Presentation on theme: "Pharmacologic Principles Chapter 2"— Presentation transcript:
1Pharmacologic Principles Chapter 2 Cristen Walker, MS, CRNPLevel I
2Pharmacology DRUG PHARMACOLOGY Any chemical that affects the physiologic processes of a living organismPHARMACOLOGYStudy (science) of drugsIncludes:AbsorptionDistributionMetabolismExcretionMechanism of ActionTherapeutic effectsToxic effectsMetabolism of drug = biochemical modification
3Pharmacology Subspecialty Areas of Pharmacology Pharmaceutics PharmacokineticsPharmacodynamicsPharmacotherapeuticsPharmacognosyToxicologyNURSES MUST UNDERSTAND BASIC PRINCIPLES OF PHARMACOLOGYTherapeutic and Toxic
4Pharmacology – Drug development Drugs will acquire 3 namesCHEMICAL (N-4 hydroxyphenyl acetamide)Drugs chemical composition, molecular structureGENERIC (acetaminophen)Shorter than chemical nameUsed as official listing of drugsTRADE (Tylenol)Registered trademark, “brand” nameName is restricted to “owner” (company, ie, Merck)**Patent lasts 17 years- 10 years for research and development- 7 years of marketability
6Pharmaceutics Process of turning chemicals into safe medications Science of dosage form & designie – tablet, capule, liquid, powder, etc.Study of how various dosage forms/designs influence a drugs metabolism and use in the body
7Pharmaceutics Drug routes Oral Enteral Rectal Parenteral Topical Via mouthIncludes sublingual, buccalEnteralVia intestineVia NG tube, feeding tube (or rectal)RectalParenteralIntramuscular, Subcutaneous, Intravenous,TopicalDirectly applied to skinMucosal
8Pharmaceutics **Forms/designs of drugs: Oral Enteral Rectal Parenteral Tablets, capsules, powder, liquid, elixir, suspensionEC, ER, SREnteralMeds given via NG or feeding tube (solid or liquid)Crushed meds – must be dissolvedRectalSuppositories, creams, enemaAlso considered as ENTERAL routeParenteralInjections (solutions, powder)
10Pharmaceutics Drug Dissolution & Absorption Oral Preparations **Drugs must dissolve 1st (before absorbed)Oral PreparationsLiquids, elixirs, syrups Fastest Suspension solutions ê Powders ê Capsules ê Tablets ê Enteric coated tablets ê Extended release tablets Slowest*Extended Release (forms) = SR (slow release), CR (controlled release), XL (extended length)Pharmaceutics
11Pharmaceutics Drug Dissolution & Absorption Parenteral Preparations Do NOT have to dissolve 1stSubcutaneous, IntramuscularIntravenous*directly into bloodstream*immediate absorption
12PharmacokineticsStudy of what happens to a drug from entrance into body until it leaves the body4 phasesAbsorptionDistributionMetabolismExcretion4 phases
13Pharmacokinetics - absorption Occurs after dissolution of drugDrug → GI tract → blood/body fluids → tissueAffected by form of drugAffected by ROUTE of administration (oral, parenteral,etc.)Movement of drug from its site of administration into bloodstream for distribution to tissuesExtent of drug absorption = BIOAVAILABILITY
14Pharmacokinetics—Absorption Factors That Affect AbsorptionAdministration routeDosage formulationFood or fluids administered with the drugGrapefruit, fruit juices, antacids, fat soluble vitaminsRate of blood flow to the small intestineAcidity of the stomachStatus of GI motilityEmpty stomach vs. “take with food” ie: Lasix ½ hr. before meals **certain meds can also decrease nut. Absorp.GrapefruitAntacids ie: 1 hour before or after meds, may bindFat soluble vitamins – take with food, fat
15Pharmacokinetics - Absorption BioavailabilityExtent of drug absorptionAmount of drug actually available to circulationDepends upon “first pass effect”First pass reduces bioavailabilityDrugs must enter hepatic portal system, metabolized by liver, this reduces bioavailability of the drug
16Pharmacokinetics - absorption First Pass effectDrugs must dissolve & be absorbed by GI tractMust pass through LIVER before reaching circulation (bloodstream)Drug GI system Portal vein LiverHepatic vein Heart (distribution)Liver may metabolize drug into smaller metabolitesTherefore, less amount of drug will pass into circulationIntravenous drugs = no “first pass” in liver
