drug administration and absorption

8/8/2019 Drug Administration and Absorption

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First, drug absorption from the site of administration

permits entry of the therapeutic agent (either directly or

indirectly) into plasma (input). Absorption is defined as

the passage of a drug from its site of administration

into the plasma.

Second, the drug may then reversibly leave the bloodstream and distribute into the interstitial and

intracellular fluids (distribution).

Third, the drug may be metabolized by the liver,

kidney, or other tissues.

Finally, the drug and its metabolites are eliminated

from the body (output) in urine, bile, or feces.


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Routes of drug administration

The route of administration is determined primarily

- by the properties of the drug (such as water or lipid

solubility, ionization, etc.) and

- by the therapeutic objectives (for example, the

desirability of a rapid onset of action or the need for

long-term administration or restriction to a local site).

The route of administration (ROA) that is chosen mayhave a profound effect upon the speed and efficiency

with which the drug acts.


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Enteral: oral, sublingual,

rectal

Parenteral: intravascular(intravenous), intramuscular,

subcutaneous

Other: inhalation, intranasal,intrathecal (in CSF), topical,

transdermal

The main routes of drug administration are:

Figure: Commonly used routes of drug

administration.


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Enteral routes:Drug placed directly in the GI tract:

Oral- swallowing

Sublingual- placed under the tongue

Rectum- absorption through the rectum


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OralGiving a drug by mouth is the most common route of

administration but it is also the most variable, andrequires the most complicated pathway to the tissues.

Little absorption occurs until the drug enters the small

intestine.

Drug absorption from the intestine:

The drug absorbed by passive transport mechanism in

intestine at a rate determined by the ionization and

lipid solubility of the drug molecules.

Strong bases of pKa 10 or higher are poorly absorbed,

as are strong acids of pKa less than 3, because they

are fully ionized.


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Figure: Absorption of drugs from the intestine, as a function of pKa,

for acids and bases.

Weak acids and bases are well absorbed; strong acids and bases

are poorly absorbed.


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There are a few instances where intestinal absorption

depends on carrier-mediated transport mechanismrather than simple lipid diffusion.

For example levodopa, iron, calcium.

Advantages:

Convenient- can be self-administered, pain free, easyto take

Absorption- takes place along the whole length of the

GI tractCheap- compared to most other parenteral routes


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Disadvantages:

- Unpleasant taste of some drugs

- Irritation to gastric mucosa - nausea and vomiting

- Destruction of drugs by gastric acid and digestive

juices

- Sometimes inefficient- only part of the drug may beabsorbed

- Effect too slow for emergencies

- First-pass effect - drugs absorbed orally are initially

transported to the liver via the portal vein- Unable to use in unconscious patient or who have

had GI surgery


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Most of the drug is absorbed in the small intestine,

Why?

1. Small intestine has a much larger surface area forabsorption (~200 m2) as compared to the stomach

(~1-3 m2).

2. Drug spends more time in the small intestine (~4

hrs) than the stomach (~0.5-1 hrs).

Food in the stomach can decrease absorption

- Food may delays gastric emptying time so that drugsmay destroyed by acid.

- Interactions between drug and food particles.

- Exception: propranolol- due to o blood flow.


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First-pass effect

When a drug is absorbed across the GI tract, it enters

the portal circulation before entering the systemic

circulation.

A drug can be metabolized in the gut wall or even in

the portal blood, but most commonly it is the liverthatis responsible for metabolism before the drug reaches

the systemic circulation (plasma). In addition, the liver

can excrete the drug into the bile (fluid secreted by

liver).

Any of these sites can contribute to this reduction in

bioavailability, and the overall process is known as

first-pass effect or first-pass elimination.


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Portal circulation

Figure: First-pass effect


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The greater the first-pass effect, the less the agent will

reach the systemic circulation when the agent is

administered orally. (imp)Lidocaine (anesthetic agent) is a drug with a first-pass

effect that is so great that oral administration is not

practical.

In the case ofpropranolol, a significant portion of theorally administered dose is metabolized through a first-

pass effect.

More than 90% ofnitroglycerin is cleared during asingle passage through the liver.

Therefore, a much larger oral dose is required to

achieve the same therapeutic response as that

obtained from a dose administered intravenously.


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Sublingual/BuccalPlacement under the tongue allows the drug to diffuse

into the capillary network and therefore to enter thesystemic circulation directly.

When only small amounts of drugs are required to gain

access to the blood, the sublingual route may be very

satisfactory.

For example, nitroglycerin in angina pectoris.

Because the stomach is bypassed, acid-liability andgut-permeability is not important.

Drugs are absorbed from the mouth straight into the

systemic circulation without entering the portal system

and so escape first-pass metabolism by the liver.


