Ch 2: Pharmacologic principles

Metabolites

A chemical form of a drug that is the product of one or more biochemical reactions involving the parent drug.

How does a drug bind to the receptor?

A drug becomes bound to the receptor through the formation of chemical bonds between the receptor on the cell and the active site on the drug molecule. Drugs interact with receptors in different ways either to elicit or to block a physiologic response.

what can a drug NOT do?

A drug cannot cause a cell or tissue to perform a function that is not part of its natural physiology

Adverse Drug Event (ADE)

Any undesirable occurrence related to administering or failing to administer a prescribed medication.

Adverse drug reactions (ADR) AKA side effects

Any unexpected, unintended, undesired, or excessive response to a medication given at therapeutic dosages (as opposed to overdose).

tx of poisoned pt

Effective treatment of the poisoned patient is based on a system of priorities, 1) preserve the patient's vital functions by maintaining the airway, ventilation, and circulation. 2) The second priority is to prevent absorption of the toxic substance and/or speed its elimination from the body using one or more of the variety of clinical methods available

how does CYP450 decrease or increase toxicity of drugs

Ex: Here's an irony...acetaminophen (Tylenol) is converted by the liver enzymes into a metabolite that is potentially very toxic to itself! It is not the original drug itself that is so potentially hepatotoxic, but its metabolite. Too many Tylenols --> potential liver damage.

*Enzyme Interactions*

Drugs can produce effects by interacting with these enzyme systems. For a drug to alter a physiologic response in this way, it may either inhibit (more common) or enhance (less common) the action of a specific enzyme. This process is called *selective interaction*

mutagens

Drugs that are capable of inducing mutations

antagonistic effect (2+2 = 3)

when the combination of 2 drugs results in drug effects that are less than the sum of the effects for each drug given separately Let's say you took a drug to lower your blood pressure but also took an herb that blocked the effect of that medicine --> less chance of complete therapeutic effect of lowering your BP effectively

Onset of action

when the drug starts working. In general, the more quickly a drug is absorbed (gets into the blood stream), the quicker it can be delivered to the site of action and the quicker the onset of action.

*RRD stuff that u need to KNOW *

yay!

what kind of drugs do plants provide?

Plants provide many weak acids and weak bases (alkaloids) that are very useful and powerful drugs. Alkaloids are more common

another name for cell membrane

Plasma membrane

TOXICOLOGY

The study of poisons and unwanted responses to both drugs and other chemicals the science of the adverse effects of chemicals on living organisms Poisoning can result from a variety of causes, ranging from drug overdose to ingestion of household cleaning agents to snakebite

topically applied dosage

Work directly on the surface of the skin. Once the drug is applied, it is already in a form that allows it to act immediately. However, with other topical dosage forms, the skin acts as a barrier through which the drug must pass to get into the circulation time I; once there, the drug is then carried to its site of action

In general, the person who takes a Scheduled substance for the relief of pain as prescribed may be ______ to/on that medication—this means that if they stopped taking it suddenly, they would have not only a lot more pain, but also withdrawal-related S&S. 1) addicted 2) dependent 3) tolerant

dependent (psychological)

chemical name

describes the drug's chemical composition and molecular structure EX: N-acetyl-para-aminophenol

suppositories

dissolve and enter the blood directly via blood vessels in the membrane of the rectal cavity. alternative when nausea & vomiting prevents PO patient must be placed of left side --> safe & effective insertion

_____ determine the rate of drug dissolution

dosage forms

partial agonist aka agonist-antagonist aka mixed agonist

drug binds to the receptor but the response is diminished

Drug classifications

drugs are grouped together based on their similar properties

enterohepatic recirculation

drugs that are excreted by biliary excretion are taken up by the liver, released into the bile, and eliminated in the feces. Once certain drugs, such as fat-soluble drugs, are in the bile, they may be reabsorbed into the bloodstream, returned to the liver, and again secreted into the bile.This process is called enterohepatic recirculation.

noncompetitive antagonist

drugs which block receptors by inserting themselves in the "keyholes" but not activating anything. --There they are essentially inert and do not respond to any attempts by other drug molecule or endogenous substances to "nudge" them out of the way. --Thus the receptors are considered IRREVERSIBLY BLOCKED and ENDOGENOUS SUBSTANCES ARE COMPLETELY, IRREVERSIBLY BLOCKED FROM DOING THEIR JOBS (or at least, for quite some time). --Note: this type of drug—a NONcompetitive antagonist-- is rarely used because of that irreversible aspect,

competitive antagonist

drugs which reversibly bind receptors by inserting themselves in the "keyholes," not activating anything, and blocking the endogenous substance, same as the irreversible type above. --BUT if there are enough agonistic molecules around they can usually eventually "nudge" some of those antagonists out of the receptor site—it's a competition

*Pharmacodynamics*

effects of drug on body This phase can be distilled down to two issues—the why and the how: 1) "What do we want to accomplish?"... ie, what therapeutic effect do we want? Why are we giving this drug to this patient?(*THERAPEUTIC EFFECT*) 2) "How does that drug achieve the therapeutic effect?" (*MECHANISM OF ACTION*)

alkaline drugs, for instance, may need to be ______ coated—that is, protected by a special coating until they have traveled through the stomach acid into an alkaline environment such as the intestines, where they can be dissolved without ionization.

enteric

biliary excretion

excretion of drugs by intestines

how does Body type affect drug activity

extremes of fat distribution can affect drug activity a) The drug effect in someone with a BMI (body mass index) of 30 (obese) versus someone with BMI of 17 (too thin) may be quite different. b) Sometimes with extremes in weight, "usual" dosages are adjusted up or down by the prescriber.

Contraindication

factor that serves as a reason to withhold a certain medical treatment due to the harm that it would cause the patient.

Pharmacoeconomics

focuses on the economic aspects of drug therapy

allergy

genetically- programmed hypersensitivity that has developed to some substance that you have (knowingly or unknowingly) been exposed to at some point in your life. A molecule of a substance entered your body and your immune system developed "hyper-antibodies" to it so that upon subsequent exposure, those hyper-antibodies ATTACKED the substance and a hyper-inflammatory response occurs.

Supplemental Therapy THINK ADDITION

supplies the body with a substance needed to maintain normal function. This substance may be needed either because it cannot be made by the body or because it is produced in insufficient quantity. EX: 1) administration of insulin to diabetic patients 2) administration of iron to patients with iron-deficiency anemia.

steady state

the amount of drug removed via elimination is equal to the amount of drug absorbed with each dose

Carcinogenic effects

the cancer-causing effects of drugs, other chemicals, radiation, and viruses.

indication

the condition that the drug is targeting in its treatment or prevention

termination of action point

the end of the duration of action

Bioavailability

the fraction of the original drug amount that actually makes it into the systemic circulation.

