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Lecture 1Units 1 & 2

N307:Pharmacology for NursingBy Juan M Gonzalez BSN, RN

+History of Pharmacology

(from Greek words meaning medicine and study)

Began with the use of plants (Herbal Medicine) Known as “Materia Medica”

Term Pharmacology 1st used in text 1693 (Samuel Dale)

Modern Pharmacology Fredrick Serturner (morphine from opium) 1805

Injected himself and 3 friends with massive dose… survived it 1st Dept. of Pharm 1847 in Estonia American Pharm John Jacob Abel

Father of American Pharmacology 1890 1st Pharm Dept in US

University of Michigan

+Nursing & Pharmacology

Pharmacology was developed in the early stages to relieve suffering

To comprehend pharmacology, other areas such as patho and chemistry must be understood

Medications used improperly is the most common cause of harm to our patients

Nurses are the frontline of medication in patients

It’s not enough to know the medication, you must know the patient

All medications are potentially fatal

+Definitions

Therapeutics Branch of medicine to relieve suffering and disease prevention

Pharmacotherapy Application of drugs for disease prevention and relief of suffering

Drug Chemical agent before it’s administered

Medication Chemical agent that has been given

Biologics Naturally produced agents (hormones, antibodies)

OTC Over-the-counter

Formulary List of drugs and their recipes

+Regulations & the FDA

1906- pure food & drug act

1912- Shirley amendment

1938- Food, drug, & cosmetic act (FDA) 1st law preventing sale of non-tested drugs

1988- FDA established (improved) Agency of the US Dept of Health & Human Services Center for Drug Evaluation & Research (CDER) Center for Biologic Evaluation & Research (CBER) Center for Food Safety & Applied Nutrition (CFSAN)

1994- Dietary supplement health & education act

+FDA

US Dept of Health & Human Services

1988- FDA established as an agency Center for Drug Evaluation & Research (CDER)

Controls PTC & Rx drugs Must show safety & efficacy before selling drug

Decides if they are allowed to be used in US All information should be clear for safe use

ALL Rx MUST get FDA approval to be used in US Center for Biologic Evaluation & Research (CBER)

Regulations vaccines, blood, & serums 1986- Childhood vaccine act

Center for Food Safety & Applied Nutrition (CFSAN) Monitors & regulates herbal supplements

These do not have to have FDA approved (1938)

+Approval Stages

4 Phases 1. Preclinical investigation 2. Clinical investigation 3. Review of the New Drug Application (NDA) 4. Postmarketing surveillance

+Preclinical Investigation

Can take up to 3 years

Use of animal studies & cultured cells

Need to try and determine safety Will it cause harm to humans? Tested in variety of doses Actual human risk is not determined

Results are inconclusive

+Clinical Investigation

3 Stages Clinical Phase trials 1-3

Longest part of approval process Can take up to 10 years Average is 5 years

Start with healthy individuals, then large groups with the disease

+Clinical Phase Trials

Phase I A ‘new drug application’ must be submitted before moving

to the next stage An IND (investigational new drug) application may be

submitted for Phase I if there is enough evidence to prove safety in humans and there are significant benefits to getting the medication out to the public (cancer, AIDS)

Naming the drug begins here

Phase II

Phase III

+NDA review

Finalizing the ‘brand name’ of the drug

Clinical Phase III and animal testing continue depending on results from pre-clinical testing

May take up to 24 months

FDA has 6 months to initially review this by law Approved- will move to next stage Rejected- process is suspended until concerns are

addressed

+Postmarketing surveillance

Final stage in the FDA approval process

Looking for any harmful effects in a very large population

Looking for adverse effects that take time to be discovered

+FDA Recalls

At any given time, the FDA has the power to pull drugs that have been approved off the market

There must be significant harm to humans before they pull a drug

The benefits must outweigh the risks for any drug

+Recent Changes

Due to the cost ($802 million) to bring a drug to market and the lengthy waiting time for the approval process, the Prescription Drug User Fee act (1992-1996) was negotiated. Over a 5-year period, manufacturers provide a yearly product fee that goes to fund more personnel and restructuring in the approval departments. This decreases the time needed to reach approval status

In 1997, the FDA Modernization Act reauthorized the Prescription Drug User Fee Act

