Pharmacology and Nutrition

LEARNING OUTCOMES

By the end of the topic, students will be able to;

1. Define the common terminology used in Pharmacology.

2. Explain the principles and three phases of drug action.

3. Explain the legal aspect of drug administration and its implications in nursing practice.

 

1.1 The terms below are commonly used in Pharmacology:

Pharmacotherapeutics: Study of how drugs may be best used in the treatment of illnesses – most or least appropriate to use for specific disease

Pharmacokinetics: The study of drug distribution rates between various body compartments: absorption, distribution, metabolism and excretion

Pharmacodynamics: The study of biochemical and physiologic effects of drugs; drugs mechanism of action

Pharmacognosy: The study of drugs that are obtained from natural plant and animal sources

Pharmacogenetics:  Study of how each individual will respond to specific drugs

Toxicology: The study of poisons. Deals with the effects of drugs and chemicals in living systems, their detection and the treatment to counteract their poisonous effects

Drug: Any chemical that affects the physiologic processes of a living organism

Prescription: A written direction or order by a doctor for dispensing and administering drugs 

Dosage: The amount of drug given for a desired effect

Minimum Dose: smallest amount of a drug that will produce therapeutic effect

Maximum dose: Largest amount of a drug that will produce a desired effect without producing toxicity

Loading dose: Initial high dose (often max) used to quickly elevate the level of drug in the blood (often followed by a series of lower maintenance doses)

Maintenance dose: Dose required to keep the drug blood level at a steady state in order to maintain the desired effect

Toxic dose: amount of a drug that will produce symptoms of poisoning

Lethal dose: Dose that causes death

Efficacy/ effectiveness/ action of drug: The ability to cause the expected or intended effect of a drug in the treatment of disease

Potency: Strength of a medicine ~ It is a measure of how much a drug is required in order to produce a particular effect

Interaction: When one drug modifies the action of another drug interaction occurs

Indications: a list of medical conditions or diseases for which the drug is meant to be used

Actions: a description of the cellular changes that occur as a result of the drug.

Contraindication: a list of conditions for which the drug should not be given

Warnings and cautions: a list of conditions or types of patients that require closer observation for specific side effects when given the drugs

Adverse drug reaction (ADR): Any unexpected, unintended, undesired or excessive response to a medication. May or may not be preventable. May or may not cause harm

Adverse drug event (ADE): An injury caused by a medication or failure to administer an intended medication. May or may not cause harm. May or may not be preventable. Includes all ADR and expected side effects of the drug

Medication Error: Any preventable ADE involving inappropriate medication use by a patient or health care professional; may or may not cause patient harm

Resistance: The ability to oppose

Teratogenicity effect: effect from maternal drug administration that causes the development of physical defects in a fetus.

Drug abuse: It is inappropriate intake of substance either continually or periodically.

Drug dependence: It is an individual’s physiological or psychological reliance on or need to take a drug or substance

Drug habituation: It denotes a mild form of psychological dependence. The habituated individual develops the habit of taking the substance and feels better after taking it

Tolerance:  An increase in dosage may be needed to cause a therapeutic effect in persons with low metabolism in response to a drug

Generic name: When a drug is approved by the Food and Drug Administration it is given a generic (official) name and a trade (proprietary or brand) name.

The trade name is developed by the company requesting approval for the drug and identifies it as the exclusive property of that company.

OTC: Over the counter, no restriction by the FDA       

Legend drug: prescription drug, because of possible harmful side effects if taken indiscriminately include birth control pills

Controlled substance: drug controlled by prescription requirement because of the danger of addiction or abuse.

1.2  During preparing and administering the medication, there are principles to follows;

Drug therapy plays a major part in the treatment of patients. It is the nursing responsibility to ensure safe and reliable administration and to monitor side effects.

PHASE ONE: PHARMACEUTICS

Dosage form design determines the rate of at which drug is dissolved and absorbed in the body. It involves two phases:

i) DISINTEGRATION

ii) DISSOLUTION

DEFINITION OF TERMS:

DISINTEGRATION – the breakdown of tablet or capsule into smaller parts

DISSOLUTION – dissolving of the smaller particles in the gastrointestinal fluid before absorption

RATE LIMITING – the time it takes the drug to disintegrate and dissolve to become available for the body to absorb it

After ingestion, a solid drug (tablet or capsule) must first disintegrate into smaller particles.

