PHARMACOLOGY|WEEK 3 be used to support the process to ▪ Food in Gl may interfere with the

produce an effective. dissolution and absorption

PHARMACEUTICS and PHARMACOKINETICS Role: It can enhance the patient's acceptance
of a drug formulation by masking unpleasant FACTORS AFFECTING DISSOLUTION
tastes or odors, and improving palatability, • Form of drug (LIQUID VS. SOLID) -
ingestion, or appearance. liquids more absorbed than solid, already
in solution, rapidly available for Gl
absorption
• Gastric pH (acidic vs. alkaline) - acidic
media faster disintegration & absorption
• normal gastric pH: 1.5 - 3.5
• Age - young & elderly - increase pH
PHARMACEUTICS
decrease absorption
▪ is the area of study concerned with the Enteric coated drugs - resist disintegration in
formulation, manufacturing stability and gastric acid
effectiveness of pharmaceutical dosage • Disintegration occurs only in alkaline
form. 1. DISINTEGRATION: break down of tablet environment (intestine)
into smaller particles • Should not be crushed
PHARMACEUTICS PHASE Presence of food - interfere with dissolution
2. DISSOLUTION: dissolving of the smaller
▪ It is the first phase of drug action & absorption, enhance absorption of other
particles in Gl fluid before absorption
▪ drug becomes a solution so that it can drugs, may be protectants of gastric mucosa.
cross the biologic membrane
Pharmacokinetics
2 PHASES: • the process of drug movement to achieve
• Disintegration > Dissolution drug action.
• Dissolution: a solid form must
RATE LIMITING: is the time it takes the drug to
disintegrate into small particles to
disintegrate and dissolve to be come available
dissolve into a liquid.
for body to absorb it.
• EXCIPIENT: are considered as inert
▪ Acidic fluid increase disintegration
substances, i.e., they do not have any
and absorption
active role in therapeutics, but they can

EMD 1
 absorption, active absorption, or ABSORPTION of Drugs
pinocytosis. ▪ drugs that are lipid soluble pass rapidly
▪ oral drugs are absorbed into the surface through the Gl membrane.
area of the small intestine through the ▪ Water-soluble drugs need a carrier, either
action of the extensive mucosal villi. enzyme or protein, to pass through the
(X) Protein-based drugs such as insulin and membrane.
growth hormones ▪ Certain drugs need acidic environment to
achieve greater drug absorption:
THREE MAJOR PROCESSES FOR DRUG antifungal & calcium carbonate
Pharmacokinetics - Drug Transport Pathways ABSORPTION ▪ Hydrochloric acid destroys some drugs:
THREE MAIN PATHWAYS OF DRUG 1. Passive absorption - occurs mostly by penicillin G
MOVEMENT ACROSS CELL MEMBRANE diffusion (movement from higher ▪ Drugs administered by many routes do
1. Most common is direct penetration by concentration to lower concentration) not pass through the Gl tract or liver
lipid soluble drugs 2. Active absorption - requires a carrier ▪ Remember, drugs that are lipid soluble
2. 2nd pathway involves passage through such as an enzyme or protein to move the and non-ionized are absorbed faster
protein channels. drug against a concentration gradient. than water-soluble and ionized drugs.
Gates open and close: 3. Pinocytosis - is a process by which cells ▪ Some drugs do not go directly into the
▪ voltage gating or by assist of chemical carry a drug across their membrane by systemic circulation
substances (Na+ and K+ ions engulfing the drug particles ▪ Pass from the intestinal lumen to the liver
affecting some cardiac drugs)
via the portal vein.
3. 3rd is by carrier proteins that transport
▪ Hepatic first pass: process in which the
molecules from one side of the cell
drug passes to the liver first
membrane to the other.
▪ Bioavailability is a subcategory of
▪ An example would be oral drugs that carry
absorption.
hormones to their sites of action
▪ It is the percentage of the
PHARMACOKINETIC PHASE administered drug dose that
1. ABSORPTION reaches the systemic circulation
▪ the movement of drug particles from the and is available to act on body
GI tract to body fluids by passive cells

EMD 2
 BIOAVAILABILITY ▪ lipid soluble drugs and have a transport Metabolism cont.
Factors that alter bioavailability include: system can cross the blood-brain barrier ▪ Excretion usually is by kidneys. Need to
1. drug form and reach concentrations be water soluble for this to occur.
2. route ▪ during pregnancy and lactation ▪ function of metabolism is to convert fat
3. Gl mucosa and motility distribution of drugs is unique - drugs soluble medications to water soluble
4. Food and other drugs cross the placenta and pass into breast ones.
5. changes in liver metabolism caused by milk ▪ Hepatic drug metabolism or clearance is
liver dysfunction PROTEIN BINDING a major mechanism for terminating drug
▪ IV administration is 100% bioavailable action and eliminating drug molecules
▪ Most drugs form a compound with
▪ Subcutaneous and Oral route from the body
plasma proteins, mainly ALBUMIN, which
▪ Mucous membranes allow for rapid and ▪ Most drugs are metabolized by the
act as carriers
direct absorption into the bloodstream cytochrome P450 enzymes in the liver
▪ Only the free or unbound portion of a drug
▪ Liver contains complex system of
DISTRIBUTION acts on body cells
enzymes, three of which are key in the
▪ Involves the transport of drug molecules ▪ As unbound drug acts on cells, the
metabolism of medications/drugs
within the body decrease in plasma drug level causes
➢ Cytochrome p450
▪ After the drug is absorbed into the some of the bound drug to be released
▪ enzymes catalyze the chemical
bloodstream, it is carried by the blood or ▪ Protein binding allows a part of a drug
reactions which ultimately
tissue fluids to its sites of dose to be stored and released as needed
metabolize the medications
pharmacologic action, metabolism and METABOLISM ▪ Enzyme induction accelerates drug
excretion metabolism.
▪ Method by which drugs are inactivated or
▪ Protein binding is an important factor in
biotransformed by the body
drug distribution HALF - LIFE
▪ Some drugs yield metabolites that are
Half-life/ Elimination half-life (t ½) - time it
DISTRIBUTION CONT. also active and exert effects on the body
takes for one half of drug concentration to be
▪ Drug distribution into the CNS is limited until they are excreted (normeperidine)
eliminated
▪ Blood-brain barrier: composed of ▪ Most drugs are lipid soluble which aids
▪ Short t 1/2 - 4 - 8hrs: given several times a
capillaries with tight walls which their passage across the cell membrane
day (ex. Penicillin G)
limits movement of drug molecules ▪ Long t ½ - >12 hours: given 2x or 1x/day
(Ex. Digoxin)

EMD 3
▪ By knowing the HALF-LIFE, the time it
takes for a drug to reach a steady state
(plateau drug level) can be determined.
▪ it can be achieved when the amount of
drug being administered is the same as
the amount of drug being eliminated.
▪ a steady state of drug concentration is
necessary to achieve optimal therapeutic
benefit.

EXCRETION
▪ Refers to the elimination of a drug from
the body
▪ Most are excreted by the kidneys although
some are excreted in the bile then the
feces

DRUG EXCRETION
▪ KIDNEYS - main route of drug excretion
▪ bile, lungs, saliva, sweat and breast milk.
▪ urine pH influences drug excretion.
▪ normal urine pH 4.6-8
▪ acidic urine promotes elimination of weak
base drugs.
▪ alkaline urine promotes elimination of
weak acid drugs.
▪ prerenal, intrarenal and postrenal
conditions.

EMD 4