2. ADVERSE DRUG EVENT
An adverse drug event (abbreviated ADE) refers to any
injury caused by the drug (at normal dosage and/or due to
overdose) and any harm associated with the use of the drug
(e.g. discontinuation of drug therapy).
An adverse drug reaction (abbreviated ADR) is an
expression that describes harm associated with the use of
given medications at a normal dosage during normal use.
ADRs are a special type of ADEs.
3. ADVERSE DRUG REACTION
ADRs may be classified by Cause
Type A: Augmented pharmacologic effects
- dose dependent and predictable
Type B: Bizarre effects (or idiosyncratic)
- dose independent and unpredictable
Type C: Chronic effects
Type D: Delayed effects
Type E: End-of-treatment effects
Type F: Failure of therapy
Type G: Genetic reactions
4. ADVERSE DRUG REACTION
Type A: Augmented pharmacologic effects - dose dependent and
predictable
Drug intolerance or drug sensitivity
Drug intolerance is uncommon and idiopathic, thus extremely difficult to
predict except in persons with a prior history or a family history of intolerance
to that specific drug and general health.
Side effect
secondary effect which occurs in addition to the desired therapeutic effect of
a drug or medication. Side effects may vary for each individual depending on
the person's disease state, age, weight, gender, ethnicity
Ex. NSAIDs intolerance & side effect
Intolerance:
Its cause is believed to be variation in the metabolism of arachidonic acid.
Symptoms include chronic rhinosinusitis with nasal
polyps, asthma, gastrointestinal ulcers, angioedema, and urticaria.
Side effect :
NSAIDs predispose to peptic ulcers, renal failure and they can increase the
risk of hemorrhage by affecting platelet function.
7. Condition Substance
Abortion, miscarriage or
Uterine hemorrhage
misoprostol, a labor-inducing drug
Addiction many sedatives and analgesics (diazepam, morphine, etc.)
Birth defects thalidomide and isotretinoin
Bleeding of the intestine aspirin therapy, NSAIDs
Cardiovascular disease COX-2 inhibitors (i.e. rofecoxib)
Deafness and kidney failure gentamicin (an antibiotic)
Death, following sedation propofol
Depression or hepatic injury interferon
Depression tetrabenazine, rimonabant and other CB1 antagonists
Diarrhea orlistat
Erectile dysfunction many drugs, such as antidepressants
Fever vaccination
Flatulence acarbose
Glaucoma corticosteroid-based eye drops
Hair loss and anemia Chemotherapy against cancer, leukemia, etc.
Headache spinal anesthesia
Hypertension
ephedrine users, edra extractswhich prompted FDA to remove the
status of dietary supplement of eph
Impaired glucose
tolerance and diabetes
atypical antipsychotic medications, such
as clozapine and olanzapine
EXAMPLES OF ADVERSE EFFECTS ASSOCIATED
WITH SPECIFIC MEDICATIONS
8. EXAMPLES OF ADVERSE EFFECTS ASSOCIATED
WITH SPECIFIC MEDICATIONS
Condition Substance
Insomnia stimulants (e.g. methylphenidate, amphetamine, etc.)
Kidney stones indinavir, carbonic anhydrase inhibitors (such as topiramate)
Lactic acidosis
stavudine (an antiretroviral drug) or metformin (oral anti-diabetic
medication)
Liver failure paracetamol
Melasma and thrombosis
estrogen-containing hormonal contraception such as
the combined oral contraceptive pill
Irreversible Peripheral neuropathy fluoroquinolone medications
Rhabdomyolysis statins (a class of lipid-lowering drugs)
Seizures withdrawal from benzodiazepines
Stroke or heart attack Sildenafil when used with nitroglycerine; COX-2 inhibitors
Suicide, increased tendency antidepressants
Parkinsonism MPTP, a meperidine related drug considered highly neurotoxic
Tardive dyskinesia
long-term use of metoclopramide, cinnarizine and
many antipsychotic medications
Spontaneous Tendon rupture
fluoroquinolone drugs even occurring as late as 6 months after
treatment had been terminated.
