How a drug gets into the body and is distributed

(Absorption, Distribution, Metabolism, Excretion)

How a drug affects the body processes

(Including therapeutic and undesirable effects)

1. Alter the drugs ability to produce its therapeutic effects or increase its side effects

2. Might cause an idiosyncratic reaction, like a drug allergy, or other effects particular to the patient

1. Pregnancy

2. Age

3. Other drugs the patient is taking

4.Health status, inclduing cognitive function

5. Lifestyle, diets and habits

6. Environment

7. Cultural/Ethnicity

8. Idiosyncratic reactions (allergies)

9. Characteristics that would affect the patients ability to respond to a drug or produce a therapeutice effect

Patient Evaluation:

Lifestyle, diet and habits

* Use of OTC medications, herbals, etc

* Substance Abuse

* Health insurance/prescription drug coverage

* Support system: Family, significant other

Patient Evaluation:

Environment

* Occupational or other eposure to toxic substances

* Setting in which the drug will be administered

Patient Evaluation:

Culture/Ethnicity

* Religious, social and ethnic background

* Genetic Traits

* Past Medical History

* Physical

* Family members, friends, etc

The Nursing Process in Pharmacology:

Assessment

The Nursing Process in Pharmacology:

Diagnosis

The Nursing Process in Pharmacology:

Planning

* Maximize therapeutic effects and minimize adverse effects

* Include the patient & family in the planning

The Nursing Process in Pharmacology:

Intervention

* 5 Rights of Drug Administration

Right Time

Right Route

Right Patient ID

Right Medication

Right Drug

Right Documentation

* Patient education must be a part of the intervention

The Nursing Process in Pharmacology:

Evaluation

* Is the patient taking the drug as prescribed?

* Is the drug producing the effect it is supposed to?

* Are the adverse effects acceptable?

* Should the dose be increased or decreased, or a different drug substituted?

* Does the patient need to continue this therapy?

The Nursing Process in Pharmacology:

Explain the Whole Process

4.  Intervention:

5.  Evaluation:

Every drug has atleast _##_ names.

What are they?

1. Chemical Name

2. Generic Name

3. Trade Name

*Not used by health care providers*

* Describes the chemical structure of the drug

* This is usually irrelevant to healthcare practitioners and patients because we want to know what the drug does, not its structure

* Drugs with different chemical structures can do the same thing

Used no matter where or what the setting, prep (IV, Pills), International name (in a differnt country , the drug will have a different trade name, but the same generic name

* Assigned to the drug when it is first given to humans

* The drug is always known by this generic name

* The generic name is printed on a bottle or in advertisements in parentheses

* Is not capitalized

* Sometimes hard to say

Trade Name

* Advertised name

* Name is given to the drug by the drug company that makets it

If more than one drug company markets a particular drug, it will have a different name for each company

* Name is capitalized

1. Avoids confusion (generic names are universal)

* In clinical practice, always look at the generic name to avoid giving the same drug twice

In the drugstore, you see pill bottles iwth the following names:

1. Advil (ibuprofen) 200 mg

2. Ibuprofen, 200 mg

3. Motrin (ibuprofen) 200 mg

4. Nuprin (ibuprofen) 200 mg

Which of the following is true?

A. They all contain the same drug.

B. People with muscle pain should only take Motrin

C. Motrin is the generic name

D. Nuprin is only for headaches

1. According to their use (ex: Antihypertensive)

Confusing because many drugs have more than one use

2. According to their mechanism of action (Preferred)

Most useful classification since it explains all the actions of the drug

3. According to their chemical structure

Limited usefulness for healthcare providers; irrelevant

Ex: Calcium channel blockers block calcium channels in smooth and cardiac muscles; When blocking smooth muscle, they reduce blood pressure; when blocking cardiac muscles they slow conduction

USE: We would have to memorize 2 uses

MECHANISM OF ACTION: Learn about the drug once, and apply the knowledge to different uses

* Allows us to know what a new drug will do (since we can put it into a class whose mechanism of action we know)

(Ex: If a new calcium channel blocker was introduced, we would already know what it does and possible side effects)

