SYMPTOMS ASSOCIATED WITH DRUG ABUSE OF OPIOID

ANALGESICS USE AS A NON MEDICAL SUBSTANCE

TERM PAPERS PHARMACEUTICAL



by:


FACULTY OF MEDICINE
UNIVERSITAS WIJAYA KUSUMA SURABAYA
2014

CHAPTER I
INTRODUCTION

Drug abuse is the use of drugs that can lead to a state that is not possessed
by individuals and conducted outside of medical supervision, or which can cause
a dangerous situation / threaten society (1).
In the United States, the problem of drug abuse tops the causes of
preventable disease (Prevent-able illness) and mortality. Each year, more than
500,000 deaths or 1 of 4 deaths related to drug misuse within the last 15 years
(1992-2007) (2).
Opioid analgesics are a group of drugs that have properties such as opium.
Particularly opioid analgesics used to relieve or eliminate pain, although it also
shows various other pharmacodynamic effects. The term is often used narcotic
analgesics used for this group of drugs, but because this class of drugs can induce
analgesia without causing sleep or decrease the term narcotic analgesic awareness
becomes less precise. (3)
The number of prescriptions for opioid analgesics have increased
substantially over the past decade (4,5). In the U.S., opioid analgesics are the most
commonly prescribed drugs in 2009, to 202 million prescriptions (6). Coinciding
with the increased use of opioids, prescription opioid abuse has become a
significant public health problem (7, 8, 9). In 2010, there were 2 million new
patients for nonmedical use of prescription opioids in the United States, a figure
that surpassed all other substances of abuse with the exception of marijuana (10).
Along with the increasing misuse of prescription opioids, there has been a large
increase in the number of substance abuse treatment admissions for prescription
opioid addiction. (11)
The problem of drug abuse is a serious concern of all parties. President
through the Presidential Instruction No. 6/1971, about overcoming the trafficking
and abuse of drugs such as morphine, heroin, drugs containing opium and
smoking marijuana. Laws governing these substances is clear, namely Law No. 9,
1976 relating to narcotics. (2)
In the Narcotics Act, which is classified as a narcotic marijuana, cocaine,
and opioids / opiates. While that includes the type opiates are morphine and
heroin. Drug abuse among teenagers increasingly difficult to stop. As a result,
over the last decade in this country have discovered hundreds of thousands of
drug addicts and other addictive substances. (2)
This study aims to determine the symptoms that result from abuse of
opioid analgesics in non-medical.
1.1. Research Objectives
To know the symptoms caused by drug abuse associated with the use of
opioid analgesics as non-medical substance

1.2. Problem Formulation
1. Symptoms that can be caused by any misuse of opioid analgesics as non-
medical substance?
2. How treatment of opioid analgesic abuse as non-medical substance?







CHAPTER II
LITERATURE REVIEW

2.1. Pharmacy - Pharmacology
Physical properties - Chemical
Opium or opium is papaversomniferum L sap that has been dried.
Opium is chemically divided into two groups:
1. The Group fenatran: morphine and codeine
2. Benzilisokinolin Group: noskopin and paparin
On the basis of how it works these drugs can be divided into four groups:
1. The full agonists (strong)
2. Partial agonists (agonists weak to moderate)
3. Mixed agonist and antagonist
4. Antagonists
Strong opioid agonist class only has the effect of agonists whereas partial
agonists can cause agonist effects atu as antagonists with potent agonist of the
bond shift in opioid receptor and reduces its effect. Opioids are a mixture of
opioid agonists and antagonists are agonists that have an effect on the opioid
receptor subtypes and as a partial agonist or antagonist at other receptor
subtypes. Based on the formula in the opioid class of drugs awakening to be
derivatives venantren, venil hepilamin, phenyl piperidine, morfinan and
benzomorfin. (Pharmacology UI case 211)

General Pharmaceutical
Preparation containing a mixture of alkaloids in rough shape for example
pulvus opii containing 10% morphine and codeine is less than 0.5%. Pulvus
Doveri containing 10% pulvus opii the status of 150 mg containing 1.5 mg
pulvus Doveri mofin. Preparations containing pure alkaloids can be used for
oral or parenteral administration. Commonly used is the HCl salt, sulfate salt,
or phosphate morphine alkaloid with levels of 10 mg / ml. Codeine is
available in the free base or the hydrochloride salt form. One tablet contains
10, 15, or 30 mg of codeine. (Farmako UI case 218)

General Pharmacology
Opioids are analgesics that reduce pain juice, aggression and sexual desire.
These substances also cause respiratory depression, miosis, bradycardia, a
decrease in tension, obstipation, feeling dizzy and fall of body temperature.
The emergence of comfortable or euphoria juice occasionally caused by the
loss of a great pain. (Essential drugs case 364)

