Download General Introduction to Pharm 2

Drugs in Everyday Life
GES 1510
John H.K. Yeung
Department of Pharmacology
C.U.H.K.
PHARMACOLOGY
Scientific study of the interactions
between drugs and the body
What are drugs?
Where do drugs come
from?
Origin of Drugs
Plant
Animal
Synthetic
The relationships between
science and medicine
Pharmaceutical
(Medicinal)
Chemistry
Pharmacology
and
Toxicology
Therapeutics
Pharmacy
Patients
Naming of a Drug
HO
Chemical :
.
NHCOCH3
N-acetyl-p-amino-phenol
Naming of a Drug
HO
NHCOCH3
Chemical :
N-acetyl-p-amino-phenol
Generic :
Paracetamol (BP)
Acetaminophen (USP)
.
Naming of a Drug
HO
NHCOCH3
Chemical :
N-acetyl-p-amino-phenol
Generic :
Paracetamol (BP)
Acetaminophen (USP)
Panadol (500)
Tylenol (300)
Calpol etc.
Trade
:
Drugs = Medicines only?
DRUG
Living
Tissue
DRUG
Living
Tissue
Effect
INSECTICIDES
HERBICIDES
COSMETICS
POISON
DRUG
FOOD
ADDITIVES
MEDICINE
AIR
POLLUTANTS
Living
Tissue
Effect
Drugs in Everyday Life
Medical use
 Non-medical use

 “Social
Drugs”
 Health and diet supplements
 Drugs of abuse
Pharmacological Effects of
Smoking
CNS effects
 inhibits
spinal reflexes to produce skeletal
muscle relaxation
 produces sense of alertness
Pharmacological Effects of
Smoking
Peripheral effects
 increases
cardiac output
 increases blood pressure
 vasoconstriction
 sweating
 decreases gastrointestinal motility
Addictive ?
Withdrawal Syndrome to Nicotine
Increased irritability
Impaired performance of psychomotor
tasks
Aggressiveness
Sleep disturbance
Harmful Effects of Smoking
Cancer
 mouth, throat, oesophagus and lung
Coronary heart disease
Chronic bronchitis
Affects pregnancy
 decrease in birth weight
 increase perinatal mortality
Pharmacological Effects of Alcohol
Depressant effect on the Central Nervous
System
Impairs intellectual and motor performance
Produces cutaneous vasodilatation (central in
origin) which causes a warm feeling but
actually increase heat loss
Increases salivary and gastric secretions
Diuretic effect
Pharmacological Effects of Alcohol
Acute intoxication
 slurred speech
 decrease in motor coordination
 increased self-confidence
 euphoria
Excessive consumption long-term causes liver
damage
Affects fetal development
Withdrawal Symptoms of Alcohol
Develops after about 8 hours
 severe tremor, sometimes hallucinations,
which lasts for about 24 hours
 confused and agitated over the next few days
 aggressive behaviour
 nausea and vomiting, sweating and fever
NITRITE
+
PROTEIN
Combustion
NITROSAMINES
Good drugs vs. Bad drugs ?
Narcotics
Origin
Morphine
Plant
Endorphins
Animal
Methadone
Synthetic
Narcotic Properties
Analgesia
Euphoria
Constipation
Pupil constriction
Respiratory
depression
Nausea vomiting
Hypotension
Addiction
NSAID
Origin
Salicylates
Plant
-Aspirin
Animal
Synthetic
NSAID = Non-Steroidal Anti-Inflammatory Drug
Properties of Aspirin
Analgesia
Anti-inflammatory
Antipyretic
Anti-platelet
aggregation
Gastric bleeding
Acid-base
imbalance
Reye’s syndrome
How do drugs work ?
HOW DRUGS WORK
Nonspecific
Specific
Receptor
Drug
More serious stuff
starts here !!
Basic Concepts in Pharmacology
Pharmacodynamics
Pharmacokinetics
Routes of Administration
Dosage and dosing intervals
Drug receptors and specificity
Toxicity
Pharmacodynamics and
Pharmacokinetics
Pharmacodynamics
Drug
Body
Pharmacokinetics
SYSTEMIC
CIRCULATION
BLOOD
DRUG
SITE
OF
ACTION
EFFECTS
Pharmacokinetics
Absorption
Distribution
Metabolism
Excretion
Disposition : D + M + E
Drug
Body
Molecular size
Absorption
Lipid solubility
Distribution
Ionization
Elimination
Routes of administration
Enteral administration
Sublingual
Oral
Rectal
Routes of administration
Parenteral administration
intravenous
intra-muscular
subcutaneous
intrathecal
intra-arterial
Routes of administration
Others
topical
inhalation
intra-vaginal
How fast does the drug act ?
How long does the drug effect
lasts ?
Onset and duration of drug action
0
2
4
6
Time (hour)
8
10
12
Onset and duration of drug action
MEC
0
2
4
6
Time (hour)
8
10
12
Onset and duration of drug action
MTC
MEC
0
2
4
6
Time (hour)
8
10
12
Onset and duration of drug action
MTC
MEC
0
2
4
6
Time (hour)
8
10
12
How are new drugs discovered ?