-   Then the smaller particles are to dissolve into a liquid which is ready for absorption in the gastrointestinal tract.

Always remember that…

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

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

Young and elderly have less gastric acidity, therefore drug absorption is generally slower for those drugs that are absorbed primarily in the stomach.

Food in the G.I. Tract may interfere with the dissolution and absorption of certain drugs. Some foods can also enhance absorption of other drugs; thus, some drugs should be taken with food.

Enteric-coated drugs do not disintegrate in the stomach since they are formulated to withstand gastric acidity

Disintegration of enteric-coated tablets or capsules only occurs when they reach an alkaline environment like the small intestine.

These tablets or capsules should never be crushed.

Topical applied dosage forms work directly on the surface of the skin

- Other topical dosage form, the skin acts as a barrier through which the drug must pass to get into circulation

 Example: fentanyl transdermal patch for pain

Dosage forms administered via injection = parenteral forms

must have certain characteristics to be safe and effective

-> if too concentrated or corrosive, can damage arteries and veins

pH of injections must be similar to blood pH

100% absorption occurs in IV route

 

PHASE TWO: PHARMACOKINETIC

is what the body does to a drug

-> how a drug is altered as it travels through the body

-> the process of drug movement to achieve drug action and the study of the concentration of a drug during its 4 process (absorption, distribution, metabolism or biotransformation and excretion)

Properties that Influence Pharmacokinetic Activity:

I) Physiochemical Properties of Drugs

In general, drugs exist as weak acids or weak bases.

-They appear in either ionized or non-ionized form.

II) Physicochemical Properties of Cell Membrane

- The membrane consists of a bimolecular layer of lipids that contain protein molecules which are irregularly dispersed throughout the lipid bilayer.

- The protein molecule may act as a carrier, an enzyme, a receptor or an antigenic site

- Drugs that are lipid (fat) soluble can pass through the lipid membrane, but those that are water soluble cannot.

- In this instance, the membrane which appears to contain pores permits the passage of small water-soluble substances such as urea, alcohol, electrolytes and water itself

- Drug molecules that are free are transported from one body compartment to another by way of the plasma.

- However, these movements are limited because various sites are enclosed by membranes.

- Barriers to drug transport may consist of single layer of cell (such as the villus in intestinal epithelium) or several layers of cell (such as skin).

*  Nevertheless, in order for the drug to gain access to the interior of a cell or a body compartment, it has to penetrate cell membranes

 

PHARMACOKINETIC ACTIVITIES

I) ABSORPTION

- the process that involves the movement of drug molecules from the site of entry until it reaches the circulating fluids & tissues.

- the movement of drug particles from the G.I. tract to body fluids by passive absorption, active absorption, or pinocytosis.

Variables That Affect Drug Absorption

a.  Nature of the absorbing surface (cell membrane) through which the drug must traverse.

b.  Blood flow in the site of administration.

c.  Solubility of the drug.

d.  Acidity of the stomach

e.  Drug concentration.

f.   Dosage form

Routes of Drug Administration

 -  Classified into:

Enteral (via the GIT):

Methods used in giving drugs:

a) oral

b) sublingual

c) buccal medications

Advantages:

-Safest (because it can be retrieved)

-Most convenient and economical route of administration

Disadvantages:

-Most unreliable

-Oral administration can lead to inactivation of certain drugs

-> e.g. Penicillin G cannot be taken orally because it would be destroyed by stomach acid)

Patient requirements:

# Conscious and cooperative patient.

-> Drugs cannot be administered to comatose individual or individual who for whatever reason (psychosis, seizures, etc.) are unable or unwilling to swallow medication

# Local Irritation.

-  Some oral preparations cause local irritation of the GIT, which can result to discomfort, nausea and vomiting (e.g. aspirin)

# Rapid absorption in small intestine

# Presence of food diminishes absorption

# Absence of food increases absorption

# Liquid absorb more rapidly than solids

Absorption occurs within 3 to 5 min. with SL or buccal

Increased intestinal motility decreases available time of absorption

Absorption through the GI tract may be undependable

A) Oral preparation: Troche (lozenges)

 flat, round or oval preparation that dissolves and releases a drug when held in mouth

Not for digestion.