Weight loss some antidepressants, like fluoxetine and bupropion
Weight gain
some antipsychotics (e.g. olanzapine and clozapine) and
antidepressants (mirtazapine)
9. ADVERSE DRUG REACTION
Type B: Bizarre effects (or idiosyncratic) - dose independent and
unpredictable
The proposed mechanism of most idiosyncratic drug
reactions is immune-mediated toxicity.
To create an immune response, a foreign molecule must be
present that antibodies can bind to (i.e. the antigen) and
cellular damage must exist.
Very often, drugs will not be immunogenic because they are
too small to bind antibodies.
However, a drug can cause an immune response if the drug
binds a larger molecule.
Hypersensitivity
History and testing**
10.
11. HYPERSENSITIVITY
Comparison of hypersensitivity types
Type Alternative names Often mentioned disorders Mediators
I Allergy (immediate)
•Atopy
•Anaphylaxis
•Asthma
•IgE and IgG4
II Cytotoxic, antibody-dependent
•Autoimmune hemolytic anemia
•Thrombocytopenia
•Erythroblastosis fetalis
•Goodpasture's syndrome
•Membranous nephropathy
•Graves' disease *see type V explanation below
•Myasthenia Gravis *see type V explanation below
•IgM or IgG
•(Complement)
III Immune complex disease
•Serum sickness
•Arthus reaction
•Rheumatoid arthritis
•Post streptococcal glomerulonephritis
•Lupus Nephritis
•Systemic lupus erythematosus (SLE)
•Extrinsic allergic alveolitis
(Hypersensitivity pneumonitis)
•IgG
•(Complement)
IV
Delayed-type
hypersensitivity(DTH), cell-mediated
immune memory response, antibody-
independent
•Contact dermatitis
•Mantoux test
•Metal joint replacement
•Chronic transplant rejection
•Multiple sclerosis
•T-cells
V
Autoimmune disease, receptor
mediated
•Graves' disease
•Myasthenia Gravis
•IgM or IgG
•(Complement)
Coombs and Gell classification
12. ATOPY
A person with atopy typically presents with one or more of the following: eczema (atopic
dermatitis), allergic rhinitis (hay fever), allergic conjunctivitis, or allergic asthma. Patients with atopy also
have a tendency to have food allergies.
eczema (atopic dermatitis)
16. DRUG MISUSE AND DRUG ABUSE
Drug misuse is a term used commonly for prescription
medications with clinical efficacy but abuse potential and
known adverse effects linked to improper use, such as
psychiatric medications with sedative, anxiolytic, analgesic,
or stimulant properties.
Substance abuse, also known as drug abuse, is a patterned
use of a substance (drug) in which the user consumes the
substance in amounts or with methods neither approved nor
advised by medical professionals.
17. DRUG MISUSE AND DRUG ABUSE
IN SPORT
World Anti-Doping Agency : http://www.wada-ama.org/en/
Prohibited At All Times
Prohibited In-Competition
http://www.wada-ama.org/rtecontent/document/WADAC_Thai.pdf
S1. ANABOLIC AGENTS
S2. PEPTIDE HORMONES, GROWTH FACTORS AND RELATED SUBSTANCES
S3. BETA-2 AGONISTS
S4. HORMONE AND METABOLIC MODULATORS
S5. DIURETICS AND OTHER MASKING AGENTS
18. Anabolic-Androgenic Steroids
Anabolic steroids, technically known as anabolic-androgenic
steroids (AAS), are drugs that have similar effects
to testosterone in the body.
They have both an anabolic effect (increasing muscular strength and
size) and an androgenic effect (masculinizing) on the user.
They increase protein within cells, especially in skeletal muscles.
