intestines Mouth Stomach MuscleMouthA patient comes into your pharmacy with concerns that his doctor prescribed him a "steroid", a 1% hydrocortisone cream, for his eczema. He has heard that steroids can have serious systemic side effects and wants to know if he should change to something else. Which of the following is the best response? A."This is a low dose corticosteroid. You shouldn't experience any side effects." B."This is a topical form and it can't be absorbed into your body well to cause systemic side effects, although there could be local ones." C."You're right. I will call your doctor to ask him if you can switch to an oral corticosteroid to avoid systemic side effects." D."All forms of corticosteroids have equally serious systemic side effects. You might want to consider a different class of medication."B."This is a topical form and it can't be absorbed into your body well to cause systemic side effects, although there could be local ones."T/F Patient consultation is needed for more complicated dosage forms.TrueT/F Corticosteroids are commonly used for their anti-inflammatory properties.TrueRoute: Intravenous injectionPotential Use: kidney rejection Advantages: fast action Disadvantages: inconvenientRoute: OralPotential Use: Rheumatoid Arthritis Advantages: convientent Disadvantages: systemic side effectRoute: InhalationPotential Use: asthma, allergies Advantages: systemic pharmacological effect Disadvantages: difficult to useRoute: TopicalPotential Use: Eczema, dermatitis, poison ivy, insect bites Advantages: avoiding systemic side effects Disadvantages: local pharmacological effect onlyIn which phase of clinical trials are healthy volunteers usually needed? Phase 1 Phase 2 Pre-clinical phase Phase 3Phase 1Which of the following is true regarding the investigational new drug (IND) application and the new drug application (NDA)? A. NDAs are filed immediately after phase 2 clinical trials B. IND applications are filed after NDAs C. NDAs include data from both pre-clinical and clinical studies D. IND applications are always filed after pre-clinical and phase 1 trials are completeC. NDAs include data from both pre-clinical and clinical studiesThis phase of clinical trials examines the effectiveness of a compound, and typically involves 100 to 300 patients who suffer from the condition the new drug is intended to treat. Phase 2 Phase 1 Pre-clinical phase Phase 3Phase 2Phase ______ clinical trials usually involve thousands of patients across multiple sites. These studies are used to demonstrate the safety and efficacy of a new drug in a large population. 1 Pre-clinical phase 3 23The main purpose of the pre-clinical phase of drug development is to: Assess safety and biological activity Determine safety and dosage Verify effectiveness and monitor long-term use Evaluate effectiveness and side effectsAssess safety and biological activityBefore a new drug is approved, a pharmaceutical company "must submit clinical data and other information to the FDA for review. The company must show that the drug is safe and effective for it's intended used." What does "safe" mean here? A. the drug does not have any side effects B. Scientists and clinicians did to observe any side-effects at the doses and dosing scheduled tested in humans C. Clinical study data showed that the drug causes side effects. However, the FDA has determined that the benefits of using the drug for a particular indication outweigh the potential risks.C. Clinical study data showed that the drug causes side effects. However, the FDA has determined that the benefits of using the drug for a particular indication outweigh the potential risks.The ivermectin clinical trial mentioned above is most likely a _______? Phase 1 Phase 2 Phase 3 Phase 4Phase 2Phase 1focus on safety, frequently using a single-blind study design; designed to determine drug dosing, identify the most frequent side effects of a drug, measure the kinetic activity(metabolism and excretion) of a drug, and, most importantly, minimize risk to human; 20-80 healthy volunteers; last about 2 yearsPhase 2studies emphasize efficacy, continue to monitor safety, and seek preliminary data (eg, effective doses) based on a specific disease within an identified population; identify short-term, common side effects; 100-300 patients; last 2 yearsPre-clinical phasepreclinical laboratory testing (including ani-mal studies) assesses the biological activity and safety of a new drug and, on average,takes 5.5 years to completePhase 3studies are used to confirm the efficacy and validate the safety findings of previous studies in a larger population, using randomized clinical trials; studies evaluate diverse populations, drug dosages, and the use of the drug in combination with other pharmaceuticals; 100-3,000 patients, about 2-4 yearsThe process by which a chemical or drug becomes dissolved in a solvent is termed __________. Disintegration Absorption Partition DissolutionDissolutionThe ____________ consists of a specially coated paddle that minimizes turbulence due to stirring. Rotating basket dissolution method Dissolution Apparatus 1 Beaker dissolution method Dissolution Apparatus 2Dissolution Apparatus 2Which of the following is/are considered in drug product design? Compliance and acceptability of the drug product Pharmacokinetics of the drug Desired drug dosage form All other answers are correct. Bioavailability of the drugAll other answers are correct.Which of the following refers to the rate and extent by which a drug reaches the systemic circulation? Pharmacodynamics Drug transport Pharmacokinetics BioavailabilityBioavailabilityThe process of systemic absorption of drug in oral tablets (e.g. immediate release tablets) generally follows which order? Disintegration --> Dissolution --> Absorption Dissolution --> Disintegration --> Absorption Absorption --> Disintegration --> Dissolution Absorption --> Dissolution --> DisintegrationDisintegration --> Dissolution --> AbsorptionWhich of the following dosage forms most likely does notrequire disintegration testing? Sublingual tablets Sustained release oral tablets Immediate release oral tablets Buccal tabletsSustained release oral tabletsT/F A disintegration test presents a precise measurement of the rate of dissolution (or release) of the active drug from an oral dosage form.TrueFor orally administered solid drug products, especially immediate-release products, the test that measures drug dissolving in the test medium is referred to as a dissolution test. For non-oral dosage forms, such as topical and transdermal delivery systems, the test is preferably referred to as a __________. Drug release test Drug solubility test Drug absorption test Drug disintegration testDrug release testWhen testing the dissolution rate, it is important to note that the _____ is very sensitive to tilting. Improper alignment may drastically affect the dissolution results with some drug products. Rotating basket method Paddle methodPaddle methodRolling Basket Methoda cylindrical basket held by a motor basket shaftDissolution process (2 steps):1. Drug dissolves at the surface of particles to form a layer of saturated solution (AKA, stagnant layer) 2. Drug diffuse from the stagnant layer to the bulk the solventdM/dt=DA/h (Cs-C) M= ?mass of dissolved materialdM/dt=DA/h (Cs-C) t=?timedM/dt=DA/h (Cs-C) D=?diffusion of coefficient (cm^2/s)dM/dt=DA/h (Cs-C) A=?surface area of particlesdM/dt=DA/h (Cs-C) Cs=?concentration of drug in the stagnant layer (saturated)dM/dt=DA/h (Cs-C) C=?concentration of drug in the bulk solventdM/dt=DA/h (Cs-C) h=?thickness of the stagnant layerThe pH of the duodenal contents is closest to __________. 10 1 8 55The correct sequence of processes involved in the passive diffusion of drugs from the gastrointestinal tract to the blood circulation is _________.partition from aqueous phase to lipid phase, diffusion across the lipid membrane, partition from lipid phase to aqueous phaseHexylsalicylate can pair with quinine, an antimalarial drug, to enhance the oral absorption of quinine. Which of the following most likely explains the enhancement in absorption? Active Transport Ion pair formation and then the absorption of the pair Solvent DragIon pair formation and then the absorption of the pairThe pH partition theory assumes the gastrointestinal tract as a barrier preferentially allows the passive diffusion of the______________ forms of weak acids or weak bases. The gastrointestinal tract as a barrier equally allows the passage of ionized form and unionized form of weak acids and weak bases.. Ionized form Unionized formUnionized formBiotransport isthe translocation of a solute from one side of a biologic barrier to another with the transferred solute appearing in the same form on both sides of the biologic barrier.Semipermeableallowing certain chemicals to pass freelyTransport Mechanismsmechanisms underlying the transfer of chemicals across biologic barriersIntegral or intrinsic proteinstightly bound to membranes by hydrophobic forcesFacilitated diffusiona carrier-mediated transport system, differing from active transport in that the drug moves along a concentration gradient ( doesn't require energyVesicular transportthe process of engulfing particles or dissolved materials by cellsEndocytosis and exocytosisthe process of moving macromolecules into and out of a cellPinocytosis or phagocytosis,the cell membranesurroundsthe material, and then engulfs the material into the cellsActive Transporta carrier-mediated transmembrane process that plays an important role in drug absorption from the GI tract (requires transport)pH partition theorydrug is absorbed from the GI tract by passive diffusion of the unionized, lipid-soluble drug molecules across a lipid membrane.Passive Diffusionthe process by which molecules spontaneously diffuse from a region of higher concentration to a region of lower concentration (no external