DRUG PROFILE OF CONTROLLED

DRUGS
Clinical Pharmacy Assignment

SUBMITTED BY
Group A2
Amna Naeem 3013
Rabeea Rehman 3082
Muhammad Ehtisham Shafique 3066
Maria Nosheen Khan 3063
Jovaria Saeed 3053

Group B2
Aneequa Fiaz 3018
Aneeba Sajid 3020
Faiz Khan 3032
Fareed Khan 3036

DEPARTMENT OF PHARMACY
Quaid i Azam University, Islamabad.
CONTROLLED DRUG SUBSTANCES
INTRODUCTION:

The Controlled Substances Act (CSA) 

Title II of the Comprehensive Drug Abuse Prevention and Control Act of 1970 is the federal
U.S. drug policy under which the manufacture, importation, possession, use and distribution
of certain narcotics, stimulants, depressants, hallucinogens, anabolic steroids and other
chemicals is regulated. The CSA was signed into law by President Richard Nixon on October
27, 1970. The addition, deletion or change of schedule of a medicine or substance may be
requested by the U.S. Drug Enforcement Agency (DEA), the Department of Health and
Human Services, the U.S. Food and Drug Administration (FDA), or from any other party via
petition to the DEA.

The DEA implements the CSA and may prosecute violators of these laws at both the
domestic and international level. Within the CSA there are five schedules (I-V) that are used
to classify drugs based upon their abuse potential, medical applications, and safety.
Individuals who order, handle, store, and distribute controlled substances must be
registered with the DEA to perform these functions. They must maintain accurate
inventories, records and security of the controlled substances.

Schedule I drugs

The drug has a high potential for abuse. The drug has no currently accepted medical use in
treatment in the United States. There is a lack of accepted safety for use of the drug under
medical supervision.

Drugs / Substances listed in DEA Schedule I include:

 Heroin (diacetylmorphine)

 LSD (Lysergic acid diethylamide)

 Marijuana (cannabis, THC)

 Mescaline (Peyote)

 MDMA (3,4-methylenedioxymethamphetamine or “ecstasy”)

 GHB (gamma-hydroxybutyric acid)

 Ecstasy (MDMA or 3,4-Methylenedioxymethamphetamine)

 Psilocybin

 Methaqualone (Quaalude)

 Khat (Cathinone)

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 Bath Salts (3,4-methylenedioxypyrovalerone or MDPV)

 Pethidine

DRUG PROFILE OF PETHIDINE

Introduction
Pethidine or meperidine was once a popular synthetic opioid analgesic of the
phenylpiperidine class Synthesized in 1939 as a potential anticholinergic agent by the
German chemist Otto Eisleb, its analgesic properties were first recognized by Otto
Schaumann while working for IG Farben, Germany.Compared with morphine, pethidine was
thought to be safer, carry a lower risk of addiction, and to be superior in treating the pain
associated with biliary spasm or renal colic due to its putative anticholinergic effects. These
were later discovered to be all myths, and it carried an at least equal risk of addiction,
possessed no advantageous effects on biliary spasm or renal colic compared to other opioids,
and due to its toxic metabolite, norpethidine, was more toxic than other opioids, especially
during long-term use. The norpethidine metabolite was found to have serotonergic effects,
so pethidine could, unlike most opioids, contribute to serotonin syndrome.

Systematic (IUPAC) name

Ethyl 1-methyl-4-phenylpiperidine-4-carboxylate

Trade names

Demerol

Pregnancy Category C

Dependence Liability

High

Routes of Administration

Oral, intravenous, intramuscular, subcutaneous

Pharmacokinetic data

Bioavailability

50–60% (Oral), 80-90% (Oral, in cases of hepatic impairment)

Protein binding

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65-75%
Medical uses

Pethidine is the most widely used opioid in labour and delivery but has fallen out of favour
in some countries such as the United States in favour of other opioids, due to its potential
drug interactions (especially with serotonergics) and its neurotoxic metabolite,
norpethidine. It is still commonly used in the United Kingdom and New Zealand, and is the
preferred opioid in the United Kingdom for use during labour. Pethidine is the preferred
painkiller for diverticulitis, because it decreases intestinal intraluminal pressure.

