PRELIM: PHARMALEC

LESSON 1: PHARMACOLOGIC PRINCIPLES

PHARMACEUTICS
 study of how various dosage forms influence the way in which the drug affects the body
 different dosage forms have different pharmaceutical properties
 dosage form determines the rate at which drug dissolution occurs

DOSAGE FORMS

ORAL FORMS

 drugs ingested orally

 solid (tablet, capsule, powder) or liquid form (solution or suspension)
 rely on gastric and intestinal enzymes and ph environments
TOPICAL FORMS

 applied directly on the surface of the skin

✓ work immediately
 work slowly (skin acts as a barrier) – example: fentanyl transdermal patches for pain

PARENTERAL FORMS

 dosage forms that are administered via injection

 ph of injections must be similar to that of the blood for these drugs to administered safely
 usually in aqueous or oily forms

PHARMACOKINETICS
 study of what the body does to the drug
 involves the process of absorption, distribution, metabolism, and excretion
 what happens to a drug from the time it is put into the body until the parent drug and its
metabolites have left the body
 movement of drugs through the body

❖PARENT DRUG – CHEMICAL FORMS OF A DRUG THAT IS ADMINISTERED BEFORE IT IS METABOLIZED

BY THE BODY INTO ITS ACTIVE OR INACTIVE METABOLITES

❖PRODRUG – PARENT DRUG THAT IS INACTIVE THEN METABOLIZED INTO PHARMACOLOGICALLY

ACTIVE METABOLITES

1. ABSORPTION

 movement of drug from its site of administration into the bloodstream for distribution to the
tissues

❖BIOAVAILABILITY – a measure of the extent of drug absorption for a given drug and route (from 0
to 100%)

❖FIRST-PASS EFFECT – the initial metabolism in the liver of a drug absorbed from the gi tract before
the drug reach systemic circulation through the blood stream
2. DISTRIBUTION

✓transport of a drug by the blood stream to the site of action

✓distributed first to areas with extensive blood supply

✓areas of rapid distribution: heart, liver, kidneys, and brain

✓areas of slow distribution: muscle, skin, fat

❖BOUND DRUGS – USUALLY DRUGS BOUND TO PLASMA PROTEINS (E.G. ALBUMIN) AND
PHARMACOLOGICALLY INACTIVE

❖UNBOUND DRUGS – FREE DRUGS AND PHARMACOLOGICALLY ACTIVE, WITH RISK OF TOXICITY

DRUG-TO-DRUG INTERACTION

 occurs when the presence of one drug decreases or increases the actions of another drug
 occurs when patient is taking 2 or more drugs
VOLUME OF DISTRIBUTION

✓ theoretical volume

✓ describe the various areas in which drugs may be distributed

✓ compartments:

1. blood (intravascular space)

2. total body water

3. body fat

4. other body tissues or organs

✓ hydrophilic drugs have smaller volume of distribution and high blood concentrations

✓ lipophilic drugs have larger volume of distribution and low blood concentrations

✓ sites that are difficult to distribute drugs

1. poor blood supply (bone)

2. physiologic barriers (blood-brain barrier in brain)

3. METABOLISM
 ALSO REFERRED TO AS BIOTRANSFORMATION
 INVOLVES THE BIOCHEMICAL ALTERATION OF A DRUG INTO AN:
1. inactive metabolite
2. a more soluble compound
3. a more potent metabolite (conversion of an inactive prodrug to its active form example:
levodopa to dopamine)
4. or a less active metabolite
✓MAJOR ORGAN: LIVER
✓OTHER ORGANS: SKELETAL MUSCLE, KIDNEYS, LUNGS, PLASMA, INTESTINAL MUCOSA
HEPATIC METABOLISM OF DRUGS
 INVOLVES CYTOCHROME P-450 ENZYMES
 TARGET LIPOPHILIC DRUGS

