Pharmacology Lecture Series: Exam 1 Review (Lectures 1 and 2)

pharmacology

broad description of a drug or medication; includes mechanism of action, pharmacokinetic/dyname parameters, drug interactions, adverse effects, toxic effects

pharmacotherapeutics

pharmacology + disease state + patient; takes into consideration pharmacology of a medication and broadens the concept by looking at how to use the medication in patients with various disease states

pharmacokinetics

what the body does to the drug (Absorption, distribution, metabolism, elimination)

pharmacodynamics

what the drug does to the body (MOA/SE/ADR)

Efficacy vs toxicity

-you have to monitor for efficacy (is the drug doing the job its intended for) while trying to avoid adverse effects (toxicitis)

-everytime you use a drug there is a desire intent and downside to it

receptor

drug target where the medication will do its job/exert its effect

examples of receptors

nucleic acid, protein, enzyme

what best describes the drug and receptor complex

lock and key

agonist

med that bind to the receptor and activates it (morphine, oxy were examples in lecture)

antagonist

med that binds to the receptor but do not have the right structural features needed to activate it (fits well but like an imposter)

functions of antagonist

either turns down or off a receptor so that the agonist cant sit there (narcan is the example from lecture) it sits in the receptor and competitively binds

chemical name example

atorvastatin calcium

issues with chemical name

sometimes long and hard to pronounce/recognize

generic name example

atorvastatin

Generic name info

-internationally recognized

-only one generic name per drug

-nonproprietary

-helps identify type/class is belongs too

-becomes available when patent on brand med expires

brand name (proprietary) example

lipitor

Brand (proprietary) name info

-Patented property name from pharm company that discovered/made name

-some drugs/meds have more than one brand/propriety name

-gives no indication of pharmacologic action

give some examples of dosage forms

tablets, capsules, ointments, creams, sprays, lotions

Enteral administration of drugs

Oral (PO)

parenternal administraion of drug

IV, IM, SC (anything using a needle)

describe TOPICAL TRANSDERMAL PATCHES

absorbed through the skin and will go into the blood stream (intended to go into the blood stream)

Topical administration of a drug

place med on skin or mucous membranes for absorption (almost always systemically absorbed)

-ex: skin cream, vaginal products, patches

which is the only topical med that truly stays topical

otic (unless there is a perforated eardrum)

systemic definition

circulation/vascular space; where most meds go once they are absorbed PO or immediately post IV

what is the quickest route of absorption

iv

what is the second fastest route of absorption

sublingual

How is sublingual absorbed

through the salivary ducts and bypasses the gut

what method of admin does the most chopping up of a drug

PO

how is buccal absorbed

salivary glands in cheek; bypasses the gut

which administration type acts right on the area of intent

inhaled (inhaler for asthma)

which type of administration gives you a steady state in the bloodstream

topical

Food and drug administration function

-administrative body that oversees drug evaluation process in USA

-grants approval for marketing of new drugs

Drug enforcement agency function

-enforce the controlled substances law and regulations of the US

-Can bring civil/criminal charges to those involved in growing, manufacture, or distributing of controlled suubstances

-Makes Schedules 1-5 for controlled substances

-(they really only care about controlled substances; their manufacturing and distribution-NOT ABUSE OF THESE DRUGS)

how many schedules are there

5

explain schedule 1 drugs

research only; they have no medical use

-most highly adictive

examples of schedule 1 drugs

heroin, crystal meth, "medical marijuana"

Category 2 drugs

-more likely to be abused

-Narcotics

what drugs are in category 2

all of our narcotics (morphine), fentanyl, meperine, hydromorphone, oxycodone, methadone, and hydrocodone

also our ADD/ADHD meds: methylphenidate, dexmethamphetamine, amphetamine salts

Schedule 3

safer, less likely to get abused

what are examples of schedule 3 drugs

APAP or ASA codeine (tablet)Sc combination products

schedule 4

safe, less likely to be abused

what are some schedule 4 drugs

tramadol, benzos (lorazepam, diazepam, oxazepam) and sleep agents

Schedule 5

safest, least likely to be abused

examples of schedule 5 drugs

expectorants with codeine (cough syrup)

what is the trend w DEA drug categories

the higher the number the lower the potential for abuse

emergency use declaration

FDA allows the use of unapproved drugs to be used in emergency situations to treat or dx medical issues

--> COVID

1st federal drug regulation

dealt w interstate transport of impure or misbranded food/drugs

amendment in 1938

began requiring toxicity studies and approval of a NDA before a drug can be distributed (safety is now important but efficacy is not important at this point)

thalidomide

used in the past for morning sickness and anxiety ; if taken in early pregnancy, it causes phocomelia (malformed limbs)

-realized placenta is not a barrier

ammendment due to thalidomide

harris kefauver amendments to the food, drug, and cosmetic act in 1962 (required proof of efficacy AND safety of a drug)

-risk to benefit ratio

what are the phases of drug development

- Preclinical phase

- Drug clinical trials: phases I-III

- Post-marketing: phase IV

what is a part of the preclinical phase

in vitro studies (chemical synthesis and testing), animal testing

--> roughly 4 years in total

what is part of clinical testing

phase 1: 20-100 healthy subjects (looking for whether it is safe and what the kinetics are)

2: 100-200 pt that have dz

phase 2: 1000-6000 pt

what is step 3 of drug development

NDA REVIEW: FDA reviews it within 6 months

what is step 4 of drug development

post marketing surveillance: continuous monitoring of the drug after it goes to market(at least 10 yrs)