*receptor interactions*

the joining of the drug molecule with a reactive site on the surface of a cell or tissue Most commonly, this site is a protein structure within the cell membrane Once a drug binds to and interacts with the receptor, a pharmacologic response is produced

duration of action of drug

the length of time the concentration of drug in the blood/ tissue is sufficient to elicit a response 1) This is the time from the onset of action-- when the drug level in the body has just reached the point of beginning to work-- to the time when the drug drops below the MEC again. 2) That pain med we talked about? The patient started to feel relief at about 30 minutes, had maximum pain relief at 3 hours, and will stop having relief & be in a lot of pain again at about 6 hours. The duration of action, then, is about 6 hours.

one negative side to lipophillic drug?

the metabolites of these drugs may not be excreted as easily, because urine is mostly water, and lipophilic molecules won't "travel" in the urine as well THE FIX: the liver's metabolic enzymes can change the lipophilic molecules into hydrophilic ones so they can be excreted more easily

Psychological dependence AKA Addiction

the obsessive desire for the euphoric effects of a drug. typically involves the recreational use of various drugs such as benzodiazepines, opioids, and amphetamines. i. In general, the person who takes the Scheduled substance for other reasons than what it is prescribed for (ex—to feel "laid back," "high," etc) may also develop dependence (would have withdrawal symptoms) and tolerance. ii. BUT, usually UNLIKE the chronic pain example, they also usually develop a psychological craving for it rather than needing it for pain....this person is usually in the throes of substance abuse and considered addicted.

Polypharmacy

the simultaneous use of multiple medications (page 42); this increases the chance of the person having a medication error such as taking too much or too little of a drug and/or having negative drug interactions. important consideration in the older population

Pharmacognosy

the study of natural drug sources (plants, animals , minerals)

Pharmacoeconomics

the study of the economic factors influ- encing the cost of drug therapy

Pharmacognosy

the study of these natural drug sources (plants and animals)

enzyme

the substances that catalyze nearly every biochemical reaction in a cell

half life

the time it takes for the blood level of a drug to be reduced by 50%

why is a narrow therapeutic range bad thing?

there is no "wiggle room"—no room for individual variation & so forth. b) So what do we do about drugs like that? We have to measure blood levels of it on a regular basis, whereas in the case of drugs with known wide therapeutic ranges, we don't have to do that—we can "rest easy" that they usually predictably stay out of the toxic range.

Subcutaneous

these injections are delivered into the area (usually into a layer of fat) just under the whole skin layer. Ex—a dose of insulin.

off label use

these uses have not been officially sanctioned, but that sometimes a prescriber will choose to give the drug for different reasons than "usual."

Intra-dermal

this is an injection given barely into the dermal layer of the skin, so shallow that a wheal develops. Ex—a TB test.

IV (intravenous)

this is when the drug is mixed in a certain amount of fluid (say a 50ml bag of saline) and delivered into the vein via a pre-established IV site.

onset of action

time required for the drug to elicit a therapeutic response

if you gave a drug to a patient who had been taking a lot of St John's wort and eating a lot of watercress, both of which are P450 inhibitors, would you worry about the patient ending up with not enough of the drugs in the body (low efficacy), or too much drugs in the body (toxicity)?

toxicity ?

*Distribution*

transport of the drug via the bloodstream to its site of action

Pharmacokinetics

what does body do to drugs involves: 1) absorption 2) distribution 3) metabolism 4) Excretion

Pharmacodynamics

what drug does to body involves 1) drug-receptor interaction

GI disease

what if the patient has Crohn's disease and large portions of his small intestines are inflamed? Or what if the patient has gastroparesis—a slow-down of stomach function due to problems like diabetes

When can we expect about 100% bioavailability

when a drug is given by the IV route—ie, direct infusion into the vein—it has the best chance of 100% of the drug reaching the systemic circulation, because it is injected directly into the circulation! That is called 100% bioavailability

Drug equilibrium

when a drug is highly protein bound & the plasma contains only few free drug, as the free drug move from plasma to interstitial fluid, the plasma loses most of "free drugs". therefore, to reestablish the equilibrium in plasma , some drugs will fall of from protein to plasma.

what are the 3 different names every drug has?

1) chemical name 2) generic name 3) brand name

Carcinogens

Agents that cause cancer

Drug Activity phases

*Phase 1* : *Administration* - drug order & application *Phase 2 *: *Pharmacokinetics* - effect of body on drug *Phase 3*: * Pharmacodynamics* - effect of drug on body

Maintanance Therapy THINK PREVENTION of dz progression

1) does not eradicate problems the patient may already have but will prevent progression of a disease or condition. EX: 1) In HTN, maintenance therapy maintains the patient's BP within given limits, which prevents certain end-organ damage. 2) the use of oral contraceptives for birth control

The path of and action upon drugs, from entering the kidneys to excretion into the urine

1) glomerular filtration 2) passive tubular reabsorption 3) active tubular secretion 4) excretion

Beers list/ Criteria

1) a list of drugs that are especially dangerous to the over-65 population, 2) Drawn up to minimize dangers related to age-related changes in the body's ability to adequately process drugs. 3) prescribers use them as a guide as to what drugs to avoid for those in the older part of the age spectrum.

categories of drug interaction

1) additive effects 2) synergistic effect 3) antagonistic effect 4)Incompatibility

2 types of drug classification

1) by structure 2) therapeutic use

Individual Variations

. Always consider possible individual variations: *Physical* -- gender, body type, health spectrum, genetics, idiosyncrasies, life span issues (age, pregnancy) *Psychosocial/economic* --economics [homelessness, rx cost—affects adherence], ethnicity, cultural issues, mental/emotional health, education level

routes of administration

1) *Enteral* - via GI tract ----> PO ----> Sub-lingual, spray, buccual ----> Rectal 2) *Parenteral* - outside GI tract ----> IM ----> Subcutaneous ----> Intra-dermal ----> IV 3) *Topical* - other routes ---> Aerosols - inhaler ---> paste -- NTG ---> ointments ---> drops (eye/ear)

Physical variations

1) *Gender*: Normal hormonal and body-fat-versus-muscle status can differ between the genders and affect drug activity. 2) *Body type*: extremes of fat distribution can affect drug activity 3) *Health/illness spectrum*: 4) *Genetic influence* (Read ch 5) 5) * Life Span issues* (ch 3) -----------> pregnancy, children, older adults, polypharmacy

Direct penetration of phospholipid bilayer

1) *Lipophillic drug* --> "blend in" with the cell membrane's fatty layer and thus it can "ooze" into the cell. 2) *Hydrophillic drug* --> the drug cannot enter as above—it must use other means, such as the pores or channels mentioned above, or transport molecules

Classifications of "perfect drug"

1) 100% safe (no way it could harm you) 2) 100% effective for every person in meeting its "indications"— . IE, what is this drug used for? --Example: The drug acetaminophen (Tylenol) is usually effective in meeting its indications of headache and fever. Or said another way: Acetaminophen is indicated for fever. 3) 100% selective—only affecting the target organ or microbe or body part or enzyme, etc, that it is supposed to --Example: Certain beta-blockers (drugs that block beta receptors) are considered very selective and only block ONE type of beta receptor, which cuts down on the possibility of blocking receptors that you don't want to block. 4) have no side effects at all (never cause nausea, for example—the most common side effect) 5) be easy to take so that patient adherence (similar word is compliance) would be 100% --Example—a one-a-day, small pill that is easy to swallow beats out a huge horse-pill that has to be taken 3 times a day—a patient is unlikely to stick with the latter (ie, the patient compliance would be very low for the 3x/day horse pill!) 6) free of unwanted interactions with any other meds or food 7) be reversible if necessary Example: What if Mr. Watson, our patient in our scenario above needed to have the effect of the enoxaparin quickly reversed so that there would be no worsening of bleeding? Is there a reversal agent or antidote (two words close in meaning in this context)? (Just to start to get to know your drug resource, see if it says anything about a reversal agent or antidote.) 8) easily eliminated : easy to be metabolized by the liver and have left-over metabolites easily excreted by the kidneys 9) be accessible by everyone who needs it: ie, inexpensive (ha!), quickly available, and as convenient as possible to obtain.

