1 - Introduction to Pharmacology

Federal Food, Drug, and Cosmetic Act (FDCA)

1906, FDA established to protect public from drugs that cause harm because they are adulterated and/or mislabeled

How was the FDCA amended in 1938?

to protect people from drugs being marketed before they had been proven safe

Duram-Humphrey Amendment

1951, establishment of two drug classes (legend (prescription only) and OTC)

Legend (prescription-only) drug class

must come with adequate directions for a health professional to prescribe it

OCT drug class

no prescription required; manufacturer must provide general directions for use

Kefauver-Harris Amendment

1962, made it so drugs had to be proven effective

What must manufacturers demonstrate to the FDA regarding the drugs they produce?

- free from adulteration

- free form misbranding

- safe for use

- effective for the claims they are making

Controlled Substance Act (SCA)

1971, enforced by DEA and Department of Justice, enforced substances are placed into one of five categories (schedules) according to their relative potential for abuse or addition

What are the enforced substances?

opiates, sedatives, stimulants, and hallucinogens

Describe the drug schedules.

Schedule I (C-I) = high potential for abuse

Schedule V (C-V) = low potential for abuse

True or False: The DEA has a registration requirement?

True

What is the registration requirement of the DEA?

Under the CSA, every person who produces, distributes, or dispenses any controlled substance must register with the DEA

Schedule I

- high potential for abuse

- drugs with no currently accepted medical use

- heroin, LSD, marijuana, peyote, methylenedioxymethamphetamine (ecstasy)

Schedule II

- high potential for abuse

- no refills

- paper, electronic, fax prescriptions (only if original is presented prior to dispensing)

- use potentially leading to severe psychological or physical dependence

- oxycodone, hydrocodone, amphetamines, fentanyl, cocaine

Schedule III

- some potential for abuse

- moderate psychological dependency

- up to 5 renewals within six months

- paper, fax, electronic, oral prescriptions allowed

- ketamine, codeine with Tylenol, anabolic steroids, testosterone

Schedule IV

- low potential for abuse

- limited psychological and physical dependency

- up to 5 renewals within six months

- paper, fax, electronic, oral prescriptions allowed

- benzodiazepines, tramadol

Schedule V

- subject to state/local regulation; may be sold Rx or OTC, depending on what it is

- Lomotil, Robitussin with codeine, pregabalin

Dietary Supplement Health and Education Act

1994, dietary supplements are defined and given a regulatory framework

What do "dietary supplements" include?

- vitamin or mineral

- herb or other botanical

- amino acid

- substance consumed to supplement the diet by increasing the total dietary intake

- concentrate, metabolite, constituent, or extract

- combination of the preceding ingredients

When does the FDA have the authority to remove dietary supplements from the marketplace?

- post a "significant or unreasonable risk to consumers"

- are adulterated

- are marketed with inaccurate labeling

Comprehensive Addiction and Recovery Act (CARA)

2016, attempts to address the opioid epidemic

- makes naloxone available to police and first responders

- expand disposal sites for unwanted prescription medication

- strengthen prescription drug monitoring programs (CT Prescription Monitoring and Reporting System, CPMRS)

Describe the drug development process.

Step 1: discovery and development

Step 2: preclinical research

Step 3: clinical research

Step 4: FDA review

Step 5: FDA post-market safety monitoring

Discovery (Step 1)

new drugs are found through:

- testing new compounds (natural or synthetic) for possible medical therapies

- looking at existing treatments that have unanticipated effects

- new technologies, such as those that provide new ways to target medical products to specific sites within the body or to manipulate genetic material

Development (Step 1)

once a compound is identified, experiments are conducted to determine:

- absorption, distribution, metabolism, excretion

- mechanism of action

- best route of administration

- side effects

- interactions

- effectiveness compared to existing drugs

Preclinical Research (Step 2)

research conducted to determine dosing and toxicity levels

What are the two types of preclinical research?

in vivo and in vitro

In vivo

research conducted within a living organism

In vitro

research conducted outside a living organism

Clinical Research (Step 3) - explain the steps/phases

- Investigational New Drug (IND) Application

- Phase 1 (20-100 healthy volunteers, assess safety and dosage)

- Phase 2 (several hundred people with the disease/condition, assess efficacy and side effects)

- Phase 3 (several thousand volunteers who have the disease/condition, assess efficacy and monitor adverse side effects)

FDA Review

New Drug Application (NDA) submitted by drug company, which includes everything about the drug (from preclinical data to phase 3 trial data)

What information must be included on an NDA?

