Pharmacology Chapters 1-13

Drug

Any substance that is taken to cure, or reduce symptoms of a medical condition.

Pharmacology

The study of medicine.

Pharmacotherapy/Pharmacotherapeutics

Application of drugs for the purpose of disease prevention and treatment of suffering.

Indications and Contraindications

The conditions for which a drug is approved are its indications. Every drug has at least one indication. Some drugs are used for conditions for which they have not been approved; these are called unlabeled or off- label indications.

Therapeutic classification

-Based on their usefulness in treating a specific disease
-The key to therapeutic classification is to simply state what condition is being treated by the particular drug.
-The prefix anti- refers to therapeutic classification.

Pharmacologic Classification

-Addresses a drugs mechanism of action or how a drug produces its effect in the body.
-More specific than therapeutic
-Requires biochemistry and pathophysiology

Chemical name

-Assigned using standard nomenclature.
-A drug has only one chemical name
-Helpful in predicting a drugs physical and chemical properties.

Generic name

Name assigned by the United States Adopted Name Council.
Less complicated and easy to remember.

Trade Name

Sometimes called the proprietary product, or brand name is assigned by the pharmaceutical company maketing the drug.

Exclusivity

Typical length of exclusivity for a new drug is 5 years.

Combination drug

Drugs with more than one active generic ingredient.

Pros and Cons of Generic Drugs

Generic drugs are less expensive than brand name drugs, by they may differ in bioavailability. (The rate at which drug produces its effect.)

The nurses responsibility for knowledge in regards to pharmacotherapeutics...

Is what drug is ordered including name and drug classification, intended or proposed used, effects on the body, contraindications, special considerations (how age, weight, body fat distribution, and pathophysiologic states affect pharmacotheraputic response), expected and potential adverse events, why the drug was prescribed how the drug is supplied by the pharmacy, administration of the drug, and what considerations apply to the patient.

The major goal to study pharmacology...

is to eliminate medication errors and to limit the number and severity of adverse drug events.

To prevent medication errors RN's can

Routinely apply their experience and knowledge of pharmacotherapeutics to clinical practice. It is vital the nurse be prepared to cognized and respond to potential adverse effects of the medication.

Pharmacotherapy and the older adult
(pharmokinetic and pharmodynamics).

Normal aging processes can alter pharmacokinetic and pharmacodynamics responses to drugs.

Pharmacotherapy and the older adult
(absorption)

Overall, absorption of nutrients and drugs tend to slow with aging.

Pharmacotherapy and the older adult (plasma levels drug concentration in tissues)

Age related increases in fat storage cause lipid soluble drugs to be stored in the body for extended periods, leading to lower plasma levels and increased drug concentrations in the tissues.

Age related changes in the liver

Include reduced hepatic function, decreased liver mass, diminished blood flow, and alteration in the activity of hepatic enzymes.

Frequency of administration for older adults

Should be decreased to avoid toxicity due to drug accumulation.

Older adults and receptors

Pharmacodynamic changes are usually associated with drug receptors. Evidence suggests that older adults have a decreased number of receptors.

The government agency that is responsible for regulating drugs in the United States.

FDA-Food and Drug Administration.
o Protect the public health.
o Speeding innovations that make medicines and food more effective.
o Helping the public get more accurate information.

Overall process to get new drugs on the market.

o Step 1-Pre-Clinical research: Involves extensive lab testing by the parmacutical company. If the drug appears promising the pharmaceutical company submits an investigational New drug (IND) application. (contains animal testing)
o Step 2: After animal testing comes clinal phase trials which is the longest part of the approval process. The clinical trial has three different phases.
• Phase 1- testing is conducted on 20-80 healthy volunteers for several months to determine proper dosage and to assess for adverse effects. If unaccepted levels of toxicity are noted, trials are stoped.
• Phase 2- Several hundred patients with the disease are treated with drug. Compared with a placebo to test effectiveness. Also can be compared to a drug already available.
• Phase 3- Large numbers of patients with the disease are given the drug to determine patient variability. Patients with chronic conditions are given the drug to determine safety.
o Step 3: If the new drug shows promise a New Drug application is submitted to the FDA. If accepted, manufacturer may be able to start selling the drug.
o Step 4- Post market surveillance: Occurs after the NDA review has been completed. The purpose of stage 4 is to survey for harmful drug effects in a larger population.

