c. drug action 1

DRUG ACTIONDRUG ACTION

N. M. HernandezN. M. Hernandez

3 Phases of Oral Route of 3 Phases of Oral Route of AdministrationAdministration

1.1. Pharmaceutic (dissolution)Pharmaceutic (dissolution)

2.2. PharmacokineticPharmacokinetic

3.3. PharmacodynamicPharmacodynamic

PHARMACEUTIC PHASEPHARMACEUTIC PHASE

• The first phase of drug actionThe first phase of drug action• Drug in solid form is disintegrated into small particles to Drug in solid form is disintegrated into small particles to

dissolve into a liquid (dissolution)dissolve into a liquid (dissolution)

• Tablets are not 100% drugTablets are not 100% drug• Filler & inert substances Filler & inert substances (excipients)(excipients) used in drug used in drug

preparation allows drug to take a particular size and preparation allows drug to take a particular size and shape to enhance drug dissolutionshape to enhance drug dissolution

• Additives: K & Na in penicillin increase the absorbability Additives: K & Na in penicillin increase the absorbability of the drug.of the drug.

*penicillin is poorly absorbed by the GIT because of *penicillin is poorly absorbed by the GIT because of the the gastric acid. Making the drug potassium or sodium gastric acid. Making the drug potassium or sodium salt salt then can be absorbed. then can be absorbed.


• Disintegration: the breakdown of a tablet into Disintegration: the breakdown of a tablet into smaller particlessmaller particles

• Dissolution: is the dissolving of the smaller Dissolution: is the dissolving of the smaller particles in the GI fluid before absorption.particles in the GI fluid before absorption.

• Rate Limiting: the time it takes the drug to Rate Limiting: the time it takes the drug to disintegrate and dissolve to become available disintegrate and dissolve to become available for the body to absorb itfor the body to absorb it


*Drugs in liquid form are more rapidly available *Drugs in liquid form are more rapidly available for GI absorption than are solids.for GI absorption than are solids.

*Generally drugs are both disintegrated & *Generally drugs are both disintegrated & absorbed faster in acidic fluids with a pH of 1 or 2 absorbed faster in acidic fluids with a pH of 1 or 2 rather than alkaline.rather than alkaline.

*Young & elderly have less gastric acidity=drug *Young & elderly have less gastric acidity=drug absorption is generally slower for those drugs absorption is generally slower for those drugs absorbed primarily in the stomach.absorbed primarily in the stomach.


Food in the GI tract may interfere with the Food in the GI tract may interfere with the dissolution and absorption of certain drugsdissolution 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.

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.

PHARMACOKINETICPHARMACOKINETIC PHASEPHASE

• The process of drug movement to achieve The process of drug movement to achieve drug actiondrug action

4 PROCESSES:4 PROCESSES:

AbsorptionAbsorptionDistributionDistribution

Metabolism (biotransformation)Metabolism (biotransformation)Excretion (elimination)Excretion (elimination)

ABSORPTIONABSORPTION(Pharmacokinetics Phase)(Pharmacokinetics Phase)

• The movement of drug particles from the GI The movement of drug particles from the GI tract to body fluids by:tract to body fluids by:

passive absorptionpassive absorption

active absorption active absorption

pinocytosispinocytosis

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


The GI membrane is composed mostly of lipid(fat) & The GI membrane is composed mostly of lipid(fat) & protein = drugs that are lipid soluble pass rapidly protein = drugs that are lipid soluble pass rapidly through the GI membrane.through the GI membrane.

Water soluble drugs need a carrier, either enzyme or Water soluble drugs need a carrier, either enzyme or protein to pass through a membrane.protein to pass through a membrane.

Weak acid drug (less ionized): aspirin, pass through Weak acid drug (less ionized): aspirin, pass through the stomach lining easily & rapidly.the stomach lining easily & rapidly.


Drugs that are lipid soluble & non-ionized are absorbed Drugs that are lipid soluble & non-ionized are absorbed faster than water-soluble & ionized drugs.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.


Some drugs do not go directly into the systemic circulation Some drugs do not go directly into the systemic circulation following oral absorptionfollowing 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 drugsFirst-pass effect: the process by which the drug passes to the

liver first (hepatic first pass)


Some drugs do not undergo metabolism at all in the liver.Some drugs do not undergo metabolism at all in the liver.