Concept map of Drug Activity phases

1) 6 rights + why --> *Administration* --> measurement of drug progression in body 2) ADME (absorption, distribution,metabolism, excretion)--> *Pharmacokinetics* --> impact of body on drug --> measurement of drug progression in body 3) Interaction of drug & receptor cells --> *Pharmacodynamics*

Incompatibility

1) A term most commonly used to describe parenteral drugs. 2) Drug incompatibility occurs when 2 parenteral drugs or solutions are mixed together and the result is a chemical deterioration of one or both of the drugs or the formation of a physical precipitate

4 phases of Pharmacokinetics (ADME)

1) Absorption 2) Distribution 3) Metabolism 4) Excretion

Absorption barriers of PO drugs

1) Acid Base environment 2) drug-drug / drug-food interaction 3) GI disease

Types of therapy

1) Acute Therapy 2) maintanance 3) Supplemental 4) Pallative 5) Supportive 6) Prophylatic therapy 7) Empiric therapy

2 categories of ADE

1) Adverse drug reactions (ADR) 2) medication errors

*Excretion*

1) After a drug is absorbed, distributed, and metabolized into a form that can be handled well by the kidneys, it will be eliminated from the body, most commonly in the urine (as you would expect from the kidneys.) 2) One of the most important factors in this last step of pharmacokinetics is how healthy are the kidneys? Sick kidneys generally = less excretion of drugs into the urine = too much of the drug stays in the body = possible drug toxicity.

pharmacologic reaction

1) An extension of the drug's normal effects in the body. 2) Pharmacologic reactions that result in adverse effects are predictable, well-known adverse drug reactions resulting in minor or no changes in patient management. They have pre-dictable frequency and intensity, and their occurrence is related to the dose. They also usually resolve upon discontinuation of drug therapy. EX: a drug that is used to lower blood pressure in a patient causes a pharmacologic adverse drug reaction when it lowers the blood pressure to the point at which the patient becomes unconscious.

how does old age affect drug activity

1) As a person gets older, cells are not repaired and/or replaced as quickly and effectively in the body, so that every aspect of drug activity is affected. Ex: If you wonder why your older patient sleeps all day despite getting a very small dose of sleeping pill the night before, it may be that his/her kidneys are atrophied (shrunken), and thus unable to eliminate the metabolites ("left-overs") into the urine 2)

nonselective interactions

1) Drugs with nonspecific mechanisms of action do not interact with receptors or enzymes. 2) Instead, their main targets are cell membranes and various cellular processes such as metabolic activities. 3) These drugs can either physically interfere with or chemically alter cellular structures or processes. EX: Some cancer drugs and antibiotics have this mechanism of action. By incorporating themselves into the normal metabolic process, they cause a defect in the final product or state. This defect may be an improperly formed cell wall that results in cell death through cell lysis, or it may be the lack of a necessary energy substrate, which leads to cell starvation and death

Empiric Therapy think prevention based on probability

1) Empiric therapy is based on clinical probabilities. 2) It involves drug administration when a certain pathologic condition has an uncertain but high likelihood of occurrence based on the patient's initial presenting symptoms. EX: use of antibiotics active against the organism most commonly associated with a specific infection before the results of the culture and sensitivity reports are available

what affect MEC—minimal effective concentration?

1) How is the med absorbed (IV, IM) 2) distribution— does this person have a good blood supply to get that drug to its target to start working? 3) metabolism and elimination— if these are not working properly, they can ultimately affect how quickly a drug can attach to its site of action.

Dosage forms

1) Liquid oral drug(syrups, elixirs) 2) Solid oral drugs (tablet,capsule, powder) 3) Enteric coated tablet 4) particle size within tablet/capsule 5) injectable drugs 6) Combination dosage forms 7) Extended-release tablets & capsules 8) immediate release dosage 9) drugs that dissolve in mouth 10) topically applied dosage

Palliative therapy THINK IMPROVE LIFE QUALITY

1) Makes pt as comfortable as possible 2) focuses on providing patients with relief from the symptoms, pain, and stress of a serious illness. 3) The goal is to improve quality of life for both the patient and the family. 4) It is typically used in the end stages of an illness when attempts at curative therapy have failed; however, it can be provided along with curative treatment. EX the use of high-dose opioid analgesics to relieve pain in the final stages of cancer

*Metabolism*

1) Namings a) "breaking down" of substances b) changing of substances—in our case, those substances being drugs-- for more effective usage or (more often) elimination. 2) So, once a drug molecule is distributed and serves the purpose for which it was given, it is essentially "spent" and needs to be metabolized so that it can be eliminated or changed in some way. a) Metabolization usually occurs in the liver and then excretion from the body occurs via the kidneys. b) If these steps don't adequately take place for some reason, toxicity can develop (harmful drug accumulation in the body), or, conversely, drugs can be too rapidly metabolized and then not be as effective.

2 overarching motifs that run throughout all the above activity phases

1) Nursing process 2) Individual Variations

2 facets of pharmacokinetics

1) Onset of action 2) Bioavailability

what must a prescription include?

1) Patient's name 2) Date & Time order is written 3) Name of the drug & formulation 4) Dosage amount & frequency 5) Route of administration 6) prescriber's signature

3 basic areas of Pharmacology

1) Pharmaceutics 2) Pharmacokinetics 3) Pharmacodynamics

what are some ways drugs can pass through plasma membrane?

1) Pores and Channels 2) Direct penetration of phospholipid bilayer 3) Transport system

Prophylactic Therapy think: guards to a prophet's lecture / prevention during planned event

1) Prophylactic therapy is drug therapy provided to *prevent* illness or other undesirable outcome *during planned events*. EX: 1) the use of preoperative antibiotic therapy for surgical procedures. The antibiotic is given before the incision is made, so that the antibiotic can kill any potential pathogens. 2) administration of disease-specific vaccines to individuals traveling to geographic areas where a given disease is known to be endemic

therapeutic range/ index

1) The therapeutic range of a drug is the amount of drug in the body that falls somewhere between minimal effective concentration (MEC) and toxicity—ie, it's the range that helps or cures the patient without making him toxic! 2) One goal of effective medication therapy is to maintain doses and dose intervals (as discussed above) that keep a person's blood level in the ideal therapeutic range (sometimes called therapeutic window).