In 2007 the FDA Amendments Act expanded the reform

In 2008 target base revenue for new drugs was over $392 million

+Nursing & Approval Process

Most commonly nurses participate in the approval process during the postmarketing surveillance

In clinical trial phase II & III, nurses monitor for side effects, adverse effects, and therapeutic benefits

+Definitions in Classes and

Schedules of Drugs

Therapeutic classification Combination drug

Pharmacologic classification Bioavailability

Mechanism of action Negative formulary list

Prototype Dependence

Chemical name Withdrawal

Generic name Scheduled drugs

Trade name Controlled substance

+Classification of Drugs

Therapeutic classification- how it’s useful in treatment of a disease (usually too broad to really learn the drug)

Pharmacologic classification- the way it works at a molecular or system level (more specific)

See tables 2.1 & 2.2 page 12 in text

Nurses use both of these classifications to learn the drugs, and to monitor their patients’ safety and benefits from the drugs

+Prototypes

A drug that is well understood in the classification

May be one that is seldom used now due to newer, safer drugs available

If you learn the prototype correctly, you will be able to ascertain outcomes and averse effects of any drug in the same class

Prototypes differ from text to text and source to source

+Drug Names

Combination Drugs

Chemical Name Has only 1 Names the physical and chemical properties Very hard to remember most of these

Generic Name Assigned by the US Adopted Name Council Usually less complicated than the chemical names Only 1 generic name Lower case

Trade Name Assigned by the company that marketed it

US gives them the rights for 17 years after a NDA is submitted Helps the developing company get back some of the cost

Also called the product or brand name Capitalized

+Brand Name or Generic???

Does it really matter?

Dosages may be the same, but the formulary may not be May have a different ‘look’ (tablet, capsule) Look for the bioavailability of the drug

How long it takes to get to the source of the problem Inert ingredients can hinder this

Negative Formulary List (Florida) Can’t dispense as generic version

Brand Name For the 1st 17 years, the only available form is the brand name drug It’s typically expensive because it has ‘cornered’ the market

Generic Name Less expensive (usually) than brand name Some can be automatically used in lieu of brand name No generic if prescription states do not substitute

+Controlled & Scheduled

Scheduled drugs are classified by their potential to be abused Not all scheduled drugs are controlled I-V (V has lowest potential of abuse) II- has a LOT of limitations I- usually in cancer patients OR research DEA #s are recorded and monitored as to how much each provider

dispenses Some states are trying to limit the amounts providers and

pharmacies can dispense

Controlled is a drug that has restrictions, and requires a ‘count’ at the end and beginning of all shifts Doesn’t have to be a scheduled medication

Some hospitals count Protonix

+Pharmacokinetics (Definitions)

Pharmacokinetics Active Transport

Absorption Passive (diffuse) Transport

Distribution Affinity

Drug-protein Complexes Blood-Brain Barrier

Fetal-Placental Barrier Conjugates

Cytochrome P-450 Prodrugs

Enzyme induction 1st Pass Effect

Excretion Minimum Effect Concentration

Toxic Concentration Therapeutic range

Plasma ½ Life Loading Dose

Maintenance Dose

+How the Body Handles Meds

Pharmacokinetics means ‘medicine’ & ‘movement/motion’

The greatest barrier is crossing membranes As a drug is taken, it changes formulary each time it

crosses a system or membrane Depending on how the drug enters the body determines

which barriers it comes up against Stomach acid Liver enzymes Immune system

If seen as a threat to the body

+Passing Through

Lipid Bilayers

May use other means to produce effects

Bind to receptors

Activate a 2nd messenger within the cell

Impermeable to large molecules/ions & water soluble

Ionized drugs & water soluble drugs

Easily permeated if molecules are small, nonionized, and lipid soluble

Urea, alcohol, water (lipid soluble)

Active Transport

Passive (Diffuse) Transport

+Active transport

the movement of solutes (or molecules) across a plasma membrane from a region of low concentration to a region of high concentration which requires energy.

Think of this as you requiring energy to carry pebbles from the bottom of a mountain up and putting them on a huge pile of pebbles at the top of the mountain.

+Diffuse (Passive) Transport

the movement of solutes down the concentration gradient across a plasma membrane from a region of high concentration to a region of low concentration.

Think of this as flowing down the concentration gradient: going from being crowded to not crowded. The molecule wants space so this is what it will naturally do, so it doesn't take any energy, like a waterfall.

