1.       Pharmaceutic phase

2.       Pharmacokinetic phase

3.       Pharmacodynamic phase

There are a number of factors which affect drug absorption. What are they?

1. The first factor is the Route, or how the drug enters the body. The route affects both the rate (speed) at which the onset of action occurs and the magnitude of the therapeutic response.

2. Drug form, which means how the drug is delivered,

3.  surface area of the GI mucosa: in other words, the cell membrane through which the drug  must pass.

4.  Blood supply to the site of administration

5. Solubility of the Drug

6. Liver Function.

 Enteral or Parenteral. 

Enteral routes include: oral, sublingual, buccal, gastrointestinal, and rectal.

Enteral routes include: oral, sublingual, buccal, gastrointestinal, and rectal.

• Oral is the most common route, and is the safest, most economical and most convenient means of drug administration, however, it is also the most unreliable and slowest route to have an effect.

Parenteral route refers to administration by injection and includes: subcutaneous, intramuscular, intravenous, intradermal, intrathecal (directly into subarachnoid space), epidural (into epidural space). Often, when a person refers to the parenteral route, they are talking about an injectable medication.

• Parenteral technically means outside GI tract so it also includes drugs that your text classifies as topical, i.e., transdermals, eye drops, ear drops, nose drops, inhalation drugs, vaginal drugs. In general, the parenteral route provides the most rapid form of systemic absorption.

• In general, the more extensive the absorbing surface, the greater the drug absorption and more rapid its effect.
• Examples: inhaled anesthetics are immediately absorbed from the pulmonary epithelium because of the vast surface of the lung
• Example: the small intestines have a much greater mucosal surface than the stomach and therefore absorption is more rapid in small intestines than in stomach.

Distribution: Refers to the transport of a drug in the body by the bloodstream to the site of action.

By what 3 factors is distribution influenced?

Blood flow – Distribution of drugs is directly related to the cardiac output. The person's cardicac output affects the rate and extent  of distribution as well as the blood flow to the target organ or tissue.

2. Affinity to tissue - Most of the drug is first distributed to organs that have a rich blood supply: the heart, liver, kidney, and brain.Then the drug enters organs with a poorer blood supply: skin, muscles, fat.

3. Plasma protein binding - Once in the blood stream, drugs may become attached to proteins, mainly albumin.Not all of the drug becomes protein bound – some drug remains free in the plasma.

• The amount of protein bound drug and the amount of free drug establish an equilibrium.
• The drug-protein molecule is too large to diffuse through the cell membrane so the drug molecule is trapped in the plasma and does not exert any pharmacologic activity.
• This creates a store of the drug as a protein- drug complex, then as the free drug is eliminated, the drug protein complex is dissociated so more free drug is released to replace what is being eliminated.
• So in other words, the body temporarily stores the drug by way of the protein – drug molecule allowing the drug to be available in the plasma for longer periods of time.
• So if you think about it, a patient who is malnourished and has a low protein level in their body, might have too much free drug circulating and this could be toxic.

1. What happens during the metabolism of drugs.

2. WHat organ is most responible for metabolism?

Metabolism refers to the biotransformation of a drug from an active state to an inactive state. (In other words, the drug is broken down or detoxified.)

2. The organ most responsible for metabolism is the liver (other tissues involved in metabolism include the plasma, kidneys, lungs, intestinal mucosa).

• Metabolism by the liver involves an enormous variety of enzymes that control the chemical reactions and help to transform the drugs to the inactive state.
• Patients with liver disease or liver function are at risk for drug accumulation which can lead to toxicity.

• This phase refers to the excretion of a drug from the body.
• The primary organ responsible for elimination is the kidney, although the liver, the bowel, and lungs also play a role in elimination.
• By the time most drugs reach the kidneys, they have been extensively metabolized by the liver and only a small fraction of the drug is excreted as the original compound – Excretion happens by passive glomerular filtration and active tubular secretion.
• The function of the kidneys is very important to monitor. Kidney disease which results in lower glomerular filtration or ↓renal tubular secretion can impair or slow down drug excretion.
• Creatinine clearance (normal = 85-135 ml/min) is the most accurate test to determine renal function. It is a 24 hour urine collection and blood test.
• A decrease in GFR (glomerular filtration rate) results in higher serum creatinine level and a decrease in urine creatinine. Creatinine is a waste product caused by cellular metabolism. The serum concentration of creatinine is a direct indicator of glomerular filtration rate. BUN is an indirect indicator of GFR (urea are smaller molecules than creatinine and some molecules are reabsorbed). All filtered creatinine is eliminated in urine.
• Creatinine clearance lowers with age (60 ml/min), therefore drug doses in the elderly may have to be lowered.

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A. Drug actions

B. Therapeutic effects

C.  Side effects, adverse reactions, and toxic effects

 Drug receptor interaction:

• With this mechanism, a certain portion of the drug interacts with a reactive site on the cell surface to produce a biologic effect
• When the drug binds to the receptor, it will either elicit a response or block a response
• Drugs that produce a response are called agonists
• Drugs that block responses are called antagonists

• In this mechanism, the drug will interact with enzyme systems to "fool" the enzyme into binding to it rather than the normal target cell – example:
• ACE inhibitors (angiotensin-converting enzyme) fools the ACE into binding to it rather than with angiotensin I and thereby prevents the formation of angiotensin II – thus preventing vasoconstriction and causing vasodilatation. This is how ACE inhibitor drugs lower blood pressure.