Pharmacology

Mechanism of Action:
Narcotic agonist-analgesic of opiate receptors; inhibits ascending pain pathways, thus
altering response to pain; produces analgesia, respiratory depression, and sedation

Absorption:
Bioavailability: 50-60%; hepatic impairment, 80-90%

Onset: Rapid

Duration: PO/SC, 2-4 hr

Peak plasma time: SC, 40-60 min; IM, 30-50 min

Distribution:
Protein bound: 65-75%

Metabolism:
Metabolized in liver via hydrolysis, partial conjugation with glucuronic acid, N-
demethylation

Metabolites: Meperidinic acid, normeperidine (active)

Elimination:
Half-life: 2.5-4 hr (adults); 7-11 hr (liver disease)

Excretion: Urine (primarily)

Dosage and when to be taken:

Adult: PO- Moderate to severe acute pain -50-150 mg 4 hourly.

IV- Adjunct to anesthetic- 10-25 mg.

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IV/IM/SC- Moderate to severe acute pain- 25-100 mg 4 hourly.
IM/SC- Obstetric analgesia- 50-100 mg as soon as contractions occur at regular intervals;
repeat after 1-3 hr if needed. Max: 400 mg/24 hour.
Pre-op medication 25-100 mg 1 hour pre-op.
Post-op pain-25-100 mg 2-3 hourly if needed.

Contraindications:

 Isocarboxazid
 Linezolid
 Phenelzine
 Procarbazine
 Rasagiline
 Selegiline

Serious - Use Alternative

 Amitriptyline
 Amoxapine
 Buprenorphine
 Buprenorphine buccal
 Buspirone
 Butorphanol
 Cimetidine
 Clomipramine
 Cyclobenzaprine
 Desipramine

Significant - Monitor Closely:

 5-htp
 Albuterol
 Alfentanil
 Almotriptan
 Alprazolam
 Amisulpride
 Amitriptyline
 Amobarbital
 Amoxapine
 Amphetamine

Adverse effects:

 Agitation

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  Angina
 Bradycardia
 Cardiac arrest
 Coma
 Constipation
 Dizziness
 Dry mouth
 Dysphoria
 Euphoria
 Faintness
 Hypotension
 Mental clouding or depression
 Myocardial infarction

Cautions:

Potential for tolerance and drug dependence

Caution in acute abdominal conditions (may obscure diagnosis or clinical course of patient),
pseudomembranous colitis, toxin-mediated diarrhea

Narrow therapeutic index in certain patient populations, particularly in combination with

CNS-depressant drugs

Cardiac arrhythmias, drug abuse or dependence, emotional lability, gallbladder disease,

head injury, increased intracranial pressure, benign prostatic hyperplasia, hepatic or renal
impairment, seizures with epilepsy, urethral stricture, urinary tract surgery

Use with caution in following conditions: Sickle cell anemia; pheochromocytoma; acute
alcoholism; adrenocortical insufficiency (eg, Addison disease); CNS depression or coma;
delirium tremens; debilitated patients; kyphoscoliosis associated with respiratory
depression; myxedema or hypothyroidism; prostatic hypertrophy or urethral stricture; head
trauma; billiary tract impairment; severe impairment of hepatic, pulmonary, or renal
function; toxic psychosis

Interaction with mixed agonist/antagonist opioid analgesics (eg, pentazocine, nalbuphine,

butorphanol, buprenorphine) may precipitate withdrawal symptoms

May cause less smooth muscle spasm and constipation than equipotent doses of morphine

Chronic high-dose therapy or administration to patients with renal impairment may result in
accumulation of active metabolite normeperidine, leading

Pregnancy & Lactation:

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Pregnancy category: B; use for prolonged periods or near term not established

Lactation: Drug excreted in breast milk

Schedule 2

The drug has a high potential for abuse. The drug has a currently accepted medical use in
treatment in the United States or a currently accepted medical use with severe restrictions.
Abuse of the drug may lead to severe psychological or physical dependence.

 Fentanyl
 Amphetamine
 Hydrocodone
 Morphine
 Cocaine
 Chlorpheniramine

DRUG PROFILE OF MORPHINE

Morphine is a pain medication of the opiate type. It acts directly on the central nervous

system (cns) to decrease the feeling of pain. It can be used for both acute pain and chronic
pain. Morphine is also frequently used for pain from myocardial infarction and
during labour.
The extended-release form of this medicine is for around-the-clock treatment of pain. This
form of morphine is not for use on an as-needed basis for pain.
Morphine is not for treating short-term pain just after surgery unless you were already
taking morphine before the surgery.