DAILY

1. Introduction of new drugs

2. New administation routes for older drugs

3. New adverse effects and/or warning may be issued

4. Drugs taken off the market

1. Pharmacology book (Not a good way for updates; website stays current)

2. Physicians Desk Reference (PDR) for prescription and OTC drugs - comes with the drugs to protect the drug companies

3. Formularies

4. Drug compendiums - useful for dosage, not mechanism of action or class

5. Reputable websites (Mayoclinic, associations (heart, diabetic), advocacy websites

-PDR's come with drugs

-Main purpose is to protect the drug company from lawsuits

-Black box warnings (adverse effects)

-Only information given in the PDR is what the drug was approved for by the FDA

Food and Drug Administration (FDA)

* Dietary supplements and herbals do not go through the same approval process as medical drugs

Efficacy

* Drug company must have an indication (disease or condition) that the drug is supposed to make better)

Efficacy = power to produce a desired effect

A drug is approved by the FDA for _##_ uses at a time.

A drug could be effective for _##_ uses.

ONE - A drug can be approved for one indication at a time.

A drug might be good for more than one use, but the drug company has to choose which use they want to seek approval for at a time.

*Drug companies choose the use that can be marketed to the largest amount of people.

Once a drug is approved for marketing, it can be prescribed for anything by anyone authorized to prescribe drugs (off-label use)

There is nothing illegal about giving a drug for an off-label use; however, if an adverse effect occurred, the provider could be sued for malpractice

There is usually literature that supports the off-label use

NO

Danger presented by the drug has to be balanced against the benefits

YES

Example: Chemothrapy is a life=saving drug that will cure cancer, but has severe adverse effects

Example: Cough Medicines for young children are dangerous and they do not work that well for children; there are more dangers then benefits for cough medicines for children

Give an example of a drug with high benefits but low safety.

Give an example of a drug with low benefits and low safety.

Example: Chemothrapy is a life-saving drug that will cure cancer, but has severe adverse effects

Example: Cough Medicines for young children are dangerous and they do not work that well for children; there are more dangers then benefits for cough medicines for children

Before being able to test a new drug on humans, the drug company will run clinical trials on animals with the understanding that it is meant for evenutal use in humans.

Initial pre-clinical animal studies are done on mice and rats because they are cheap and have a short life span

For more complex drugs, such as drugs that make you vomit (ntiemetic drug), cats, dogs or ferrets will be used

1. Provide evidence of safety and efficacy in animals

2. To determine an estimated effective does that can be upscaled for humans

Safety Studies in Animals:

Increasing doses of the drug are used in animal studies to determine __________.

Safety Studies in Animals:

Adverse effects are determined in animals by __________ in clinical studies.

Safety Studies in Animals:

Animal blood, urine and organs provide data about how the drug is ________________________.

Drug company presents all pre-clinical data to the FDA (safety, efficacy and animal studies) in an IND application to request the FDA's approval to enter clinical trials on humans.

IND also includes a plan of how human testing will be conducted

Phase I:

** Conduct human testing to determine the dose to be used during future studies **

Phase I Testing:

What type of participants are used?

What is the purpose of Phase 1? How the purpose accomplished? 

Purpose of Phase I Testing: To determine the dosage of the drug for future studies

* Normal, healthy people are used, with the exception for drugs that treat cancer and AIDS

* Started with a low dose and increase the dose until participants cannot tolerate it

-Maximum tolerated dose: Dose is increased in a stepwise fashion until intolerable adverse events occur

* Measurements of blood and urine are taken to determine how the drug is distributed and eliminated

* Most Phase I trials have 10-50 subjects

Participants: Patients with the condition or disease are treated

Dosages: Are adjusted based on response

Blood and urine are taken to determine drug distribution and elimination

Purpose: Learn about drug distribution and elimination and an effective dosage range to treat the condition

*Less then 50 people

Phase I: Tolerable Dosages

Phase II: Drug distribution and elmination; dosage range

Phase III: Determine safety and efficacy

Phase IV: Continue surveillance and reported side-effects

Explain Phase III of the process to approve a new drug.

Who participates in the trial? What is the phase demonstrating? What is the drug compared with in this phase?

* Large clinical trial with 100's of subjects who have the condition

* Demostrates safety and efficacy of the drug when treating the indication

* The drug must be compared with something: Placebo, or if not ethical, with a standard treatment for that condition

Phase III:

In Phase III the new drug must be compared with ______ or _______.