Medical reconciliation

1) This is the practice of going over medications with the patient and/or family and/or another RN upon admission to a facility, transfer from unit to unit, and discharge... or any other time. 2) It is an important part of combining assessment and education and an important tool in avoiding adverse medication events. 3) It has 3 basic parts: verification, clarification ,reconciliation,

Drug interaction

1) This reaction occurs when the presence of two (or more) drugs in the body produces an unwanted effect. 2) This unwanted effect can result when one drug either enhances or reduces the effects of another drug. 3)Some drug interactions are intentional and beneficial 4) However, most clinically significant drug interactions are harmful 5) A drug interaction can either increase or decrease the actions of one or both of the involved drugs.

hypersensitivity (allergy)

1) immunoglobulins recognize the drug molecule, its metabolite(s)/ another ingredient in a drug formulation as a dangerous foreign substance --> immunoglobulin proteins bind to the drug substance in an attempt to neutralize the drug (immune response) --> Various chemical mediators (Histamine, cytokines prostaglandins ) usually are released . S&S 1) skin erythema or mild rash 2) constriction of bronchial airways 3) tachycardia

generic name

1) non-propriety name 2) shorter & simpler than chemical name 3) used in most official documents 4) This name is assigned by the United States Adopted Names Council. 5) One drug / one generic name—this is the name that "sticks" to the drug no matter what company produces it. 6) The generic name is also known as the non-proprietary name or the non-brand ¬name. 7) It is written without capitalization (eg, acetaminophen). EX: acetaminophen

factors that disrupt drug movement from circulatory system into the interstitial fluid

1) passage through walls 2) Plasma Protein bound

4 categories of adverse drug reaction

1) pharmacologic reaction 2) hypersensitivity (allergy) 3) idiosyncratic reaction 4) Drug interaction

medication use process

1) prescribing 2) dispensing 3) administrating 4) monitoring

idiosyncratic reactions

1) reactions that occurs unexpectedly in a particular patient. 2) Such a reaction is a genetically determined abnormal response to normal dosages of a drug. 3) Idiosyncratic drug reactions are usually caused by a deficiency or excess of drug-metabolizing enzymes. EX: An example is glucose-6- phosphate dehydrogenase (G6PD) deficiency. This disease affects approximately 100 million people. People who lack proper levels of G6PD have idiosyncratic reactions to a wide range of drugs. There are more than 80 variations of the dis- ease, and all produce some degree of drug-induced hemolysis.

3 ways drug can work

1) receptor interactions 2) enzyme interactions 3) nonselective interactions

Trade name

1) the commercial name given to a drug product by its manufacturer 2) shorter & easier to pronounce than generic name 3) Names created by pharmaceutical companies and approved by the FDA (Food and Drug Administration). 4 They are based on being appealing and easy-to-remember for prescribers and other health-care providers such as physicians and nurses, and especially for the consumer -----a) Unfortunately, the brand name and the generic often don't sound even remotely alike -----b) Examples-- clopidogrel : Plavix; ondansetron : Zofran 3) The brand name is also known as the proprietary name, the manufacturer's name, or the trade name. 4) Any given drug can have many brand names, especially if it has been around awhile. 5) A brand name is usually written with the first letter capitalized (Tylenol). EX: Tylenol, Liquiprin, Tempra

What does pharmacokinetics include

1. Drugs time to onset of action 2. Time to peek effect 3. Duration of action P.S: pharmacokinetics is the study of what happens to drug in the body

Drugs that should not be crushed

1. Extended-release oral dosage forms 2. Enteric coated tablet 3. Granules contained in capsule

what is typical for a true allergic reaction:

1. If it is a local reaction, say to a topical cream, you may see a rash there and the patient will complain of itching. 2. If it is a systemic reaction, say to an oral medication, you may see urticaria—these are itchy, scattered skin welts. 3. If the systemic reaction is even more serious, the patient may be experiencing anaphylaxis, in which there is usually urticaria, but also more dangerous S&S such as wheezing and shortness of breath. If the blood pressure also drops to a very low reading, we call this anaphylactic shock.

A drug given via the _______ route, is already in a dissolved state when it is administered, having been mixed in fluid 1) Oral 2) IV 3) IM 4) Subcutaneous

2) IV Thus an IV drug is introduced immediately in the blood stream & on its way to its target of action with virtually no barriers in regards to absorption (getting into the circulation

_____ routes have onset of action time usually somewhere between PO and IV times 1) Oral 2) IV 3) IM 4) Subcutaneous

3) IM 4) Subcutaneous

when does steady state occur?

4 half lives of administered drug

After how many 1/2 lives are most drug removed from the body?

5 half lives 97% drug is eliminated

Prodrug

A drug that is inactive in its given form, and which must be metabolized to its active form in the body, generally by the liver, to be effective.

Medicine

A drug used for therapeutic purposes i.e : to fix / prevent a pathology

Medication errors

A medication error is a preventable situation in which there is a compromise in the "Six Rights" of medication use: right drug, right dose, right time, right route, right patient, and right documentation. Medication errors are more common than adverse drug reactions. Medication errors occur during the prescribing, dispensing, administering, or monitoring of drug therapy.

prodrug

A parent drug that is not pharmacologically active A proDRUG then is metabolized into pharmacologically active metabolites.

_________: activation, affinity, additive acts like endogenous substances ("mimics")

AGONIST

________: blocks activation, blocks endogenous substances from doing their normal "jobs;" or can inactivate endogenous substances.

ANTAGONIST

*Absorption*

Absorption is the phase of getting the drug from the site of administration across various cell membranes, and into the systemic circulation

*Dependence* on a medication (ie, if it is taken away, there would be withdrawal S&S, depending on the drug and amount being taken) *+* *Craving + using the substance for purposes other than what is intended*. (ex—craving and using opiate pain medicines without being in pain) *=* *________*.

Addiction

teratogens

Compounds that produce structural defect in fetus

Combination dosage forms

Contain multiple drugs and one dose.

mechanism of action

Drugs can produce actions (therapeutic effects) in several ways. The effects of a particular drug depend on the characteristics of the cells or tissue targeted by the drug

dependence

Dependence is a physiologic or psychological need for a drug.

How does a drug bind to the enzymes?

Drug-enzyme interaction occurs when the drug chemically binds to an enzyme molecule in such a way that it alters (inhibits or enhances) the enzyme's interaction with its normal target molecules in the body.

enzyme inducers (drug)

stimulate drug metabolism decrease pharmacological effects often happens as a result of repeated administration of certain drugs

The biggest barriers to bioavailability in PO drugs is called _________________

First Pass effect

normal kidney function

Healthy kidneys excrete wastes like creatinine and urea nitrogen into the urine & thus get rid of it as needed. Therefore the serum (blood level of) creatinine & urea nitrogen is normally very low. If the kidneys are "sick" such as in CKD - chronic kidney disease—they cannot excrete wastes as well as normally, and serum creatinine & urea increase

Transport system

If a drug has a certain structure, it can fit like a key into a transport molecule and be "allowed in or out."

Agonist

If a drug has affinity for a certain receptor and activates a reaction agonists are mimics of endogenous substances in your body; whatever activities those substances normally ignite, the drug will add to and cause an increase in that activity

urine creatinine clearance.

If the normal level of creatinine "cleared"—that is excreted—goes down, what do you think that means? Yes, it means there is likely renal impairment. So HIGH serum creatinine and LOW urine creatinine clearance = sick kidneys = drugs might not be excreted well enough! If a person has higher-than-normal levels of these substances, we know the kidneys are also likely to not be able to get rid of drug metabolites.

One of acetylcholine's many "jobs" is to travel across the synapse between the vagus nerve and certain receptors in the heart cells, and when it fits into certain "keyholes," it SLOWS the heart down. So, a drug that acts like acetylcholine is an *antagonist* (activator) that would heart __________rate. 1) increase 2) decrease

Increase

what does cell membrane do ?