History

Morphine was first isolated between 1803 and 1805 by friedrich serturner. This is generally
believed to be the first isolation of an active ingredient from a plant. Merck began marketing
it commercially in 1827.  Morphine was more widely used after the invention of
the hypodermic syringe in 1853–1855.sertürner originally named the
substance morphium after the greek god of dreams, morpheus, for its tendency to cause
sleep.
The primary source of morphine is isolation from poppy straw of the opium poppy. In 2013
an estimated 523,000 kilograms of morphine were produced. About 45,000 kilograms were
used directly for pain, an increase over the last twenty years of four times. Most use for this
purpose was in the developed world. About 70% of morphine is used to make other opioids
such as hydromorphone, oxycodone, heroin, and methadone

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Trade name(s)

 Astramorph pf
 Avinza
 Doloral [canada]
 Duramorph pf
 Embeda
 Epimorph [canada]
 Infumorph
 Kadian
 M-eslon [canada]
 Morphine h.p [canada]
 M.o.s [canada]
 M.o.s.-s.r [canada]
 Ms contin
 Statex [canada]

Pregnancy category
Category C

Therapeutic class
Opioid analgesics
Pharmaceutical class

Opioid agonists

Controlled substance schedule: ii

Important information

You should not take morphine if you have severe asthma or breathing problems, a blockage
in your stomach or intestines, or a bowel obstruction called paralytic ileus.
Morphine can slow or stop your breathing. Never use this medicine in larger amounts, or for
longer than prescribed. Do not crush, break, or open an extended-release pill. Swallow it
whole to avoid exposure to a potentially fatal dose.
Morphine may be habit-forming, even at regular doses. Never share this medicine with
another person, especially someone with a history of drug abuse or addiction. Keep the
medication in a place where others cannot get to it.
Misuse of narcotic medicine can cause addiction, overdose, or death, especially in a child or
other person using the medicine without a prescription.

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Tell your doctor if you are pregnant. Morphine may cause life-threatening withdrawal
symptoms in a newborn.
Do not drink alcohol. Dangerous side effects or death can occur when alcohol is combined
with morphine.

Indications

Severe pain (the 20 mg/ml oral solution concentration should only be used in opioid-
tolerant patients).
Management of moderate to severe chronic pain in patients requiring use of a continuous
around-the-clock opioid analgesic for an extended period of time (extended/sustained-
release).
Pulmonary edema.
Pain associated with mi.

Contraindications

You should not take this medicine if you have ever had an allergic reaction to morphine or
other narcotic medicines, or if you have:

 Severe asthma or breathing problems;

 A blockage in your stomach or intestines; or
 A bowel obstruction called paralytic ileus.
Do not use morphine if you have used an mao inhibitor in the past 14 days. A dangerous
drug interaction could occur. Mao inhibitors include isocarboxazid, linezolid, methylene blue
injection, phenelzine, rasagiline, selegiline, tranylcypromine, and others.
You may not be able to take morphine if you are not already being treated with a similar
opioid (narcotic) pain medicine and are tolerant to it. Talk with your doctor if you are not
sure you are opioid-tolerant.
To make sure morphine is safe for you, tell your doctor if you have:

 Any type of breathing problem or lung disease;

 A history of head injury, brain tumor, or seizures;
 A history of drug abuse, alcohol addiction, or mental illness;
 Urination problems;
 Liver or kidney disease; or
 Problems with your gallbladder, pancreas, or thyroid.
It is not known whether this medicine will harm an unborn baby. If you use morphine while
you are pregnant, your baby could become dependent on the drug. This can cause life-
threatening withdrawal symptoms in the baby after it is born. Babies born dependent on

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habit-forming medicine may need medical treatment for several weeks. Tell your doctor if
you are pregnant or plan to become pregnant.

