UNIT TWO

THREE PHASES OF DRUG

ACTION
 OBJECTIVES
At the end of the unit, you should able to:
1.State the differentiate the three phases of drug action
2.Identify the two process of the pharmaceutical phase
3.Identify the four process of the pharmacokinetic phase
4.Differentiate the types of drug absorption
5.Differentiate the three forms of drugs in the blood
6.Differentiate two phases of biotransformation
7.Define first pass effect
8.List the factors that influence drug effects
9.Describe undesirable AND SECONDARY EFFECT
• THREE PHASES
I. PHARMACEUTIC PHASE
II. PHARMACOKINETIC PHASE
III. PHARMACODYNAMIC PHASE
 I. PHARMACEUTIC PHASE
• Applicable only for oral drugs, like tablets,
capsules
• Drug given parenterally will not undergo
pharmaceutical phase
• Divided into 2 steps:
1. Disintegration-
2. Dissolution
❑Oral tablets are not 100% drugs : they also
contain excipients which are fillers and inert
substances that enhances drug dissolution:
❑Rate limit time- the time it takes the drug to
disintegrate and dissolve
❑The faster the rate limiting time, the faster
the drugs to dissolve, the faster the effect
 II. PHARMACOKINETIC PHASE
• Deals with the movement of drugs in the body
from absorption to elimination
• 4 PROCESS
1. Absorption
2. Distribution
3. Metabolism
4. Elimination
 ABSORPTION
• 2 TYPES OF DRUG ABSORPTION
1. Passive absorption
1. Simple diffusion-substance cross the membranes
2. Facilitated diffusion- substances use carriers or channels to
cross the membranes
2. Active absorption
1. ATP activated transporters- are pumps that binds with the
drugs, then uses energy to push the drugs across the
membranes: EX: glucose, minerals and vitamins, amino
acids
2. Pinocytosis- is the ingestion of the fine drug particles by
invagination of the cell membrane of the living cells
• FACTORS AFFECTING DRUG ABSORPTION
– Solubility of drugs
– Ionization
– Surface area of the membrane
– Vascularity of the site
– Concentration gradient
– External factors
– Forms and route of administrations
• FIRST PASS EFFECT- were portion of drugs are
initially metabolized or changed in the liver,
thus reducing the original concentration
before reaching the systemic circulation
• BIOAVAILABILITY-the percentage of
unchanged drug that reaches the systemic
circulation
 DISTRIBUTION
• Is the delivery of the drug to body tissues through the
blood streams
• After absorption and first pass effect, there will be 3
forms of drug in the blood
– Metabolite- fraction of the drug that underwent
metabolism; mostly inactive and uncreatable
– Protein bound- fraction of the drug bound to plasma
protein (primarily albumin)
– Free form- drug not bound to protein nor metabolized by
the liver; active drugs that are readily bind to specific
receptors, thus producing pharmacologic response
 FACTORS AFFECTING DRUG
DISTRIBUTION
1. Blood flow through the tissues-
2. Tissue affinity
3. Solubility
4. Protein binding effect
5. Special membranes
 METABOLISM
• Is also known as biotransformation
• Enzymatic medication or degradation of drug
structure
• Liver is the primary site of metabolism
• Other sites- epithelial cells of the GIT, lungs,
kidneys and the skin
FACTORS AFFECTING METABOLISM
1. AGE
2. SEX
3. DIET AND STATE OF NUTRITION
4. PRESENCE OF LIVER AND OTHER DISEASE
5. BODY TEMPERATURE
6. GENETIC VARIATION
7. ENVIRONMENTAL FACTORS
8. DRUG-DRUG INTERACTIONS
❑When drug metabolism is decreased- there
will be less transformation of active drugs into
their inactive, excreatable forms
❑Different drugs have different rates of
elimination and this is measured by their half-
life (t ½ )
❑Important of half life- is the determination of
loading interval or when the next dose will be
given
 EXCRETION
• Also known as elimination
• Excreted through kidney
• Others: GIT(bile and feces), skin, lungs, saliva,
breast milk, tears
 FACTORS AFFECTING EXCRETION
1. Binding to tissue and plasma proteins
2. Solubility
3. Ionization
4. Urine Ph
5. Alteration of drug metabolism
6. Renal impairment
7. Presence of other drugs
SAMPLE COMPUTATION OF 30 MG 1V MORPHINE WITH HALF LIFE OF 3 HOURS