Difference between over the counter and prescription drugs.

o Prescription medications are judged by the FDA to be potentially addictive or too harmful for self administration
o Prescriptions give an opportunity for a doctor to assess your problem and treat more complex problems.
o OTC drugs allow patients to treat themselves and are obtained much easier.
o A prescription drug can become OTC when there is a high margin of safety that exists with the medicines.
o Herbal medicines are different from prescription and OTC drugs because they are not considered drugs. They are not marketed to treat any disease and are not subjected to the same regulatory process as drugs. Some herbal products can interact with medications.

Drug adherence

Is defined as taking medications in the manner prescribed by the health care provider.

The nurses role in facilitating drug adherence

Is asking questions about taking the medication, effective teaching, create a personalized care plan, and during follow ups the nurse should re-enforce this drug education and assess whether the patient is taking or receiving the drugs correctly.

Standing orders

Medications given on a regular schedule are called standing orders.

Stat Order

Refers to a medication that is needed immediately, usually because of an emergency or life threatening situation.

Prn

Order is administered as required by the patients condition (when needed/necessary).

Prn q4n

Administer drug only once every 4 hours.

Enteral Medications

Includes drugs delivered to the GI tract, either orally or through nasogastric or gastrostomy tubes. o Most common, most convenient and least costly
o Intended for absorption to the general circulation.
o Extended release formulations: contain a high amount of medication that is intended to be released over an extended period. Opening the capsule or crushing the tablet will release the entire drug immediately, possibly resulting in a toxic effect.

Enteric-Coated drugs

When crushed or opened these drugs are exposed to stomach acid, which may destroy them. The drugs may irritate the stomach mucosa and cause nausea or vomiting.

Topical medications

Applied to the skin or mucous membranes.
o Includes medications applied to the skin or the membranous linings of the eye, ear, nose, respiratory tract, urinary tract, vagina, and rectum.
o Dermatologic are applied to the skin
o Instillations and irrigations are applied to the body cavities or orifices (eyes, ears, nose, bladder, rectum, and vagina)
o Inhalations are drugs applied to the respiratory tract by inhalers, nebulizers, or positive pressure breathing machines.

Parenteral Administration

Dispensing of drugs by routes other than enteral or topical. A needle is used to deliver drugs into the skin layers, subcutaneous tissue, muscles, or veins. More invasive than topical or enteral because of the potential for introducing microbes directly to blood and tissues.

Pharmacokinetics

-Derived for the root words pharmaco, which refers to medicines and kinetics, which means "movement" or motion. Pharmacokinetics is the study of drug movement throughout the body.
-Majority of drugs produce their effects in target cells. First they must cross the plasma membrane and enter cells to produce their effects.

The process of pharmacokinetics is grouped into 4 categories...

Absorption, distribution, metabolism, and excretion.

Absorption

-Process by which drug molecules move from their site of administration to the blood.
-Absorption is the primary pharmacokinetic factor determining the onset of drug action

The faster the absorption...

the faster the onset time.

Drugs administered by IV route bypass...

absorption entirely.

Inhalation is rapid because...

the membrane separating the inhaled drug from the bloodstream is very thin.

Tablets and capsules must dissolve before the drug is available for absorption which means onset is slow...these are...

Oral liquid pills don't undergo dissolution therefore they are faster than other pills.

Topical medications applied to the skin are absorbed slowly because...

it is difficult for penetration through the thick keratin. Topicals applied to mucous membranes are absorbed faster because they are thin with a richer blood supply.

Higher doses produce a faster and greater response because...

a high dose produces a greater concentration gradient for diffusion.

Most absorption occurs in the...

small intestine.
• Rapid GI motility may speed the drug without complete absorption.
• Slow motility may cause the drug to be retained in the stomach where it is exposed long to destructive enzymes and stomach acid.
• Fatty food slow drug absorption. Absorption is most complete between meals, full stomach may lessen nausea but slows absorption.

