DRUG ACTION

N. M. Hernandez

3 Phases of Oral Route of Administration

1. Pharmaceutic (dissolution) 2. Pharmacokinetic 3. Pharmacodynamic

PHARMACEUTIC PHASE
The first phase of drug action Drug in solid form is disintegrated into small particles to dissolve into a liquid (dissolution) Tablets are not 100% drug Filler & inert substances (excipients) used in drug preparation allows drug to take a particular size and shape to enhance drug dissolution Additives: K & Na in penicillin increase the absorbability of the drug.
*penicillin is poorly absorbed by the GIT because of the gastric acid. Making the drug potassium or sodium salt then can be absorbed.

PHARMACEUTIC PHASE
Disintegration: the breakdown of a tablet into smaller particles Dissolution: is the dissolving of the smaller particles in the GI fluid before absorption. Rate Limiting: the time it takes the drug to disintegrate and dissolve to become available for the body to absorb it

PHARMACEUTIC PHASE
*Drugs in liquid form are more rapidly available for GI absorption than are solids. *Generally drugs are both disintegrated & absorbed faster in acidic fluids with a pH of 1 or 2 rather than alkaline. *Young & elderly have less gastric acidity=drug absorption is generally slower for those drugs absorbed primarily in the stomach.

PHARMACEUTIC PHASE
Food in the GI tract may interfere with the dissolution and absorption of certain drugs Food can also enhance absorption of other drugs. Some drugs irritate the gastric mucosa = fluids or foods may be necessary to dilute concentration & to act as protectants.

PHARMACOKINETIC PHASE
The process of drug movement to achieve drug action
4 PROCESSES: Absorption Distribution Metabolism (biotransformation) Excretion (elimination)

ABSORPTION
(Pharmacokinetics Phase)

The movement of drug particles from the GI tract to body fluids by:
passive absorption active absorption pinocytosis

Most oral drugs are absorbed into the surface area of the small intestine through the action of mucosal villi. ( small intestine). Absorption is reduced when the villi are decreased in number

ABSORPTION
(Pharmacokinetics Phase) The GI membrane is composed mostly of lipid(fat) & protein = drugs that are lipid soluble pass rapidly through the GI membrane. Water soluble drugs need a carrier, either enzyme or protein to pass through a membrane. Weak acid drug (less ionized): aspirin, pass through the stomach lining easily & rapidly.

ABSORPTION
(Pharmacokinetics Phase) Drugs that are lipid soluble & non-ionized are absorbed faster than water-soluble & ionized drugs.

FACTORS THAT AFFECT DRUG ABSORTION:

Blood flow, Pain, Stress, Hunger, Fasting, Food , pH Blood flow: poor circulation ( shock ) exercise: decrease blood flow by causing more
blood to flow to the peripheral muscle = decreasing blood circulation to the GI tract.

Pain, stress & foods that are solid, hot and fatty can slow gastric emptying time = drug remains in the stomach longer.

ABSORPTION
(Pharmacokinetics Phase) Some drugs do not go directly into the systemic circulation following oral absorption

Pass from the intestinal lumen to the liver via the portal vein Drugs may be metabolized to an inactive form which may then be excreted reducing the amount of active drugs
First-pass effect: the process by which the drug passes to the liver first (hepatic first pass)

ABSORPTION
(Pharmacokinetics Phase) Some drugs do not undergo metabolism at all in the liver. Drugs may be metabolized to drug metabolite which maybe equally or more active than the original drug.

ABSORPTION
(Pharmacokinetics Phase) Bioavailability : is a subcategory of absorption. it is the percentage of the administered drug dose that reaches the systemic circulation. Bioavailability for the oral route of drug administration occurs after absorption & hepatic drug metabolism.

Percentage bioavailability for:

oral route : is always less than 100% IV : usually 100%

ABSORPTION
(Pharmacokinetics Phase) FACTORS that alter bioavailability: drug form route of administration GI mucosa & motility food & other drugs changes in liver metabolism Drug that increases the bioavailability can cause increase in drug concentration causing drug toxicity.

