PHARMACOKINETICS

-- how the body acts on the drug including absorption, distribution, biotransformation, & excretion
-- includes the ff:

… onset of drug action … drug half-life

… timing of the peak effect … metabolism & site of excretion
… duration of drug effects … biotransformation of the drug

CRITICAL CONCENTRATION / Recommended Dose

-- amount of a drug that is needed to cause a therapeutic effect
-- too much of a drug will produce toxic (poisonous) effects
-- too little will not produce the desired therapeutic effects

LOADING DOSE
-- a higher dose than that usually used for treatment to reach the critical concentration
-- critical concentration then is maintained by using the recommended dosing schedule
-- some drugs may take a prolonged period to reach a critical concentration
-- if their effects are needed quickly, a loading dose is recommended

EG: Digoxin (Lanoxin) = increase the strength of heart contractions

Xanthine bronchodilators = treat asthma attacks are often started with a loading dose

DYNAMIC EQUILIBRIUM
-- actual concentration that a drug reaches in the body results from a dynamic equilibrium involving several processes:

Absorption from the site of entry Biotransformation (metabolism) in the liver

Distribution to the active site Excretion from the body

These processes determine the amount of drug (dose) & the frequency of dose repetition (scheduling) required to achieve the
critical concentration for the desired length of time.
When administering a drug, the nurse needs to consider the phases of pharmacokinetics so that the drug regimen can be made
as effective as possible.

DRUG HALF-LIFE
-- time it takes for the amount of drug in the body to decrease to one half of the peak level it previously achieved
-- important in determining the appropriate timing for a drug dose / determining the duration of a drug’s effect on the body
-- half-life for a healthy person = indicated in any drug monograph
-- used to estimate the half-life of a drug for a patient with kidney or liver dysfunction allowing the prescriber to make changes in the
dosing schedule

PHASES OF PHARMACOKINETICS:

1. LIBERATION
= a pharmaceutical substance is released from the formulation it is delivered in
= release of the drug from its dosage form
= must occur before the drug can be absorbed into the body

2. ABSORPTION
= refers to what happens to a drug when it is introduced to the body until it reaches circulating fluids & tissues

SITE OF ABSORPTION:
GI tract either orally or rectally Skin Subcutaneous tissues
Mucous membranes Lungs Muscles

GENERAL CLASSIFICATION OF ROUTES:

ENTERAL PARENTERAL PERCUTANEOUS

- directly in the gastrointestinal tract - by-pass the gastrointestinal tract - thru skin or mucous membranes
ROUTES OF ADMINISTRATION:

ORAL ROUTE
- slow absorption ; most frequently used ; less expensive ; safest
- patients can easily continue their drug regimen at home when they are taking medications
- subjects the drug to a number of barriers aimed at destroying ingested foreign chemicals

When food is present, stomach acidity is higher and the stomach empties more slowly, thus exposing the drug to the acidic
environment for a longer period.

Certain foods that increase stomach acidity, such as milk products, alcohol, and protein, also speed the breakdown of many
drugs. Oral drugs ideally are to be given 1 hour before or 2 hours after a meal.

INTRAVENOUS
- reach their full strength at the time of injection & avoids initial breakdown
- immediate onset & fully absorbed at administration since they directly enter the bloodstream
- more likely to cause toxic effects because the margin for error in dose is much smaller

INTRAMUSCULAR
- directly into the capillaries in the muscle & sent into circulation
- takes time since the drug must be picked up by the capillary & taken into the veins

Men have more vascular muscles than women do. As a result, drugs administered to men via the IM route reach a peak level
faster than they do in women.

SUBCUTANEOUS
- under the skin, where it is slowly absorbed into circulation
- timing of absorption varies with subcutaneous injection, depending on the fat content & state of local circulation

TOPICAL NGT BOLUS ROUTE

- suitable on intact skin and others that contain a medication
- used for the treatment of broken skin or a wound INTRAVAGINAL ROUTE

TRANSDERMAL INTRAVENOUS PIGGY BACK

- absorbed from the surface of the skin.
RECTAL ROUTE
OPTHALMIC BUCCAL AND SUBLINGUAL ROUTES
- administered & absorbed in the eyes
INTRATHECAL
OTIC
- absorbed from the ears. INTRACARDIAL

INHALATION INTRA-ARTICULAR
- absorbed in the lungs via the nose NASAL
INTRADERMAL