Indication
Pain: myocardial Infrak, neoplasms, pneumothorax spontant, trauama eg
burns, fractures
Cough: cough reflex inhibits unproductive
Acute pulmonary edema: morphine intravenously to parse shortness of
breath due to pulmonary edema accompanying left heart failure.
antidiarrheal: alkoloid morphine useful for stop diarrhea by direct effect on
intestinal smooth muscle. (Farmako UI case 216)

Contra indications
Impaired liver function
Impaired renal function
Pregnant women

Side effects (essential drugs case 349)
Suppression CNS: hypotermia, mood changes, nausea, vomiting, delirium.
Channels breath: bronchokontriksi, breathing becomes more shallow and the
frequency decreases.
The circulatory system: peripheral vasodilation, hypotension occurred at
high doses and bradycardia.
Gastrointestinal tract: reduced motility (opstipasi).
Channels Urogenital: urinary retention due to increased tone of the bladder
spingter

2.2. Pharmacodynamic (UI Farmako case 231)
Effects of morphine occurs in the central nervous system and organs
containing smooth muscle. Effects of morphine on the central nervous system
has two properties, namely depression and stimulation. Depression is
classified analgesia, sedation, emotional changes, alveolar hypoventilation.
Including stimulation of parasympathetic stimulation, miosis, nausea,
vomiting, hyper active spinal reflexes, convulsions and secretion of anti-
diuretic hormone.
Morphine can cause respiratory depression in primary

Mechanism of action
The main effects of opioid receptor activation is lowered
neurotransmission. The decrease neurotrasnmisi can occur due to inhibition
of presynaptic release of neurotransmitters (acetylcholine, dopamine,
norepinephrine, substance P), and sometimes also occur seizure inhibition in
post-synaptic activity. Biochemical events initiated by the binding of opioid
receptors by opioid agonists is characterized by an increase in potassium
conductance (which causes hyperpolarization), calcium channel inactivation,
or a combination of both. Such a process would lead to a sudden decrease in
the release of neurotransmitters. Adenyl cyclase inhibition mediated by
opioid receptors do not play a role in the rapid effects of opioids, but most
likely this mechanism plays a role in the slow effect through decreased
response of cyclic adenosine monophosphate neuropeptidea gene(CAMP)
and a decrease in the concentration of neuropeptide messenger (messenger)
RNA / m-RNA.
Opioid receptors located in the peripheral end of the primary afferent
neurons and activation of these receptors causes a decrease in inhibitory
neurotransmission or release of neurotransmission processes of excitation,
such as substance P. With these considerations, it is injected intra-articular
morphine (3 mg) may provide longer analgesia although the procedure has
been completed artoskopi knee. Cholinergic transmission in the CNS
depression caused by inhibition of the release of acetyl-choline from nerve
endings play an important role in the analgesic effect and side effects of
opioid agonist drugs. Opioids do not affect the level of response in the
afferent nerve endings to noxious stimulation. Opioids also does not interfere
with the conduction of nerve impulses along peripheral nerves.