DISTRIBUTION
(Pharmacokinetics Phase)

the process by which the drug becomes available to body fluids and body tissues Factors that influenced distribution:
blood flow, its affinity to the tissue & protein-binding effect.

METABOLISM
(Pharmacokinetics Phase) aka Biotransformation occurs in both the GI tract and the liver (the primary site of metabolism) A large percentage of drugs are lipid soluble liver metabolizes the lipid soluble drug substance to a water soluble drug substance for renal excretion.

When drug metabolism rate is decreased, excess drug accumulation can occur- toxicity.

METABOLISM
(Pharmacokinetics Phase) half-life (t): the time it takes for one-half of the drug concentration to be eliminated.
A drug goes through several half-lives before more than 90% of the drug is eliminated. e.g. 650mg of aspirin(t1/2) is 3 hours, then it takes 3 hours for the 1st half life to eliminate 325mg & 6 hours for the 2nd half life to be eliminated. short half life : 4-8 hours long half life: 24 hour or more ( takes several days for the body to completely eliminate the drug.

EXCRETION or ELIMINATION
(Pharmacokinetics Phase) Main route : Kidney Other routes: Hepatic metabolism bile feces lungs saliva sweat Breast milk

Urine pH influences drug excretion. Acid urine promotes elimination of weak base Alkaline urine promotes elimination of weak acid Aspirin toxicity: give sodium bicarbonate to change the pH to alkaline

PHARMACODYNAMIC PHASE
the study of drug concentration and its effects on the body
Drug response can cause a primary or secondary physiologic effect or both.
Primary effect is desirable & secondary effect maybe undesirable.

e.g. Diphenhydramine : Benadryl

Primary effect: to treat the symptoms of allergy Secondary effect: causes drowsiness

PHARMACODYNAMIC PHASE
Dose-response: the relationship between the minimal vs. the maximal amount of drug dose needed to produced the desired drug response
Some clients respond to a lower drug dose while others need a high drug dose to elicit the desired response

All drugs have a maximum drug effect ( maximal efficacy )

e.g. morphine vs mefenamic acid

PHARMACODYNAMIC PHASE
ONSET PEAK DURATION OF ACTION

PHARMACODYNAMIC PHASE
Onset of Action: the time it takes to reach the minimum effective concentration (MEC) after drug administration Peak of Action: occurs when the drug reaches its highest blood or plasma concentration Duration of Action: the length of time the drug has a pharmacologic effect

Agonists: drugs that produce a response Antagonists: drugs that block a response

Therapeutic Index (TI)

The safety of drugs is a major concern

estimates the margin of safety of a drug through the use of a ratio that measures the effective therapeutic dose in 50% of persons or animals (ED50) and the lethal dose in 50% (LD50)
Drugs with a low therapeutic index have a narrow margin of safety. Drug dosage might need adjustment & plasma serum need to be monitored, because of the small safety range between ED & LD. Drugs with a high therapeutic index have a wide margin of safety & less danger of producing toxic effects

PEAK & THROUGH LEVELS

Peak drug level : is the highest plasma concentration of a drug at a specific time. Indicate the rate of absorption Through level : is the lowest plasma concentration of a drug & measures the rate at which the drug is eliminated Indicate the rate of elimination of the drug Peak & through levels are requested for drugs that have a narrow TI & are considered toxic.
If either the peak or through level is too high, toxicity can occur. Peak is too low, no therapeutic effect is achieved.

LOADING DOSE
a large initial dose administered when an immediate drug response is desired

after a large initial dose a prescribed dosage per day is ordered.

PHARMACOGENITICS
Is the effect of a drug action that varies from a predicted drug response because of genetic factors or hereditary influence
People have different genetic make-up. They do not always respond identically to a drug dosage or planned drug therapy Some persons are less or more sensitive to drugs and its action because of genetic factors.

TACHYPHYLAXIS
drug tolerance to a frequently repeated administration of a certain drug Narcotics, barbiturates, laxatives

Placebo Effect
a psychologic benefit from a compound that may not have the chemical structure of a drug effect

Many clinical drug studies involve a group of subjects who receive a placebo