# OF T 1/2 TIME ELAPSED DOSE REMAINING IN % LEFT IN PLASMA

PLASMA

0 0 30mg 100%

1 3 HRS 15mg 50%

2 6HRS 8 mg 25%

3 9HRS 4mg 12.5%

4 12HRS 2mg 6.25%

5 15HRS 1mg 3.1%

6 18HRS 0.5mg 1.55%

 III. PHARMACODYNAMICS
• Deals with the physiologic effect of the drugs on the
body, whether beneficial or harmful
• TYPES:
1. Primary
2. Secondary
• Drug plasma concentration and therapeutic response
• All drugs must first reach a certain plasma concentration
level to produce an effect (MINIMUM EFFECTIVE
CONCENTRATION /MEC)
• As the plasma concentration rises, the drugs become
more effective, but it will reach a certain amount where
the toxic effect of the drug become more evident
(MINIMUM TOXIC CONCENTRATION / MTC)
 • The range of the plasma concentration from the
minimum effective concentration to the minimum
toxic concentration – (THERAPEUTIC RANGE/
WINDOW)
• 3 PARAMETERS FOR EVALUATION
• Onset of action
• Peak of action
• Duration of action
 DRUG RECEPTORS
• Drug binds to specific sites within the body,
called receptors- which are protein
macromolecules found in the cell membrane
• It can provoke the receptor's response
• In can block the action of the receptors
• AGONIST-
• ANTAGONIST-
• PARTIAL AGONIST-
• 4 TYPES OF RECEPTORS
1. Cell mediated – embedded enzymes
2. Ligand-gated ion channel
3. G- protein coupled receptors system
4. Transcriptional factors
 GENERAL EFFECTS OF DRUGS
1. Stimulation or depression
2. Replacement
3. Inhibition or killing of microorganism
4. irritation
 CATEGORIES OF DRUGS ACCORDING
TO ACTION
1. CATEGORY 0- Drugs that prevent disease before it starts
2. CATEGORY 1- drugs that act on the etiologic factors of the
disease
3. CATEGORY 2- drugs that act on specific disease processes
4. CATEGORY 3- drugs that act on specific disease
manifestation or symptoms
5. CATEGORY 4- drugs that act on non specific symptoms
6. cATEGORY 5- drugs used to diagnosed or facilitate
treatment of the disease
 DOSE EFFECT PARAMETERS
1. EFFICACY
2. POTENCY
 DRUG SAFETY
• PARAMETERS
– THERAPEUTIC RANGE OR THERAPEUTIC WINDOW
– THERAPEUTIC INDEX
 FACTORS INFLUENCING DRUGS
EFFECTS
1. AGE-very young and old
2. WEIGHT- overweight and underweight
3. SEX- hormonal differences
4. PHYSIOLOGIC EFFECT-
5. PATHOLOGICAL EFFECT
6. GENETIC FACTORS
7. IMMUNOLOGICAL EFFECT- immune response
8. PSYCHOLOGICAL EFFECT- attitude and expectation
9. ENVIRONMENTAL EFFECT- smoking, alcohol, chronic lead exposure
10. DEPENDENCE- psychological and physical dependence
11. TOLERANCE- tachyphylaxis and cross tolerance
12. CUMULATION-
13. DRUG TO DRUG INTERACTIONS
 Drug to Drug interactions
1. Additive effect- 1+1=2
2. Synergistic effect- 1+1=3
3. Antagonist effect- 1+1=1 or 1+1=0
4. Potentiation- a + b=B
5. Displacement-
6. Interference
7. Incompatibility-
14.Drug-Food interactions-
15.Drug- Laboratory test interactions-
 UNDESIRABLE EFFECT OF THE DRUGS
1. SIDE EFFECTS
2. ADVERSE REACTIONS
1. Allergic/hypersensitivity reaction
2. Anaphylactic reactions
3. Carcinogenic effects
4. Teratogenic effects
3. TOXIC EFFECTS/TOXICITY