Research clearly shows that anabolic steroids use is
associated with increased body weight and mass, altered body comp
osition, increased muscle size and
strength, increased blood volume, and increased number
of red blood cells.
a. Exogenous* AAS, including:
b. Endogenous** AAS when administered exogenously:
S1. ANABOLIC-ANDROGENIC STEROIDS
20. S1. ANABOLIC-ANDROGENIC STEROIDS
androstenediol (androst-5-ene-3β,17β-diol)
androstenedione (androst-4-ene-3,17-dione)
dihydrotestosterone (17β-hydroxy-5α-androstan-3-one)
prasterone (dehydroepiandrosterone, DHEA, 3β-hydroxyandrost-5-en-17-one)
testosterone
2013 List of Prohibited Substances and Methods
B. Endogenous** AAS when administered exogenously:
Other Anabolic Agents, including but not limited to:
Clenbuterol
selective androgen receptor modulators (SARMs)
Tibolone
Zeranol
zilpatero
21. 1. TESTOSTERONE
It is the principal male sex hormone
and an anabolic steroid.
In men, testosterone plays a key role
in the development of male
reproductive tissues such as
the testis and prostate as well as
promoting secondary sexual
characteristics.
Anabolic effects include growth of muscle mass and strength, increased bone
density and strength, and stimulation of linear growth and bone maturation.
Androgenic effects include maturation of the sex organs, particularly the penis and
the formation of the scrotum in the fetus, and after birth (usually at puberty) a
deepening of the voice, growth of the beard and axillary hair. Many of these fall into
the category of male secondary sex characteristics.
23. 2. METHYLTESTOSTERONE
Used to treat men with
a testosterone deficiency.
17α-Methylation (upper-right corner)
enhances oral bioavailability
Methyltestosterone
24. 3. METHANDROSTENOLONE
Methandrostenolone also known
as metandienone or methandienone, is an
orally-effective anabolic synthetic steroid.
17α-Methylation (upper-right corner)
enhances oral bioavailability.
Indications: Testosterone replacement
therapy on male, hypogonadal disorder.
Methandrostenolone
25. 4. FLUOXYMESTERONE
Fluoxymesterone is an anabolic
steroid with strong androgenic properties.
It has been used in the treatment of
male hypogonadism, delayed puberty in
males, and in the treatment of breast
neoplasms in women.
It is approximately 5 times as potent
as methyltestosterone.
No brands in Thailand.
Fluoxymesterone
26. 5. MESTEROLONE
Mesterolone is an orally
applicable androgen,
and DHT derivative.
Indication & Dose :
Reduced efficiency in middle & advanced age
due to androgen deficiency
1 tab tid.
After satisfactory clinical improvement try to reduce the
dose. Treatment may be continued to 1 tab once daily
or bid.
Hypogonadism
Max: 1-2 tab tid for several mth.
Maintenance dose: 1 tab 2-3 times daily.
Infertility for the improvement of sperm
quantity & quality
1 tab bid-tid for about 90 days & repeated after at several
wk if necessary.
Mesterolone
27. 5. MESTEROLONE
Mesterolone had seen widespread use
in bodybuilding primarily for antiestrogenic activity
in anabolic steroid stacks.
Most significant benefits of current Mesterolone use are
considered to be maintaining libido off-cycle and also
relatively and temporarily improving vascularity.
Mesterolone
28. S2. EPTIDE HORMONES, GROWTH FACTORS
AND RELATED SUBSTANCES
The following substances and their releasing factors are prohibited:
Erythropoiesis-Stimulating Agents
[e.g. erythropoietin (EPO), darbepoetin (dEPO), hypoxia-inducible factor
(HIF) stabilizers, methoxy polyethylene glycol-epoetin beta (CERA),
peginesatide (Hematide)]
Chorionic Gonadotrophin (CG) and Luteinizing Hormone (LH) in
males
The importance of measuring hCG and luteinizing hormone (LH) in the
control of testosterone misuse.
CG is used in sports in an attempt to avoid the hormone deficiency resulting
after anabolic steroids are discontinued. The production of testosterone,
suppressed by the use of anabolic agents, is stimulated once more.
29. ERYTHROPOIETIN (EPO)
Treatment of anemia associated
w/ chronic renal failure & in cancer patients
treated w/ chemotherapy.