Drug Discovery
Chemical modification of a known
molecule
Screening of natural products or
previously discovered chemical entities
for biological activity
Rational drug design based on an
understanding of biological mechanisms
Possible Pathways in Drug Development
natural
drug source
chemical synthesis
programme
metabolism
toxicology
pharmacological profile
of active principle
mechanism of action
potential clinical utility
animal models of
the disease state
formulation
clinical trials
use in medicine
Pharmacological Profile Tests
Molecular levels
Cellular levels
System / Disease Models
Pharmacological Profile Tests
Molecular levels
Receptor binding
 affinity and specificity
Enzyme activity
 inhibition and selectivity
Cytochrome P450
 effects on drug metabolism
Pharmacological Profile Tests
Cellular levels
Cell function
 receptor activity
Isolated tissue
 vascular activity
 effects on other smooth muscles
Pharmacological Profile Tests
System / Disease Models
Blood pressure
Central nervous system
Cardiac effects
Gastrointestinal effects
Respiratory system
Diuretic activity
Blood coagulation
Peripheral autonomic nervous system
Circulating hormones, cholesterol and blood
sugar
Pre-clinical Safety and
Toxicity
Acute toxicity
LD50, maximum tolerated dose, use 2
species, 2 routes, single dose
Sub-acute toxicity
Use 2 species and 3 doses to study up to 6
months
Chronic toxicity
1-2 years; for drugs intended for prolonged
use,
usually runs concurrently with clinical trial
Pre-clinical Safety and
Toxicity
Effect on reproduction
Animal mating behaviour, reproduction,
parturition, progeny, birth defects
Carcinogenic potential
Use 2 species for 2 years, for drugs intended
for prolonged use
Mutagenic potential
Effects on genetic stability of bacterial and
mammalian cells in culture
Clinical Testing
Volunteer studies (25-50)
Phase I clinical studies (25-50)
Phase II clinical studies (50-200)
Phase III clinical studies (250-1000)
Clinical Testing
Volunteer studies (25-50)
 human
pharmacology
 adverse effects
 pharmacokinetics after single or multiple
dose
Clinical Testing
Phase I clinical studies (25-50)
 clinical
pharmacology of the drug
 short term safety, efficacy
 pharmacological and pharmacokinetic
effects in disease
Clinical Testing
Phase II clinical studies (50-200)
 further
evidence of efficacy and safety in
larger number of patients
Phase III clinical studies (250-1000)
 full
scale clinical trial
PLACEBO
Drugs in Everyday Life
Commonly used drugs
analgesics
anti-inflammatory
drugs
antibiotics
drugs
for gastrointestinal tract
disorders
Analgesics
Morphine-like drugs
 opioids
Non-steroidal anti-inflammatory drugs
 aspirin
and related substances
Local anaesthetics
Other drugs used for specific conditions
 e.g.
migraine, labor
Antibiotics
Substances produced by some microorganisms which kill or inhibit the growth
of other micro-organisms
antibacterial drugs
antiviral drugs
antifungal drugs
Basic concepts of antibiotics
Static and cidal effects
Resistance to antibiotics
Adverse effects
Host factors
 severity
of infection, host defense
mechanisms, pharmacokinetic factors
Drug combinations
Patient compliance
Drugs for G.I. Disorders
Ulcer healing drugs
Antacids
Laxatives
Anti-diarrhoea drugs
Drugs for G.I. Disorders
Ulcer-healing drugs
Acid secretion reducers
 cimetidine, ranitidine, omeprazole,
pirenzipine
Mucosal strengtheners
 sucralfate, bismuth subcitrate,
carbenoxolone
Antibiotics
 metronidazole, tetracycline or amoxycillin
Drugs for G.I. Disorders
Antacids
Sodium hydrogen carbonate
Calcium carbonate
Magnesium hydroxide
Aluminium hydroxide
Drugs for G.I. Disorders
Laxatives
Bulk laxatives (increase the volume of the
intestinal contents, stimulate peristalsis)
 cellulose, methyl-cellulose
Stimulant laxatives (increase gut motility)
 anthraquinones (senna and cascera),
bisacodyl
Lubricants (softening and/or lubricating)
 liquid paraffin
Drugs for G.I. Disorders
Anti-diarrhoea drugs
Morphine-like agents
 morphine,
codeine, diphenoxylate,
loperamide
Adsorbents
 kaolin,
chalk
Drugs for non-medical
purpose
Drugs which are rigidly controlled by law in their
production, distribution and sale. Use of these
drugs is prohibited.
Drugs which are potentially dangerous. Use of
these drugs is under vigilance: penalties for
misuse; taxes for sale of these drugs.
Drugs which may cause damage to individuals if
used in excess. Controls mainly by taxation.
Drugs in Everyday Life
Drugs for non-medical purpose
alcohol
caffeine
tobacco
“health
products”
Drugs in Everyday Life
“illegal” drugs
cannabis
sedative-hypnotic
drugs
opium
morphine
and related drugs
cocaine
amphetamine
and related drugs
SOME DRUGS OF ABUSE
Drug
Trade Name “Street Name”
Amphetamine
Brotizolam
Cannabis
Chlordiazeproxide
Cocaine
Diazepam
Flunitrazepam
Ketamine
--Lendormin
--Librium
--Valium
Rohypnol
Ketalar
大力丸 安菲他命
13A 屋仔
大麻 “Grass”
綠豆仔 利眠寧
可卡因 Coke Crack
羅氏五號 十號
White Cross（十字架）
K仔
SOME DRUGS OF ABUSE
Drug
LSD (Lysergic acid
diethylamide)
Trade Name “Street Name”
---
迷幻藥
Methaqualone
Mandrax
Methylenedioxy--methamphetamine
忽得
MDMA “Esctasy”
忘我
Methamphetamine
--Midazolam
Dormicum
Scobarbital
Seconal
Triazolam
Halcion
冰
羅氏藍精靈
Lily 40 莉莉四十
藍精靈 藍瓜子