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What is a drug?
Any chemical that affects the physiologic process of a living organism.
What is pharmocology?
- It is the study of the science of drugs. Incorporates knowledge from these areas:
- Biohchemical effects
- Drug History
- Drug Origin
- Mechansims of action
- Physical and chemical properties
- Physical effects
- Drug receptor mechanisms
- Therapeutic effects
- Toxic effects
What is pharmacognosy?
It is the study of natural drug sources including plants, animals, minerals.
Alkaloids are the most active component in plants, reacts with acid to form a salt that is able to disolve more readily in body fluids.
Usually end in "-in" (digoxin) foxglove=heartconditions.
Gives the products the ability to attract and hold water (seaweed extracts, seeds with starch)
Antibacterial properties as well as a laxatinve, local irritant or caustic agent
- Classified as volatile or fixed.
- Volatile oils=peppermint, spearmint and juniper, dissipates in air quickly.
- Fixed oils-do not evaporate easily eg: castor or olive oil
body fluids or glands can be a drug source.
insulinnn and steroids
Oils and Fats:
cod liver oil and olive oil
pancreatic, sometimes can come from an animal
flu, measles, mumps, hapatitis B
Iron, iodine, epsom salts. Provide inorganic materials not available from plants and animals.
laboratory researchers have used traditional knowledge along with chemical science for the development of drugs. Most drugs produced today are made in labs.
Naming of drugs:
- During the process of drug development a drug will acquire 3 different names:
- Brand or trade name
What is pharmaceutics?
The science of preparing and dispensing drugs, including dosage form design (tablets, capsules, injections, etc.
What is dissolution?
The process by which solid forms of drugs disintegrate in the gastointestinal tract, become soluble, and are absorbed into the circulation. Once dissolved, the effect is systemic.
Three types of drug preparation:
- Aqueous preparations-dissolve in water
- Alcohol preparations-dissolve in alcohol, tinctures
- Solid and semisolid preparations-suppositories, ointments, patches, tablets, capsules etc.
Fastest to slowest absorbed drugs:
- liquids, elixirs, syrups
- suspensions, solutions
- coated tablets
- enteric coated tablets
Tablets, capsules, pills, TR capsules, TR tablets, elixirs, suspensions, syrups, emulsions, solutions, lozenges, rectal suppositories
Injectable forms, sublingual or buccal tablets
Aerosols, ointments, creams, pastes, powders, solutions, foams, gels, transdermal patches, inhalers, vaginal suppositories.
What is Pharmacokinetics?
The rate of drug distribution among various body compartments after a drug has entered the body. It includes the phases of absorption, distribution, metabolism, and ecretion of drugs.
What is Absorption?
The movement of a drug from its site of administration into the bloodstream for distribution to the tissues.
What is Bioavailablility?
The term used to express the extend of drug absorption
What is Bioequivalent?
If 2 drugs have the same bioavailability and the same concentration of active ingredients they are said to be bioequivalent.
What is Solubility?
The solubility of the administered drug must match the cellular environment of the absorptive site. Drugs must be in solution. Lipid solubility is nedessare for any drug that must cross the lipid rich cell membrane. This includes most medications. Solubility depends on the drug's chemical structure and is influenced by the cellular environment at the absorptive site.
- Drugs pass through a cell membrane in 3 ways-
- Through channels or pores- very few drugs pass this way.
- Aid of transport system-may require energy
- Direct penetration of cell membrane-most common and must be lipid soluble.
Systems of transport:
- Passive processes-diffusion, osmosis (problem here is that it is inefficient and slow. Cell and capillary must sit up next to each other) High to low flow. Edema can inhibit this process.
- Active processes-Active Transport; requires ATP, send from low concentration to high.
- Facilitated diffusion- carrier eg insulin. Insulin is the doorman of a fancy hotel. Lets mr. glucose in by opening the door. Cell would die without this glucose.
- Pinocytosis-cell drinking which is a rare phenomenon.
Factors that affect drug absorption:
Food in the stomach and intestines, some meds require food to buffer stomach lining.
Rate of blood flow to the stomach/intestines ex: diabetes will have problems with GI motility.
Acidity of stomach, alkalinity of the intestines Ex: aspirin in the stomach.
FIRST PASS EFFECT- Oral drugs are absorbed through the small intestine into the portal venous system that flows through the liver. The drugs are metabolized in the liver and some of the active drug will be inactivated or diverted before itcan reach the general circulation and its intended site of action. First-Pass reduces the bioavailablily of a drug to elss than 100%. Some drugs which undergo First-Pass may have a bioavailability of 50% or less.
