How drugs work?

Or

How do they know to go

from my stomach to my head
and not my foot?

Basic
Biopharmaceutics

Objective of Drug Therapy

To deliver the right drug, in the right
concentration, to the right site of action and
at the right time to produce the desired
effect.
(of course in the right patient!)

Clinical Trials
10-15 years from lab to US patients
Only 1 in 5000 compounds make it to human
testing
Only 1 in 5 tested in humans is approved
Testing Phases in Humans
Phase I (ADME)
Phase II (w/dz)
Phase III (Special study)
Phase IV (post-mkt)

Generic Medications
Patent on parent agent
Hatch-Waxman Act 1984
Pharmaceutical Co
ANDA filed with FDA
Bioequivalent
Labeling Review

Pharmaceutically equiv.
Therapeutically equiv.

Types of Drug Action

React physically
React chemically
Modify metabolic activity & enzyme systems
Change osmolarity of blood
Interfere with normal cell function
Modify ion channels
Modify creation, release or control of
neurotransmitters or hormones

Receptors
Cellular material at the
site of action
Lock & key
Agonist
Antagonist

The Love Cocktail

Concentration & Effect

Blood concentration time profile
MEC minimum effective concentration
MTC minimum toxic concentration
Onset of action
Therapeutic window
Duration of action
Half-life
The time taken for the drug
Concentration to decline by 50%

.OR
The time taken for 50% of the drug to be
eliminated
The time taken for the drug concentration to
fall to half the original value
After 4 half lives, elimination is 94% complete
After 7 half lives, elimination is 99% complete
After 1 half life, elimination is_____complete

Bioequivalence Terms
Bioavailability
Bioequivalency
Pharmaceutical
equivalent
Pharmaceutical
alternative
Therapeutic equivalent

Pharmacokinetics
How a drug Moves
What the body does to
a drug
ADME
Absorption
Distribution
Metabolism
Excretion

Diffusion
Passive diffusion
Active transport

Pharmacodynamics
How a drug Behaves
What the drug does to
the body
Beneficial
Toxic

Absorption
Gastric emptying
Intestinal movement
rate

Distribution
Blood flow rate
Permeability of tissue
membranes
Protein binding

Metabolism
Liver
Enzyme induction
Enzyme inhibition

Gall bladder
Stores metabolites
Enterohepatic cycling

First-Pass metabolism

Excretion
Kidneys
Nephron
Glomerular filtration
rate

Factors Affecting Drug Response

Age
Gender
Pregnancy
Genetics
Body weight
Psychological factors

Adverse Drug Reactions

CNS effects
Hepatotoxicity
Hypersensitivity or
Allergy
GI effects
Nephrotoxicity

Hematological effects
Drug dependence
Teratogenicity
Carcinogenicity
Idiosyncrasy

Drug-Drug Interactions

Absorption

Distribution

Binding in
GIT
GI empty

Displacemt Enzyme
induction
and effect

Gastric pH
Intestinal
Metabolism

Metabolism

Enzyme
inhibition

Excretion

GFR
Renal
Secretion
Urinary Reabsorption

Drug-Diet Interactions
Absorption

Distribution

Metabolism

Food

Food Mix

Gastric emptying Hi fat meals

Gastric motility
Level of
Dosage form
nourishment
Interacting
AdminTime
chemically

Protein
Carbohydrate
Fat
Calories

Excretion

Protein
Inc.GFR
Dec.reabsorption
Dec.secretion in
the kidney

Drug Disease States

Hepatic

Circulatory

Renal

Thyroid

Cirrhosis
Obstructive
jaundice
Acute viral
hepatitis

Cardiovascular
Disorders
Decrease Blood
Flow
erratic absorptn
liver metabolm

Effect on drug
Hypo- Hyperelimination
Effect on plasma
protein binding
Creatinine levels

Types of drug action

Receptors
Concentration & effect
Pharmacokinetics & dynamics
Absorption, distribution,metabolism, excretion
Factors affecting drug responses

Adverse drug reactions

Interactions

CASE STUDY!

Precipitating Event 1st Week SRJC

Professional Program
35yr old, average wt to ht male presents to
clinic with facial flushing, anxiety,
palpitations, mild temporal HA
Hx: S/P Hep C in remission
Personal Hx: unremarkable
Social Hx: smokes ppd, coffee 4-6 cups
Drinks tangerine juice with a splash of lime
VS: BP 146/90 P 99 T normal

MED List: APAP 1000mg qid prn HA,

Mylanta prn gastritis, Inderal 20mg
BID,
OTC herbal aphrodisiac
Dx: anxiety reaction frequently ppts
migraine
POINTS TO PONDER
Treatment plan?
Lifestyle modifications?
Pharmacokinetics?
Factors altering drug response?