It what surrounds a cell, keeping its contents neatly inside and "deciding" what can come and go into and out of the cell.

Rules for acid-base environment for PO drugs

LIKE DISSOLVES LIKE molecule keeps a neutral charge neutral molecule absorbed easily into lipophilic cell membranes & from there into circulation. UNLIKE IONIZES UNLIKE develops a charge and thus becomes hydrophilic/lipophobic not absorbed as well. ACIDIC SUBSTANCES WILL IONIZE IN AN ALKALINE MEDIUM. ALKALINE SUBSTANCES WILL IONIZE IN AN ACIDIC MEDIUM. "Moral of the story"—drug manufacturers will aim to make LIKE DISSOLVE IN LIKE—acid drugs "aim" for the stomach; alkali drugs "aim" for the intestines (pH higher)

bolus dosing or loading dose

Large dose required to achieve an immediate plasma concentration equivalent to steady state concentration achieve immediate therapeutic concentration

How will you know if your patient is having an allergic reaction to a drug?

Many people will tell you that they are allergic to, say, codeine. But if you question them further, they will say it makes them nauseated. That is an adverse reaction, yes, but not usually an allergic reaction

Active metabolite

Metabolites that have pharmacologic activity of their own even if the parent drug is inactive

how does CYP450 work differently in different years of the age spectrum

Newborns often have livers that aren't quite mature; the elderly have livers that are often atrophied and/or damaged.

what CAN a drug do?

Once the drug is at the site of action: 1) it can modify (increase or decrease) the rate at which that cell or tissue functions 2) it can modify the strength of function of that cell or tissue

A drug given the _______ route must be dissolved (turned into smaller molecules) in the stomach and/or intestines before being able to pass into the blood. 1) Oral 2) IV 3) IM 4) Subcutaneous

Oral

particle size within tablet/capsule

Particle size within an a tablet or capsule can make different dosage forms of the same drug dissolve at different rates. Thus, they have different times to onset of action. Ex: micronized (fast)vs non- micronized (slow) drug

immediate release dosage

Release all of the active ingredient immediately upon dissolution in the GI tract

Extended-release tablets & capsules

Release drug molecules in the patient's GI tract over a prolonged period Of time. This ultimately prolongs drug absorption as well as duration of action. Ex of Nomenclature: SA(sustained action), SR( Sustained release), CR (controlled release), XL (extended length), XT (extended time )

Supportive Therapy THINK BABY-SITTER (SECONDARY tx)

Supportive therapy maintains the integrity of body functions while the patient is recovering from illness or trauma. Examples 1) provision of fluids and electrolytes to prevent dehydration in a patient with influenza who is vomiting and has diarrhea, and administration of fluids, 2) volume expanders, or blood prod- ucts to a patient who has lost blood during surgery

Teratogenic effects

Teratogenic effects of drugs or other chemicals result in structural defects in the fetus. . Prenatal development involves a delicate program of interrelated embryologic events. Any significant disruption in this process of embryogenesis can have a terato-genic effect. Drugs that are capable of crossing the placenta can cause drug-induced teratogenesis. Drugs administered during pregnancy can produce different types of congenital anomalies. The period during which the fetus is most vulnerable to tera-togenic effects begins with the third week of development and usually ends after the third month.

drug actions

The cellular process that changes in response to the presence of drug molecule The cellular process involved in the interaction between a drug and body cells

Parent drug

The chemical form of the drug that is administered before it is metabolized by the body's biochemical reactions into its active / in active metabolites. A parent drug that is not pharmacologically active itself is called *prodrug*. A proDRUG then is metabolized into pharmacologically active metabolites.

Pharmacotherapeutics

The clinical use of drugs to prevent and treat diseases. It defines the principles of

affinity

The degree to which a drug attaches to and binds with a receptor

Therapeutic effect "WHY"

The desired or intended effect of a particular medication There are some broad general categories of pharmacologic therapy: a) Example-- prophylactic therapy or just "prophylaxis" is about prevention, referring to such medications as vaccines. b) Acute therapy, such as giving antibiotics for infections, or maintenance therapy, such as giving daily pills for high blood pressure, are probably the most common categories of drug therapy that you will see in your nursing practice.

trough levels

The lowest blood level of a drug he lowest concentration of drug reached in the body after it falls from its peak level, usually measured in a blood sample for therapeutic drug monitoring. If the drug has a known termination of action point (the end of the duration of action) of 10 hours from administration, then the trough level will be ordered to be drawn 10 hours from when the nurse gave the drug.

Trough level

The lowest concentration of drug reached in the body after it falls from its peak level, usually measured in a blood sample for therapeutic drug monitoring.

Physical dependence

The physiologic need for a drug to avoid physical withdrawal symptoms (e.g., tachycardia in an opioid-addicted patient)

Dissolution

The process by which solid forms of a drug disintegrate in the gastrointestinal tract and become soluble before being absorbed into the circulation

Pharmaceutics

The study of how various drug dosage forms influence the way in which the drug affects the body. involves: 1) disintegration of dosage forms 2) dissolution of drug in body

peak level

The time required for a drug to reach its maximum therapeutic response in the body. 1) This usually is when the drug is at its highest concentration at the target site. EX: If the known peak of a drug (such as the pain med in our example) is about 3 hours, then you know that the patient is supposed to be at maximum pain-depletion level 3 hours after administration. (Again, many things may affect this in "real life" including individual variances with the patient, but at least you have a general idea.)

Blood-brain barrier

The walls of the capillaries in the brain have cells that tightly fit together—ie, don't have the usual gaps between cells-- so that most drugs cannot just go through the gaps

injectable drugs

These tend to be more straightforward than oral dosage form. However some injections are carefully formulated to reduce drug toxicity. These must contain certain characteristics to be safe and effective The arteries and veins that carry drug throughout the body can easily be damaged if the drug is too concentrated / corrosive. the pH of injections must be very similar to that of the blood for the drugs to be administered safely. Drugs injected intravenously are immediately placed into solution in bloodstream and do not have to be dissolved in body. Therefore, hundred percent absorption is assumed to occur immediately upon intravenous injection

Can the drug get out of the circulatory system into the interstitial fluid of the tissue bed?

This involves a drug molecule being able to leave the inside of the capillaries (ie, leave the intravascular compartment) and enter the fluid surrounding cells—ie, the interstitial or intercellular fluid.

glomerular filtration

This is based on the simple principles of size and protein-binding: i. Size: if you are a small drug molecule, you can get through the gaps of the glomerular capillary lining into Bowman's capsule and flow with the urine via the tubules of the nephron out of the body. (Remember the drawing on a previous page of gaps in capillary lining cells? Same thing here.) ii. But if you are a drug with high PPB (plasma protein binding), you will not get excreted that way: --First off, protein molecules are by design TOO BIG to go from the blood through the lining of glomerular capillaries (ie, glomerular filtration) into the Bowman's capsule and then into the urine (it isn't normal to have protein in the urine—we need to keep as much protein in our body as possible.) --Thus if you are a drug molecule bound to a protein molecule (usually albumin) in the plasma (blood), you cannot get usually excreted via glomerular filtration

Intra-muscular

This is the typical "shot" that people think of. Ex—a penicillin shot.

excretion

Though most attention in our "Excretion" section has been on the kidneys, there are other ways of eliminating, drugs including breast milk, bile, feces, and the lungs

Nursing process

Use critical thinking and a structured approach to understanding and applying drug activity knowledge.

indication

WHY the drug is given? WHAT is the use of the drug?

additive effects (2+2= 4)

When 2 meds for same purpose are taken together, you don't have to use as much as either one by itself. An example of this is the aforementioned acetaminophen / hydrocodone combination. i. Each type of medication is for pain, though they work in different ways.

