Phases of drug therapy o Hepatic first-pass effect

Pharmaceutic o Enterohepatic recycling

o Disintegration - Breakdown of a tablet into smaller o Route of administration
particle  Nature of absorbing surface
o Dissolution - Dissolving process of the smaller o Absorption through a single layer of
particles in the GIT fluid prior to absorption cells is faster compared to the multi-
o Depends on: layered skin
 Rate limiting  Respiratory epithelium (steroids)
 Time it takes for the drug to disintegrate,  Intestinal epithelium (carbohydrates)
dissolve, and be available for the body to  Hepatic First-Pass effect: Inactivation of
absorb drugs by hepatic enzymes before the drug
 Excipients reaches systemic circulation for distribution
 Fillers (inert substances/additives) to allow o Bioavailability  percentage of
a drug to take on a particular size and shape administered drug dose that reaches
 Enhances drug dissolution systemic circulation
 Increases absorbability of a drug  Enterohepatic recycling: Absorption of drug
 Examples: from bile into small bowel and then into
o Potassium  Penicillin potassium circulating system
o Sodium  Penicillin G sodium  Route of Administration - Linked to the
blood supply (vascularity)
Pharmacokinetics Route of Factors Affecting
o Process of drug movement to achieve drug action Administration Absorption
o Four (4) processes: (ADME)
 Absorption - Movement of drug particles from Intravenous (IV) Blood volume (vascularity)
GI tract to body fluids through passive or active
absorption, or pinocytosis Intramuscular (IM) and Perfusion, fat content, and
 Passive - Drug molecule moves from a Subcutaneous (SQ) temperature
region of relatively higher to lover Acidity of the stomach,
concentration without requiring energy length of time in stomach,
 Active - Process that uses energy to actively Oral blood flow to GIT,
move a molecule across a cell membrane presence of interacting
o Pinocytosis (Cell Drinking) - Process by food or drug
which cells carry the drug across the
membranes through engulfing the drug Perfusion, integrity,
particles presence of food,
Mucus Membrane
 Factors affecting absorption: smoking, length of time in
o Blood flow the area
o Pain
o Stress and food  Distribution - Process by which drug becomes
o Exercise available to body fluids and body tissues
o Nature of the absorbing surface  Factors influencing distribution:
o Drug solubility o Blood flow
o pH o Affinity to body tissues
o Drug concentration o Protein-binding effect
o Dosage form - many factors affect  Manner of Distribution
absorption of drugs including changes o Protein-binding - Drugs that bind with
within the stomach, absorption changes specific protein components such as:
in the intestines and the presence or  Bound portion is inactive (does not
absence of food and fluid exert pharmacologic response)
- ENTERIC COATING is designed to  Unbound portion is active (free
protect stomach by having drug drug)
dissolution and absorption occur in the  Toxicity may occur:
intestine (tablet should not be crushed)
  Too much of free-circulating 3 6 hours 2.5 mg 12.5%
drug  When 2 highly-protein
bound drugs are given to a 4 8 hours 1.25 mg 6.25%
patient with liver disease or low
albumin  Excretion
o Blood-brain barrier - Protective system  Process of eliminating substances by body
of cellular activity (keeps foreign organs or tissues (as part of natural
invaders/poisons away from CNS) metabolic activity)
 Highly lipid-soluble drugs most  Kidneys (main route of elimination [free,
likely to pass through blood-brain water-soluble, and unbound drugs])
barrier  Urine pH  influences drug excretion
 Antibiotics cannot pass through o Acidic  elimination of weak base
 CNS effects by medications result drugs
from indirect processes and not by o Alkaline  elimination of weak acid
the actual response of the CNS to drugs
the drug
 Others (bile, feces, lungs, saliva, sweat,
o Placenta (and breastmilk)
breastmilk)
 Drugs readily pass through (can
affect the developing fetus)
Summary of Pharmacokinetics
 Secreted into breastmilk
Category Description

A NO RISK evident
NO RISK evident in human or animal
B
studies
C RISK cannot be ruled out
D (+) evidence of risk exists
X CONTRAINDICATED in pregnancy

 Metabolism - Chemical changes a substance

undergoes in the body (such as through
enzymatic action)
 Drugs are metabolized in both GI tract and
liver
 Most drugs inactivated by liver enzymes
and converted into water-soluble
substances (for renal excretion)
 Half-life (t ½) - Time it takes for ½ of the
drug concentration to be eliminated
o First order - Proportional rate of Pharmacodynamic
elimination to concentration o Study of drug concentration and its effects on the
o Zero order - Constant rate of body
elimination regardless of concentration o Drug response can cause a primary and secondary
Time Dosage (at physiologic effect
T1/2 Percentage left  Primary  desirable
Elapsed 20mg start)
 Secondary  may or may not be desirable
1 2 hours 10 mg 50%  Example:
 Diphenhydramine HCL (1st generation
2 4 hours 5 mg 25%
antihistamine)
o Treats allergies (primary)
 o CNS depression (secondary)
o Receptor Theory:
 Drugs act through receptors by binding through
a receptor to produce (initiate) a response or to
block (prevent) a response
o Drug Actions:
 Replace or act as substitutes for missing
chemicals
 Increase or stimulate certain cellular activities
 Depress or slow cellular activities
 Interfere with the functioning of foreign cells
(such as invading microorganisms)
o Onset of Action: Time it takes to reach the
minimum effective concentration (MEC) after a
drug is administered
o Peak of Action: Condition that occurs when the
drug reaches its highest blood or plasma
concentration
o Duration of Action: Length of time the drug exerts a
pharmacological effect
o Agonists: Drugs that produce a response
o Antagonists: Drugs that block a response
o Therapeutic Index: Measures margin of safety of a
drug
 Narrow margin of safety (low therapeutic index)
 Wide margin of safety (high therapeutic index)
 The closer the ratio is to “1”, the greater
the danger of toxicity
o Therapeutic Range (therapeutic window): Between
minimum effective concentration in the plasma and
minimum toxic concentration
 e.g. Paracetamol (10 mg to 15 mg /kg)
o Peak Drug Level: Highest plasma concentration of a
drug at a specific time
o Trough Level: Lowest plasma concentration of a
drug and measures rate at which drug is eliminated
 Indicates rate of elimination of a drug