17Pharmacokinetics—Absorption Oral/Enteral RouteDrug is absorbed into the systemic circulation through the oral or gastric mucosa, the small intestine, or rectumOral – high “first pass” effectSublingual – dissolve under tongue, highly vascular area, these drugs bypass liver, no “first pass” effectBuccal – same as sublingualRectal (suppository or topical) – rectal drugs have SOME “first pass” effect
19Pharmacokinetics — Absorption Routes that bypass the liver:Sublingual TransdermalBuccal VaginalRectal* IntramuscularIntravenous SubcutaneousIntranasal Inhalation*Rectal drugs may have some degree of first-pass effect
20Pharmacokinetics—Absorption Parenteral Route*No “first pass” effectIntravenous*IntramuscularSubcutaneousIntradermalIntraarticular (physician)*Fastest delivery into the blood circulationIntrathecal – within the spinal canalIM absorbed faster due to increased blood supply (when compared to SQ)Specially formulated IM’s: depo – 3 mos, methylprednisolone to joint/knee - weeks
21Pharmacokinetics—Absorption Topical/Mucosal RouteSkinIncludes transdermal route, patchesEyesEarsNoseVaginaTopicals = slower onset, longer durationNo “first pass” effect, bypass liverException = rectalTopicals: slower onset, delivers more uniform amt. of drugMay have less chance for toxicityTransdermals: nicotine patch, fentanyl patch, NTG, estrogen, clonidine
22Pharmacokinetics —Distribution Transport of drug by bloodstream to site of actionAreas of “rapid” distributionHeartLiverKidneysBrainAreas of “slower” distributionMuscleSkinFatAreas “difficult” to reachBoneBlood brain barrier **Distribution aka: The transport of a drug in the body by the bloodstream to its site of action.Protein-bindingWater soluble vs. fat solubleBlood-brain barrier (BBB)– does not allow passage of certain drugs – most drug books will have a notation citing a drugs affect on the BBB – NEXT SLIDEAreas of rapid distribution: heart, liver, kidneys, brainAreas of slow distribution: muscle, skin, fatA drug may be sub therapeutic or toxic. Many times blood levels are drawn to ensure adequate drug or not too much given.
23Pharmacokinetics - distribution BLOOD BRAIN BARRIERRestricts passage of various chemicals between the bloodstream and the central nervous systemCNS = brain, spinal cordBBBallows oxygen to passmay restrict certain bacteria & virusesNot all meds can pass through
24Pharmacokinetics - distribution Distribution depends upon protein-bindingAlbumin = most common blood protein, carries protein-bound drug molecules“bound” portion of drug = pharmacologically inactive“unbound” portion = pharmacologically activeEasily distribute to body tissues (outside of bloodvessels) and reach site of actionLasix, Coumadin, AspirinLasix, digoxin, dilatin, coumadin, asa - highly protein bound
25Pharmacokinetics —Metabolism aka “Biotransformation”Process by which a drug is biochemically alteredinactive metabolite (compound)more potent, active metaboliteLess potent, active metaboliteLIVER – most responsible for metabolism of drugsAlso involved = kidneys, lungs, skeletal muscle, intestines
26Pharmacokinetics — Metabolism Factors that decrease metabolism:Cardiovascular dysfunctionKidney failureLiver failureGeneticsStarvationFactors that increase metabolism:Certain drugs (dilantin, barbiturates, rifampin)
27Pharmacokinetics —Metabolism Delayed drug metabolism results in:Accumulation of drugs (toxicity)Prolonged action of the effects of drugs
28Pharmacokinetics — Excretion Elimination of drugs from the bodyAll drugs must eventually be excretedKidney = organ most responsible for excretion of drugs (urine)Also, liver (bile), bowel (feces), sweat glandsLiver metabolizes most drugs, kidney excretes what is “left behind”Kidneys can also metabolize certain drugsinsulinPts with kidney dx, children (have immature kidney function), elderly may require dosage reduction and kidney function tests more frequentlyDrug metabolized by KIDNEY = INSULIN
29Pharmacokinetics — Half-Life Time required to eliminate (½) 50% of a drugExample:Digoxin hr. half-lifeTakes 7.5 days to clearTakes 5–6 half-lives to eliminate ~ 98% of a drugLiver or kidney diseaseCan prolong half-lifeIncreases risk of toxicityDrugs with a shorter half-life need to be administered more frequently to maintain blood levels. Example: digoxin has a long half-life = 36 hours and only requires once daily dosing. ASA has a shorter half-life and is given more frequently.EXAMPLE:To clear a drug completely:Digoxin = 36 hoursIn 36 hours half drug cleared but will take 4 to 5 more 36 hours periods to clear 98% of drug36 x 5 = 180 hours or 7 ½ days to clear 98% of digoxin