B) Parenteral Route: Refers to the administration of drugs by injection.

It is the most rapid form of systemic therapy.

Types:

a)  subcutaneous:

- Injection into the connective tissue or fat immediately underlying the dermis the site can be used only for drugs that are not irritating to the tissue

- the rate of absorption is slow and can provide a sustained effect

- have effects within 10 to 15 min

b) intramuscular:

- injection into the skeletal muscle

- absorption occurs more rapidly than with subcutaneous injection because of greater tissue blood flow

c) Intravenous:

- immediate pharmacologic response because the desired concentration of the drug is injected into the bloodstream

- drugs should be administered slowly to prevent adverse effects

- requires no absorption; effect is immediate

d) Intrathecal:

- injection directly into the spinal subarachnoid space, bypassing the blood-brain barrier

- when rapid effects of drugs are desired, as in spinal anesthesia or in treatment of acute infection of the CNS

- has effects within 10 to 15 min.

- Poor circulation may hinder IM or SQ absorption

- Shock, edema, trauma, and coolness to tissue slow absorption

- Massage and heat tissue increase absorption

C) Pulmonary Route:       

- to ensure that normal gas exchange of oxygen and carbon dioxide is continuous in the lungs, drugs must be in the form of gases or fine mist (aerosols) when they are administered by inhalation

- the lung provides a large surface area for absorption

-the rich capillary network adjacent to the alveolar membrane promote ready entry of medication into the bloodstream

D) Inhalation:

- May be absorbed systemically; analgesic agents

- May be absorbed locally; corticosteroids

- Absorption enhanced because of the large surface area

E) Topical: applied topically to the skin and mucous membrane

- usually drugs applied to the skin are employed as topical remedies to produce a local effect.

- Only lipid-soluble compounds are absorbed through the skin.         

Eyes: administration of drops into the eyes produces a local effect on the conjunctiva or anterior chamber.

- Eyeball movement promote the distribution of drugs over the surface of the eye

Ears: Administration of drops into the auditory canal may be chosen to treat local infection or inflammatory conditions of the external ear.

 Suppository: Drugs mixed with gelatin and shaped for insertion in to a body cavity (eg: rectum), the base dissolves gradually at body temperature, releasing the drug

Pessary-is a small plastic or silicone medical device which is inserted into the vagina or rectum and held in place by the pelvic floor musculature for local effects

e.g.  Nystatin Pessary

 

II) DISTRIBUTION

- it is the transport of a drug in body fluids from the bloodstream to various tissues of the body and ultimately to its site of action.

Factors affecting distribution:

DRUG’S LIPID SOLUBILITY- those that are not lipid soluble cannot pass through

PERFUSION OF REACTIVE TISSUES

-Rich perfusion: heart, liver, kidney and brain

-Poor perfusion: fat, muscle

DRUG RESERVOIRS

Storage reservoirs allow a drug to accumulate by binding to specific tissue in the body. This sustains the pharmacologic effect of a drug at its point of action.

-  2 General types of drug pooling:

a) Plasma protein binding: on entry into the circulatory system, drugs become attached to proteins (mainly albumin). Thus, free drugs enter the plasma. Binds to the protein to form a drug-protein complex.

Free drug + Protein = Drug protein complex

-The formula indicates that equilibrium is established between the amounts of free drug (drugs not bound to protein) and amount of drug that is bound to protein (drug-protein complex).

DEGREE OF DRUG BINDING

-Plasma protein binding (primarily with albumin) is expressed as a percentage, which refers to the percentage of total drug that is bound.