Drug routes that undergo first pass-effects:
- Hepatic Artery
Drug routes that do not undergo first-pass effects:
- topical including some rectal drugs
Refers to the transport of a drug in the body by the bloodstream to its site of action.
Three factors that affect movement of drugs throughout the body:
Blood supply- areas with biggest blood supply get it first: brain,heart, lungs, guts
Ability to exit the vascular system. problems may arise if edema, trauma, scar tissue is present.
Ability to enter into the cell.
Protein Binding (Distribution under Pharmocokinetics)
Some portion of a drug binds to protein in the blood. The most common of these proteins is albumin. Once a portion of a drug binds to protein in the blood it isi not free to rpoduce its desired effects. However, the unbound portion of a drug can produce the desired effect. When two or more drugs are competing for binding sites on protein molecules more of each drug is available to the cells and may cause a drug-drug reaction.
Plasma Protein Competition:
- Drugs that bind to the plasma proteins may compete with other drugs for the protein binding sites. Displacement of a Drug A from plasma proteins by Drug B could lead to toxic levels.
- ONLY UNBOUND DRUG IS FREE TO PRODUCE A THERAPEUTIC AFFECT
Volume of Distribution:
describes various areas where drugs may be distributed. These areas can be blood, total body water, body fat or other tissues and organs.
WATER SOLUBLE-highly water soluble drugs have a small volume of distribution and high blood concentration and tend to stay in the blood. Produces a very slow onset of action EX: Psychotropics.
FAT SOLUBLE-Highly fat soluble drugs have a large volume of distribution and low blood concentration. Chemically repelled by the high water content of the blood. Also cell membranes are mostly lipid soluble and fat molecules pass through these membranes more easily.
Blood Brain Barrier:
It is a protective system of cellular activity that keeps many things away from the CNS. Drugs that are highly lipid soluble are more likely to pass through the blood-brain barrier and reach teh CNS. Drugs used to treat diseases of the CNS must be highly lipid soluble to be effective.
Also referred to as BIOTRANSFORMATION. Involves the biochemical alteration of a drug into an inactive metabolite, a more soluble compound, or a more potent active metabolite.
Where are drugs metabolized?
- Liver is mostly responsible for the metabolism of drugs, can also occur in the plasma, kidneys, and membranes of the intestines. Liver is the primary organ for cleansing the blood.
- Cytochrome P-450 is part of the ensymatic system in the liver.
Factors that alter metabolism-
Genetic, diseases, medications, disease conditions.
- The elimination of drugs from the body. Whether they are active, metabolized or unchanged, all drugs must eventually be removed from the body.
- BUN and Creatinine are tests done to determine kidney function.
Organs of excretion:
- Primary: kidneys
- Secondary: skin, lungs, bile, feces, liver and the bowel
Half Life (Pharmacokinetics)
The time is takes for one half of the original amount of drug to be removed from the body. It is a measure of the rate at which drugs are removed from the body. It takes APPROX. 5 half lives to eliminate drug from the body.
When a drug is taken in successive doses at intervals that are shorter than recommended or when the body is not able to eliminate a drug properly, the drug can accumulate in the body, leading to toxic levels and adverse effects.
Steady State (Pharmocokinetics):
The physiological state in which the amount of drug removed via elimination is equal to the amount of drug absorbed. Steady State is reached in approx. 5 half lives of administered drug. Also takes this long for drug to reach its therapeutic level. Critical concentration is where you start to see the therapeutic effect.
The amount of a drug that is needed to cause a therapeutic effect.
Drugs whose effects may be needed quickly have a recommended higher loading dose. Usually used for drugs that take a prolonged period to reach a critical concentration.
After higher drug levels have been established with a loading dose, smaller doses of the drug are given to maintain the blood concentration of the drug.
Onset of Action:
The time from drug administration to the first observable effect.
The time required for a drug to reach its maximum therapeutic effect. Peak level is the highest blood level of a drug.
Duration of Action:
The length of time that the drug concentration is sufficient to elicit a therapeutic response.
The lowest blood level of a drug. Drug is still in therapeutic range.
Dose Response Curve:
The exact amount of a drug that is administered in order to produce a specific effect. When the relationship between the dose response is plotted as a graph, it is referred to as the dose-response curve. Mechanise use by pharmacologists.
The measure of the strength or concentration of a drug rerquired to produce a specific effect, eg: Morphine 10 mg=dilaudid 1 mg.
Refers to the largest effect a drug can produce.