30Pharmacokinetics – Onset—Peak—Duration The time it takes for the drug to elicit a therapeutic responseInsulin: minPeakThe time it takes for a drug to reach its maximum therapeutic response30-60 minDurationThe time a drug concentration is sufficient to elicit a therapeutic response2-4 hoursInsulin: Onset minutesPeak minutesDuration 2-4 hours
31PHARMACOKINETICS – ONSET-PEAK-DURATION Peak effect, maximum therapeutic responseHighest blood level of the drugIf too high = toxicity of drugTroughLowest blood level of the drugIf too low, then may not be therapeuticPeak, Trough - Vancomycin
33Pharmacokinetics: Example Furosemide (LASIX)Pharmaceutics: Tablet, Oral solution, InjectionPharmacokinetics:Absorption: Bioavailability = 64% tablet, 60% oral soln, 100% IVTablet, oral soln – 60 min. delay if taken w/ foodDistribution: highly protein bound to albumin, 91-99%Metabolism: metabolized in liverElimination: excreted by kidneysOnset: hr. (oral) minutes (IV) *storePeak: hr. (oral) ½ hr. (IV) roomDuration: 6-8 hrs. (oral) 2 hrs. (IV) temp
34Pharmacodynamics Mechanism of drug action - how drugs act at sites of activityInvolves receptors and enzymesNot all drugs have a known mechanism of actionMost drugs produce more than one effectTherapeutic effect – desired or primary effectSecondary effect – may be desirable or not1. Drug-receptor interaction: drug binds to a receptorsite on cell surface, causes or blocks an action2. Enzyme interaction: drug binds to enzyme molecule &either enhances or inhibits its action3. Nonselective interactions: do not bind to enzyme orreceptor, act on cell membrane or cell wallWellbutrin – antidepressant, smoking Neurontin – sz and neuropathy, post-herpetic Glucophage – diabetes and PCODDrug-receptor = PPI (prilosec) – blocks Beta blockersEnzyme interactionNonselective = abx, change cell membrane/wall
35Pharmacodynamics Drug-Receptor Interaction Drug binds to specific receptorAlters cell functionProduces desired effectCan bind completely or partiallyAgonistsDrugs that bind and produce desired effectexample, MorphineAntagonistDrugs that block agonist effect at binding siteexample, Narcan, reverses effect of narcoticExample, Toprol, beta-blocker, lowers HR**MSO4 – binds to opiod receptors, decrease pain = AgonistMost drugs alter cellular function. A drug usually does not completely change the function of the cell but alters part of the function. It can increase or decrease a physiologic function – ie, increase HR, decrease BP or increase urine outputDrugs that bind completely will have a better effect.An antagonist will bind more tightly than the agonist – NARCAN – is a narcotic antagonist and blocks the effects of morphine-like drugs
36Pharmacodynamics Enzyme Interaction Drug interacts with enzyme system Inhibits the action of the enzymeThe action of the cell is changed or alteredExample: ACE inhibitor (Lisinopril)Inhibits conversion of angiotensin I to angiotensin IIEnzymes are substances that catalyze nearly every biochemical reaction in a cell.Inhibits the action of the enzymeBy “fooling” the enzyme into binding to the drug instead of its normal target cell.The target cell will not have the intended actionIe, ACE causes a enzymatic reaction that results in the production of angiotensin II, a potent vasoconstrictor. The drugs ACE inhibitors fools the ACE into binding to it rather than angiotensin I, preventing formation of angiotensin II. This results in vasodilatation and helps decrease BP
38Pharmacotherapeutics The treatment of pathologic conditions through the use of drugs“drug therapy”Desired therapeutic outcomeShould be established before drug startedWhat is expected ?Must be measurable and realisticProgress must be monitored (example = antibiotics)Examples of outcomesCuring diseaseEliminating or reducing a existing symptomArresting or slowing a disease processPreventing a disease or other unwanted conditionImproving the quality of lifePatient therapy assessment should be done prior to drug administrationCurrent meds pt is on (OTC), prescription or illicitPregnancy and breast-feeding statusCo-morbiditiesContraindication to specific drug use