Portal system

a "mini-circulation area" (as opposed to the systemic circulation) - a series of veins that bring blood from all over the body to the huge PORTAL VEIN which branches throughout the liver. The liver sort of "checks out" the blood-- the liver says "let's see: what do I need to metabolize in this blood that has been brought to me via the portal veins?" This is a GOOD THING normally, but when applied to "first pass effect" it means that the liver can prematurely inactivate certain oral drugs before they get to the systemic circulation and then to their target cells.

Tolerance

a decreasing response to repeated drug doses this is when higher doses are needed over time to achieve the same effect.

Antagonist

a drug that prevents / blocks activation of receptors, usually by endogenous substances

Sublingual

a pill placed under the tongue that dissolves rapidly and passes directly into the blood via membrane blood vessels

receptor

a reactive site on the surface or inside of a cell

how does a child's age affect drug activity

a) At each end of the age spectrum, the is higher likelihood that a person will have problems related to drug activity, so the more likely they will need special considerations. b) In neonatal and pediatric settings, this will mean for the nurse absolute confidence and skill in calculating drug dosages, as the dose will often be weight-based.

how does genetic influences affect drug activity

a) Clarification of the term "genetic" as applied to pharmacology: "Genetic" is an all-encompassing term that, depending on context, can be used with a variety of meanings. b) It can be used to mean a spontaneous mutation in how a gene codes for a certain protein. Ex: Glycoproteins embedded in our cellular membranes often help to transport drugs in and out of the cell; if there is a mutation in the gene that codes for certain types of glycoproteins, there may be problems with drug transport. c) It can mean an inherited difference in how a person reacts to certain drugs. i. Ex: You may inherit a predisposition to develop an allergy to the drug family called "penicillins," and if you receive a drug in that family, you may have an allergic reaction. ii. Similarly, you may have inherited genes that cause a particular kind of adverse reaction similar to allergy; example: Stevens-Johnson syndrome--exhibited by fever, body aches, skin & lip blistering-- is a potentially deadly, idiosyncratic reaction to certain drugs such as sulfa drugs. d) "Genetic" can also be used to a problem that happened during pregnancy--a drug taken by the mother can have profound effect on the genetic events of the fetus (example given previously-- thalidomide babies)

Dosage amount & frequency

a) Dosage will in most cases be in metric format and should always have a zero before the decimal for fractions, but NOT one after the last number ex: 0.625 mg is correct but NOT .625 or 0.6250 or .6250 b) Examples of frequency are "TID" or "Q 6 hours prn pain

Name of the drug & formulation

a) Examples of formulation that would need to be clarified include "SR"—sustained release—so that there will be no confusion with the "regular" version/formulation of a drug b) Ex: "Ritalin-SR" as opposed to "Ritalin-LA" (LA = long-acting) or just plain "Ritalin."

how does pregnancy affect drug activity

a) Physical changes of pregnancy can affect drug activity in the mom. b) Also, there are very few drugs that are completely risk-free for the fetus, because he/she is undergoing so much genetically-programmed cellular development and most drugs that the mom takes can cross the placenta to affect this development. c) There is much uncertainty about the drugs a pregnant woman can take, because of reluctance to conduct drug trials that might endanger the fetus. d) So pregnancy safety categories were developed (see Table 3-1, pg 39); Category A is the only one in which studies have proven no risk to the fetus. e) Breast feeding issues: certain levels of maternal medication can reach a child via breast-feeding.

Can the drug get from the interstitial fluid into the target cell?

a) Some drugs (not all) must enter the cells to act upon them, a facet of pharmacodynamics (effect of drug on body, discussed later), and their ability to do so depends on drug composition and/or cell membrane properties as discussed above. b) Almost every drug must be able to enter certain cells, though—especially hepatocytes and renal cells—to be metabolized and excreted

3 main factors that determine effectiveness of drug distribution

a) Status of blood flow to tissue beds (interchangeable with "capillary beds"of the body. b) How well a drug can get from inside a capillary into the fluid surrounding the cells of a capillary bed (ie, the interstitial fluid of the capillary bed). c) How well a drug can get from the interstitial fluid into the cells or onto the cells (some drugs work by attaching to the cell membrane, some by getting inside the cell).

cytochrome P450 system AKA microsomal enzyme system

a) The P450 system (AKA CYP system) is divided into families called CYP1 CYP2, and CYP3, whose members have different affinities for metabolizing different drugs; ex—CYP2D6 or CYP3A4 b) So as a drug molecule is taken into the liver it is acted upon by the CYP system of enzymes. i. A drug molecule that is acted upon by a certain enzyme is called that enzyme's *substrate*. ii. Ex-- if CYP123 metabolizes a penicillin molecule, the penicillin is a CYP123 substrate

Is the drug/blood flowing well to the capillary beds?

a) The blood vessels can be thought of as the "conduit" part of distribution—they deliver drugs to the places that the action takes place --the effector tissues. i The most highly vascular tissues in the body include heart, liver, kidneys, and the brain, so it's pretty easy to get blood to those tissue beds. ii In contrast, skin, fat, and bone tissue beds have less vascularity, so it is a bit more difficult to get drugs to those areas

MEC—minimal effective concentration.

a) This is the minimal amount of the drug that has to be present for therapeutic action to begin. b) If the onset of action of a drug is 30 minutes (the time at which the patient says, "Ah, the pain is just now starting to ease") and the drug concentration at the site of action at that moment is 6mg/L, then we would say that the MEC is 6mg/L.

One of acetylcholine's many "jobs" is to travel across the synapse between the vagus nerve and certain receptors in the heart cells, and when it fits into certain "keyholes," it SLOWS the heart down. So, a drug that acts like acetylcholine is an *agonist* (activator) that would heart __________rate. 1) increase 2) decrease

decrease

Route of administration

a) This refers to how the drug should be applied to the patient, ie, how it should get into the patient's body. b) Sometimes the same drug is available in many different routes, so it is very important to know which route is ordered --Ex: Nitroglycerin, in different dosages, can be given as a pill that is swallowed, a pill that dissolves under the tongue, an IV solution, and as paste or patch to be absorbed from the skin. c) The route (just like everything else) should make sense. --What would you do as a nurse if a drug was ordered in oral pill form, but you knew the patient's diagnosis of stroke had left him with dysphagia (difficulty swallowing)? d) Examples of routes: PO, SubQ, IM, IVP, IVPB, PR, SL.