+Medication Absorption

Involves movement from the site of administration, across membranes, to circulating fluids

Can be across skin or membranes

Primary factor determining how long it takes to get an effect of the drug

Speed of absorption depends on form of drug

The critical nature of a patient’s condition depends on a faster absorption rate of a medication

+Absorption Factors

Dose of medications can affect the rate of absorption

Ionization of the meds

pH of the local environment

Drug-Drug & Food-Drug factors affect it as well

+Absorption in the Lifespan

Pregnancy & Lactation Hormone changes Slowed GI motility & increased acidity Increased respiratory rate Teratogens Categories (7.1) Lactating

Shorter ½ life is best High protein-binding ability best

Children IM sites vary on age & muscle mass Safety containers

Middle-Age Health-wise is comparable with the young adult until after the age of 45

Elderly Need lower doing Polypharmacy is an issue Higher rate for adverse effects Slower absorption rate, faster toxicity levels

+Distribution

How the drug (agent) is transported through the body to the system

Factors that can affect this include: Amount of blood flow to the tissues Lipid solubility of the med Type of tissue and affinity

Adipose tissue, bone marrow, teeth, eyes Calcium salts, lipid-soluble vitamins, valium

Drug-Protein complexes have to be unbound Competing medications Barriers

Blood-brain Fetal-Placental

+Lifespan &

Distribution/Metabolism/Excretion Pregnancy & Lactation

Higher circulating volume

Children Depending greatly upon development age and maturity of systems

Middle-Age Adult After 45 y/o, may begin taking multiple meds for Dz

Elderly Increased body fat leads to more drug storage Have decrease in plasma levels because of this Easily dehydrate, increasing toxicity possibility Aging liver, heart, kidneys

+Metabolism

Chemical conversion of a drug to a form the body can access and then eliminate

Sites of metabolism Liver

Primary site for majority Cytochrome P-450 enzyme

Can inactivate a drug to be excreted Can increase activation of a drug

Prodrugs have no action until they are changed into their active form

Enzyme induction is the increase of metabolic activity in the liver They need higher doses to reach a beneficial effect

Kidney Cells

+Metabolism Factors

Age Elderly and children

Always start low and go slow Can become toxic easily

First Pass Effect Oral meds are the biggest problem here These meds need to be administered in alternate forms if

too much of the med is inactivated by the 1st pass (hepatic metabolic reaction)

+Excretion

Removing the drugs from the body

Factors that can affect this: Renal failure Liver failure

Sites of excretion Bile

Biliary secretion can take several weeks Saliva, sweat, breast milk Respiratory

Faster the breaths per minute the faster the excretion Kidneys (most common)

Glomerulus Renal tubule Distal tubule of the nephron

+Plasma, ½ Life, Dosing

Therapeutic responses correlate with plasma levels Minimum effective concentration Toxic concentration Therapeutic range

½ Life Determines how long a drug stays in circulation Determines dosing regimen

Loading Dose Larger than the maintenance dose To bring up plasma levels

Maintenance Dose To keep plasma levels at a constant

+Pharmacodynamics

Means ‘medicine’ & ‘change’

Therapeutic indexes, dose-response relationships, & drug-receptor interactions determine course of treatment Therapeutic index

Tells us the safety issue in the range of dosing Median lethal dose (LD50)

Differentiate between toxic and lethal The higher the LD50 the safer the drug

Dose-response relationship To find the most beneficial dose at the lowest mg Potency- the more potent the drug, means a therapeutic effect is reached at a low

dose range Efficacy- MORE important… it works best for the problem

Drug-receptor interaction Drugs bind to specific receptors They can stimulate or inhibit They compete for receptor sites (survival of the fittest)

+Psychosocial, Cultural, &

Gender Issues Holistic Care

Taking into account the entire individual

Psychosocial Influences It’s not just about the disease, but how they view themselves spiritually, have hope, and support Worrying about how other’s view them

Cultural & Ethnic Influences Does it go along with their belief system Does it correlate with their religious practices

Community & Environmental Influences Financial restraints Transportation issues

Genetic Influences Certain ethnicities are predisposed to diseases Some drugs have been found to either work better or are less than effective depending on the ethnicity

Gender Influences Men and women are vary different when it comes to medications Some meds work better for men, others for women Some side effects of meds effect the genders in ways that will prevent compliance with the regimen