Factors influencing the body's response to a drug:
- Physiological factors-hydration, fluids and electrolytes
- pathological factors-diseases can interfere with function of drug
- Genetic factors- some people born without certain enzymes for drug metabolism
- immunological factors- allergies
- psychological factors-placebo effect
- environmental factors-should be in cool quiet environment.
- tolerance- requires more medicine eventually to produce same therapeutic affect.
The study of what drugs do to the body and how they do it.
Mechanism of Action or Therapeutic effect
- This can happen in several ways:
- Can increase or decrease the rate at which a cell or tissue functions
- Can modify the strength of a cells function
- Can not cause a cell to perform a function that is not a part of its natural funciton.
Drugs exert their actions in three ways:
- 1. Receptors
- 2. Enzymes
- 3. Nonselective interactions
A drug binds to recpetor sites on the cell and produce an action
a. agonist- drug binds to receptor and produces a response or therapeutic effect.
b. antagonist-another drug binds to receptors and produce no effect. This drug prevents binding of agonists. Inhibitors and blockers.
Competetive antagonists (receptors, pharmodynamics)
drug competes with agonist for binding site on receptor. If it binds, no response, THIS IS A REVERSIBLE REACTION.
Noncompetitive antagonist: (receptors, pharmodynamics)
Binds to the receptor sites and blocks the effects of the agonist, nonreversible action. Giving larger doses of the drug cannot reverse its action.
Proteins that change the rate of chemical reactions without themselves being changed and without an external energy source. Enzymes catalyze nearly every biochemical reaction in a cell. Drugs either enhance or inhibit a cell's action through its interaction with teh cells enzyme system.
Nonselective interactions: (Pharmacodynamics)
Some drugs do not interact with receptors or enzymes. These drugs affect cell membranse and carious cellular processes which alter metabolic activities. These drugs can alter physically or chemically their cellular processes. This is a small group of drugs.
What is Pharmacotherapeutics?
The study of the use of drugs in the treatment of disease.
Types of drug therapy:
- Acute, major trauma
- Maintenance, prevent progress of disease
- Suplemental-needed to maintain a normal function Ex: insulin
- Palliative-used to provide comfort, terminal patiens
- Supportive-maintain integrity of bodily functions, electrolytes and fluid levels
- Prophylactic/Emperic-used to prevent illness
Pt must be evaluated to determine the pt's clinical response to the drug. All drugs are potentially toxic and can have cumulative effects.
The ratio of the drugs toxic level to the level that provide therapeutic benefits. This is how the drug's safety is rated.
Low therapeutic index:
Difference between the therapeutic dose and toxic dose is small. May cause an adverse reaction.
High therapeutic index:
Difference between the therapeutic dose and toxic dose is greater.
Certain drug levels are associated with therapeutic responses and some drug levels are associated with toxic levels.
Concurrent diseases or other medical condtions may impact the pt's response to drug therapy.
When the body becomes accustomed to a particular drug over a period of time, the resonse is decreased.
Occurs when an individual needs a drug to function noramll, can be physiological (physical dependence) or psychological (addiction).
Cross Tolerance/ Cross dependence
Occurs when tolerance or dependence develops to different drugs which are chemically related such as heroin and morphine.
Occurs when a drug is no longer administered to a dependent patient; barbiturates, benzodiazepines. Symptoms-N?V tremors, seizures, Alcoholics cannot go cold turkey.
Drugs may interact with other drugs, food, or agents given as part of a lab test.
Drug- Food Interactions:
Poorly understood, but drug-food interactions can result in toxicity or therapeutic failure. If the rate of absorption is delayed, then the effects of the medication are delayed. Changes in the GI tract can increase, decrease or stop absortpion of medicaitons.
Should be taken on an empty stomach to be absorbed properly.
Iron preparations will:
decrease absorption of calcium.
Chocolate, Spinach, and Nuts will decrease absorption of:
Wheat bran, rolled oats and sunflower seeds will decrease the absorption of:
DIGOXIN, however these food items will lower cholesterol levels in the blood.
Decreases the effects of antihypertension medications. WHen eaten with DIGOXIN it may lead to irregular heart rhythms and cardiac arrest. Licorice and diurtecs may cause potassium levels in the body to fall.
What doubles the absorption of Saquiavir (HIV infections)?
A high calorie meal more than doubles the absorption. If taken without food, absorption may be insufficient for antiviral activity.
Grapefruit and grapefruit juice:
- Can inhibit the metabolism of certain drugs, thereby raising their blood levels. Grapefruit affects the liver's ability to metabolize a drug.