For a drug to be absorbed there must be...

Be adequate blood flow. Therefore drugs are absorbed faster where blood flow is high. Large muscles have high blood flow which maximize absorption.

Distribution

Movement of pharmacologic agents throughout the body after they are absorbed

The simplest factor in determining drug distribution.

The amount of blood flow to the body tissues. Heart, liver, kidneys receive greatest % of blood flow so these organs receive the highest exposure to absorbed drugs. Skin, bone and adipose tissue receive little blood flow.

Drug solubility

Lipid solubility determines how quickly a drug is absorbed, mixes in the blood stream, crosses membranes, and becomes localized in body tissues.

Are lipid soluble drugs more distributed to the body tissues?

Yes-they are not limited by barriers that water soluble drugs are so thus they are more distributed by body tissues.

Protein binding

Many drugs bind reversibly to plasma proteins to form drug-protein complexes which are too large to cross capillary membranes. The drugs the continue circulation in the bloodstream and are unavailable for distribution to their site of action. Drugs remain trapped in the bloodstream until they are released or displaced. Only unbound or free drugs can reach their target cells or be excreted by the kidneys.

Metabolism

Also known as biotransformation is the process used by the body to chemically change a drug molecule. • Prodrug- Agents that require metabolism to produce their action. Ex: enalapril (vasotec) is converted in the liver to enaliprat which has more of an effect on lowering blood pressure than the original drug.

Role of enzymes/factors that impact metabolism

Most metabolism in the liver is accomplished by the hepatic microsomal enzyme system. (P450 system named after cytochrome P450 (CYP) which is a key component of the system.)

First pass effect

Mechanism whereby drugs are absorbed, enter into the hepatic portal circulation, and are inactivated by the liver before they reach the general circulation.

Excretion

Drugs will continue to act on the body until they are either metabolized to an inactive form or removed from the body by excretion.

The therapeutic response

Of most drugs depends on their concentration in the plasma.

Therapeutic range

is the range in which the drug produces its desired therapeutic action.

Duration of action

The length of time a drug concentration remains in the therapeutic range

Plasma half-life

The length of time required for the plasma concentration of a drug to decrease by on half after administration. As a rule of thumb, when a drug is discontinued it takes approximately four half-lives before the agent is considered "functionally" eliminated.

Loading dose

Is a higher amount of drug, often given only once or twice, that is administered to "prime" the bloodstream with a level sufficient to quickly induce a therapeutic response. Before plasma levels drop back toward zero, intermittent maintenance doses are given to keep the plasma drug concentration in the therapeutic range.

Pharmacodynamics

The branch of pharmacology concerned with the mechanisms of drug action and the relationships between drug concentration and responses in the body.

Pharmacogenetics

The branch of pharmacology that examines the role of genetics in drug response.

Therapeutic index

Describes a drug's margin of safety.

Median lethal dose (LD50)

is a value often determined in lab animals in preclinical experiments during the drug development process. It will only kill half.

Median effective dose (ED50)

is a value showing the production of a therapeutic response in half of test subjects.

Therapeutic index ratio

is defined as the ratio of a drugs LD50 to its ED50. o If the difference between an effective dose and a lethal dose is very small for drug z then the drug has a narrow safety margin.

There are two fundamental ways to compare medications within therapeutic and pharmacologic classes.

o Potency- the strength of a drug at a specified concentration or dose. A drug that is more potent will produce its therapeutic effect at a lower dose. (amount and strength given)
o Efficacy- the greatest maximal response that can be produced form a particular drug. (the max response of drug)

Receptor theory

o Most drugs produce their actions by activating or inhibiting specific cellular receptors.
o Drugs rarely create new actions in the body, instead they enhance or inhibit existing physiological and biochemical processes.
o A cellular molecule to which a medication binds to produce its effects is called a receptor.
o Receptor theory predicts that the response of a drug is proportional to the concentration of receptors that are bound or occupied by the drug. The theory explains the mechanisms by which most drugs produce their effects.
o Drugs that have the ability to bind to a receptor and produce a strong action are said to have high intrinsic activity.