2.3. Pharmacokinetics
Absorption, distribution, metabolism, and excretion (ADME commonly
known as) is an important feature of apapun.Penyerapan oral opioid
medications vary widely. Morphine is not absorbed when given orally
regularly, so it is usually injected morphine intravenous or intramuscular (IM)
(12). Most substances have the effect of oral opioids slow release, given to
patients with chronic pain, where patients are not allowed to swallow or chew
the substance directly in order to avoid overdose or poisoning. Codeine is
well absorbed in oral administration, and is usually used as a cough
suppressant. Most opioids work secata metablisme maximum on the first
pass, which plays a role in the metabolism of the liver, and has a weaker
absorption than IV or IM administration. (12,13)
Absorption of opioids in the organs vary widely. Although each type of
opioids have different affinities to the protein, opioids can quickly leave the
blood compartment, and then assembled into tissues that have a high blood
perfusion such as brain, lung, liver, kidney and spleen. (15) The concentration
of opioids and muscle is actually smaller, but the muscle tissue has a large
volume of so many who accumulates there. Although blood flow in fat tissue
is low, but the accumulation of fat tissue is an important thing because there
will be a redistribution back by opioids well with fat-soluble, such as
fentanyl. (15,16)
Most of opioids will be converted into more polar metabolites largely
glukoronid, which will then be excreted through the kidneys. For example
morphine, most will conjugated to morphine-6-glukoronid, an effect that has
kompenen neuroeksitatori. Neuroeksitatori effect is not mediated by opioid
receptors but rather by the GABA system / glisinergik. Approximately 10%
of morphine is converted into M6G, an active metabolite of the analgesic
effect of 4 to 6 times more potent than morphine. But the more polar
metabolites have limitations to penetrate the blood-brain barrier. Excessive
accumulation of this drug as in patients with renal failure or the use of large
doses will certainly cause many side effects. Seizures due neuroeksitasi
effects of M3G and employment effects of prolonged opioid produced by
M6G. (3,4,5,8) (15)
Ester groups such as heroin and remifentanyl rapidly hydrolyzed by tissue
esterase. Heroin (diasetilmorfin) hydrolyzed to monoasetilmorfin and
ultimately into morphine which is then conjugated by hepatic oxidative
glukoronat.Metabolism acid is the primary route of degradation of opioids
such as meperidine group fenilpiperidin, fentanyl, alfentanyl and sufentanyl.
Results methylated metabolites of meperidine is normeperidin may
accumulate in patients with decreased renal function or the use of high doses.
Normeperidin can cause seizures when accumulated in high enough
quantities. Instead fentanyl has no active metabolites. P450 isozymes
CYP3A4 metabolizes fentanyl through the N-dealkylation in the liver.
CYP3A4 is also found in the small intestine mucosa and contribute to the
process of first-pass metabolism when fentanyl is administered orally.
Codeine, oxycodone, and hydrocodone are metabolized in the liver by the
P450 isozyme CYP2D6 which will produce metabolites with greater effect.
For example, methylated codeine into morphine. (15)
Polar metabolites, including conjugates glukoronid of opioid analgesics,
mostly excreted through small urin.Sejumlah of parts that are not converted
can also be found in urine. In addition glukoronid conjugate was also found in
the bile, but enterohepatic circulation only a small role in the process of
excretion. (4)
The half-life of most derivative of morphine that is administered orally is 3
to 6 hours, although some classes of first-pass liver metabolites (after
glucuronidation) still has an analgesic effect is quite large. Morphine is not
metabolized by both the neonate and the relatively long acting in causing
respiratory depression, so it should not be used during childbirth, where
meperidine is a safer option.Respirasi refundable with opioid antagonist
naloxone, as required. (1,2,3)
For postoperative or chronic pain, opioids have been used for the
controlled analgesia pump control pasien.Pasien that increase or decrease the
dose to control pain but minimize the effects of this penenang. These pumps
generally do not lead to excessive treatment and dependency are widely
feared by patients. (14)
Stereospecific interaction with opioid receptor protein in certain cell
membranesel ssp, on peripheral nerve endings and the cerna.Efek duct cells is
mediated by the four main opioid receptor family Stereospecific interaction
with opioid receptor protein in certain cell membranesel ssp, on peripheral
nerve endings and the cells of the gastrointestinal tract. Primary effect is
mediated by the opioid receptor family 4 as indicated by the ancient Greek
letters , , and . In general, bond strength correlates with analgesia.
Analgesic properties mediated by receptors, but receptors in the dorsal horn
also support a more selective enkephalins interact with receptors on
peripheral . kurang specific receptors, this receptor also binds non-opioid
drugs such as halusinogenfensiklidin. (16)
Distribution of high density of opioid receptors located on five general
areas ssp known to be involved in integrating the formation of pain. The road
down from periaquaduktus gray (PAG) to the spinal cord dorsal horn. This
receptor was identified in peripheral also can. (16)
2.4. Toxicity
Toxidrome (a syndrome that is caused by the presence of toxins in the
body) is a classic of opioid intoxication include apnea (a condition of
suspension of external breathing), fainting (syncope) and miosis.Sine qua non
(condition, or a sign that the findings would not likely be present in the
absence of disease or suspected condition) in opioid poisoning is the presence
of respiratory depression. Dosing of opioid therapy in a person without
causing a decrease in respiratory activity tolernasi the drop rate depends on
the level of the dose given. Decreased respiratory symptoms are the most
easily observed and its peak is apnea. 12x/menit respiratory rate or less on a
person with a sleep condition that is not being clearly showed the presence of
physiological acute opioid poisoning especially when accompanied by miosis
or stupor. The presence of miosis alone is not sufficient to infer the presence
of a diagnosis of opioid poisoning. (17,18)
Ingestion of many substances can produce mydriasis and pupillary reaction
normalization, as it can also cause poisoning of meperidine, propoksifen or
tramadol. Instead of an overdose of opioids, anticonvulsants agent and agent-
hipnotif other sedatives can cause miosis and coma, but generally without
respiratory depression. Oxygenation failure was defined as an oxygen
saturation less than 90% while the patient inhales ambient air and with
adequate ventilation to achieve normal carbon dioxide tension (partial
pressure of carbon dioxide) is often caused by pulmonary edema. Pulmonary
edema can be caused by several conditions. One possible cause is an
inspiration occurs in a closed glottis, causing a pressure drop intraaortik and
further causing fluid extravasation. Or other possible cause is the presence of
acute lung injury that may result from a mechanism similar to that postulated
for neurogenic pulmonary edema. In this scenario, vasoactive sympathetic
response to stress in a person who has recovered from the condition of
intoxication leads to leakage of peripheral lung. Hypothermia may occur due
to the absence of a persistent response in a cold environment or due to errors
in the recovery effort opioid intoxication patients by immersing in water.