Drugs may be metabolized to drug metabolite which maybe Drugs may be metabolized to drug metabolite which maybe equally or more active than the original drug.equally or more active than the original drug.


Bioavailability :Bioavailability : is a subcategory of absorption.is a subcategory of absorption.

it is the percentage of the administered it is the percentage of the administered drug drug dose that reaches the systemic circulation. 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%


FACTORS that alter bioavailability:FACTORS that alter bioavailability:drug formdrug formroute of administrationroute of administrationGI mucosa & motilityGI mucosa & motilityfood & other drugsfood & other drugschanges in liver metabolismchanges in liver metabolism

Drug that increases the bioavailability can cause increase in drug concentration causing drug toxicity.

DISTRIBUTIONDISTRIBUTION(Pharmacokinetics Phase)(Pharmacokinetics Phase)

• the process by which the drug becomes available to the process by which the drug becomes available to body fluids and body tissuesbody fluids and body tissues

Factors that influenced distribution:

blood flow, its affinity to the tissue & protein-binding effect.

METABOLISMMETABOLISM(Pharmacokinetics Phase)(Pharmacokinetics Phase)

• aka Biotransformationaka Biotransformation• occurs in both the GI tract and the liver (the primary site occurs in both the GI tract and the liver (the primary site

of metabolism)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.

METABOLISMMETABOLISM(Pharmacokinetics Phase)(Pharmacokinetics Phase)

half-life (t½):half-life (t½):

the time it takes for one-half of the drug concentration the time it takes for one-half of the drug concentration to be eliminated.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 ELIMINATIONEXCRETION or ELIMINATION(Pharmacokinetics Phase)(Pharmacokinetics Phase)

Main routeMain route : Kidney : Kidney

Other routes:Hepatic metabolismbile 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 PHASEPHARMACODYNAMIC PHASE

• the study of drug concentration and its effects on the study of drug concentration and its effects on the bodythe 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

PHARMACODYNAMICPHARMACODYNAMIC PHASEPHASE

• Dose-response: the relationship between the minimal vs. Dose-response: the relationship between the minimal vs. the maximal amount of drug dose needed to produced the maximal amount of drug dose needed to produced the desired drug responsethe 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


ONSET

PEAK

DURATION OF ACTION


• Onset of Action:Onset of Action: the time it takes to reach the minimum the time it takes to reach the minimum effective concentration (MEC) after drug administrationeffective concentration (MEC) after drug administration

Peak of Action:Peak of Action: occurs when the drug reaches its highest occurs when the drug reaches its highest blood or plasma concentrationblood or plasma concentration

Duration of Action:Duration of Action: the length of time the drug has a the length of time the drug has a pharmacologic effectpharmacologic effect

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

Therapeutic Index (TI)Therapeutic Index (TI)

• estimates the margin of safety of a drug through the use estimates the margin of safety of a drug through the use of a ratio that measures the effective therapeutic dose in of a ratio that measures the effective therapeutic dose in 50% of persons or animals (ED50) and the lethal dose in 50% of persons or animals (ED50) and the lethal dose in 50% (LD50)50% (LD50)

The safety of drugs is a major concern

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 LEVELSPEAK & THROUGH LEVELS

• Peak drug level : is the highest plasma concentration of Peak drug level : is the highest plasma concentration of a drug at a specific time.a drug at a specific time.

Through level : is the lowest plasma concentration of a drug & measures the rate at which the drug is eliminated

Indicate the rate of absorption

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 DOSELOADING DOSE

• a large initial dose administered when an immediate a large initial dose administered when an immediate drug response is desireddrug response is desired

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

PHARMACOGENITICSPHARMACOGENITICS

• Is the effect of a drug action that varies from a predicted Is the effect of a drug action that varies from a predicted drug response because of genetic factors or hereditary drug response because of genetic factors or hereditary influenceinfluence

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.

TACHYPHYLAXISTACHYPHYLAXIS

• drug tolerance to a frequently repeated administration of drug tolerance to a frequently repeated administration of a certain druga certain drug

Narcotics, barbiturates, laxatives

Placebo EffectPlacebo Effect

• a psychologic benefit from a compound that may not a psychologic benefit from a compound that may not have the chemical structure of a drug effecthave the chemical structure of a drug effect

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

c. drug action 1

Documents

drug concentration

blood flow

small intestine

drug dosage

oral route

pharmacokinetics

gi tract

systemic circulation