- proposed labeling

- safety updates

- drug abuse information

- patient information

- institutional review board (IRB) compliance information

- direction for use

Post-Market Safety Monitoring (Step 5)

FDA has several programs that allow manufacturers, health professionals, and consumers to report problems associated with approved drugs (i.e., MedWatch, MedSun)

MedWatch

gateway for reporting problems with medical products (drugs and devices) and learning about new safety information

Medical Product Safety Network (MedSun)

monitors the safety and effectiveness of medical devices

How long does the drug development process take on average?

10-15 years

What is "off-label" use of a drug?

when an FDA-approved drug is prescribed for a condition or age group or in a manner not approved by the FDA

Describe how healthcare providers and manufacturers can use off-label drugs?

Healthcare providers may legally prescribe drugs for uses other than those officially listed in package inserts as approved by the FDA, but drugs cannot be marketed by manufacturers for off-label use.

Rational Prescribing

The WHO asked prescribers to create personal formularies containing frequently used, effective medications in a manner that assures they have:

- defined the problem

- addressed a specific therapeutic objective

- ensured that any medication in the personal formulary is safe and effective for the patient under consideration

- informed the patient about the risks and benefits of the medication

- monitored the results of the treatment

- stopped the drug when the treatment period is over

What did the landmark report To Err is Human: Building a Safer Health System tell us?

1999: 98,000 Americans die each year from preventable medical errors, many of them drug-related

What are medication errors often caused by?

- failed communication

- poor drug distribution practices (mail)

- complex or poorly designed technology

- access to drugs by non-pharmacy personnel (samples)

- dose miscalculations

- lack of information about the patient (no history)

- allowing the patient to leave without checking his or her understanding of therapy

What does the IOM recommend regarding safe medication practices?

- implementation of safe medication practices, such as having the FDA provide oversight of safety issues associated with similarly named drugs

- creation of national reporting systems for medication errors

- creation of a center for patient safety

What are the benefits of creating national reporting systems for medication errors?

- provides confidential feedback to health providers so they can learn from others' mistakes

- makes medication errors known to the public

What recommendations are included in the United States Pharmacopeia's list to improve the accuracy of prescription writing to prevent medication errors?

- all prescription documents must be legible; verbal orders should be minimized

- prescription orders should include a brief notation of purpose (i.e., cough) unless considered inappropriate by the prescriber

- all prescription orders should be written in the metric system except for therapies that use standard units, such as insulin or vitamins

- prescribers should include age and, when appropriate, weight of the patient on the prescription or medication order

- medication orders should include the drug name, exact metric weight or concentration, and dosage form

- When a dosage strength is indicated, a leading zero should always be used for the decimal expression of a quantity less than one (0.5 g instead of .5 g). Likewise, a terminal zero should never be used after a decimal because of the risk of tenfold errors in drug strength and dosage (5 g instead of 5.0 g).

- prescribers should avoid the use of abbreviations, including those for drug names

- clinians should not use vague language, such as "take as directed"

Prescriber identification - what to include on a prescription?

name, degree, office address, telephone number

Patient identifiers - what to include on a prescription?

name and address and/or DOB

Inscription

name of drug and strength (of each dosage unit, not total dose to be taken)

Subscription

instructions to pharmacist regarding dosage form and number of dosage units to dispense (for controlled substances, quantities should be written out in words as well as numbers)

Signa

Instructions given by the provider to the patient

Refills

- non-controlled prescriptions can be refilled for up to 1 year after the date it was written, pending there are enough refills

- Prescriptions for Schedule II controlled substances may not be refilled

- Prescriptions for Schedule III-V controlled substances have a 5 refill, or 6 month limit

tsp

teaspoon

tbsp

tablespoon

gm

gram

gtts

drops

mcg

microgram

mg

milligram

ad

right ear

as

left ear

au

both ears

od

right eye

os

left eye

ou

both eyes

po

by mouth

ac

before meals

am

in the morning

bid

twice a day

d/c

discontinue

hs

at bedtime

pc

after meals

prn

as needed

q

every

qd

every day

qid

four times a day

tid

three times a day

cap

capsule

tab

tablet

aq

water

True or False: Clinicians are encouraged to use generic names of drugs.