Besides someone who fainted opioid-induced rhabdomyolysis can
experience, renal failure and compartment syndrome myoglobinurik. Other
laboratory abnormalities that may occur is in conjunction with the
aminotransferase concentration of liver injury caused by paracetamol or
hypoxemia. Seizures associated with tramadol overdose, propoksifen and
meferidin. (17,18,19)
OVERDOSE DIAGNOSIS
Hipopnea presence or apnea, miosis, and fainting should direct the
physician to suspect the possibility of a diagnosis of opioid intoxication
which may be inferred by observing physical signs, medical history and
physical examination. In patients with severe respiratory depression, recovery
ventilation and oxygenation takes precedence over the patient's medical
history or obtain physical examinations or diagnostic tests. (20)
Once the patient's condition is stable, doctors should ask all who have ever
used opioid analgesics, paracetamol and other drugs and dangerous and ask if
the patient has contact with anyone who receives the treatment of chronic
pain or dependence. In the physician must perform a physical examination to
evaluate the size and reactivity of pupils and respiratory rate and auscultation
findings that lead to pulmonary edema. Patient must completely naked to find
a possible patch fentanil.The doctors also should do muscle palpation,
cohesiveness, swelling and tenderness which becomes characteristic of
compartment syndrome. Finally, plasma levels of paracetamol should also be
determined, to see the possibility of paracetamol hepatotoxicity. (20)
Qualitative urine analysis is needed to see the possibility of the use of illegal
drugs. But the discovery of the existence of the use of illegal drugs will not
significantly affect the decision of the action to be taken, this is because the
therapy is basically not too different opioid overdose. (21)
OVERDOSE TREATMENT
Patients with apnea requiring mechanical and pharmacological stimuli. For
patients who collapsed with respiratory rate 12x/menit or less ventilation
should be provided with a bag-valve mask; chin-lift and jaw-thrust should be
made to ensure that the anatomical position helps to reduce hypercarbia.
Although the relationship between the partial pressure of carbon dioxide and
acute lung injury is not clear, provide adequate ventilation is a simple
response that is beneficial to restore oxygenation and prevent sympathetic
surge that can trigger pulmonary edema after restoration of apnea with
minimal risk. (17,18)
Naloxone is one antidote for an overdose of opioid mu receptor antagonist
that competitively reversing all the signs of opioid overdose. Naloxone will
be active when administered via the parenteral route, intranasal or pulmonary.
In patients with opioid dependence, initial plasma concentrations of naloxone
should be lower because of the higher volume of distribution and elimination
half-life is longer than the patients who did not experience apioid
dependence. Onset of action of naloxone is less than 2 minutes in adults when
administered by intravenous injection, the duration of action of approximately
20-90 minutes clear, a shorter work period compared to most opioids.
(20,21). Naloxone dose is empirical. The effective dose is highly dependent
on the amount of opioid analgesic that is accepted by the patient, the relative
affinity of naloxone in opioid analgesics position on ties with mu receptors,
the patient's weight and the level of penetration of the analgesics on the
central nervous system. Because most of the information is not known, then
to determine the effective dose depends heavily on experimental therapies.
The initial dose of naloxone for adults is 0.04 mg, if no response dose should
be increased every 2 minutes, maximum dose of 15 mg. If there is no
reduction in symptoms of respiratory depression after administration of 15
mg naloxone, this means that cause respiratory depression is not an opioid
overdose. Return of opioid toxicity following administration of a single dose
of naloxone are often transient, recurrent respiratory depression is indicative
of the need for continuous infusion. (21)
Naloxone can be administered without the need to worry about including
in patients with opioid dependence. Concerns that the naloxone will harm
patients with opioid dependence unwarranted. The signs are not as exciting as
yawning, lacrimation, piloerection, diaphoresis, myalgia, nausea, and diarrhea
may occur but it was not life-threatening. In addition patients with opioid
tolerance often have an inadequate response to naloxone to increase
respiratory rate. After the respiratory rate increased after the administration of
naloxone patients should be observed for 4-6 hours before finally giving
naloxone was discontinued. (21)
Alternative methods for the administration of naloxone is via intratracheal
intubation, a procedure that ensures the safety of administration in
conjunction with oxygenation and ventilation procedures. Patients who
experience opioid intoxication due to the use of long-actingatau formulation
of extended-release can experience recurrent respiratory depression or require
intravenous naloxone or intratracheal intubation performed emergency
tagging on equipment. (21)
Once the patient's condition, must be investigated further and confirmed
that the patient's body surface there fentanyl patch. Fentanyl patches often
cause intoxication delayed. Axilla, perineum, scrotum and oropharynx should
be inspected and if found fentanyl patches should be removed and the skin
should be decontaminated with cold water and sabun.Pada patients may
swallow the fentanyl patches should be irrigated with polyethylene glycol to
accelerate the elimination of the patch. (20,21)
The presence of persistent hypoxemia after administration of naloxone
may indicate the presence of negative-pressure pulmonary edema. In cases of
mild hypoxemia supportive care alone is sufficient, but in severe cases
required intubation administration orotrakeal and positive-pressure
ventilation. Resolution of lung injury can be performed with aspiration of
gastric contents is usually done within 24 hours. Because of the possible
causes of lung injury is not due to excess fluid then the reduction of
intravascular volume by using diuretics is often ineffective and may even
worsen the condition myogloburik kidney failure, if any. Naloxone has been
mistakenly regarded as the cause of pulmonary edema. However, in cases of
fatal opioid overdose, pulmonary edema is almost always the case, including
in the case before the development of the latest nalokson. The research have
shown that pulmonary edema does not develop in patients who receive large
doses of naloxone and by means of a continuous infusion. Finally,
auscultation signs of pulmonary edema which is often not clear in patients
with apnea, it became clear after the administration of naloxone. (20,21)
Rhabdomyolysis is defined as a condition in which the concentration of
creatinine-kinase or five times higher than the normal range of the last to be
treated with fluid resuscitation to prevent precipitation (precipitation) of
myoglobin in the renal tubules; bicarbonate does not improve the condition.
Patients with compartment syndrome should have to accept emergency
consultation for possible surgical fasciotomy. (5). Patients with hypothermia
may require immediate warming. Increased aminotransferase concentrations,
the presence of paracetamol in the blood, or both indicate the possible need
for treatment with acetylcysteine. Ultimately necessary to identify the cause
of overdose to determine appropriate follow-up care for these patients (20,21)