39Pharmacotherapeutics Types of therapyAcuteMaintenanceSupplementalPalliativeSupportiveProphylacticEmpiric
40Pharmacotherapeutics Acute therapyInvolves more intensive drug therapyUsed in the acutely or critically illExample: to maintain heart rate or BPUsually needed to maintain lifeie – dopamine (vasopressor to maintain BP)Maintenance therapyMay not cure but prevents progression of diseaseMay prevent progressionUsed in chronic illnesses (example: hypertension, diabetes)ie – lisinopril, oral contraceptivesExamples of acute;Vasopressors to maintain BPVolume expanders in shockAntibiotics in high risk trauma patientsMaintenanceMay include birth control
41Pharmacotherapeutics Supplemental therapyReplaces body substances needed to maintain normal functioningMay not be produced by the bodyProduced in insufficient amountsExample: InsulinPalliative therapyGoal is to provide comfortUsed in end stage illnessesUsually all other therapy has failedExample: Morphine for painExamples of supplementalInsulin in diabetesIron in iron-deficient patientsExamples of palliativeHigh dose opioid analgesics for cancerOxygen for end stage COPDers
42Pharmacotherapeutics Supportive therapyMaintains integrity of body functions while patient recovering from illnessExamplesProviding fluids/electrolytes to prevent dehydrationIn vomiting or diarrheaBlood products or blood volume expandersBlood loss during surgery
43Pharmacotherapeutics Prophylactic therapyUsed to prevent illnessExample: pre-op antibiotics, vaccinesEmpiric therapyUse of a drug based on probability, certain illness/disease has likelihood of occurrenceExample: Antibiotic for UTI before actual diagnosisProphylactic therapy – exampleA surgeon knows, based on experience that when he makes an incision that there is a possibility of infection – thus he will give prophylactic antibiotics. Also used by dentists with patients that have valvular problems.
44Adverse Effects - Monitoring Adverse effects – unintended effectsSide EffectsTherapeutic index – ratio of toxic level to therapeutic levelLow therapeutic index: difference between toxic and therapeutic dose is low – dangerous !Example: coumadin (anticoagulant)Tolerance – Pts. decreasing response to repeated dosesie – valium, pain medsDependence – Physiologic or psychologic need for drugaddictionMust be familiar with both therapeutic action and side effects to be able to adequately monitor a drugAll drugs potentially toxic and could have cumulative effectsAdverse drug reactions (side effects)Undesirable drug effectsMay be common or rateMild, severe or life threateningMay occur with 1st dose or even many dosesOften unpredictable
45Adverse Effects – Monitoring Patient’s condition - PhysiologicalAgeInfants & children need ↓ doseImmature organ functionElderly may require ↓ doseDecreased gastric acidityDry mouth/decreased salivaDecreased liver blood flow/massIncreased body fat, decreased muscle massDecreased kidney functionDecreased gastric acidity = possible decreased or delayed absorptionDry mouth/decreased saliva = difficulty swallowing oral drugsDecreased liver blood flow/mass = delayed or decreased metabolism of certain drugsDecreased skin lipid content = possible decrease of absorption of transdermal medsIncreased body fat, decrease body water = possible increase in toxicity of water-soluble drugs, more prolonged effects of fat-soluble drugsDecreased serum proteins = possible increased effect and toxicity of highly protein bound drugsDecreased kidney function= possible increased serum levelsChanges in sensitivity to certain drug receptors -= increase or decrease in drug effectPolypharmacy is the taking of numerous drugs that can potentially react with one another. When practiced by the elderly, polypharmacy leads to an increase in the number of potential adverse reactions. Although multiple drug therapy is necessary to treat certain disease states, it always increases the possibility of adverse reactions. The nurse needs good assessment skills to detect any problems when monitoring the geriatric patient’s response to drug therapy.
