Exam I: Prescription Process, Counselling, Clinical Trials Flashcards
Advantages of E-scripts
- Reduction in medication errors
i. e. drug identification, dosage form, drug-drug interactions (warnings pop up for physicians entering E-script) - Doctors can send scripts from smartphone and other devices not just a computer now.
- Increase in medication adherence – physical scripts tend not to make it to the pharmacy as a result of the patient forgets or loses prescription
What part of a script is omitted when sent electronically vs a hardcopy?
Handwritten signature of the authorized prescriber is omitted
CI drugs
- Highly addictive, high potential for abuse.
- No approved medical uses. Illegal, not for prescribing.
- Only can be used in research.
i. e. Heroin, marijuana
CII drugs
- High abuse potential and risk for dependency.
- Approved medical used.
- Generally cannot be refilled.
i. e. Oxycodone, fentanyl, cocaine (for some surgical procedures)
CIII, CIV, CV drugs
Lower abuse potential than C-II but potential is still highly significant.
Generally can be refilled.
Three examples of CIII drugs
Tylenol with codeine, ketamine, testosterone
Why is testosterone a controlled substance?
Its a anabolic steroid that has a risk of being abused
Overuse can cause heart attack, aggression, depression etc.
i.e. Athletes and bodybuilders
Three examples of CIV drugs.
Xanax, valium, tramadol
Three examples of CV drugs.
Robitussin AC, Pregabalin (lyrica), Lomotil
What is the New Jersey Audit Trail requirement?
A NJ regulation requires that the identity of the pharmacist (and P.T.) involved in processing a Rx, be recorded electronically
How are requests for copies of prescriptions handled?
A photocopy must be made and stamped as a copy. Only to be used for information purposes.
How long are prescription kept for?
Scripts filled within 2 weeks must be readily available.
Prescriptions kept for 5 years.
A NJ pharmacy does not have to put the generic and brand name on a prescription label.
True/False
False
NJ requires that the brand name of a generic medication be put on the prescription label
What is an auxiliary label?
Warning label placed on a prescription label by the pharmacist
i.e. “Take with food”, “For external use only”, “May cause drowsiness”
What does the OBRA-90 stand for? How did states respond to this act?
Omnibus Budget Reconciliation Act of 1990
States began to mandate DUR and drug counselling
What provisions did the OBRA 90 put in place besides drug counselling?
- Administration of drugs in nursing Homes
- Inpatients right to forgo extraordinary life-sustaining procedures
- Drug prices for Medicare/Medicaid programs
Where did the concept of DUR originate and by what organization?
JCAHO – Joint Commission requirements for hospital Inpatients
What is rDUR, its main goal and what type of pharmacists does this mostly apply to?
Retrospective DUR (rDUR) in intended to improve population health.
Most applicable to pharmacists who work in Governmental agencies (like CMS or State Medicaid agencies) or Managed Care pharmacists working for PBMs or comprehensive health insurance companies
What are the five steps of rDUR?
- Establish standards
- Retrospectively collect data, facilitated by “Big Data” capabilities”
- Analyze the data
- Develop a plan of intervention to improve prescribing patterns
- Implement the plan
This is a fundamental responsibility of all practicing pharmacists.
Most frequent contemporary clinical role that pharmacists have
Prospective DUR (pDUR)
When do pDURs occur?
pDUR occurs before dispensing medication to patients.
First fills and before every refill.
Key components to look out for when conducting a pDUR? (7)
- Therapeutic duplication
- Contraindications
- Drug-drug interactions (DDIs)
- Contact prescriber to address hazardous drug-drug interactions
- Idea dosage regimen? (ie. strength, frequency etc.)
- Drug allergies?
- Patient over or under utilization of drug can be caught during a refill pDUR
What interventions can be made by a pharmacist if they are apprehensive of filling a script?
- Talk to the patient
- Contact physician to address concerns
- Refuse to dispense using clinical judgement.
What is “alert fatigue” in reference to computer generated pDUR alerts?
“Alert fatigue” happens when a pharmacist or physician is so used to overriding alerts that they mistakenly override an alert that is clinically significant.
A mass of alerts causes user desensitization.
What strategies can be implemented within computer-generated pDUR alerts to minimize desensitization?