ABSORPTION PROCESSES:

PASSIVE DIFFUSION
- movement of drug from higher to lower concentration and does not require energy
- occurs quickly to smaller molecules, soluble in water & lipids, has no electrical charge that could repel it from the CM

ACTIVE TRANPOST
- uses energy to actively move a molecule across a cell membrane
- molecule may be large, or it may be moving against a concentration gradient
- a very important process in drug excretion in the kidney

FILTRATION
- another process the body commonly uses in drug excretion
- movement through pores in the CM, either down a concentration gradient or as a result of the pull of plasma proteins (when
pushed by hydrostatic, blood, or osmotic pressure)
3. DISTRIBUTION
= involves the movement of a drug to the body’s tissues
= affected by the drug’s lipid solubility & ionization + perfusion of the reactive tissue

EXAMPLE # 1

Tissue perfusion is a factor in treating a patient with diabetes who has a lower-leg infection and needs antibiotics to destroy the
bacteria in the area.

In this case, systemic drugs may not be effective because part of the disease process involves changes in the vasculature and
decreased blood flow to some areas, particularly the lower limbs.

If there is no adequate blood flow to the area, little antibiotic can be delivered to the tissues, and little antibiotic effect will be
seen.

DISTRIBUTION PROCESSES:

PROTEIN BINDING
- some drugs are loosely bound = they tend to act quickly and to be excreted quickly
- some drugs compete with each other for protein binding sites = alters effectiveness or causes toxicity
- some drugs are tightly bound and are released very slowly = have a very long duration of action bec. they are not free to be
broken down or excreted and are released very slowly into the reactive tissue

BLOOD- BRAIN BARRIER

- a protective system of cellular activity that keeps foreign invaders, poisons, and similar materials away from the CNS
- drugs that are highly lipid soluble are more likely to pass through the BBB & reach the CNS

Almost all antibiotics are not lipid soluble and cannot cross the blood–brain barrier. Effective antibiotic treatment can occur only
when the infection is severe enough to alter the blood–brain barrier and allow antibiotics to cross.

Although many drugs can cause adverse CNS effects, these are often the result of indirect drug effects and not the actual reaction
of the drug with CNS tissue.

PLACENTA & BREAST MILK

- many drugs readily pass through the placenta and affect the developing fetus in pregnant women
- it is best not to administer any drugs to pregnant women
- drugs should be given only when the benefit clearly outweighs any risk

4. METABOLISM / BIOTRANSFORMATION
= everything that is absorbed from the GI tract first enters the liver to be “treated”
LIVER
= detoxifies many chemicals & uses others to produce needed enzymes & structures
= most important site of this process wherein drugs are changed into new, less active chemicals

FIRST- PASS EFFECT

- phenomenon in which drugs given orally are carried directly to the liver after absorption
- drugs are inactivated by liver enzymes before they can enter the general circulation
Oral drugs frequently are given in higher doses than drugs given by other routes because of this early breakdown.

HEPATIC ENZYME SYSTEM

Phase I Biotransformation
- involves OXIDATION-REDUCTION, or HYDROLYSIS of the drug via the cytochrome P450 system of enzymes
Phase II Biotransformation
- involves a CONJUGATION REACTION that makes the drug more polar & readily excreted by the kidneys
- increased activity in an enzyme system speeds the metabolism of the drug

The presence of one drug speeds the metabolism of others, preventing them from reaching their therapeutic levels.
Some drugs inhibit an enzyme system, making it less effective.
As a consequence, any drug that is metabolized by that system will not be broken down for excretion, and the blood levels of that
 drug will increase, often to toxic levels.
These actions also explain why liver disease is often a contraindication or a reason to use caution when administering certain
drugs. If the liver is not functioning effectively, the drug will not be metabolized, and toxic levels could develop rather quickly.
5. EXCRETION
= removal of a drug from the body ; excreted thru the Kidneys Saliva Bile Skin Lungs Feces

Glomerular Filtration
= passage of water & water-soluble components from the plasma into the renal tubule.
= drugs that have been made water soluble in the liver are often readily excreted thru GF
Kidney dysfunction & Urine acidity
= factors to consider in drug toxicity due to inability to excrete poisonous substances

NURSING RESPOSIBILITIES

 Dose adjustment needs to be considered if a patient has problems with either the liver or the kidneys.
 Assessment should be done before starting drug therapy.