46Adverse Effects – Monitoring Patient’s condition - PhysiologicalWeightAverage = 150lbDosage adjustmentsLarge weight differencesGenderWomenSmallerDifferent fat/water ratioMay need dosage adjustmentsWeightIn general, dosages are based on a weight of approximately 150 lb, which is calculated to be the “average”weight of men and women. A drug dose may sometimes be increased or decreased because the patient’s weight is significantly higher or lower than this average. With narcotics, for example, higher or lower than averagedosages may be necessary to produce relief of pain, depending on the patient’s weightGender:The gender of an individual may influence the action of some drugs. Women may require a smaller dose of somedrugs than men. This is because many women are smaller than men and have a body fat-and-water ratiodifferent from that of men.
47Adverse Effects – Monitoring Patient’s condition - PathologicalLiver/kidney diseaseInability to metabolize/excrete one normal dose before next drug givenLeads to drug toxicityLower doses are frequently givenLiver diseaseKidney diseaseAbove description is know as Cumulative Drug EffectDiseaseThe presence of disease may influence the action of some drugs. Sometimes disease is an indication for not prescribing a drug or for reducing the dose of a certain drug. Both hepatic (liver) and renal (kidney) diseasecan greatly affect drug response. The primary health care provider may then decide to prescribe a lower doseand lengthen the time between doses because liver function is abnormal. Patients with kidney disease may exhibit drug toxicity and a longer duration of drug action. The dosage of drugs may be reduced to prevent the accumulation of toxic levels in the blood or further injury to the kidney.
48Adverse Effects Allergic Reactions (hypersensitivity) Usually begins after 2nd dose or moreMay occur within minutes or delay for hours or even daysImmune system views “drug” as foreign substanceHistamine is releasedS/S = skin rashes, hives, itching (urticaria or pruritis), facial swelling, difficulty breathing, sudden LOC, throat swelling (angioedema), wheezingAnaphylactic ShockSevere allergic rx, severe respiratory distress, life threateningAngioedema can be dangerous if occurs in area of airway – which usually does. Eyelids, lips, mouth and throat are most commonly affected.Your outline mentions immunological effects when talking about monitoring against toxic effects in relation to the patient's condition. I assume they are referring to the formation of antibodies in response to a certain drug, thereby sensitizing lymphocytes to produce antibodies when exposed to the drug again. This is referred to as an allergic reaction.
49Mr. Carter has a rash and pruritis Mr. Carter has a rash and pruritis. You suspect an allergic reaction and immediately assess him for other more serious symptoms. What question would be most imortant to ask Mr. Carter ?
50Adverse EffectsIdiosyncratic reaction: unexpected reaction in a particular patient, not common reactionPharmacogenetics: study of genetic traits that result in abnormal metabolism of drugsie: coumadin, codeine, psych drugs (chap. 5)Teratogenic effects: result in structural defects of in fetusFDA – 5 categories (A,B,C,D,X) of teratogensCategory A – studies show NO risk (multivitamin)Category X – Completely contraindicated in pregnancy, HIGH fetal riskIdiosyncratic reaction – ie – sulfonamides – epidermal necrolysis (severe burn)
51TeratogensCategory ANo risk to fetus in first, second or third trimestersCategory BStudies have not shown fetal risk in animals, but no controlled studies in pregnant womenConsidered safe in all trimesters (benadryl,tylenol,PCN)Category CAnimal studies have revealed adverse effects on fetusDrugs should be given only if benefit outweighs riskCategory DPositive evidence of harm to fetusUse may be acceptable absolutely necessary (life threatening situations)Category XStudies have shown fetal abnormalities, drug is completely contraindicated (acutane)
52Pharmacognosy The study of natural drug sources PlantsAnimalsFour main sources of drugsSource of many hormone drugs (premarin – urine of pregnant mares; insulin – pigs & humans; heparin – pigs)Minerals (salicylic acid, sodium chloride)Laboratory synthesisThe source of all early drugs was nature.Many new drugs are synthetically derivedThe principles of pharmacognosy have enabled isolation of the naturally occurring hormone insulin, determination of its exact genetic sequence, and synthesization of that exact sequence over and over again. This has enabled the production of synthetic human insulinFour main sources of drugsPlantsFoxglove is an example – used to make cardiac glycosides – digoxinAlso provide alkaloids – atropine, caffeine, nicotineAnimalsHormone therapiesEstrogen – urine of pregnant horsesInsulin – beef, pork or humanHuman is either semi synthetic – converting pork to human by changing one amino acid – or is made by recombinant DNA techniquesHeparing – derived from cows (bovine) or pigs (porcine)MineralsSalicylic acid, aluminum hydroxide, sodium chlorideLaboratory synthesisRecombinant DNA techniques (segments of DNA from one organism artificially manipulated or inserted into DNA of another organism using gene splicing.Erythropoietin (Epogen and Procrit)Granulocyte-macrophage-colony stimulating factor (sargramostim)Granulocyte-colony stimulating factor (filgrastim)Human insulin (Humulin and Novulin)