Side effects

1. Get emergency medical help if you have signs of an allergic reaction to morphine:
hives; difficult breathing; swelling of your face, lips, tongue, or throat.
2. Call your doctor at once if you have:
3. Slow heart rate, sighing, weak or shallow breathing
4. Chest pain, fast or pounding heartbeats
5. Extreme drowsiness, feeling like you might pass out.
6. Morphine is more likely to cause breathing problems in older adults and people who
are severely ill, malnourished, or otherwise debilitated.
7. Common morphine side effects may include: drowsiness, dizziness, constipation,
stomach pain, nausea, vomiting, headache, tired feeling, anxiety, or mild itching.

Adverse reactions

1. CNS: confusion, sedation, dizziness, dysphoria, euphoria, floating feeling,

hallucinations, headache, unusual dreams
2. ENT: blurred vision, diplopia, miosis
3. Resp: respiratory depression
4. CVS: hypotension, bradycardia
5. GI: constipation, nausea, vomiting
6. GU: urinary retention
7. Derm: flushing, itching, sweating
8. Misc: physical dependence, psychological dependence, tolerance.

Drug abuse and dependence

Some patients may develop a physical and psychological dependence on morphine. They
may increase dosage without consulting a physician and subsequently may develop a
physical dependence on the drug. In such cases, abrupt discontinuance may precipitate
typical withdrawal symptoms, including convulsions. Therefore the drug should be
withdrawn gradually from any patient known to be taking excessive dosages over a long
period of time.
In treating the terminally ill patient the benefit of pain relief may outweigh the possibility of
drug dependence. The chance of drug dependence is substantially reduced when the
patient is placed on scheduled narcotic programs instead of a “pain to relief-of-pain” cycle
typical of a prn regimen.

Interactions

 Generally, effects of morphine may be potentiated by alkalizing agents and

antagonized by acidifying agents.

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  Analgesic effect of morphine is potentiated by chlorpromazine and methocarbamol.
CNS depressants such as anaesthetics, hypnotics, barbiturates,
phenothiazines, chloral hydrate, glutethimide, sedatives, MAO inhibitors (including
procarbazine hydro-chloride), antihistamines, β-blockers (propranolol), alcohol,
furazolidone and other narcotics may enhance the depressant effects of morphine.
 Morphine may increase anticoagulant< activity of coumarin and other
anticoagulants.
 Taking this medicine with other drugs that make you sleepy or slow your breathing
can cause dangerous or life-threatening side effects. Ask your doctor before taking
morphine with a sleeping pill, other narcotic pain medicine, muscle relaxer, or
medicine for anxiety, depression, or seizures.
 Other drugs may interact with morphine, including prescription and over-the-
counter medicines, vitamins, and herbal products. Tell each of your health care
providers about all medicines you use now and any medicine you start or stop using.

Administration

Route Types of opioids and doses OME (mg)

Oral Morphine 1 mg 1

Parenteral Morphine 1 mg 3

Transdermal Fentanyl 12 mcg 30

Parenteral Fentanyl 12 mcg 30

Oral Tramadol 5 mg 1

Oral Oxycodone 1 mg 2

Narcotic doses

Drug Therapeutic dose Tolerant dose Lethal dose

Morphine 15-30 mg 100 mg 500mg
Heroin 10-15 mg 60 mg 200mg
Fentanyl 25 mcg 2 mg
Oxycontin 10 mg 40mg 160 mg