- Tier alerts (Mild, moderate, severe)
- Some systems may only point out severe alerts
- Some systems require an additional level of override for severe alerts
What are type of alerts can pop up for a computer generated pDUR? (Name top 3, then give 3 additional)
- DDI alerts
- Dose alerts
- Allergy alerts
Duplicate therapy, LASA, diagnostic tests required
What are the five components of an MTM that makes it go beyond a DUR?
- Medication Therapy Review (MTR)
- Personal Medication Record (PMR)
- Medication-related Action Plan (MAP)
- Intervention and/or Referral
- Documentation and follow up
What are the components of a SOAP note?
- Subjective – Non-quantitative metrics based on observation (i.e. The patient looks frail, confused, depressed)
- Objective – Things that can be measured (quantitative) (i.e. Vital signs like blood pressure, heart rate, weight, blood test)
- Assessment – Preliminary diagnosis
- Plan – How the diagnosis will be treated. Plan of care.
Identifying a target, validating a target and identifying a lead compound in the new drug development process is done in vitro. What does in vitro mean?
Done on the cellular level in test tubes, culture dish.
When are patent applications filled during the new drug discovery process?
When a “lead compound” is identified. Patent application are filled.
Define Pharmacodynamics (PD).
What the drug does to the body.
Therapeutic index
What is a therapeutic index?
Ratio of the minimum therapeutic concentration and minimum toxic concentration
The narrower the index the more dangerous it is, more side effects.
Drugs with narrow index require Therapeutic drug monitoring (TDM).
Define Pharmacokinetics (PK).
What the body does to the drug - ADME
Drug effect is a function of drug concentration at the target site(s) in the body
Drugs administered via IV must be absorbed.
True/False
False
Drug goes directly into the bloodstream
What pathway does an orally administered drug go through in order to be absorbed?
- Absorbed across duodenal wall (metabolism) into portal vein
- Drug travels to the liver (1st pass metabolism - drug concentration is reduced)
- Drug travels to the inferior vena cava into the systemic circulation (bioavailability)
What happens during the distribution process of the drug?
Transported to various tissues depending on affinity for plasma proteins, molecular weight and polarity, and how well various tissues are vascularized.
Nonpolar molecules can freely travel to various parts of the body during distribution.
True/False
False
Nonpolar (low water solubility) molecules must bind to plasma proteins so that it can be transported throughout the body.
What occurs during the final metabolism before excretion?
May activate the drug (active drug metabolite), but usually inactivates it and makes it easier to eliminate
How are drugs excreted?
Most drugs are eliminated by the kidneys (glomerular filtration or renal tubular secretion)
or Liver (biliary excretion of water-soluble drug or metabolite, which ends up in the feces)
Like IV, IM and SUBQ administrations do not need to be absorbed.
True/False
False
IM and SUBQ still need to be absorbed into the systemic circulation
What is conducted in preclinical trials?
- Find least toxic drug dose regimen
- Identify biomarkers for ADE monitoring
- Single dose studies to determine organs that might be exposed to toxicity (in vivo or in vitro)
- Repeated dose studies used animals to mimic a drug regimen in chronic human dosing to identify potential toxicities to organs (in vivo)
- Carcinogenicity, genotoxicity, and reproductive toxicity
Single dose studies (in vivo or in vitro?)
Single dose studies (preclinical trials) can be in vivo or in vitro
Repeated dose studies (in vivo or in vitro?)
Repeated dose studies are in vivo animal studies
Genotoxicity studies (in vivo or in vitro?)
Genotoxicity studies are done in yeast cultures (in vitro)
Carcinogenicity and reproductive toxicity (in vivo or in vitro?)
Usually tested in rats (in vivo)
How can researchers get approval to conduct clinical trials across state lines (nationwide)?
If an IND is not rejected by the FDA within 30 days of submission then a waiver is granted allowing the investigational drug to be distributed to clinical trial sites throughout the U.S.
What information is included in an Investigational New Drug (IND) application?
- Disease state, drug target(s), mechanism of action
- Animal pharmacology and toxicology
- Manufacturing information – show FDA that manufacturing process will be safe and that you will be able to produce enough of the drug
- Planned clinical Protocols and Investigator Information
Difference between an NDA and BLA submitted after Phase III of clinical trials.