Erythropoiesis-stimulating agents (ESAs) have
a history of use as blood doping agents in
endurance sports
The overall oxygen delivery system (blood
oxygen levels, as well as heart stroke volume,
vascularization, and lung function) is one of the
major limiting factors to muscles' ability to
perform endurance exercise.
Therefore, the primary reason athletes may use
ESAs is to improve oxygen delivery to muscles,
which directly improves their endurance
capacity.
30. S2. EPTIDE HORMONES, GROWTH FACTORS
AND RELATED SUBSTANCES
The following substances and their
releasing factors are prohibited:
Corticotrophins
to improve strength and boost the red-
blood-cell count. A high red-blood-cell
count means that the blood can carry more
oxygen, which helps improve performance.
Corticotrophin is used in the place of
glucocorticoids following long periods of
physical stress.
Growth Hormone and Growth factor
group,
The effect of reducing body fat while
simultaneously increasing muscle mass
makes the substance prone to misuse in
sports. In bodybuilding, growth hormones
are combined with anabolic agents, which
further exacerbates the risk involved in both
substance types.
31. S3. BETA-2 AGONISTS
All beta-2 agonists, including all optical isomers
(e.g. d- and l-) where relevant, are prohibited
except
inhaled salbutamol (maximum 1600 micrograms over
24 hours),
inhaled formoterol (maximum delivered dose 54
micrograms over 24 hours) and
salmeterol when taken by inhalation in accordance
with the manufacturers’ recommended therapeutic
regimen.
33. S3. BETA-2 AGONISTS
Effects:
Beta-2 agonists have the effect of
relaxing the bronchial muscles by
stimulating the beta-2 receptors.
In this way they alleviate the
symptoms of an asthma attack.
Medical use:
Beta-2 agonists are used in medicine
to treat bronchial asthma.
A distinction is made between short-
acting substances, which are inhaled
especially during an asthma attack,
and long-acting beta-2 agonists that
are used in basic therapy to reduce
the susceptibility of muscles to
cramps.
34. S3. BETA-2 AGONISTS
Misuse in sports:
When administered in high doses,
these substances promote protein
synthesis, which in the case of
animals resulted in an increase in the
proportion of muscle mass to fat
mass.
Athletes using these substances for
doping anticipate similar effects, as
well as a short-term enhancement
of performance due to the dilation
of bronchial passages.
Some beta-2 agonists are prohibited
in sports. In some cases therapy for
medical reasons must be approved
by applying for a therapeutic use
exemption (TUE).
35. OTHER
S4. HORMONE AND METABOLIC MODULATORS
S5. DIURETICS AND OTHER MASKING AGENTS
36. WARNING SIGNS OF COMMONLY ABUSED
DRUGS
Marijuana: Glassy, red eyes; loud talking, inappropriate laughter followed by
sleepiness; loss of interest, motivation; weight gain or loss.
Depressants (including Xanax, Valium, GHB): Contracted pupils; drunk-like;
difficulty concentrating; clumsiness; poor judgment; slurred speech; sleepiness.
Stimulants (including amphetamines, cocaine, crystal meth): Dilated pupils;
hyperactivity; euphoria; irritability; anxiety; excessive talking followed by
depression or excessive sleeping at odd times; may go long periods of time without
eating or sleeping; weight loss; dry mouth and nose.
Inhalants (glues, aerosols, vapors): Watery eyes; impaired vision, memory and
thought; secretions from the nose or rashes around the nose and mouth;
headaches and nausea; appearance of intoxication; drowsiness; poor muscle
control; changes in appetite; anxiety; irritability; lots of cans/aerosols in the trash.
Hallucinogens (LSD, PCP): Dilated pupils; bizarre and irrational behavior
including paranoia, aggression, hallucinations; mood swings; detachment from
people; absorption with self or other objects, slurred speech; confusion.
Heroin: Contracted pupils; no response of pupils to light; needle marks; sleeping
at unusual times; sweating; vomiting; coughing, sniffling; twitching; loss of appetite.