Agonist

A drug that activates a receptor and produces the same type of response as the endogenous substance is called an agonist.

Partial Agonist

Partial agonist is used to describe a medication that produces a weaker, or less efficacious, response than an agonist.

Antagonist

A second possibility is that a drug will occupy a receptor and prevent the endogenous chemical from binding to produce its action. This type of drug, an antagonist, often competes with agonists for receptor binding sites.

Idiosyncratic response

An unpredictable or unexplained drug response, in the future, pharmacogenetics may allow customization of drug therapy to each patients individual molecules.

Adverse drug effect

An undesirable and potentially harmful action caused by the administration of medication. When severe, can cause treatment to be discontinue or result in permanent damage to the patient.

Side effects

Types of drug effects that are predictable and which may occur even at therapeutic doses. Less serious than adverse effects

What constitutes a serious adverse drug effect?

o Result in a patient's death, hospitalization, or disability
o Cause a congenital abnormality
o Cause a life-threatening event
o Require an intervention to prevent permanent damage
o Ex: impairment or failure of entire organs, such as cardiac, hepatic, or renal failure or loss of vision or hearing, Anaphylaxis, Stevens-Johnson syndrome (SJS), cancer, and birth defects.

Common side effects

Nausea, vomiting, and headache.

Nursing knowledge and behaviors to help prevent/minimize side effects

o Take a thorough medical history
o Thoroughly assess the patient and all diagnostic data
o Prevent medication errors
o Monitor pharmacotherapy carefully
o Know the drugs
o Be prepared for the unusual
o Question unusual orders
o Teach patients about adverse effects

Adverse event reporting system

A voluntary program that encourages health care providers and consumers to report suspected adverse effects directly to the FDA or the product manufacturer.

Drug allergy

Common events, comprising 6% to 10% of all adverse drug effects.
o All are caused by a hyper-response of body defenses.
o Signs and symptoms of drug allergies are non-specific

Teratogen

a drug that causes birth defects

Drug interaction

Occurs when a substance increases or decreases a drugs action. Potential outcomes for such interactions...
o The actions of the drug can be inhibited, resulting in less therapeutic action.
o The actions of the drug may be enhanced, causing a greater therapeutic response.
o The drug interaction my produce a totally new and different response.

Additive effect

The pharmacodynamics drug interaction that is easiest to visualize. In this reaction two drugs from a similar therapeutic class produce a combined summation response. Using lower doses of two drugs compared to a high dosage of one drug helps avoid adverse side effects.

Synergistic effect

The effect of the two drugs is greater than would be expected from simply adding the two individual drugs response. Used extensively in treating infections.

Antagonist effect

Occurs when adding a second drug results in a diminished pharmacologic response. This effect can result in drug actions being cancelled. Can be used to treat symptoms of a drug overdose.

Interactions between grapefruit juice and medications

o Grapefruit juice contains substances that increase the absorption of certain oral drugs. This occurs because grapefruit juice inhibits the enzyme CYP3A4 in the wall of the intestinal tract. As drugs are absorbed, they are not inactivated by CYP3A4, and higher amounts reach the circulation.
o This can last up to 3 days after drinking the juice
o The medications that cause this interaction are benzodiazepine, certain calcium channel blockers, and statins.

Black box warning

In some drug inserts, a requirement by the FDA that warns prescribers that the drug carries a risk for serious or fetal adverse effects.

Medication error

is "any preventable event that may cause or lead to inappropriate medication use or patient harm while the medication is in the control of the health care professional, patient, or consumer."

How to prevent medication errors

o Implement a process for obtaining and documenting a complete list of all the patient's current medications on the patient's admission.
o Communicate a complete list of the patient's medications to the next provider of service.
o When discharging from the facility, provide a complete list of medications for the patient.
o Educate patients on knowing the names, side effects, how to read labels, and contact information for a pharmacist.
o Agencies can store medications in proper conditions, avoid overstocking, removed outdated reference books, and avoid administration of expired drugs.