CHAPTER III
RESEARCH

3.1. Previous study of another person
a. Adolescents are a group at high risk for drug abuse, and can cause a
dangerous situation / threaten people. This cross-sectional study aims to
determine the rate and risk factors of drug abuse among high school
students (SMU). Respondents include 210 students from seven high
schools in the city of Pekanbaru. Drug Abuse Screening Test (DAST-
10) was used to measure the level it drug abuse and risk factors was
obtained through questionnaires completed by respondents. The study
showed that 67.2% of respondents are not problematic in drug abuse.
There is a significant relationship between sex, stay at while parents,
academic achievement, having friends who smoke and following
extracurricular activities to the level of drug abuse. From the logistic
regression analysis showed that the factor of residence (OR = 3,969, p =
0.002), followed ekstrakurile activity (OR = 0316, p = 0.001) and
smoking (OR = 0.227, p = 0.001) were risk factors for drug abuse. (22)
b. Opioid abuse increased in number from time to time and has the
potential to cause physical disorders and comorbid mental disorders. A
variety of common mental disorders such as depression, anxiety
disorders, psychotic disorders, paranoid disorders, and others. Subjects
were assisted intravenous opioid user group outreach program Bandung
Ark Foundation is willing to be the subject of research, and not
currently undergoing a rehabilitation program. This study was
conducted in London between the months of May to August 2006, is a
descriptive-cross sectional analysis. Subjects were interviewed using
the Addiction Severity Index (ASI) is an instrument for measuring the
degree of opioid dependence. Subjects consisted of 70 respondents; 35
people (50%) experienced mild dependence, 25 (35.71%) and the
weight of 2 people (2.86%) is very heavy. All subjects were in the age
group between 20-38 years old young adults. Gender subject of most of
the male (95.71%). A significant association between depression (p =
0.035), state anxiety (p = 0.05), a state hostile / suspicious (p = 0.031),
the problem of reality testing (p = 0.025) on the status of opioid users
intravenous opioid dependence. The need for increased treatment in
accordance with the status of opioid dependence (p = 0.000). This is a
good situation because it can be used as a starting point for the
treatment and rehabilitation of intravenous opioid users. Further
research needs to be conducted to find the factors that cause
dependence and the right approach to help users of intravenous opioids
to want treatment. (23)