2 PHASES:

1. PHASE I: OXIDATION, REDUCTION, HYDROLYSIS

2. PHASE II: CONJUGATION

❖ENZYME INHIBITORS – DRUGS THAT INHIBIT DRUG-METABOLIZING ENZYMES/ CAN LEAD TO DRUG
TOXICITY

❖ENZYME INDUCERS – DRUGS THAT STIMULATE DRUG METABOLISM / DECREASE PHARMACOLOGICAL

EFFECTS

4. EXCRETION
✓ ELIMINATION OF DRUGS FROM THE BODY

PRIMARY ORGAN: KIDNEYS

1. GLOMERULAR FILTRATION

2. ACTIVE TUBULAR REABSORPTION

3. ACTIVE TUBULAR SECRETION

❖ FREE DRUGS AND METABOLITES –> PASSIVE GLOMERULAR FILTRATION

✓ TWO OTHER ORGANS: LIVER AND THE BOWEL

 PHARMACODYNAMICS
 study of what the drug does to the body
 involves drug-receptor relationship

MECHANISM OF ACTION OF DRUG

 DRUG-INDUCED CHANGES IN NORMAL PHYSIOLOGIC FUNCTIONS

THERAPEUTIC EFFECT

 POSITIVE CHANGE IN A FAULTY PHYSIOLOGIC SYSTEM

 GOAL OF DRUG THERAPY

MECHANISM OF ACTION

 actions (therapeutic effects) produced by drugs

 depends on the characteristics of the cells or target tissue by the drug
 at the site of reaction, a drug can modify (increase or decrease) the rate at which the cell
functions, or it can modify the strength function of that cell or tissue

3 MECHANISMS OF ACTIONS

1. RECEPTOR INTERACTIONS

2. ENZYMES

3. NONSELECTIVE INTERACTIONS

RECEPTOR INTERACTIONS
RECEPTOR

 reactive site on the surface or inside of a cell

 protein structure in cell membrane

DRUG-RECEPTOR INTERACTION

 joining of a drug molecule with a reactive site

 once drug binds to receptor, a pharmacologic response is produced

AFFINITY

 degree to which a drug attaches to and binds with a receptor

ENZYME INTERACTION AND NON-SELECTIVE INTERACTION
ENZYME INTERACTION

 enzymes are substances that catalyze nearly every biochemical reactions in a cell
 drugs interact with enzyme systems and produce effects
 selective interaction
 inhibition or enhancement of enzyme action when drug binds to enzyme molecule

NONSELECTIVE INTERACTION

 drug with nonspecific mechanisms of action that do not interact with receptors or enzymes

MAIN TARGETS: CELL MEMBRANES AND VARIOUS CELLULAR PROCESSES SUCH AS METABOLIC
ACTIVITIES

✓ can physically interfere or chemically alter cellular structures or processes

✓ cause a defect in the final product or state

✓ DEFECTS: IMPROPERLY FORMED CELL WALL OR LACK OF NECESSARY ENERGY SUBSTRATE

✓ EXAMPLES: CANCER DRUGS AND SOME ANTIBIOTICS

 PHARMACOTHERAPEUTICS
 also called therapeutics
 focuses on the clinical use of drugs to treat diseases
 defines the principles of drug actions
 drugs are categorized into their pharmacologic classes according to physiological functions (ex.
beta-adrenergic blockers) and primary disease states (anticonvulsants, anti-infective)
 follows the nursing process
GOAL: DESIRED THERAPEUTIC OUTCOMES

PATIENT THERAPY ASSESSMENT

✓ process by which a practitioner integrates his or her knowledge of medical and drug-related facts with
information about a specific patient’s medical and social history

ITEMS TO BE CONSIDERED:

1. DRUGS CURRENTLY USED (PRESCRIPTION, OTC, HERBAL, ILLICIT OR STREET DRUGS)

2. PREGNANCY AND BREASTFEEDING STATUS

3. CONCURRENT ILLNESSES
LESSON 2: Cultural, Legal, and Ethical Considerations in Drug Therapy

LESSON 3: Life Span Considerations in Drug Therapy

CLASSIFICATIONS OF CHILDREN ACCORDING TO AGE

➢ Premature infants = less than 36 weeks gestational age

➢ Full-term infants = 36-40 weeks gestational age

➢ Neonates = first 4 postnatal weeks of life

➢ Infants = 5-52 weeks postnatal weeks

➢ Children = 1 to 12 years

➢ Adolescents = 13- 16 years

➢ Young adults = 17-18years

PHARMACOKINETIC CONSIDERATIONS DURING NEONATAL AND PEDIATRIC AGE

ABSORPTION

 Gastric pH is less acidic until 1 to 2 years of age

 Gastric emptying is slowed due to slow or irregular peristalsis
 First-pass effect is reduced because of immaturity of liver and reduced levels of enzymes
 Intramuscular absorption is faster and irregular

DISTRIBUTION

 Total body water is greater than fat content

 Decreased level of plasma protein binding of drugs ✓ Immature blood-brain barrier = more
drugs enter the brain

METABOLISM

 Immature liver; does not produce enough enzymes

 Older children may have increased metabolism, requiring higher doses than infants
 Other factors: Liver enzyme production, genetic differences, and substances to which the mother
was exposed during pregnancy

EXCRETION

 Glomerular filtration rate, tubular secretion, and resorption are decreased

 Decreased perfusion rate of kidneys may reduce excretion of drugs

DRUG DOSAGE CONSIDERATIONS FOR PEDIATRIC PATIENTS

 Skin is thinner and more permeable

 Stomach lacks acid to kill bacteria
 Lungs have weaker mucous barriers
 Body temperature is less well-regulated, and dehydration occurs easily
  Liver and kidneys are immature, and therefore drug metabolism and excretion is impaired

PHARMACOKINETIC CONSIDERATIONS IN GERIATRIC PATIENTS

ABSORPTION
 Gastric pH is less acidic due to less production of HCl in the stomach
 Gastric emptying is slower due to decline in smooth muscle tone and motor activity
 Movement through the GI tract is slower because of decreased muscle tone and activity
 Blow flow to GI tract is reduced due to decreased cardiac output and decreased perfusion
 Absorptive surface of GI tract is reduced due to blunting and flattening of villi

DISTRIBUTION

✓ Increased percent body fat

• Lipid soluble drugs are stored, decreasing plasma levels of drugs

✓ Decreased lean body mass

• Water soluble drugs distributed in smaller volume increasing concentration of drugs

✓ Decreased total body water

• Same as above

✓ Reduced concentration of serum albumin

• Free drug level rise

METABOLISM

✓ Rates of hepatic metabolism decrease with age

• Reduced hepatic blood flow, reduced liver mass, decreased activity of some liver enzymes

• Drug half lives may increase

EXCRETION
 GFR is decreased due to decreased blow flow
 Number of intact nephrons is decreased
 Drugs are cleared less effectively because of decreased excretion
 Look for creatinine clearance = indicator of renal function
LESSON 4: Over-The-Counter Drugs and Herbal and Dietary Supplements
Over-the-Counter Drugs (OTC)

 Non-prescription drugs
 Used for short-term treatment of common minor illnesses (Examples: cough and colds, pain
relief and weight control)
 Currently 300,000 OTC products
 Common OTC drugs In the Philippines are paracetamol, ibuprofen, vitamin C, phenylephrine HCl
+ chlorpheniramine maleate, bisacodyl, loperamide, aluminum hydroxide + magnesium and
multivitamins.

Difference of Dietary and Herbal Supplements with Prescription Drugs

 Does not need approval from FDA before they are marketed
 Requires no proof of efficacy
 No standards for quality control

❖ In 2007, US-FDA announced that all manufacturers of dietary supplements would be required to
comply with the same good manufacturing practices as prescription manufacturers

➢ Must demonstrate product identity, composition, quality, purity and strength of active ingredients

➢ Must demonstrate that products are free from contaminants such as microbes, pesticides, and heavy
metals

➢ May claim an effect but cannot promise a specific cure on the product label