Precautions

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 1. Take morphine exactly as prescribed by your doctor. Follow all directions on your
prescription label. Morphine can slow or stop your breathing, especially when you
start using this medicine or whenever you dose is changed. Never take morphine in
larger amounts, or for longer than prescribed. Tell your doctor if the medicine seems
to stop working as well in relieving your pain.
2. Morphine may be habit-forming, even at regular doses. Never share this medicine
with another person, especially someone with a history of drug abuse or
addiction. Misuse of narcotic medicine can cause addiction, overdose, or death,
especially in a child or other person using the medicine without a prescription.
Selling or giving away morphine to any other person is against the law.
3. Always check your bottle to make sure you have received the correct pills (same
brand and type) of medicine prescribed by your doctor. Ask the pharmacist if you
have any questions about the medicine you receive at the pharmacy.
4. Stop taking all other around-the-clock narcotic pain medications when you start
taking morphine.
5. Do not crush, chew, or break an extended-release tablet. Swallow it whole to avoid
exposure to a potentially fatal dose.
6. To make swallowing easier, you may open the avinza or kadian capsule and sprinkle
the medicine into a spoonful of applesauce. Swallow right away without chewing. Do
not save the mixture for later use.
7. Measure liquid medicine with a special dose-measuring spoon or medicine cup, not
with a regular table spoon. If you do not have a dose-measuring device, ask your
pharmacist for one.
8. Take the medicine at the same time each day.
9. Do not stop using morphine suddenly, or you could have unpleasant withdrawal
symptoms. Ask your doctor how to safely stop using this medicine.
10. Never crush or break a morphine pill to inhale the powder or mix it into a liquid to
inject the drug into your vein. This practice has resulted in death with the misuse of
morphine and similar prescription drugs.
11. Store at room temperature, away from heat, moisture, and light.
12. Keep track of the amount of medicine used from each new bottle. Morphine is a
drug of abuse and you should be aware if anyone is using your medicine improperly
or without a prescription.
13. Do not keep leftover morphine pills or liquid. Ask your pharmacist where to locate a
drug take-back disposal program. If there is no take-back program, flush any unused
pills or liquid down the toilet. Disposal of medicines by flushing is recommended to
reduce the danger of accidental overdose causing death. This advice applies to a very
small number of medicines only. The FDA, working with the manufacturer, has
determined this method to be the most appropriate route of disposal and presents
the least risk to human safety.

Schedule 3

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The drug has a potential for abuse less than the drugs in schedules 1 and 2. The drug has a
currently accepted medical use in treatment in the United States. Abuse of the drug may
lead to moderate or low physical dependence or high psychological dependence.

 Testosterone
 Oxymetholone
 Buprenorphine
 Dronabinol
 Thiopental

DRUG PROFILE OF THIOPENTAL

Generic Name: thiopental (thye-oh-PEN-tol)

Brand Name: Pentothal

Sodium thiopental, also known as Sodium Pentothal (a trademark of Abbott Laboratories,

not to be confused with pentobarbital), thiopental, thiopentone, or Trapanal (also a
trademark), is a rapid-onset short-acting barbiturate general anesthetic that is an analogue
of thiobarbital. Sodium thiopental is a core medicine in the World Health Organization's
"Essential Drugs List", which is a list of minimum medical needs for a basic healthcare
system. It was previously the first of three drugs administered during most lethal injections
in the United States, but the U.S. manufacturer Hospira stopped manufacturing the drug
and the EU banned the export of the drug for this purpose.

Mechanism of action

Sodium thiopental is a member of the barbiturate class of drugs, which are relatively non-
selective compounds that bind to an entire superfamily of ligand-gated ion channels, of
which the GABAA receptor channel is one of several representatives. This superfamily of ion
channels includes the neuronal nAChR channel, the 5HT3R channel, the GlyR channel and
others. Surprisingly, while GABAA receptor currents are increased by barbiturates (and other
general anesthetics), ligand-gated ion channels that are predominantly permeable for
cationic ions are blocked by these compounds. For example, neuronal nAChR channels are
blocked by clinically relevant anesthetic concentrations of both sodium thiopental and
pentobarbital.Such findings implicate (non-GABA-ergic) ligand-gated ion channels, e.g. the
neuronal nAChR channel, in mediating some of the (side) effects of barbiturates. The GABA A
receptor is an inhibitory channel that decreases neuronal activity, and barbiturates enhance
the inhibitory action of the GABAA receptor.

Dosage

The usual dose range for induction of anesthesia using thiopental is from 3 to 7 mg/kg;
however, there are many factors that can alter this. Premedication with sedatives such as
benzodiazepines or clonidine will reduce requirements, as do specific disease states and

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other patient factors. Among patient factors are: age, sex, and lean body mass. Specific
disease conditions that can alter the dose requirements of thiopentone and for that matter
any other intravenous anaesthetic are: hypovolemia, burns, azotemia, hepatic failure,
hypoproteinemia, etc.

Thiopental is used for:

Causing drowsiness or sleep before surgery or certain medical procedures. It is also used to
stop seizures. It may also be used for other conditions as determined by your doctor.

Thiopental is a barbiturate. It works by depressing the central nervous system, causing mild
sedation or sleep, depending on the dose.

Contraindications

Thiopental should be used with caution in cases of liver disease, Addison's disease,
myxedema, severe heart disease, severe hypotension, a severe breathing disorder, or a
family history of porphyria.