CHAPTER IV
DISCUSSION

Drug abuse is a way to use the drug only for personal enjoyment or sects.
This drug is a drug that can cause effects that happy feelings (euphoria) which
usually can make opium. That caused by the influence of drugs is seen in how
likely the drug will make the wearer become addicted. The stronger the drug,
the more likely users become addicted. 4
Physical dependence is a biological phenomenon. Physical dependence is
manifested by compulsive drug-seeking habits that people use repeatedly for
personal satisfaction. Physical dependence is present when the drugs produce
withdrawal symptoms and signs opposite to that expected. Addiction is
usually used for the merger between the physical and physical dependence. 5
Opioid analgesic drug which is often misused heroin, Morphine,
Oxycodone, Meperidine, Fentanyl.
a. Heroin
Heroin is an opioid drug that is often abused. The use of heroin can
cause effects of warmth, and a high sense of pleasure that is often
associated with sexual life. After injecting heroin effect will start a few
minutes later. Heroin has a high solubility of the fat, which is made to pass
through the blood-brain barrier rapidly. Having experienced an intense
euphoria for 45 seconds to a few minutes, there was a period of tranquility
for one hour. The effects of heroin disappears after 3-5 hours depending on
the dose taken.
Once addicted, users can consume 2-4 times per day. The effects of
heroin up and down between "pleasure" and felt pain after withdrawal
(period when the homeostatic decline due to the lack of the drug). This
imbalance causes many problems from the homeostatic system is partly
regulated by endogenous opioids. For example, the hypothalamic pituitary-
gonadal-axis and the hypothalamic-pituitary-adrenal becomes abnormal in
heroin users. Women heroin users will experience abnormal menses, and
he will have a high sexual desire. Mood also be affected. 4
In the central nervous system, repeated use can cause the following
effects. 6
sensation of pain consists of malicious input coupled reaction of the
organism to the stimulus. Analgesics on opioids may alter the patient's
perception of pain and reaction to pain. This drug may also cause an
increase in pain threeshold. However, the effect can only be inferred from
the patient's subjective effects.
Euphoria
Patients will also experience a sensation usually fun and free from
worry. However, in normal patients (feel no pain), experience
dysphoric effects may be more pronounced than fun. Dysphoria will
cause fatigue and feeling unwell.
Sedation
Drowsiness or blurring of thinking common in this type of drug
delivery coupled with damage to the ability of logic. Sometimes it can
also happen a little amnesia. Though sleepy patients more easily
aroused. However, the combination, orfin with other central depressant
drugs, may result in a deep depression. Morphine is an analgesic drug
that can disrupt sleep patterns of REM and NREM, as well as other
opioids drugs.


Depression of respiration
Drugs of this type would inhibit the respiratory mechanism in
the brain stem. Alveolar CO2 pressure may also be increased.
cough suppressants
Drugs of this type can perform on the suppression of the cough
response. Codeine, one type of drug, often used in people who
suffer from pathological cough and patients who require the
maintenance of ventilation through an endotracheal tube. However,
cough suppression can also lead to accumulation of secretions
which will menhambat airway and atelectasis.
Miosis a pharmacological action that have little or no tolerance at
all. Therefore, it is important in the diagnosis of overdose
opioids.Pupil constriction will usually appear in patients who
addict.
It is believed to be due to the activity of this drug in the spinal
cord. It also can cause the piston so that the ventilation was also
disrupted.
Analgesic opioids can activate the chemoreceptor trigger zone in
the brain stem that trigger vomiting and nausea.