Phase III:

The large clinical trial of hundreds of subjects who have the condition must demonstrate _________ & ____________ of the drug in treating that __________.

The large clinical trial of hundreds of subjects who have the condition must demonstrate safety & efficacy of the drug in treating that indication.

Phase III:

Phase III trial subjects must meet inclusion criteria and exclusion criteria. What is inclusion criteria? What is exclusion criteria?

Inclusion Criteria: Make sure the subjects actually have the disease in queastion and that they are likely to be helped by the therapy.

Exclusion Criteria: Exclude people likely to be harmed by the therapy (ex: Pregnancy) or people wtih serious comorbidities

**This explains why there is rarely any data on children or pregnant women**

Phase III:

What type of study is used during Phase III of an FDA drug approval?

Double-Blinded study with randomized subjects receiving either the investigation drug or the comparaor (placebo or standard treatment)

Double Blinded Study = neither the subject nor the person administering the drug knows whether it is the expeimental drug or the comparator)

Phase III:

How many times must a drug company complete a Phase III trial before a drug is approved?

Normally, once; however, the FDA can mandate more Phase III trials if they think its necessary

* Also, if the drug company wants to market the drug for more than one indication, there woudl be a phase III trial for each indication

Phase III:

Characteristics of Phase III Trials

* Hundreds to thousands of subjects

* Subjects have condition

* Comparator involved (Placebo or standard treatment)

* Double Blinded Study

* Last several months to years

* Subjects are monitored very closely for progression of their disease or for adverse effects

Company submits a New Drug Application (NDA)

Data from Phase 1, 2 & 3 are presented

A draft of the prescribing information is proposed (Material to be publisehd in the PDR)

Drug company and FDA negotiate the prescribing information, warnings of adverse effects, etc.

Drug company submits a New Drug Application (NDA) at the end of Phase III with data from Phase 1, 2 & 3 and a proposed draft of the prescribing information (PDR). FDA and Drug company then negotiates prescribing information and warnings.

Throughout phases 1, 2 & 3, the drug had been given to fewer then 1,000 people; when it is market, it will be givin to millions;

Therefore, several new adverse effects that were not evident during clinical trials, may occur from the new drug

What is Phase IV of the new drug approval process?

(Continuous Surveillance)

Continuous Surveillance

Not a formal study

Post-Marketing Study that relies on spontaneous reports from practitioners or patients about adverse events

*May take years for some adverse effects to be attributed/linked to the drug

Since there is no control group, it is very hard to show taht a particular adverse event is due to the drug and is not just a coincidence

No control group: It is hard to show that adverse effects is due to the drug and not a coincidence

Also, all post marketing surveillance relies on spontaneous reports from practitioners or patients - Not all adverse effects may be reported

In which stage of drug development are researchers concerned with the drug's maximum tolerated dose?

A. Phase I

B. Phase II

C. Phase III

D. Phase IV

Drug Pricing:

Describe the Drug Pricing Process of New Drugs

1. 1st Protected by a patent issued to the drug company

2. It is marketed under the company's brand name, typically priced really high (to recoup costs of developing the drug)

3. After the patent expires, anyone can make the drug (as long as it satisfies FDA approval) - Generic variations of the drug are market for very cheap

Drug Pricing:

When a drug is first approved, it is protected by a _____.

Drug Pricing:

Company will market the drug under its trade name, with the generic name in lower case letters, for (High or Low)__ prices to ____________.

High Prices

To Recoup the costs of developing the drug

Drug Pricing:

When can generic brands of the drug be marketed?

Drug Pricing:

Generic brands of the drug can be marketed after the developing drug companies patent expires. What do some drug companies do to extend their patent?

Drug Pricing:

Generic brands of the drug can be marketed after the developing drug companies patent expires. What are FDA standards the generic drug must comply to? What are differences between the generic drug and the brand/trade drug?