Addiction

an overwhelming compulsion that drives someone to repeat drug-taking behavior, despite serious health and social consequences.

Physical dependence

Occurs when the body adapts to repeated use of the substance by altering normal physiology.

Physiological dependence

Produces no signs of physical discomfort after the agent is discontinued.

Tolerance

a biologic condition that occurs when the body adapts to a substance after repeated administration.

Withdrawal syndrome

Once a patient becomes physically dependent and the substance is abruptly discontinued.

Controlled substance

A drug whose use is restricted by the Comprehensive Drug Abuse Prevention and Control Act of 1970 and later revisions. Title II of this law, known as the Controlled Substances Act (CSA), is the legal basis for regulating drugs of abuse. The CSA created five categories or schedules for drugs of abuse. These scheduled drugs are classified according to their potential for abuse and toxicity.

Schedule I

Abuse Potential + Physical Dependence + Physical/Psychological Dependence=HIGH
Heroin, GHB, LSD, Maijuana, MDMA, mescaline, methaqualone, methcathinone, peyote, and psilocybin. No prescriptions may be written.

Schedule II

AP + PD + Psy.P = High Potent opioids (such as codeine in high doses, fentanyl, methadone, morphine, oxycodone, meperidine), amphetamine, cocaine, methamphetamine, methylphenidate, PCP, short-acting barbituates. Used therapeutically with prescription; some drugs are no longer used; normally no refills are permitted (but there are a few exceptions).

Schedule III

AP: Moderate PD: Moderate PsyP:High. Anabolic steroids, buprenorphine ketamine, codeine (lower doses compounded with aspirin or acetaminophen), hydrocodone (lower doses compounded with aspirin or acetaminophen), and intermediate-acting barbituates. Used therapeutically with prescription; five refills allowed in a 6 month period.

Schedule IV

Lower + Lower + Lower. Benzodiazepines (such as alprazolam, diazepam, midazolam, temazepam), long-acting barbituates, meprobamate, pentazocine, and zolpidem. Used therapeutically with prescription; five refills allowed in a 6 month period.

Schedule V

Lowest + Lowest + Lowest. Over-the-counter (OTC) cough medicines with codeine, antidiarrheal medicines with small amounts of opioids. In some cases, these may be dispensed by a pharmacist in small amounts without prescription.

Nursing process

• Assessment- Consists of gathering subjective data, which includes what the patient says or perceives, and objective data gathered through physical assessment, laboratory values, diagnostic tests, and other measurable sources.
• Diagnosis- Assessment data are used to develop a list of problems that address the patients responses to health and life processes. These problems, or nursing diagnosis, are used to set goals and plan and direct care.
• Planning- includes developing appropriate goals and outcomes and determining nursing interventions that will help the patient achieve these.
• Implementing- when the nurse applies the knowledge, skills, and principles of nursing care to help move the patient toward the desired goal and optimum wellness. When applied to pharmacology this involves administering the drug, monitoring effects, carrying out the interventions developed in the planning phase to maximize therapeutic response and prevent adverse events, and teaching the patient or family to administer the medication at home if necessary and about the monitoring required for the drug used.
• Evaluation- Considers the effectiveness of the plan of care and interventions in meeting the established goals and outcomes. If patient has met goals then the problem is resolved, but if the patient has not met the goals the nurse reviews and rewrites the care plan.

Pharmacotherapy and the pregnant patient

o Physiological changes during pregnancy can alter normal pharmacokinetic responses.
o During pregnancy increased levels of progesterone cause a delay in gastric emptying and GI motility. This causes the drugs to remain in the GI tract longer leading to higher drug absorption of oral drugs.
o Distribution of drugs during pregnancy is affected by changes in total body water, which may increase by over 50%. This creates greater dilution of plasma proteins causing more free drugs in the plasma due to lack of binding sites. This then results in more drug molecules being available for transfer across the placenta or to be secreted in breast milk.
o Metabolism is least affected by pregnancy.
o Excretion can cause doses of medications to be adjusted due to enhanced renal plasma flow which can increase 50% to 70% during the first two trimesters.