b. Morphine
Morphine is produced from opium or opiate raw and an opium
alkaloids contained in the form of a white powder. Morphine
consumption is usually done by inhaled or injected. Because
morphine is classified as a depressant type, then it works by
pressing the central nervous system, cause a decline in the activity
of neurons, dizziness, feelings and consciousness change
periodically. Continuous morphine consumption has led to a high
risk of death.
Physical characteristics withdrawal symptoms caused by morphine:
Colds, runny nose sneeze
Body temperature increased sharply
Nausea
Vomiting
Diarrhea
Insomnia
If not given morphine would cause physical pain including muscle
pain and stiffness in the back, legs, until the entire body is
accompanied by anxiety, convulsions small, and weak. Symptoms
can be found within 6-8 hours, with peak symptoms will occur on
day 2 or day 3. The duration of the physical pain will be a state of
withdrawal usually lasts between 7-10 days.
c. Oxycodone
Oxycodone is an opioid analgesic medication synthesized from opium-
derived thebaine. Oxycodone oral medications are generally prescribed to
relieve moderate to severe pain. Currently formulated as single ingredient
products or product added. Some common examples of compounding are
oxycodone with acetaminophen / paracetamol or NSAIDs such as ibuprofen.
These formulations are available as generics but are also made under various
brand names.
Oxycodone can be taken orally in tablet form, the drug is a drug of choice
for pain morphine substitute medium to severe. Oxycodone is generally used
for pain caused by joint dislocations or fractures, as well as effective in
treating pain after surgery and childbirth. Oxycodone addiction effects
smaller than morphine and heroin (24)

