Pharmacokinetics

Pharmacokinetics

What the body does to a drug.

The four properties that determine the onset, intensity, and duration of drug action

1. Absorption.

2. Distribution.

3. Metabolism.

4. Elimination

Absorption

Permits entry of the drug (either directly or indirectly) into plasma.

Distribution

May reversibly leave the bloodstream and distribute into the interstitial and intracellular fluids.

Metabolism

The drug may be biotransformed through metabolism by the liver or other tissues.

Elimination

The drug and its metabolites are eliminated from the body in urine, bile, or feces.

Pharmacodynamics

What the drug does to the body.

Routes of drug administration are determined by

- Properties of the drug.

- Therapeutic objectives → do we need a fast response?

- The need for long-term treatment.

- Restriction of delivery to a local site.

- Properties of the drug.

Major routes of drug administration

- Enteral

- Parenteral

- Topical

Enteral Administration

- Administering a drug by mouth.

- The most common, convenient, and economical method.

Different types of enteral administration

May be swallowed (oral) and may be placed under the tongue (sublingual) or between the gums and cheek (buccal).

Advantages of enteral administration - Oral

- Easily self-administered.

- Toxicities and/or overdose of oral drugs may be overcome with antidotes, such as activated charcoal.

Disadvantages of enteral administration - Oral

- The pathways involved in oral drug absorption are the most complicated.

- The low gastric pH inactivates some drugs.

- Most complicated with having to deal with stomach acid and is subject to First-Pass Effect.

First-Pass Effect

- Drug undergoes metabolism at a particular part in the body.

- Decreases the active drug concentration once reaches systemic circulation or its site of action.

First-Pass Effect and Oral Administration

A phenomenon of a drug metabolism whereby the concentration of a drug given orally (enterally) is greatly reduced before it reaches the systemic circulation.

Liver and First-Pass

Metabolizes many drugs, sometimes to such an extent, that only a small amount of active drug emerges from the liver to the rest of the circulatory system in the hepatic vein.

Which routes of administration can avoid the first-pass effect?

Suppository, IV, IM, inhalation, transdermal, and sublingual (under tongue)

-ol

beta blockers

Drugs with high first metabolism

Nitrates.

Imipramine.

Lignocaine.

Betablockers.

Morphine.

Testosterone.

Verapamil.

Salbutamol.

Enteric-Coated Preparations

A chemical envelope that protects the drug from stomach acid, delivering it instead to the less acidic intestine, where the coating dissolves and releases the drug to be absorbed.

Enteric-Coated Preparations is useful for...

certain drugs that are acid labile (omeprazole) and for drugs that are irritating to the stomach (aspirin).

Extended-Release Preparations

Have special coatings or ingredients that control drug release, thereby allowing for slower absorption and prolonged durations of action.

Advantages of sublingual/buccal enteral administration

- Ease of administration.

- Rapid absorption.

- Bypass of harsh gastrointestinal (GI) environment.

- Avoidance of first-pass metabolism.

Sublingual/Buccal administration is given under any of the following circumstances

- Drug needs to get into your system more quickly than taking the drug orally.

- Patient has trouble swallowing medication.

- The medication doesn't absorb very well in the stomach.

- The effects of the drug would be decreased by digestion and the liver first-pass effect.

Second Pass Metabolism

- Drug circulates throughout the body and undergoes further metabolism in the liver or other tissues.

- Comes back for a second swing.

- Goes back through the IVC/SVC and to the heart.

- May require a higher dose.

Bioavailability

Proportion of a drug or other substance which enters the circulation as introduced into the body so it is able to have an active effect.

Parenteral Administration

- Introduces drugs directly across the body's barrier defense into the systemic circulation → Used for drugs that are poorly absorbed from the GI tract (heparin) and drugs that are unstable in the GI tract (insulin).

- Provides most control over the actual dose of drug delivered to the body.

Is parenteral administration subject to a first-pass metabolism?

Not subject to a first pass metabolism or harsh GI environment.

Types of parenteral drug administration

- Intravenous (IV)

- Intramuscular (IV)

- Subcutaneous (SQ)

- Intradermal

Intravenous (IV) Route

- Injected in dermis.

- Fastest route.

- Gives immediate and 100% of bioavailability of drug to tissues.

The most common parenteral route

Intravenous (IV)

Does the intravenous (IV) route avoid first-pass effect?

yes, it avoids First-Pass Effect and provides first entry into systemic circulation.

Intramuscular (IM) Route

- Drug injected into muscle tissue "reservoir."

- Muscle tissue holds the drug for a while and gradually releases into the bloodstream through the network bed of capillaries running across or surrounding the muscle tissue.

Intramuscular (IM) Route bioavailability

In IM drug administration, the bioavailability may be slightly less than 100% of IV drug administration due to diffusion from muscle through tissue fluid and into the blood.

Intramuscular (IM) Route Example

vaccines (dead) + contraceptive medroxyprogesterone.

Subcutaneous (SQ) Route

- Drug injected into subcutaneous (fat) tissue reservoir.

- SQ tissues hold drugs for a while and gradually release into the bloodstream through the network bed of capillaries running across or surrounding the SQ tissue.

Subcutaneous (SQ) Route Bioavailability

the vascularity in the subcutaneous tissue is less than that of muscle tissue, and therefore absorption may be slower than after intramuscular administration (bioavailability also may be less than 100% due to diffusion).

Subcutaneous (SQ) Route Example

Insulin, etonogestrel (Nexplanon) contraceptive - a single-rod subdermal contraceptive implant, vaccines (live).

Subcutaneous (SQ) Route Sites

Side (or back) of upper arm.

Abdomen.

Front of thigh.

Intradermal Route

Injected in the epidermis.

Topical Administration

Used for local effect of drug (clotrimazole cream).

Other Routes of Administration

- Inhalation (oral and nasal)

- Intrathecal

- Transdermal

- Rectal

Inhalation (oral and nasal) administration

- Provides rapid delivery of a drug across mucous membranes of the respiratory tract and pulmonary epithelium.

- Inhaled medications can be absorbed quickly and act both locally (albuterol for asthma) and systematically (anesthetics).

Intrathecal administration

Injected directly into the cerebrospinal fluid (CSF) and avoids the Blood Brain Barrier (BBB)(amphotericin B for meningitis).

Transdermal administration

- Achieves systemic effects by application of drugs to the skin.

- Drug diffuses from a reservoir into the SQ tissue.

- Used for sustained delivery of drugs.

- Ex → NTG, scopolamine, nicotine.

Rectal administration

- Absorption through the rectal mucosa.

- Prevents destruction of the drugs by intestinal enzymes or stomach acid.

- Avoids liver biotransformation as 50% of the drainage of the rectal region bypasses the portal circulation.