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Advantages

-rapid absorption

-drug stability-avoid first-pass effect

Disadvantages

-inconvenient-small doses

-unpleasant taste of some drugs

Rectal50% of the drainage of the rectal region bypasses the

portal circulation; thus the biotransformation of drugs

by the liver is minimized.

Drugs property:- Non-polar- Lipid soluble


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- Devoid of destruction of the drug by intestinal

enzymes or by low pH in the stomach

- Unconscious patients (postoperative) and children

- If patient is nauseous or vomiting

- Absorption may vary

- Good for drugs affecting the bowel such as laxatives

- Irritating drugs contraindicated

- Can be used for both local effects and systemic

effects


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Parenteral routes:

Parenteral administration is used for drugs that arepoorly absorbed from the gastrointestinal (GI) tract,

and for agents such as insulin that are unstable in the

GI tract.

Parenteral administration is also used for treatment ofunconscious patients and under circumstances that

require a rapid onset of action.

The three major parenteral routes are- Intravascular (intravenous or intra-arterial)

- Intramuscular

- Subcutaneous


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Intravascular:

Intravenous (IV) injection is the most common

parenteral route. For drugs that are not absorbed

orally, there is often no other choice.

- Rapid onset of action because the drug is injected

directly into the bloodstream

- Useful in emergencies and in patients that are

unconscious

- The drug avoids the GI tract and first-passmetabolism by the liver

- Smaller doses generally are required than the other

routes but cost is high


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Greater risk of adverse effects as:

a. High concentration attained rapidly

b. That are injected cannot be recalled bystrategies such as emesis or binding to activated

charcoal

c. Risk of embolism (obstruction of blood vessel)

d. May introduce bacteria through contamination,

induce hemolysis

e. Pain at application site

f. No self administration facility

Capillary: brings the blood into intimate relationship with the tissue cell

Artery Arterioles Capillary VenulesVeins


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Intra-artery

Similar properties, advantages and disadvantages of

intravascular route. Intra-artery route is specially used

when high drug concentration in specific tissue is

required than other tissue:

- diagnostic purpose and- for chemotherapy

Intramuscular

Drugs administered intramuscularly can be aqueous

solutions or specialized depot preparations- often a

suspension of drug in a non-aqueous vehicle, such as

ethylene glycol or peanut oil.


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Absorption of drugs in aqueous solution is fast,

whereas that from depot preparations is slow. Drug

passes through capillary walls to enter the blood

stream.

- Pain at injection sites for certain drugs- This parenteral route may be used when an

immediate effect is not required but a prompt effect is

desirable

- Absorption from an intramuscular depot is more

predictable and uniform than from a subcutaneous site


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Subcutaneous

Drug is injected beneath the skin and permeatescapillary walls to enter blood stream.

Absorption from the site of injection is dependent onlocal blood flow. Concurrent administration ofvasoconstrictor will slow absorption.

For example, minute amount ofepinephrine issometime used in combination with a drug to restrict

its area of action. Epinephrine acts as a localvasoconstrictorand decreases removal of a drug,such as lidocaine (local anesthetic), from the site ofadministration.


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Examples of drugs given by this route are insulin andsodium heparin, neither of which is absorbed orally,

and both of which should be absorbed slowly overmany hours.

InhalationInhalation provides the rapid delivery of a drug across

the large surface area of the mucous membranes of

the respiratory tract and pulmonary epithelium,producing an effect almost as rapidly as by

intravenous injection.


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This route of administration is used for drugs that are

gases and volatile agents (for example, some

anesthetics), or those that can be dispersed in anaerosol.

The route is particularly effective and convenient for

patients with respiratory complaints (for example,

asthma or chronic obstructive pulmonary disease) as

drug is delivered directly to the site of action and

systemic side effects are minimized.


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TopicalTopical application is used when a local effect of the

drug is desired.

Used for most dermatologic and ophthalmologic

preparations.

Clotrimazole is applied as a cream to the skin in thetreatment of dermatophytosis.

Atropine is instilled directly into the eye to dilate the

pupil and permit measurement of refractive errors.

Intra-articular

Injected into bone joints


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Intrathecal/lntraventricularIt is sometimes necessary to introduce drugs directly

into the cerebrospinal fluid (CSF): some anesthetics.

Transdermal

This route of administration achieves systemic effectsby application of drugs to the skin, usually via a

transdermal patch.

The rate of absorption can vary markedly depending

upon the physical characteristics of the skin at the siteof application. Small lipid soluble molecule.

This route is most often used for the sustained delivery

of drugs, such as the antianginal drug, nitroglycerin.

drug administration and absorption

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