d. Meperidine
Meperidine / Demerol is a pain reliever compound level below the narcotic
morphine and includes supervised use. Such as morphine, meperidine works
by occupying the 'post office' where the information about the arrival of pain,
either from inside or outside the body, to be delivered to the brain. With the
occupation, the recipient is no longer in pain medicine because there is no
more information is conveyed to the brain. These drugs are generally used in
the form of injection to overcome severe pain, such as pain during childbirth.
Provision should be accompanied meperidine careful attention to the patient,
because these drugs, even in therapeutic doses, can lead to inhibition of the
respiratory system and the cessation of heartbeat. Meperidine is not
recommended for use in the long term and in large doses as a result of
metabolism in the liver, normeperidin, can accumulate in the body and cause
tremors, twitching, and even seizures. These side effects are also caused
meperidine rarely used as the drug of choice among opioid painkillers other
groups.
e. Fentanyl
Fentanyl is a drug which is a narcotic pain reliever. Fentanyl buccal tablets
are used to treat cancer pain that can not be controlled by other drugs. This
drug does not treat the pain not caused by cancer, as usual headaches or back
pain. Fantanyl buccal also be used for other needs that are not listed here.
Fentanyl Side Effects
Itching with red spots
Difficulty breathing
Swelling of the face, lips, tongue or throat
Discontinue use if there fentanyl following serious side effects:
Weak, shallow breathing
severe fatigue, drowsiness
Skin moist, cold
Head feels light or faint
Other side effects:
Nausea, vomiting, abdominal pain, constipation
Dizziness, drowsiness, headache
Swelling
Pain or inflammation of the mouth where the tablets are given
Fentanyl buccal tablets are used to treat cancer pain that can not be
controlled by other drugs. This drug does not treat the pain not caused by
cancer, as usual headaches or back pain.
Fentanyl is not good to use for people who are using MAO inhibitor such
as isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect),
selegiline (Eldepryl, Emsam), or tranylcypromine (Parnate) within 14 days.
Fentanyl is the generic name of Fentanyl (buccal) and brand names are
Fentora, Onsolis.
Common Side Effects
Morphine and other opioida cause a large amount of unwanted ES,
namely:
suppression of CNS: eg sedation, respiratory and suppress coughs,
miosis, hipothermia, and swings the soul (mood). As a result of direct
stimulation of the CTZ (Chemo Trigger Zone), nausea and vomiting arise. At
higher doses result in decreased mental activity
-gastrointestinal tract: reduced motility (obstipation), contraction of
sphincter gallbladder (stone-biliary colic).
channel-Urogenital: urinary retention, decreased uterine motility
(extended delivery time).
airways: bronchoconstriction
circulatory system: vasodilatation, hypertension, bradycardia
custom: the risk of addiction
Habits and Addiction
Physical dependence is for long-term use in most consumer habits and
cause dependence. The cause may be due to reduced resorption opioids or
overhaul / elimination is accelerated, or due to decreased tissue sensitivity.
The drug becomes less effective, requiring higher doses to achieve the
original effect. This is called tolerance.
Psychological dependence that is going to effect the mental needs
psikotrop (euphoria, a sense of comfort and fresh) can be an advanced very
strong, to the patient as if forced to continue using the drug.
Abstinence symptoms always occur when drug use is stopped (abruptly)
and the original can be evaporated, great sweat and tears, restless sleep, and
feeling cold. Then arises vomit-munath, diarrhea, tachycardia, mydriasis,
tremors, muscle spasms, blood pressure rises, which can be accompanied by
severe psychological reactions (anxiety, irritability, worries die).
These effects cause why people with difficult patients who are already
addicted to halt all use opiad. In order to avoid the bad effects of this, they are
"forced" to continue its use.
There are strong indications that the occurrence of tolerance and
dependence is closely related to the activation of the dopaminergic system in
the brain. All of addiction to substances that are efficacious in acute increases
the amount of dopamine, which is associated with eufori effects, emotional
lability, confusion and hysteria, for example, the abuse of morphine. trigger
the release of dopamine, while cocaine blocks the reuptake of more than ten
other neurotransmitters noradrenaline and serotonin whom also play a role in
addiction but the effect is much lighter. Dopamine levels that are too high can
cause hallucinations and psychosis akut.dimana hallucination is a sensory
experience (sensory perception) in the absence of sensory stimulation
(sensory stimulation)., And in the case of abuse of opioid analgesics
(morphine which most often is) used to receive the body of a peptide
exogenous (morphine) without a clinical indication that the body responds by
not generating an endogenous peptides (eg, endorphins) that will be
discontinued if the use of morphine endogenous peptides would not be
formed, because accustomed supplied from outside the body, so it can happen
dependence.
Opioid addiction treatment is primarily aimed at two aspects, namely the
cessation of use (withdrawal) and social rehabilitation of the patient. In the
treatment of a number of factors must be considered:
o The level of physical dependence of patients
o Patients should be given another drug (eg methadone) to suppress
abstinence symptoms seriously while gradually reducing the dose
(substitution therapy)
In farmakotepeutis, a type of treatment that is more specific to eliminate
the addiction to opiate analgesics based on the theory that when the receptor
is inhibited by the opioid antagonist substances, the use of opiates will not
cause a physical dependence. In this case, a specific opiate antagonist
naloxone has been clinically tested but the results are much less satisfactory
than metadon.naltrekson therapy is a pure morphine antagonist (without the
agonist) can avoid opioida effects, such as euphoria these drugs are used as
auxiliaries during the process of tackling addiction to support,, to stay clean.
"should only be used on addicts who had not used drugs for 7-10 days. when
opiates are used again within 15 minutes will appear serious acute abstinence
symptoms and can last 48 jam.daya work lasts for 24-72 jam. Naltrexone
dosage 50 mg per day or 3 times a week. Handling hooked done by the
method of "cold turkey" in which the administration of narcotic substances to
patients discontinued at once, although withdrawal symptoms arise great as
abdominal cramps, diarrhea, vomiting, muscle pain, runny nose, watery eyes,
cold sweats and chills .
Therefore, the use of these drugs should be under the supervision of
physicians and pharmacists. If not, the user will be hooked and will be
referred to as "people who abuse drugs".
TREATMENT PROGRAMME OR TREATMENT (ANTI DOTUM)
Naloxone is a drug to counteract poisoning narcotics or opiates called
antagonists. Other drugs to counter the influence of morphine or heroin is
nalorphine, levallophan, cyclazocine, but the risk is quite dangerous.
Naloxone can help quickly if it is given in the form of injections. The
provision in the form of an injection of naloxone HCl (Narcan, Nokoba)
which begins with a dose of 0.4 mg / dl, can improve the situation of
respiratory disorders. Provision should go straight into a vein or
intravenously. After the injection, note the state of breathing. If not improved,
as can be observed within 3-5 minutes plus one ampoule is repeated again
until the effect is achieved with a sustained response of consciousness, loss of
respiratory depression, and pupil dilation.
Drug abuse treatment program consists of two phases, namely:
detoxification therapy
Maintenance therapy (maintenance)
Both of the above should be continuous therapy, for detoxification therapy
alone is not a cure. After the patient passes through the critical phase, he has
to stop its reliance through therapy program above. The increasing number of
drug addicts is increasing. Medical cure for drug addicts often lead to relapse
condition, again relapses. Patients undergoing detoksifiksi possible drug
addiction in his home for 5 consecutive days. Additionally, for healing
requiring maintenance therapy (maintenance). Especially for dependency
opioida, required a special treatment program. Besides given drug therapy,
therapy should be social, occupational therapy, or religious therapy. A
holistic approach involves a team of professionals such as doctors /
psychiatrists, nurses, psychologists, religious leaders, and social workers will
provide satisfactory results. (9)












CHAPTER V
CONCLUSION
Opioid analgesics used in the treatment of pain caused by factors other
than the presence of inflammatory mediators and in very severe pain that can
not be addressed with non-opioid analgesics
Drugs that opioid analgesics are often misused heroin, Morphine,
Oxycodone, Meperidine, Fentanyl.
Agonist opioids (methadone) is the best therapy in the treatment of
opioid dependence.
There needs to be awareness of all parties to prevent abuse of opioid
medications (narcotics) can cause dependence.












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