MedWatch

-FDAs program to report reactions, quality problems, therapeutic failutes, product errors

Do you have to report to MedWatch

-NO ITS VOLUNTARY REPORTING

-anyone can but doesn't have to

-it's better to so FDA can see trends

What is considered mandatory to report

vaccines

pharmacogenetics

-growing area of interest

-analyzes genetic variations as part of trial that may influence whether a person responds to a particular drug

-age, gender, pregnancy

-tells you generally, but not specific

what are fast-tracked drugs

-drugs that meet unmet medical needs

-Speeds time to market by years

-patients with serious, life threatening conditions

-HIV, chemotherapy drugs, COVID vaccine

FDA safety and innovation act of 2012

-renewed FDA auth for accelerated approval of urgently needed drugs

Orphan drugs

provides incentives for development of drugs that treat diseases with fewer than 200,000 patients in the US

-pharm companies get paid to research/produce meds for more rare diseases

Nutritional supplements-dietary supplement health and education act 1994

-no disease modifying structure function claims allowed

-must be safe for human consumption

-amount of active priniciple in preparations vary (no standardization)

-As long as you say it wont prevent, cure, or treat a disease, FDA can't get you in trouble

-FDA can remove from market if it present risk of illness/injury

Medical foods

-foods that are specifically made for dietary managment of diseases or conditions that have distinctive nutritional needs that cannot be met by normal diet alone

-Packaged like prescription meds

-not FDA approved like typical prescription meds

-Not a dietary supplement

-Axona, Limbrel, Metanx

-Her example: Soup in a capsule

A medical food must

-be for PO administration

-be labeled for dietary management of specific medical problem with distinctive nutritional requirements

-intended for use under medical supervision (prescription only)

-intended for patient receiving ongoing medical care

"labeled" use

An indication that has been studied and is approved by the FDA

"off-labeled" use

a drug used for an indication that has not been studied by manufacturer of the medication

when are off label uses found

after the patent on the brand name drug expires

What type of use with pharma company answer questions about

labeled

-they do not comment on off labeled drugs

Types of adverse effects

-predictable side effects/adverse effects

-idiosyncratic (not something you would except from the drug)

-allergic reactions

Black box warning

-most serious type of warning mandated by US FDA

-labeling of drugs to warn about serious adverse reactions or problems

-on package inset, FDA website and web sites of drug marketing companies

-provider mysct provide info to patient about risks

Risk evaluation and mitigation strategy (REMS)

-mandatory classification/literature by FDA for drugs that are considered to have a narrow therapeutic window

-helps ensure benefits outweigh the risks

-sometimes requires special training for prescriber, patient, and pharmacist

-Example: accurate

-All REMS have a black box (but not all black box have REMS)

Four (3 things) asteps of the body hitting "the big red body"

-body never wants a drug internally

-when you take a med, the first thing your body does is try to figure out how to eliminate it

-Orally administered drug are the most affects by the body

absorption

process of drug moving from administration site to bloodstream

what effects absorptions

molecular weight, charge, water and lipid solubility

-IV meds dont need to be absorbed

Structure of GI Tract

-stomach: site of drug release and dissolution

-small intestine: most important region of absorption of oral meds, large surface area, long period of time here

-large intestine: not important absorption site for most orally administered drugs

OTC vs BTC

- OTC is something bought w/o prescription and is considered safe if you are using it as labeled

- BTC is something you can buy w ID only for age and tracking quantities of the drug

Bioavailability (F)

fraction of drug absorbed into systemic circulation after extravascular administration

-F=quantity of drug reaching systemic circulation/quantity of drug administered

F of oral meds

less than 1

F of IV meds

1

First-pass effect

take oral med, drug absorbed and enter liver via portal vein, liver extracts portion of drug prior to entering systemic circulation

what type of meds undergo the first pass effect

oral

what is half life

time needed for blood concentration of a drug to increase or decrease by half of its concentration

does a drug that is quickly eliminated have a long or short half life

short

what determines the time needed to reach concentration steady state

half life of a drug

what determines how often we give a drug

half life

what is steady state concentration

average drug concentration in body remains constant

how many half lives does it take to reach concentration steady state

5

If a drug has a half life on 1 hr, how long does it take to get to steady state

5 hours

what is true at concentration steady state

rate of elimination = rate of administration

what is a maintenance dose

dose needed to achieve concentration in therapeutic range for an extended period of time

-equal to rate of elimination at steady state

-function of clearance

what is the maintenance dose equal to

elimination rate

what is a loading dose

large dose given initially to achieve therapeutic concentration rapidly

-useful for drugs with long half life

what is peak concentration

max drug concentration achieved during repeated dosing cycles

-achieved after drug administration

what is trough concentration

minimum drug concentration achieved during repeated dosing cycles

--> help us ID toxicity; if the blood concentration is not zero, you cannot give the next dose of certain abx

what kinetics do most drugs follow

linear

explain linear kinetics

serum drug concentrations change proportionally w long term daily dosing

-double dose means you double serum concentration

explain non-linear kinetics

serum concentrations change more or less than expected

--> different for each person (alcohol)

what is the therapeutic range

concentration range that produces pharmacologic responses and minimizes adverse effects

what is the therapeutic window

dosage range between minimum effective concentration and minimum toxic concentration