4 Categories

1) Highly Protein-bound:  Drugs that are greater than 89% bound to protein

2) Moderately Highly Protein-bound: Drugs that are 61-89% bound to protein

3) Moderately Protein-bound: Drugs that are 30-60% bound to protein

4) Low Protein-bound:  Drugs that are less than 30% bound to protein   

Competition for binding sites.

-albumin and other plasma proteins provide a number of binding sites

- two drugs can compete with one another for the same site and displace each

E.g. Warfarin, an anticoagulant, if simultaneously given Aspirin an analgesic

b) Tissue Binding:

Fat tissue- lipid soluble drugs have a high affinity for adipose tissue. Relatively low blood flow in fat tissue makes it a stable reservoir e.g. Thiopental stays in low concentration in body fat for as long as 3 hours

Bone- Usually some drugs have an unusual affinity with bones. It is stored in the crystal lattice of bone for discoloration

 Blood brain barrier: special anatomical arrangement that allows distribution of only lipid soluble drugs (e.g. general anesthetics, barbiturates)

Placental Barrier; tissue enzyme in placenta can also metabolize agents (e.g. catecholamines).  Unlike blood brain barrier, it is less selective. (e.g of drugs that can cross the placental barrier: steroids, narcotics, anesthetics and antibiotics) 

Fetal drug effects

- 1st trimester: teratogenic effect- physical defects in developing embryo

 

III) BIOTRANSFORMATION or METABOLISM

Activates a drug by converting (transforming) it into a more water-soluble compound or metabolite, that can be excreted from the body

Liver- primary site of metabolism of drugs

Other sites of metabolism include the plasma, kidneys, lungs and intestinal mucosa

Hepatic biotransformation

-  The chemical alterations are produced by microsomal enzyme system, located largely in the liver, which consist of endoplasmic reticula, a series of membrane that appears as a network of canals within the cells

 Hepatic first pass effect  

orally administered drugs absorbed from the GIT normally travel first to the portal system.

-> However, some drugs may first be taken up by the hepatic microsomal enzyme system so that a significant amount is metabolized before the drug ever reaches the systemic circulation.

Factors that decrease metabolism:

·       Cardiovascular dysfunction

·       Renal insufficiency

·       Starvation

·       Obstructive jaundice

·       Slow acetylator

·       Erythromycin or ketoconazole drug therapy

 

IV) EXCRETION

A process whereby drugs and pharmacologically active or inactive metabolites are eliminated from the body, primary though the kidneys

Organs of excretion:

1.  Kidneys;

·       Glomerular Filtration= filtration moves drugs from blood to urine. Protein-bound drugs are not filtered only free, unbound, water soluble and metabolites

·       Active tubular reabsorption= occurs at the level of the tubules. Substances are taken back up into the circulation and transported away from the kidneys. This is the body’s attempt to retain needed substances

·       Tubular secretion= secretion of substances into the nephron from the blood vessels, surrounding it.

·       Urinary pH= (4.6-8.2) affects the amount of drug reabsorbed in the renal tubule by passive diffusion

·       Weak acids are secreted more readily in alkaline urine

·       Urine pH may be altered

·       Made more acidic with Vitamin C or Ammonium chloride resulting to increase excretion of basic drug

·       Made more alkaline with sodium bicarbonate resulting to increase excretion of acidic drugs

Dialysis-substances that are completely or almost completely excreted by kidneys. It can be removed by hemodialysis. Causes rapid reduction of increase plasma levels of a drug.

2.  Intestines

·       after metabolism by the liver, the metabolite is secreted into the bile and passed into the duodenum. It is eliminated with the feces.

·       Certain drugs such as fat-soluble agents may be reabsorbed by the bloodstream and returned to the liver.   -> known as the enterohepatic cycletestines

3.  Lungs

·       most drugs removed by pulmonary route generally intact and not metabolized.

·       Process: inspiration leads to the alveolar membrane to the bloodstream. Upon excretion from alveolar membrane results to excretion. (Increase RR= increase excretion

4. Sweat & salivary glands

·       Excretion of drugs through sweat and saliva is relatively unimportant.

è This process depends on diffusion of lipid-soluble drugs through the epithelial cells of the glands 

5.  Mammary glands

·       many drugs cross the epithelium of breast   tissues. Breast milk is acidic.