There is NO difference between the generic and trade drug because FDA regulations has standards that force the company marketing the generic brand to make sure the generic drug is the same as the trade name drug in terms of its activity and purity

* Generic drug is much cheaper then the trade name drug

Drug Enforcement Administration (DEA)

*Not the FDA*

Controlled Substances:

Drug Schedules

Explain the differences between schedule 1-5 controlled substances

Controlled Substances:

Drug Schedules

Explain the differences between schedule 1-5 controlled substances

Schedule 1: High Abuse, No acceptable use, research only (ex: Heroin, LSD)

Schedule II: High Abuse, triplicate prescriptions, no refills (ex: Amphetamines, Opiods)

Schedule III: Moderate Abuse, Written or telephone prescription every 6 months refills allowed (Stimulants, Anabolic steroids)

Schedule IV: Low Abuse, Written or telephone presciription every 6 months refills allowed (Tranquilizers, weak opoids)

Schedule V: Limited Abuse, Many OTC, (Ex: Antidiarheals)

What is pharmacokinetics?

(2 Functions)

1. Study of how a drug gets to its receptor in the body (This is broken down into absorption and distribution)

2. Study of how a drug leaves the body changed or excreted by the body processes (Elimination)

Explain the Receptor Theory

(Erilich, 1916)

* Drugs produce specific affects because they interact with specific molecules in teh body

* Drugs alter the rate of the natural function of the macromolecule (Drugs do not create new functions; they increase or decrease the rate of the curent function)

Erilich, 1916: Receptor Theory

Drugs produce effects because they interact with _____________ in the body.

Erilich, 1916: Receptor Theory

Drugs alter the _______ of the natural function of the macromolecule.

Any molecule inthe body can serve as a drug receptor

Enzymes, neurotransmitter receptors, ion channels, transport proteins

Definition of a receptor

(by pharmacologists)

A receptor is a macromolecule with endogenous ligands.

A ligand is a chemical that binds to a receptor and activates it, causing some change to occur

A ligand is a chemical that binds to a receptor and activates it, causing some change to occur

A receptor is a macromolecule with endogenous ligands.

1. Membrane-Bound enzymes with activating ligands

2. Ligand-gated ion channels

3. G-Protein coupled neurotransmitter receptors

4. Transcription factors with activating ligands

Examples of Endogenous Ligands:

Neurotransmitters bind to ________________.

Examples of Endogenous Ligands

Steroids bind to their respective receptors which are ____________________ factors.

Other macromolecules drugs can bind to in order to initiate change in function

(These are not classical receptors)

Enzymes

Ribosomes

Tubulin

DNA

RNA

Transporters (Na- or K+ Pumps)

Most drugs bind to more than one receptor type and ahve effects due to activity at all those receptors.

Example: Explain how this is true with Beta Blockers

Good or Bad.

Good: A drug that blocks both Beta and Alpha receptors are good anti-hypertensive agents

Bad: B Blocker might also block serotonin receptors and cause bad dreams

1. Pre-Threshold: Few receptors in the body are bound by a drug. It is such a small response, it is not detectable in a whole animal or person.

2. Threshold is Reached: Response can be detected. More drug produces a bigger effect because more receptors are bound.

3. Plateau: All receptors are bound by a drug. No matter how much more drug is received, no additional response is produced.

Drug Response Curve

Once the threshold is reached, will a response be detected?

Drug Response Curve

What occurs at the plateau of the drug response curve?

Drug Response Curve

Before the threshold is reached, can a response be detected?

The amount of drug needed to produce the same a desired result.

A more potent drug binds to the receptors more avidly, so that a high proportion of receptors are bound with the drug, even at low doses.

Less potent drug is not attracted to the recetpors to the same extent and it takes higher doses to produce the same degree of receptor occupancy

Efficacy - we want the drug to work.

Some drugs will never create a desired response like others - Example: Morphine for pain will create a needed result for someone going through surgery, where tylenol would not even compare. In this situation, tylenol would have less efficacy and morphine would have more

Modified Occupancy Theory

What are the 3 things the Modified Occupancy Theory takes into account that the Simple Occupancy Theory did not?

A drug binding to a particular receptory may:

1. Mimic the endogenous ligand's activity at that receptor

2. Produce a lesser effect than the endogenous ligand

3. Produce no effect

** A drug that produces no effect at the receptor will produce an effect in the body by preventing the bindg of the endogenous ligand.

Modified Occupancy Theory

A drug that produces no effect at the recetpor will produce an effect in the body by .......

Full

A receptor is a macromolecule with endogenous ligands.

A ligand is a chemical that binds to a receptor and activates it, causing come change to occur

Explain the types of agonists and how they are related to the endogenous ligand.