- Calcium channel blockers, statins, psych meds, estrogen, oral contraceptives, and many alergy meds.
Orange juice should not be consumed with:
antacids containing aluminum
Leafy green vegetables high in vitamin K should not be taken in great quantities while taking:
- anticoagulant medications like COUMADIN
- Don't drink Carnberry juice and COUMADIN either. May increase bleeding.
Milk does not mix with some laxatives, will increase effects of laxatives.
Regular and diet soda:
decreases the absorption of calcium.
A combination of MOA inhibitors and aged cheese, wines, yeast extracts, CHianti wine can raise blood pressure to a life threatening level.
Theophyllin(an asthma medicaiton) + caffeine=
excessive CNS stimulation. Charcoal broiled meats and smoking can decrease theophylline levels reducing effectivenss.
Potassium sparing diuretics (Spironolactone) + salt substitutes(main ingredient is KCL)=
dangerously high potassium levels.
Drugs being administered according to the patient's circadian rhythms.
when you add two drugs together smaller doses of each drug are used and produce the same therapeutic effect as if the drugs were given alone in a greater quantitiy. Acetemenophine + oxcycodone, for example.
Response of both drugs is greater than drugs given alone.
drug inhibits the effects of another drug.
When two parenteral drugs or solutions are mixed together and results in chemical deterioration of one or both drugs. Do not give anything with blood in IV (NSS solution)
Drug misadventures: ADE
Adverse drug events-any reaction to a drug that is not expected. This is a broad term to describe any adverse outcome of drug therapy in which a pt is harmed due to interanl (body) or external (staff errors) factors. ADRs can be preventable or non preventable.
Most common ADE is a medicaiton error.
Four ways to prevent medication errors:
- 3 checks 5 rights
- Never use trailing zeros
- Use leading zeros for decimal doses
- Only use metric
Adeverse drug reactions (ADR):
any reaction to a drug that is unexpected and occurs at therapeutic dosages. Less predictable and may or may not be preventable.
Categories of ADR:
- Pharmacologic reactions
- Hypersensitivty reactions
- Idiosycratic reactions
- Drug interactions
a drug used to treat a disease may be more effective than desires, e.g. antihpertensive drug lowers B?P to the point that pt may faint.
An allergic reaction involves the pt's immune system which can result in a mild rash to anaphylaxis, a life threatening rx with airway constriciton caused by bronchospasms, tachycardia and cardiovasular collapse which may result in death.
Sensitivity to one group of drugs may cause a cross sensitivity to another group of drugs that are chemically similar eg: penicillin->cephalosporin
is an unexpected and unpredictable rx to a drug, a genetically determined abnormal response to a drug.
Expected, well-known rxs resulting in little or no change in the pt's management. The presence of side effects may not be a reason for the prescriber to stop a medication. Side effects generally disappear with time.
may threaten life. It can result from a single ingestion of a lrg amt of a drug such as an overdose. If pt is exhibiting toxic effects of a medicaiton, do not admnister the next scheduled dose and notify the prescriber.
Other drug effects:
- Teratogenic-drug induced birth defects
- Mutagenic-drugs can cause genetic mutation by changing a cell's DNA
- Carcinogenic-some drugs have cancer causing effects
Other Allergy Types:
Cytotoxic Rx- the drug attached to a cell site is perceived as an antigen and is attacke by antibodies in the blood destoying the cell. This Rx takes place over time, several days=hives, rash, difficulty breathing, increased B/P and HR, dilated pupil diaphorese, "panic" feeling, and respiratory arrest. The drug must be stopped immediately and the prescriber notified
Serum Sickness Rx:
appears 2-3 weeks post ingestion of a drug.fever, rash, joint pain, and ENLARGED SPLEEN. Stop drug and notify prescriber.
Delayed allergic Rx.
occurs several hours after exposure and involves antibodies that are bound to specific white cells - rash, hives, swollen joints, edema of the face and limbs. Notify prescriber.
A rash that is usually cause by an immune response to drugs. IT may express itself on teh skin in "multiforme" ways including macules, papules, blisters, and hives. It may involve the palms and soles, the mucous membranes, the face and extremities. In the extreme form, which may be fatal, when the eyes, mouth and internal organs are involved it is called Steven-Johnson Syndrome or Toxic Epidermal Necrolysis (30-40%). Multi antibiotics at same time.
THe nurse is responsible for checking all clinical responses to medication, both positive and negative. If hasn't been documented it hasn't been done.
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