·       Basic compounds have increase concentration in breast milk (e.g morphine).

·       While weak acids are less concentrated

 

Pharmacokinetic Considerations

Onset: The time it takes for the drug to elicit a therapeutic response

Peak: The time it takes for a drug to reach its maximum therapeutic response

Duration: The time a drug concentration is sufficient to elicit a therapeutic response

 

PHASE THREE: PHARMACODYNAMIC

·       It is the study of the mechanism of drug action on living tissues

1.3  PRINCIPLES OF DRUG ACTION

1. Drugs do not create new cellular functions but alter existing ones

- Drugs may interact with the body in many different ways - some act by altering chemical composition of a body fluid

- Different drugs with molecules precisely fit into a given receptor (e.g., penicillins)

- Drugs don’t confer any new functions on a body tissue/organ. They only modify existing functions

- They do not stop the function of the body tissue but it allows it even more and modifies existing function

- It will not give a new function to the tissue /organ

Examples

Cathartics: compensate the role of large intestine

Atropine Sulfate: given before surgery (interrupts salvation in the pre-op patients)

2. Drug action results from a Physio Chemical Interaction between the drug and a functionally important molecule in the body

- Combine with macromolecular tissue components (major mechanism) receptors (Beta 1- acts more on heart and Beta 2- acts more on lungs)

- Combine with small molecules (Example: antacids will neutralize gastric acids)

- Alter cell membrane action (Example: Local anesthetics)

Therapeutic effect: a positive change in a faulty physiologic system (the goal of drug therapy)

Mechanism of Action

Once the drug is at the site of action, it can do either one of the two ways:

1.  modify (increase or decrease) the rate at which that cell or tissue functions

2.  modify the strength of function itself of that cell or tissue

3 Basic Ways of Drug Actions

·       Through receptors

·       Through enzymes

·       Through nonselective interactions

1. Drug-Receptor Interactions

 Receptor – a reactive site on the surface or inside of a cell

 Affinity – the degree to which a drug attaches to and binds with a receptor

Efficacy – the ability of the drug to initiate biologic activity as a result of binding to a given receptor

Agonist – a drug that combines with receptors and initiates a sequence of biochemical & physiologic changes

Partial Agonist – an agent that has affinity some efficacy but may antagonize the action of other drugs that have greater efficacy

Antagonist – an agent designed to inhibit or counteract the effects produced by other drugs

Competitive Antagonist - an agent with an affinity for the same receptor site as an agonist

Noncompetitive Antagonist: an agent that combines with different parts of receptor mechanism & inactivates the receptor so that the agonist cannot be effective regardless of its concentration

 

What is a Drug-Receptor Interaction?

-  This theory hypothesizes that drugs are   selectively active substances with a high affinity for a specific chemical group or a particular constituent of a cell

2.Drug-Enzyme Interactions

-  also called selective interaction

 Enzymes = substances that catalyze nearly every biochemical reaction in a cell

 Antimetabolites = drugs resembling enzyme substrates

What is a Drug-Enzyme Interaction?

- It occurs when the drug chemically binds to an enzyme molecule in such a way that it alters the enzymes interaction with its normal target molecules in the body.

- Antimetabolites can either block normal enzymatic action or result in the production of other substances with unique biochemical properties.

3. Nonselective Interactions

- Drugs with this action target the cell membranes and various cellular activities by either:

*  interfering physically or * altering chemically

 

What is Nonspecific Drug Interaction?

-  Drugs with this mechanism of action incorporate themselves into the normal metabolic process, thus causing a defect in the final product or state.

 

PHARMACOGNOSY

·       The study of natural (plant and animal) drug sources

Why study drug sources?

·       To identify chemical features of a substance that produce a desired clinical response

·       To gain understanding of the actions and effects of natural drug sources is essential to new drug development

 

Main Sources of drugs:

Plants

Animals

Minerals, and

laboratory synthesis

SELF CHECK 1.1

1. Define different terminology.

2. Explain the pharmacokinetic process.