Date & Time order is written

a) Time is almost universally written in military format in hospitals. Note: we will use this system in this course, so be sure you get familiar with it. (page 13 of book) b) Ex: 1800 = 6pm; 0600 = 6am

how does Health/illness spectrum affect drug activity

a) What is the patient's PMH (past medical history)? Does he/she have a chronic disease that would change the effect of a drug? b) Is he on other medications or CAM (Complementary and alternative medicine) substances? If so, are they known to interact with the drug you are about to give? c) What is his/her nutritional status? Ex: Does labwork show a low protein level in his blood --hypoproteinemia? (As we will see later, protein in the blood is an important factor in drug effects.) d) What is his/her general diet? Are there certain foods that might interfere with some medications? --Ex: Some leafy vegetables chemically interfere with an anticoagulant drug called warfarin (Coumadin)

Actions of CYP450 mnemonic : EnzInh = SubIncr EnzInd = SubDecr (the two "ds" go together)

a) enhance/increase renal excretion of a drug by changing it into a more polar, hydrophilic (water soluble) drug instead of lipophilic (lipid soluble). b) inactivate drugs by changing them into what's called inactive metabolites that won't have an effect on the body. c) increase therapeutic action of the drug --Ex—codeine can be changed to a stronger-acting molecule called morphine d) activate prodrug e) decrease or increase toxicity of drugs; decreasing toxicity is good, but of course the opposite is not. f) be inhibited by certain drugs and other substances (slow down metaolism) g) be induced by certain drugs and other substances (speed up metabolism) h) work differently in different years of the age spectrum

volume of distribution

a) how evenly do our drug molecules spread out throughout the body b) The tendency of molecules in fluids is to spread evenly, and then if there are less of them in the next fluid compartment, they will try to spread into that compartment in an effort to equilibrate. (Remember the body is always seeking equilibrium and homeostasis through such movements as diffusion and osmosis.) c) But as we have already talked about, drug molecules aren't created equally: i. If I tell you a drug is highly hydrophilic, would you expect the molecules to hang out in the watery environment of the blood, or spread out through a bunch of lipophilic (hydrophobic) cell membranes and distribute themselves throughout tissue pretty evenly? --Most likely you would think they would stay in the blood and not spread out too much, right? -- This is called having a small volume of distribution. ii. What about lipophilic drugs... when those molecules equilibrate (spread out as evenly as possible through tissues fluid throughout the body), would you expect there to be a high or low volume of distribution? Yup—high.

Administration (Drug Activity Phase 1)

a. encompasses drug ordered to drug applied to patient b. begins with a prescriber's (physician, NP, PA) order c. The order is usually entered into the computer by clerical personnel, received and prepared in the pharmacy of the hospital, and sent to the patient's unit, where it is frequently stored in some sort of computerized dispensing machine such as a PYXIS (see pic and info on page 102 of text) d. Also, a document called an MAR (medical administration record) is generated and used to guide the nurse in the administration process (see pic on page 106) and to use for documentation. e. Medical reconciliation

neurotransmitters

acetylcholine epinephrine, norepinephrine, dopamine; hormones such as insulin, thyroid hormone, and so forth.

Toxicology

adverse effect of drugs & other chemicals toxic effects are often extension of therapeutic action

The drug with the best "fit" and strongest _______ for the receptor will elicit the greatest response from the cell or tissue.

affinity

Drug

any chemical that affects our physiologic processes

the quicker the drug can get into the circulation and remain as _________ as possible, the faster it can get to the next step of distribution to its therapeutic target and thus be able to "do its job."

bioavailable

another word for metabolizing is —"____________" transformation means change

biotransformation

how can prescribers hurry things along?

bolus dosing

a "________" drug is an inactive drug 1) bound 2) free

bound

how does CYP450 enhance/increase renal excretion of a drug

by changing it into a more polar, hydrophilic (water soluble) drug instead of lipophilic (lipid soluble). i. Remember that we often want drugs to be lipophilic in formulation to cross membranes. ii. But then, for easiest excretion process, we want the "left-overs" to be hydrophilic so they can be "peed out" with the urine. iii. Ex—pentobarbital is highly lipophilic, and without CYP enzymes to convert it to hydrophilic metabolites, it may take years for the kidneys to even get rid of a single dose.

PO

by mouth For people w/ GASTROSTOMY TUBE ? a pill can be crushed or a capsule can be opened and the powdery substance can then be mixed with water or tube feeding or even sprinkled on soft food for ease of chewing and swallowing. BUT rinse tube w/30-60 mL water befor administration of drug EX : Tablets, capsules, pills, timed release capsules, elixirs, etc.

Endogenous substances

chemicals you make in your body such as

If the mechanism of action of a drug involves a receptor interaction, then the molecular structure of the drug is __________

critical

passive tubular reabsorption

glomerular capillaries into the tubular lumen, joining other substances as the beginning of urine. ii. If this drug molecule is a lipophilic drug molecule it will tend to have affinity with those lipophilic cell membranes of the cells that line the tubule. iii. As it flows along with the urine, it will therefore tend to be easily reabsorbed back into the blood. (Another term you might see elsewhere is resorption, a term that is used to mean "comes back into the blood"). iv. Is this a good thing? Usually not, because the whole idea is to get rid of the drug metabolites from the body. v. Therefore, the more a drug can be formulated to be hydrophilic, or be changed to a hydrophilic form by the CYP system of the liver (see above metab section), the more likely it will NOT be reabsorbed in the kidneys and will then appropriately pass out of the body. vi. So, polar/hydrophilic drug molecule = better urinary elimination /excretion out of body

Enteric coated tablet

have a coating that prevents them from being broken down in acidic pH environment of stomach and therefore are not absorbed until they reach the higher pH of intestine

Since a drug is useless while bound and inactive inside a blood vessel, the manufactures know that if their drug tends to be highly protein-bound, they need to recommend __________ enough dosage ranges that will take into account that a certain number of molecules will become inactive. 1) high 2) low

high

what kind of drugs do animals provide?

hormone drugs

Hydrophillic molecule

i. *An ionized drug molecule*—ie, carries a net electrical charge, either negative or positive; since it is hydrophilic, it will tend to stay in or aim for more watery medium like the blood or urine. ii. *A polar molecule*; this is a molecule with an uneven distribution of charges (like H2O has) and dissolves very well in water but not fat (oil & water don't mix) --Like ionized molecules, since it is hydrophilic, it will tend to stay in or aim for more watery medium like the blood or urine.

Explain the difficulties of drug distribution when there are perfusion problems

i. A person with good arteries can perfuse tissues very well—that is, deliver blood to cells -- and therefore the arteries can deliver drug molecules to where they need to be. ii. But let's say someone has terribly "corroded" arteries because of atherosclerosis—their arterial vessels would have a hard time perfusing tissues and therefore would not be able to get drugs to all the areas they need to be

how does CYP450 activate Prodrug

i. A prodrug is taken in an inert, inactive form, and it would remain inactive if not acted upon by the CYP system. ii. Why give a prodrug? Sometimes prodrugs can be absorbed better or have some other appealing property; they are later activated by the liver and then can do their job.