Co-administration of pentoxifylline and thiopental causes death by acute pulmonary edema

in rats. This pulmonary edema was not mediated by cardiac failure or by pulmonary
hypertension but was due to increased pulmonary vascular permeability.

Before using thiopental:

Some medical conditions may interact with thiopental. Tell your doctor or pharmacist if you
have any medical conditions, especially if any of the following apply to you:

 if you are pregnant, planning to become pregnant, or are breast-feeding

 if you are taking any prescription or nonprescription medicine, herbal preparation, or
dietary supplement
 if you have allergies to medicines, foods, or other substances
 if you have kidney or liver problems, lung or respiratory tract disease, heart
problems, low blood pressure, adrenal gland problems (eg, Addison disease),
asthma, myasthenia gravis, thyroid problems, or increased pressure in the brain
 if you have a history of substance abuse or dependence, depression, or suicidal
thoughts or behavior

Some MEDICINES MAY INTERACT with thiopental. Tell your health care provider if you are
taking any other medicines, especially any of the following:

 Monoamine oxidase (MAO) inhibitors (eg, phenelzine), probenecid, or sodium

oxybate (GHB) because side effects may be increased
 Aminophylline, beta-blockers (eg, atenolol), clozapine, corticosteroids (eg,
prednisone), doxycycline, estrogens (eg, micronized estradiol), griseofulvin,
metronidazole, narcotic pain medicine (eg, codeine), oral contraceptives (birth

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 control pills), phenytoin, quinidine, theophylline, valproic acid, or zimelidine because
their effectiveness may be reduced by thiopental

This may not be a complete list of all interactions that may occur. Ask your health care
provider if thiopental may interact with other medicines that you take. Check with your
health care provider before you start, stop, or change the dose of any medicine.

Usual Adult Dose for Anesthesia

When used for induction in balanced anesthesia with a skeletal muscle relaxant and an
inhalation agent:
The total dose can be estimated and then injected in two to four fractional doses. With this
technique, brief periods of apnea may occur which may require assisted or controlled
pulmonary ventilation. As an initial dose, 210 to 280 mg (3 to 4 mg/kg) is usually required
for rapid induction in the average adult (70 kg).

When used as the sole anesthetic agent:

Moderately slow induction can usually be accomplished in the "average" adult by injection
of 50 to 75 mg (2 to 3 mL of a 2.5% solution) at intervals of 20 to 40 seconds, depending on
the reaction of the patient. Once anesthesia is established, additional injections of 25 to 50
mg can be given whenever the patient moves. The desired level of anesthesia can be
maintained by injection of small repeated doses as needed or by using a continuous
intravenous drip in a 0.2% or 0.4% concentration. With continuous drip, the depth of
anesthesia is controlled by adjusting the rate of infusion.

Usual Adult Dose for Seizures

For the control of convulsive states following anesthesia (inhalation or local) or other
causes, 75 to 125 mg (3 to 5 mL of a 2.5% solution) should be given as soon as possible after
the convulsion begins. Convulsions following the use of a local anesthetic may require 125
to 250 mg given over a ten minute period.

Usual Adult Dose for Coma Induction

In neurosurgical patients, intermittent bolus injections of 1.5 to 3.5 mg/kg of body weight
may be given to reduce intraoperative elevations of intracranial pressure, if adequate
ventilation is provided.

Usual Adult Dose for Psychosis

For narcoanalysis and narcosynthesis in psychiatric disorders, premedication with an

anticholinergic agent may precede administration of thiopental. After a test dose, thiopental
is injected at a slow rate of 100 mg/min (4 mL/min of a 2.5% solution) with the patient
counting backwards from 100. Shortly after counting becomes confused but before actual
sleep is produced, the injection is discontinued. Allow the patient to return to a semidrowsy
state where conversation is coherent. Alternatively, thiopental may be administered by

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rapid IV drip using a 0.2% concentration in 5% dextrose and water. At this concentration,
the rate of administration should not exceed 50 mL/min.

Usual Pediatric Dose for Anesthesia

Induction anesthesia:
less than 1 month: 3 to 4 mg/kg intravenously
less than 1 year: 5 to 8 mg/kg intravenously
1 year to 12 years: 5 to 6 mg/kg intravenously
over 12 years: 3 to 5 mg/kg intravenously

Maintenance anesthesia:
1 year and older: 1 mg/kg intravenously as needed

Usual Pediatric Dose for Seizures

1 year or older: 2 to 3 mg/kg/dose intravenously, repeat as needed.

