The study of drug movement throughout the body.

It determines how much of a drug dose gets to its site(s) of action.

 Composed of four processes:

1.) Absorption

2.) Distribution

3.) Metabolism

4.) Excretion

The first process of pharmacokinetics. It's the movement of drug particles from the site of administration (GI tract, skin, muscle) into body fluids and bloodstream by passive or active absorption or pinocytosis.

It is the primary pharmacokinetic factor determining the length of time it takes a drug to produce its effects.

It is the second process of pharmacokinetics.

The process by which the drug moves from the blood to interstitial space of tissues and from there into cells to become available to body fluids and body tissues.

Responsible for drugs moving into one or more parts/compartments in the body where they can be (1) stored, (2) exert a pharmacologic action or (3) be metabolized and excreted.

It is the third process of pharmacokinetics.

The process and breaking down of drugs by body enzymes and chemical transformation, converting them to a form that is more easily removed from the body. Primarily done in the liver, but also in GI tract.

Most drugs are metabolized/inactivated in the liver by liver enzymes and converted/tranformed to inactive metabolites or water soluble substances for excretion

• The liver metabolizes the large number of lipid soluble drugs to water soluble for more efficient renal excretion
• The resulting drug metabolite may be more active or more difficult to excrete.

The fourth and final process of pharmacokinetics.

The movement of drugs and their metabolites out of the body. The kidneys are the main route of excretion but the liver, feces, lungs, saliva, sweat, bile, and breast milk can also be portals for excretion.

• Dosage Formulation
• Water Soluble vs. Lipid Soluble
• Membranes
• Particle Size
• Acidity of the Stomach
• Circulation/Blood Flow
• Gastric Emptying/Digestive Motility

Oral medications can be given in many different forms.

ie: capsule, tablet, solution, etc.

It depends on the form how quickly the drug is absorbed.

Water Soluble: need to have a carrier to be absorbed

Lipid Soluble: able to pass through the GI-membrane by itself and usually are absorbed faster.

GI Membrane: mostly allow Lipid solubles through.
Plasma Membrane: lipid bi-layer with proteins and other molecules interspersed in the membrane and is mostly impermeable to large molecules.

Small: generally faster and can enter through pores in the plasma membrane.

Large: have more difficulty but can pass through the membrane if nonionized (no +/- charge) or if they use carrier proteins or active transport.

• A lower pH of 1-2 typically increases drug disintigration and absorption.
• Milk products and antacids will make the stomach less acidic.
• Acidic drugs (ASA) are absorbed better in acids.
• HCI may destroy some drugs (pen G). To offset this larger doses are needed to make up for what is lost.
• The Small intestine is an alkaline environment and more readily absorbs alkaline medications.
• Bases are better absorbed by bases.

Shock, vasoconstriction, disease: hamper absorption

Exercise: can decrease blood flow to stomach/intestine by shunting to peripheral muscles.

Slowed/decreased by:

• Pain, Stress
• Solid, hot or fatty foods
• Drugs that inhibit the vagus nerve (ie: anticholinergics, opiods, antidepressants, antipsychotics)
• Loss of mucosal villi (disease, surgery)
• Poor circulation
• Exercise

Increased by:

• Empty stomach
• Lying on right side
• PO meds with cold water

Food: can enhance absorption of some drugs but may be necessary to dilute drug concentrations and may also act as protectants to lessen gastric mucosa irritation.

Plasma protein-binding

Blood flow to tissues

Ability of the drug to move into cells

Because most drugs are bound in varying degrees/percentages to plasma proteins for distribution to sites of action.

Only unbound drug molecules can leave the vascular system and cause a pharmacologic response. So if there is a decrease in free drug in the serum then there is a decrease in how much drug can enter a given tissue/organ to produce a response. This will cause more bound drug to be released from the plasma proteins to maintain the balance.

While bound drugs are inactive to receptors and restricts the amount distributed at one time.

Drug dose is determined by the percentage in which the drug binds to protein.

It is the most prevalent and important protein in plasma to which drugs bind. It is a large molecule so it stays in the plasma. This means that when drugs are bound to it they are too large to fit through the pores in the capillary walls so they can not reach their sites of action, metabolism, or excretion.

Conditions that decrease albumin will increase the free drug levels (ie:malnutrition, liver disease, kidney disease, aging, trauma)

Each albumin molecule has only a few sites to which drug molecules can bind. So that means that those drugs that can bind will compete with one another for those binding sites.

This can cause one drug to displace another drug from binding and will cause a higher free concentration of the displaced drug. This will cause an increased intensity of the drug's responses and can lead to toxicity.

The study of drug concentration and its impact/effects on the body.

"what a drug does to the body"

1.) Stimulation- rate of cell activity or the secretion from a gland increases

     Depression- cell activity and function of a specific organ are reduced

 2.) Replacement- drugs replace essential body compounds (vitamins, minerals, hormones)

 3.) Inhibition or killing of organisms- interfere with bacterial cell growth (antibiotics)

 4.) Irritation- such as laxatives

Idiosyncratic reaction

Paradoxical reaction

Pharmacogenetics

Tolerance

Tachyphylaxis

Dependence

Allergic reaction

Anaphylaxis

A genetically determined unusual or abnormal response to a drug; generally not related to drug dose.

Results from extreme sensitivity to a low dose of a drug, extreme insensitivity to a high dose of a drug indicating abnormal tolerance, or results in unpredictable and unexplained symptoms.

Response produced is opposite the desired/expected response.

The rapid decrease in response to the drug.

"Acute tolerance".