Explain the difficulties of drug distribution when there is a tumor

i. Blood supply to these pathologic tissues is often very low—the arteries have a hard time penetrating certain tumors. ii. Therefore the drugs also have a hard time penetrating into the tumor to do their job of destroying it. iii. This concept of penetration is an important one: to have high drug efficacy (success), a drug must be able to penetrate - get to and into an effector site—in order to do its job.

drug-drug / drug-food interaction

i. Foods can interfere with absorption too—some medications are formulated to work best on an empty stomach and if taken with food might not be dissolved and absorbed properly. ii. On the other hand, many people get nauseated if they take a drug on an empty stomach

Lipophillic molecule

i. In terms of electrical charge: *A "neutral" drug molecule*—one without a net electrical charge— can be thought of as more lipophilic. ii. And any time you see in your drug handbook that a drug is "highly lipophilic" you will know that it can usually "go more places"—IT CAN USUALLY GET INTO MORE TISSUES, ie, can be more widely distributed. iii. In general lipophilic drugs are the most common in manufacturing formulation

Plasma-protein bound (PPB)

i. Many types of protein molecules with many different "jobs" travel in our blood, the most common type of protein being albumin. ii. There are quite a few drugs whose molecules, once they get into the blood, have an affinity for albumin, and bind to it—ie, become protein-bound. iii. Once bound to albumin, the drugs cannot get out of the blood vessel because albumin is WAY too big to get through those capillary lining gaps we discussed. iv. Only a "free" drug—NOT bound to albumin—can make its way to the interstitial fluid

Acid Base environment

i. PO drugs are usually formulated as a *weak acid* or a *weak base* and can either exist in a charged form (an ion with a *positive or negative charge*) or an uncharged form (let's call this "*neutral*"). ii. The drugs that are *neutral weak acids* will dissolve quickly in the acid environment of the stomach and will maintain a NEUTRAL charge—they thus quickly pass into the stomach cellular lining and then into the blood. (Non-charged = lipophilic = absorbed quickly.) ii. *Weak bases* (alkaline-formulated drugs) will undergo a transformation called *ionization* when exposed to stomach acid: the drug molecule will go from having a neutral charge to having a positive or negative charge (an ion)

narrow therapeutic range

small difference between therapeutic range & toxic level

The more surface area available for absorption, the better, so most drugs are formulated to be absorbed in the ________, which have a HUGE surface area, thanks to the villi

small intestines

name the test to measure effects of following drugs ___________ - synthroid (thyroid hormone) ___________ - supplements for anemia ___________ - Warfarin (Coumadin)

spot checks- synthroid (thyroid hormone) CBC - supplements for anemia PT/PTT- Warfarin (Coumadin)

passage through walls

i. Picture a capillary: it has a lumen where blood flows, and it has a wall/lining which, because a capillary is very tiny, is made up of one layer of cells. ii. Often there are good-sized gaps between the cells that compose the walls of the capillaries, so most of the time, a drug molecule is small enough to slip through the gap & go from the intravascular fluid (the blood) into the intercellular fluid. iii If the drug too big to go through the gap but is *lipophilic*, it can pass right through a cell that lines the capillary and end up on the other side. iv. If a drug is *lipophobic* AND too big to go through a gap in the capillary lining cells, it may be able to latch onto a cell membrane transporter on the cell & be allowed through that way (see the previous section on cell membranes).

active tubular secretion

i. Remember those transmembranous transport molecules that are found at intervals in the plasma cell membrane of most cells? ii. Some of them are "pumps" of various kinds, and the cells lining the tubules of the nephron can "pump" drug molecules from blood to urine, thus excreting /secreting them--this is called active transport. An example is P-glycoprotein, which is an important active transport molecule/pump that is abundantly found in kidney tubular cell membranes. iii. An example of a drug that is actively secreted into the tubule is penicillin G; only 10% of it is filtered through the glomerular membrane—the other 90% is actively transported (pumped) from capillaries around the tubules into the tubular cells into the lumen of the tubule. iv. So, our ideal drug metabolite for excretion is a small, hydrophilic remnant that easily flows out with the urine... but if it is not ideal—too big or not hydrophilic enough—it can be actively pumped into the urine (sort of "forced out") by an active transporter along the way.

synergistic effect AKA potentiation 2+2 = 5

i. This is when the effect of two or more meds adds up to be more than just the simple sum of them. ii. Example: Phenergan is for nausea and morphine is for pain, but when they are given together, the pain-lowering effect is enhanced. Most of the time synergism and potentiation can be used interchangeably.

First Pass effect

i. Whether absorbed from stomach to blood or intestines to blood, a molecule of PO drug will often immediately enter the portal system because it is so intricately tied in with the stomach circulatory system. ii. This is basically an unavoidable "side trip" that unfortunately results in a large amount of the drug losing a lot of its bioavailability. iii. Drug manufacturers take this into consideration into their recommendation for timing of the drug—a drug that ends up with only 50% bioavailability due to first pass effect would have to be taken for a longer period of time, for instance, than one with 75%.

Drug competition

if any other drug also has an affinity for albumin, there might be competition-- a drug-drug interaction that results in the original drug molecule being "knocked off" the albumin molecules and becoming "free." increased original drug in plasma --> equilibrium imbalanced --> may lead to drug toxicity

And what would happen if you, say, had a patient with cirrhosis (liver disease) whose diseased liver could not make very many proteins? Would you agree he would be hypoproteinemic (have hypoproteinemia)? How will that hypoproteinemia affect taking drugs that are formulated to account for a certain amount of protein-binding?

increased drug effect

enzyme inhibitor (drug)

inhibit drug metabolizing enzymes decrease/delay in drug metabolism -->accumulation of drug --> prolonged drug effect--> drug toxicity

Before administering any _________ medication, the nurse must always inspect the bag for precipitate. If the solution appears cloudy or if visible flecks are seen, the bag must be discarded and not given to the patient

intravenous (Parenteral)

Acute Therapy think TREATRMENT

involves more intensive drug treatment and is implemented in the acutely ill (those with rapid onset of illness) or the critically ill. It is often needed to sustain life or treat disease. EX: administration of vasopressors to maintain 1) blood pressure and cardiac output after open heart surgery, 2) he use of volume expanders for a patient who is in shock, 3) intensive chemotherapy for a patient with newly diagnosed cancer.

Drugs that are successful in crossing this so-called blood-brain barrier are usually very ___________ drugs-- they can go ¬through the cell membranes of the capillary lining cells and don't have to rely on gaps or transport molecules in the cell membranes of the capillary lining cells

lipophilic EX: a highly lipophilic IV drug called *propofol* (Diprivan) which zips right through the "blood-brain barrier" and sedates a patient within fractions of a minute.

if you gave two drugs to a patient, and one was a CYP inducer, would you worry about the patient ending up with not enough of the drugs in the body (low efficacy), or too much drugs in the body (toxicity)?

low efficacy ?

age spectrum

neonate : younger than 1 mo Infant : 1 mo - 1 yr Child - 1 - 12 Elderly : 55/65 or older

Pores and Channels

only tiny drug molecules can pass through them

Blood tests that measure therapeutic range are known as serum ________ and __________

peak and trough levels

Mutagenic effects

permanent changes in the genetic composition of living organisms and consist of alterations in chromosome structure, the number of chromosomes, or the genetic code DNA. Radiation, viruses, chemicals (e.g., industrial chemicals such as benzene), and drugs can all act as mutagenic agents in humans. Drugs that affect genetic processes are active primarily during cell reproduction (mitosis).

Pharmacology

pharmacology is the study of drugs and their interactions with living systems.

The plasma cell membrane is composed of "____________"

phospholipid bilayer a) The lipid part makes up most of it, so think of the plasma cell membrane as sort of a wall of fat. b) However, it does have protein molecules embedded in it, that serve as transport systems

spray

same principle(sublin) except liquid is sprayed into mouth.