A. Full Agonist

B. Partial Agonist

C. Antagonists

Full Agonist: Full intrinsic activity (mimcs the endogenous ligands)

Partial Agonists: Less than full intrinsic activity (Less efficacious than full agonists)

Antagonists: No intrinisic activity; block the activity of the endogenous ligand by occupying the receptor

Agonist (intrinsic ligand)

If there is no endogenous ligand, there was no effect anyway, so blocking it won't do anything

Which of the following terms is defined as "the ability of a drug to activate a receptor upon binding"?

A. Affinity

B. Intrinsic Activity

C. Efficacy

D. Potency

1. A competitive antagonist binds reversibly to the receptor, causing the bound drug to be in equilibrium with the unbound drug

2. As a molecule unbinds from the receptor, its place will be taken by another molecule of the same drug or by a molecule of the endogenous ligand

3. If we want to overcome the effect of the 1st drug (antagonist), we could give a 2nd drug (agonist) in a high dose, increasing the chance that a vacant receptor will be occupied by the 2nd agonist drug in place of the 1st antagonist drug

4. At high enough concentrations of the agonists, we "win the competition", ensuring that vacant receptors will always bind to agonist.

Receptor Sensitivity

What happens to receptors that are continually exposed to an agonist?

Rapid Downregulation: Tachyphylaxis (diminished response) or Desensitization

Slow/Permanent Downregulation: Tolerance or tachyphylaxis

Ex: Opiate drugs need to increase dose for the effect

People who take opioid drugs for chrnoic pain gradually have to increase teh dose because the dose they are taking becomes ineffect in relieving their pain (Opioid tolerance)

As a result, they may be taking doses that will cause a respiratory arrest in a drug-naive person. However, they are able to remain active and alert because they have tolerance to the drug.

* Receptor downregulation

Anythign that speeds up elimination of the drug will result in lower drug levels and a less effect (pharmacokinetics)

When a person takes an antagonist for a long period of time, receptors may upregulate so there are more of them per cell

The antagonist still has an effect if its present in high concentrations

The problem comes when the person stops taking the antagonist; Since there are more receptors, the endogenous agonists will have a pronounced effect called supersensitivity

Downregulation: Process by which a cell decreases the quantity of cellular components

Upregulation: Process by which a cell increases the quantity of cellular components

True or False

Sudden discontinuation of a drug allows the endogenous agonist to have access to the receptors, is not dangerous.

False

It is very dangerous

Desensitization causes the endogenous agonist to produce a deficiency state (whatever natual fucntion that drug was affecting, they are not able to produce the same function)

Increased sensitization causes the endogenous agonist to produce greatly exaggerated effects

1. Response is strictly defined. (Ex: 10% reduction in BP)

2. If a low dose is given, a few people will exhibit a response. These people are removed from the mix.

3. As the dose increases, more and more people will achieve a response

4. At some dose, ll of the subjects will achive a response.

5. When the curve is plotted, there will be some dose at which 50% of the population tested will have an achieved response. This dose is called the effective dose 50% or ED50

Lethal Dose 50

How is it determined?

Lethal Dose 50 (LD50): Is the point on the frequency distribution where 50% of people have had a deadly reaction due to the dosage

Not determined in animals; instead we determine the maximum tolerated dose in humans

Therapeutic Index is LD50 divided by ED50

Larger the TI, the safer the drug.

Ex: If a Drugs ED is 50mg but the LD is 100mg - the TI is only 2 - meaning there is a severe chance of overdosing

Ex: If a drugs ED is 50mg, but the LD is 1,000mg - the TI is 20 - meaning that a person would need to take 20 times the ED for the drug to become lethal - this is a safer drug

A frequency distribution curve for an antihypertensive agent shows an ED50 of 10 mg when the response is defined as a 10% lowering of blood pressure. What would happen if the response definition were changed to a 25% lowering of blood pressure?

A. The curve will shift to the right (toward higher doses)

B. The curve will shift to the left (towards smller doses)

C. The cuve will not change

D. The curve will broaden

Anaphylaxix, rashes, hives

Patients should discontinue the drug right away

The patient could be given another drug that produced the same therapeutic effect in the hope that he/she would not be allergice to the new drug

Exception to this is an allergic reaction to nonsteroidal anti-inflammatory agents (NSAIDs), such as aspirn on ibuprofen