An acquired hyper-response of the body defenses to a foreign substance (allergen).

 Does not occur with the first exposure to a drug, but are manifested after a second or subsequent exposure.

• Half-life (t1/2): describes the relationship between drug volume in the body and its clearance from the body.
• The time it takes for 1/2 the drug concentration to be eliminated
• roughly correlates with the duration of action of a drug (how long it will take to plateau and when it will go below the MEC once drug is stopped).
• A drug goes through several t1/2 before 90% has been eliminated.
• Impacted by the absorption rate, distribution to the tissues, the speed of metabolism, and how fast a drug is excreted.
• Drugs have 2nd, 3rd, 4th, ....9th half-lives.

Liver disease alter drug metabolism by inhibiting the drug-metabolizing enzymes in the liver.

• May lead to excess drug accumulation and toxicity.
• A reduction in drug dosage in necessary.

Most drugs are metabolized/inactivated by liver enzymes and converted or transformed to inactive metabolites or water soluble substances for excretion.

More severe than side effects and are always undesirable; may be life-threatening.

• A range of untoward, unintended effects occuring at normal doses.
• Must be reported and documented and represent variances from planned therapy.
• Usually requires changing dosage, stopping the drug, or administering an antidote.

Physiologic effect not related to desired drug effects.

• All drugs have side effects- desirable and undesirable, predictable and unpredictable
• Result mostly from drugs that lack specificity

Low therapeutic index: have a narrow margin of safety and serum drug levels need to be monitored closely and dosages may need to be adjusted carefully.

High therapeutic index: wide margin of saftey and less danger of producing toxic effects. No need to routinely monitor these drug plasma levels.

Drugs that bind to or activate a receptor to produce a response (mimic endogenous substances "the bodies own")

Increases or decreases the cell's activity.

Drugs that produce effects by binding to receptors and block/inhibit a response.

• Block the access or attachment of the body's natural agonists (such as neurotransmitters) to their receptors and thereby prevent or reduce cell responses to natural agonists.
• They do not have any pharmacologic actions/effects of their own on receptor function.

Peak Level: The highest plasma concentration of a drug at a specific time; indicates the rate of absorption

Trough Level: The lowest plasma concentration of a drug; measures the rate at which the drug is eliminated. It is drawn immediately before the next dose of the drug is given, no matter the route.

Goal: To maintain a steady level within the therapeutic range. If either the peak or the trough is too high, toxicity can occur, if the peak is too low, no therapeutic effect is acheived.

When an immediate drug response is desired, a higher initial dose is given to achieve a rapid immediate drug response (MEC) in the blood.

After this large initial dose a prescribed dosage per day is then ordered/given.

Drug interacts with only one type of receptor/specific target cells/tissues where they produce their intended effects; that receptor type regulates just a few processes. ie: NSAIDs- target any area where inflammation is present.

• Nonselective: drug affects many different tissues or organ receptors; elicits a wide variety of responses.
• Atropine: relaxes many muscles.

The degree to which the effects of a drug are due to the one pharmacological action.

 Nonspecific drugs: affect various sites and evoke a variety of responses throughout the body. They are desirable, undesirable, or harmful. ie: cholinergics.

A special protein molecule present on the cell membrane surface or on an organelle within the cell.

• Control normal physiolgic processes
• Drug-binding sites are primarily on proteins
• Specifically designed to interact with body chemicals but can also interact with drugs.

The action of many drugs is determined by the ability of the drug to bind to a specific receptor; the better the drug fits at the receptor site, the more biologically active the drug is.

One of the following is likely to occur:

• An ion channel is opened or closed
• Biochemical messengers are activated to initiate a series of chemical reactions within the cell
• Normal cell function is inhibited/blocked
• A cell function is 'turned on' or activated

1.) Additive

2.) Synergistic interaction

3.) Potentiation

4.) Antagonism

1. Drugs are absorbed
2. Enter hepatic portal circulation and go directly to liver
3. Hepatic microsomal enzymes metabolize drugs to inactive form
4. Drug conjugates leave liver
5. Drug is distributed to general circulation.

Traditional Five:

1. Right client: 2 forms of ID
2. Right drug: read medication packet/container label 3x
3. Right dose
4. Right time of delivery
5. Right route

Plus Five:

1. Right assessment
2. Right documentation
3. Right evaluation
4. Patient's right to educate
5. Patient's right to refuse

• Administer drugs
• Assess drug effects
• Intervene to make the drug regimen more tolerable
• Proved patient teaching about drugs and the drug regimen
• Monitor the overall patient care plan to prevent medication errors

SubQ

IM

IV

SL

Topical

I: Drugs w/high abuse potential; no accepted medical use. ie: heroin

II: High potential for drug abuse; can lead to strong physical and psychologic dependence; medically accepted. ie: morphine

III: Potential abuse is less than that for I & II; medically accepted. ie: codeine preparations

IV: Medically accepted; may case dependence. ie: phenobarbital

V: Medically accepted, limited potential for dependence. ie: opiod controlled substances for cough or diarrhea

Category I: Safe and effective

Category II: Unsafe or ineffective

Category III: Insufficient data to judge

• Delay in professional diagnosis and treatment
• Symptoms may be masked
• Read labels
• Consult health care provider before use
• Inactive ingredients may cause adverse reactions
• Potential for overdose
• Interactions of prescription and OTC medications

1. OTC cold and cough remedies

2. OTC sleep aids

3. OTC weight-control drugs

• Have chronic health conditions
• Take multiple medications
• See more than one health care provider
• Use multiple pharmacies