True

Describe drug substitution laws.

They permit or mandate that pharmacists substitute a generic bioequivalent drug for a brand-name one.

True or False: Clinicians can exercise their perogative that a substitution not be made.

True, "dispense as written"/DAW

Which medications should NOT be substituted?

Warfarin, Digitalis, Phenytoin, Levothyroxine, Theophylline

What is in the "orange book"?

approved drug products with therapeutic equivalence evaluations

What are the CT requirements for controlled substances?

- name and address of patient

- age

- the compound or preparation prescribed and the amount thereof

- direction for use of the medication

- name and address of the prescribing practitioner

- date of issuance

- DEA number

- no prescription for a Schedule II substance shall contain more than one prescription

Pregnancy Category A

- no risk to fetus in first trimester

- no evidence of risk in later trimesters

Pregnancy Category B

no risk to fetus in animal studies, but no well-controlled studies in pregnant women

Pregnancy Category C

- adverse effects on fetus in animal studies, but no well-controlled studies in humans

- benefits may outweigh risks

Pregnancy Category D

- Positive human fetal risk has been reported

- Considering potential benefit versus risk may, in some select cases, warrant the use of these drugs in pregnant women

Pregnancy Category X

- fetal abnormalities were reported, and positive evidence of fetal risk in humans is available from animal or human studies

- risks clearly outweigh the benefits

- drugs should not be used in pregnant women

What problems arose with the pregnancy letter category system?

- overly simplistic

- misinterpreted as a grading system

- A drug with adverse information in animals could be labeled as the same category as a drug with no animal information

What new pregnancy system went into effect on June 30, 2015?

Pregnancy & Lactation Labeling Rule (PLLR)

When did all prescription drugs have to remove pregnancy letter categories by?

June 2020

PLLR

more clearly describes available data that can be used to aid in complex risk/benefit discussions between prescribers and their patients

What are the three main subsections of the PLLR?

8.1 Pregnancy pregnancy registry

8.2 Lactation

8.3 Females and Males of Reproductive Potential

Conscientious prescribing involves having pharmacology knowledge and considering:

- patient factors (age, sex, weight, culture, etc.)

- disease factors

- drug factors

- social factors

- knowledge factors

- third-party factors

- government and learned society factors

- collaborating colleagues

Questions all prescribers should ask themselves before writing a presctiption

1) Have I selected the most appropriate drug and drug dosage?

2) Have I weighed all the risks and benefits to my patient?

3) Have I addressed the need to monitor the effects of this medication?

4) Am I fully informed about this patient's condition, other medications, comorbidities, allergies, and adverse events with other medications?

5) Have I made the prescription as legible to the pharmacist as it is to me?

6) Have I done all I can to ensure the patient will be compliant?

7) Have I considered what the medication will cost the patient?

8) Have I considered the health literacy of my patient?

9) Have I involved my patient in a shared decision-making process?

10) Have I done all I can to minimize tisks and increase patient safety?

What are the two main principles of conservative prescribing?

think beyond drugs and heightened adverse effects vigilance

What are the principles of "think beyond drugs"?

- seek non-drug alternatives as first, rather than last, resorts

- treat underlying causes, rather than solely treating symptoms

- look for prevention opportunities, rather than exclusively focusing on established disease or symptom amelioration

What are the principles of "heightened adverse effects vigilance"?

- maintain a high index of suspicion for adverse drug effects

- educate patients about potential adverse effects to ensure more timely recognition

- be alert to clues of drug withdrawal symptoms masquerading as disease "relapses"

What does patient-centered care mean?

patients are treated as partners in health-care decision-making and are encouraged to take responsibility for their health

What does patient-centered communication focus on?

the patient's needs, values, and wishes

What are some barriers to effective communication?

- physical barriers (space, 'white coat syndrome')

- language barriers

- personal and emotional barriers