energy is used)dM/dt=P(S)(Ctd) dM/dt=?rate of diffusion across a biological membranedM/dt=P(S)(Ctd) Ctd=?total drug concentration in donor sidedM/dt=P(S)(Ctd) P=?permeability coefficientdM/dt=P(S)(Ctd) S=?exposed surface area for diffusionP= (D)(K)/h D=?diffusion coefficientP= (D)(K)/h h=?membrane thicknessP= (D)(K)/h K=?intrinsic partition coefficientWhat can possibly affect the rate of passive diffusion of a drug across a biological membrane?dM/dt=(D)(K)(S)(Ctd)/hBrodie's D weak acidD= (1+10^(pH1-pKa)) / (1+10^(pH2-pKa))Brodie's D weak baseD= (1+10^(pKa1-pH1)) / (1+10^(pKa-pH2))Membrane transport of a substrate, S1, that is energetically driven by the transport of another substrate, S2, is called ___________________. Passive diffusion Secondary active transport Primary active transport Facilitated diffusionSecondary active transportWhich of the following is not a member of the SLC superfamily of transporters? PepT1 MCT1 BCRP OATP1A2BCRPAll of the following are characteristics of a channel except: Acting as pores in the open state Having two primary states, open and closed Forming an intermediate complex with the substrate Returning to the closed state as a function of time after openingForming an intermediate complex with the substrateMembrane transport that directly couples with ATP hydrolysis is called ____________. Passive diffusion Facilitated diffusion Secondary active transport Primary active transportPrimary active transportConcerning membrane transporter inhibition, ____________ inhibition assumes that the inhibitor has an allosteric effect on the transporter and does not inhibit the formation of an intermediate complex of substrate and transporter, but does inhibit the subsequent translocation. Noncompetitive Competitive UncompetitiveNoncompetitiveWhich of the following are most likely the substrates of PepT1 transporter? Peptidomimetics L-amino acids Weak organic acids with the carboxyl group attached to a relatively small R groupPeptidomimeticsWhich of the following are most likely the substrates of MCT1 transporter? L-amino acids Peptidomimetics Weak organic acids with the carboxyl group attached to a relatively small R groupWeak organic acids with the carboxyl group attached to a relatively small R groupWhich of the following are most likely the substrates of LAT1/2 transporters? Peptidomimetics Weak organic acids with the carboxyl group attached to a relatively small R group L-amino acidsL-amino acidsTwo major superfamiliesATP binding cassette (ABC) and solute carrier (SLC) transportersPepT1 (SLC15A1) is alow-affinity, high-capacity transporter and is known to play a pivotal role in the absorption and distribution of peptidomimetics; H+ dependent transporterOrganicAnion-Transporting Polypeptides (OATPs):mediate the proton-dependent transport of a wide range of amphipathic endogenous and exogenous organic compounds across the plasma membrane; plays a key role in the uptake of various xenobiotics(e.g. drug molecules)Monocarboxylate transporter 1 (MCT1)movement of monocarboxylic acids across the plasma membrane is facilitatedby a family of proton-linked MCTs; ighly expressed in the small and large intestine, where it is responsible for the absorption of short chain fatty acids; low affinity, high capacity transporter that has been shown to transport unbranched aliphatic monocarboxylatesP-glycoprotein (P-gp)localized in a wide range of tissues, including the columnar epithelial cells of the lower gastrointestinal tract, capillary endothelial cells of brain and testis; speculated to play a majorphysiological role in the absorption, distribution and excretion of xenobiotics andendogenous substrates; prevents or reduces (i) drug absorption from the GI tract (to the blood circulation) or (ii) the transport of drugs from the blood circulation to brain tissuesBreast Cancer Resistance Protein (BCRP)highly expressed on the apical membrane of enterocytes and can efflux substrates back into the lumen, it has been noted to play an important role as a detoxification efflux transporter and in limiting drug absorption in the gastrointestinal tract; substrates of BCRP can be either negatively or positively charged, hydrophobic or hydrophilic, and unconjugated or conjugated; substrates are molecularly similar to substrates of P-gp and other efflux pumpsSt. John's wortcommon anti-depression herbal supplement; strongly affects P-glycoprotein (P-gp), as well as having many other effects on drug metabolismIn order to effectively treat schizophrenia and bipolar disorder, risperidone must cross the blood-brain barrier in sufficient concentrations to reach the appropriate receptors in the brain.Which of the answer choices below correctly describes the movement of risperidone when bound by P-gp? A. Brain --> Plasma, plasma -->Gut B. Gut -->Brain, brain -->Plasma C. Brain -->Gut, gut -->Plasma D. Gut -->Plasma, plasma -->BrainA. Brain --> Plasma, plasma -->GutBlood Ph is: 5.4 6.4 7.4 8.47.4