• This mechanism of action does not involve a receptor or enzyme, rather such drugs either interfere with or chemically alter cellular processes – example:  cancer drugs and antibiotics
• They incorporate themselves into the normal metabolic process and alter the final product, for instance cause a defect such as faulty cell wall.

There are other factors which affect Pharmacodynamics, specifically drug action and dosing:

Age: neonates/infants have an underdeveloped GI system, less muscle mass, underdeveloped metabolic enzymes and inadequate renal function. The elderly have lower renal and liver function and diminished muscle mass.

Genetic factors: Some people lack certain enzymes which interfere with drug metabolism and produce abnormal sensitivity.

Height/weight: This is especially significants in infants, children, and the elderly. Many medications  are weight-based.

Gender: The amount of body fat and water distribution can alter drug distribution (some drugs, i.e. digoxin are poorly distributed to fatty tissues). Women generally have more body fat than men

Each unit is a body system, i.e. neuro, resp., cardiovascular and each chapter of the unit lists drugs according to their clinical indication.

Example: The unit on Cardiovascular Agents has a chapter on

• Drugs for cardiac disorders
• Diuretics
• Antihypertensives
• Drugs for circulatory disorders

Pharmacology becomes easier when one understands the common characteristics of each drug classification. For example, all diuretics have some common characteristics.

When a new drug comes along – you can make some basic inferences based on the classification of the drug

When a drug is developed the first name it is given is its chemical name, based on its chemical composition

Then it is given a generic name by the USAN (United States Adopted Name) council.  It is usually shorter and simpler than the chemical name.

Then the owner of the drug usually the manufacturer, will give it a brand name (or trade name).

Example:

• propionic acid - chemical
• Ibuprofen – generic
• Motrin – trade

Legal requirements – According to federal law, a record must be kept for each narcotic that is administered. Health care agencies provide forms for keeping such records, these forms are kept with the narcotics.  Although the forms differ, the following information is usually required:

• Name of patient
• Name and amount of narcotic
• Date, time used
• Name of physician who prescribed it
• Name of nurse who administered it
• Name of nurse who witnessed wastage

Anytime that a full or partial dose of a controlled med is wasted for any reason, another nurse must witness its disposal and cosign the narcotic sheet.

Example:

When a narcotic is prepared and the client refuses it

• When a narcotic is accidentally dropped
• When a client requires a smaller dose than is supplied in the one time dose.

Legally, you must observe the actual wasting of the drug if you are cosigning.

Medications are supplied in a number of ways.

1. Multiple dose system – more than one dose per package, examples: tablets, syrups, vials. Example – the way that prescriptions from the doctor are supplied.

2. Unit dose system – only one dose per package, examples: each tablet is individually wrapped in a foil or paper container.

3. Containers :some meds must be kept in specific types of containers. Examples: DARK – brown or opaque for light sensitive drugs.

• GLASS – some have a reaction to plastic and must come in glass containers.
• STOPPERED VIALS -  multi-dose vials must be dated, timed when opened.

4. Storage – some meds must be refrigerated and are deactivated by heat. Some are deactivated by cold and must not be refrigerated. Check med label for proper storage.  A med with an unexpected precipitate should not be used. A med which has changed color should not be used.

5. Labeling – may be done by a pharmacist only.

1) pharmaceutic phase

2) pharmacokinetic phase

3) pharmacodynamic phase

How fast a drug goes into the body.  How a drug goes from a solid state to a liquid state and how it disolves.  Liqiud drugs act faster.

solid ---> small particles---> solution

II) Pharmacokinetics:

1) What is it?

2) What are it's phases?

1) The study of what happens to a drug then it enters the  body.

2) 4 phases: absorption, distribution, metabolisim, elimination

the movement of drug molecules from teh site of entry into the circulation.

• passive transport
• active transport
• pinocytosis

route

drug form

GI mucosal surface

blood supply to site of administration

solubility of drug

liver function (decreased liver function makes bioavailbility raise b/c drugs are not getting broken down.

This is when drugs can first go to the portal vien into the liver. The liver tries to break down drug before it get to circulation.

****NOTE: nurses must know which drugs are first pass****

morphine and cumidin both have 1st pass effect. When they're given orrally instead of IV the dose is higher.

transport of a drug in the body by the bloodstream to the site of action.  It's influenced by 3 factors:

1) blood flow- ie- it takes longer for a drug to get to the toe and to the neck.

2) affinity to tissue- liver, kidney- good vascularization.  Fat tissue- not so much.

3) plasma protein binding PPB:  a molecule of the drug is bound to and carried thru the blood by a molecule of protein. Once the free (non bound) molecules are used us, then the bound ones break free

FALSE

The patient with liver failure will not have as great a first-pass effect as the healthy patient. Therefore, the liver failure patient will end up with more morphine entering the circulation and needs a smaller dose.