53Drug Classifications Place drugs in similar categories Similar general useSimilar mechanisms of actionsSimilar contraindicationsSimilar precautionsSimilar nursing implicationsIf the student is familiar with the drug classificationWill be familiar with every drug in that classExampleAntihistamines – 1st generationIf the student knows all the above about benadrylLooks up another drug classified as a 1st generation antihistamine – will know that drug as well
54Drug Classifications Examples: Antibiotics Antihypertensives AntiepilepticsSedativesAnestheticsDecongestantsAntineoplasticsEtc.AntidiarrhealsFor control and symptomatic relief of acute and chronic nonspecific diarrheaAntiepileptics (anticonvulsants)Used to decrease the incidence and severity of seizures due to various etiologies.SedativesUsed to provide sedation, usually prior to proceduresAnestheticsProvide anesthesiaDecongestantsUsed to decrease nasal and sinus stuffinessAntineoplasticsUsed to treat cancer
55Drug References Physicians Desk Reference (PDR) U.S. Pharmacopia National FormularyVarious Nursing Drug Handbooks/ReferencesDavis Drug GuideDrug resources maintain currency of the nurse’s knowledge:PDR –drug reference utilized by physicians and other medical personalAnnually publishedDetailed info – prescribing issues6.2 United States Pharmacopeia/ National Formulary – From the US Food & Drug Administration WebsiteTHE UNITED STATES PHARMACOPEIA/NATIONAL FORMULARYEdited and Published by, and Available from: United States Pharmacopeial Convention, Inc., Twinbrook Parkway, Rockville, MD 20852The USP/NF enjoys official status through recognition by statute [Food Drug,Formulary Cosmetic Act (FD&C Act), 201(g)(1), 201(j), and 501(b)]. The methods and tests described in this compendium are accepted as official methods, and any drug or preparation bearing a name recognized in this compendium will have its strength, quality, and purity defined by the test and assays in the compendium.Format and Purpose: The hardbound volume is a compilation of individual monographs arranged alphabetically by principal drug entity, for the application and interpretation of standards, tests, assays, and other specifications for drug substances, dosage forms, and pharmaceutical ingredients. The combination of tests and assays provided in each monograph are intended to measure the strength, quality, and purity of that product/entity. The methodology in the USP/NF is recognized as official in the Food, Drug, and Cosmetic Act.Format and Purpose: The hardbound volume consists of general information and individual monographs arranged in alphabetical order, which set specifications for quality and purity of the food additive substance and tests to measure those specifications. This compendium is recognized by regulation as setting the standards for quality and purity of those food additive substances listed as GRAS in 21 CFR 18, or affirmed as GRAS in part 184 or section [See 21 CFR (h)(1)].Updates: The USP/NF is under continual revision. A new compendium is published every five years with supplements on an annual basis and interim revisions as applicable. The supplements and interim revisions are not included in the compendium purchase price and must be ordered by separate subscription.An ancillary publication, "Pharmaceutical Forum," is distributed bimonthly and presents proposed USP and NF text for public review and comment; occasional articles and commentary relating to USP and NF analytical methods; and the review process in general. It is also available on subscription from the U.S. Pharmacopeial Convention. lt is a valuable adjunct to the USP/NF for those laboratories that perform a moderate number of drug analyses and provides them with the means to keep updated on progress of the U.S. Pharmacopeial Convention.Other related publications available from USP include USAN ("United States Adopted Names and the USP Dictionary of Drug Names") and the USP DI ("United States Pharmacopeia Dispensing Information"), which includes dispensing information for pharmacists, such as dosage form, warnings, and drug incompatibility or known interactions. Some analysts will find these volumes useful, particularly those persons involved in drug research projects.