New Drug Application (NDA) - Small molecule drugs reviewed by the Center for Drug Evaluation and Research (CDER)
Biologic License Application (BLA) - Vaccines, monoclonal antibodies etc. reviewed by the Center for Biologics Evaluation and Research (CBER)
How long does it typically take the FDA (CDER or CBER) to approve an NDA?
6 months - 2 years
What is included in an NDA?
- All information included in the IND
- Results of Phases I to III clinical trials—safety, efficacy, PK
- Statistical proof of efficacy from at least 2 Phase III trials
Proposed drug label, - Package Insert, packaging, manufacturing
What four ways can a drug receive accelerated approval?
- Priority Review
- Breakthrough Therapy
- Fast Track
- Accelerated approval
Priority Review applies to investigational drugs with?
- Improved efficacy in disease treatment, prevention, or diagnosis
- Decrease in adverse drug reactions
- Increased patient compliance
- Evidence of safety and efficacy in a new patient population
Breakthrough Therapy applies to what kind of drugs? What special privileges do these drugs get?
- Used to treat a serious disease
- Provides substantial improvement over any drugs currently approved to treat the disease
Drugs given Breakthrough Therapy status earn Fast Track review
What is Fast Track for a drug?
Facilitate development and hasten review of a drug that meets an unmet medical need
Fast Track drugs qualify for Breakthrough Therapy and/or Accelerated Approval status
What phase in clinical trials are open-label, controlled and/or blinded?
Early Phase I and Phase I - open label
Phase II - Open-label or controlled and blinded
Phase III - Randomized, controlled, clinical trial (RCT) - almost always double blinded
What specifically is studied in Phase I of clinical trials?
- PK
- Dose-ranging
- Bioequivalence
- Adverse drug effects (ADEs)
- Maximum Tolerated Dose (MTD)
What specifically is studied in Phase II of clinical trials?
- PK/PD and preliminary efficacy in target population (n=100s)
- More extensive Adverse drug effects (ADEs) studies
- Does benefit outweigh risks?
What specifically is studied in Phase III of clinical trials?
- Compare drug to current standard of care or placebo
- Further prove safety and efficacy for NDA
- Initiate phase Ib or IIb if necessary
What specifically is studied in Phase IV of clinical trials?
- Long-term safety data (rare ADEs)
- Late effects
- Morbidity
- Drug-drug interactions
- New indications
How is Early Phase I (Phase 0) conducted for cancer trials?
- Open-label
- Very small dose to 10-15 refractory cancer patients – terminally ill, current treatment options failed
- Do these patients have an increased efficiency from new drug development?
How is Phase I conducted for cancer trials? (also Ia vs Ib)
- Open-label
- Less than 10 patients
- Phase Ia - PK, MTD
- Phase Ib - Recommended Phase II Dose (RP2D), preliminary tumor effect at MTD
How is Phase II conducted for cancer trials? (also IIa vs IIb –> same as Ib)
- Controlled (compared to standard of care) and usually blinded
- Up to 100 patients
- Phase 2a: MTD
- Phase 2b: RP2D, preliminary tumor effect at MTD
Explain the graph that comes from Phase I pk study. Where does the data come from? Define x and y axis.
“Two-stage” design
- 15-18 healthy adult volunteers, 12-15 blood draws in each
- Blood draws should be more frequent during first 1-2 hours after drug administration
- Stage 1—establish drug concentration-time profile in each subject
- Stage 2—average the results from each subject at each time point to create the “population PK” profile
X - Time
Y - Drug concentration in blood (** ln (concentration)** natural log of concentration)
What is the clearance of a drug and how is it calculated from the Phase I PK study?
Clearance is the volume of plasma from which a substance is completely removed per unit time
CL = F x Dose / AUC
Area Under the Curve (AUC)
Half life equation. Define the variable in the equation.
0.693/Ke
Ke - slop from concentration x time graph - elimination rate of the drug
What is the percentage of cancer drugs that gain FDA approval? What stages do most drugs fail in?
5% gain FDA approval
Most fail during late-phase testing (Phase 2b, Phase III) due to lack of efficacy
Most expensive phase of clinical trials?
Phase III