Usual Pediatric Dose for Head Injury

1 year or older: 1.5 to 5 mg/kg/dose intravenously; repeat as needed to control intracranial

pressure - larger doses (30 mg/kg) to induce coma after hypoxic-ischemic injury do not
appear to improve neurologic outcome.

Side effects

As with nearly all anesthetic drugs, thiopental causes cardiovascular and respiratory
depression resulting in hypotension, apnea and airway obstruction. For these reasons, only
suitably trained medical personnel should give thiopental in an environment suitably
equipped to deal with these effects. Side effects include headache, agitated emergence,
prolonged somnolence, and nausea. Intravenous administration of sodium thiopental is
followed instantly by an odor and/or taste sensation, sometimes described as being similar
to rotting onions, or to garlic. The hangover from the side effects may last up to 36 hours.

Although individual molecules of thiopental contain one sulfur atom, it is not a sulfonamide,
and does not show allergic reactions of sulfa/sulpha drugs.

 Respiratory

 Respiratory side effects have included respiratory depression, sneezing, coughing,

bronchospasm, and laryngospasm.

 Nervous system

 Nervous system side effects have included prolonged somnolence and recovery.
Radial nerve palsy has been reported rarely

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  Hypersensitivity

 Hypersensitivity side effects have included anaphylactic and anaphylactoid reactions,

e.g., urticaria, bronchospasm, vasodilation and edema

 General

 General side effects have included shivering.

Schedule 4

The drug has a low potential for abuse relative to the drugs in schedule 3 The drug has a
currently accepted medical use in treatment in the United States. Abuse of the drug may
lead to limited physical dependence or psychological dependence relative to the drugs in
schedule 3. These include

 Zolpidem
 Lorezepam
 Tramadol
 Flurezepam
 Diazepam
 Clonazepam
 Alprazolam
 Oxazepam
DRUG PROFILE OF LORAZEPAM

Lorazepam, sold under the brand name Ativan among others, is a benzodiazepine
medication often used to treat anxiety disorders. Lorazepam reduces anxiety, interferes
with new memory formation, reduces agitation, induces sleep, treats seizures, treats nausea
and vomiting, and relaxes muscles. Lorazepam is used for the short-term treatment of
anxiety, insomnia, acute seizures including status epilepticus, and sedation of hospitalized
patients, as well as sedation of aggressive patients. Due to tolerance and dependence,
lorazepam is recommended for short-term use, up to two to four weeks only.

Among benzodiazepines, lorazepam has possible physical addiction potential. Lorazepam

also has misuse potential; the main types of misuse are for recreational purposes. Long-
term effects of benzodiazepines include tolerance, dependence, benzodiazepine withdrawal
syndrome, and cognitive impairments which may not completely reverse after stopping
treatment. In most people cognitive impairment is not severe. Withdrawal symptoms can
range from anxiety and insomnia to seizures and psychosis. Adverse effects, including
inability to form new memories, depression, and paradoxical effects, such as excitement or
worsening of seizures, may occur. Children and the elderly are more sensitive to the adverse

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effects of benzodiazepines. Lorazepam impairs body balance and standing steadiness and is
associated with falls and hip fractures in the elderly.

Lorazepam was initially patented in 1963 and went on sale in the United States in 1977. It is
on the World Health Organization's List of Essential Medicines, the most important
medications needed in a basic health system.

TRADE NAMES Ativan and others

DEPENDENCE LIABILITY Moderate–high
ROUTES OF Oral, intramuscular, intravenous, sublingual, and transdermal
ADMINISTRATION
PHARMACOKINETIC DATA
BIOAVAILABILITY 85% of oral dose
METABOLISM Liver glucuronidation
BIOLOGICAL HALF LIFE 10–20 hour
EXCRETION Kidney
CHEMICAL DATA
FORMULA C15H10Cl2N2O2
MOLECULAR MASS 321.2 g/mol

Pharmacology

Lorazepam has anxiolytic, sedative, hypnotic, amnesic, anticonvulsant, and muscle relaxant
properties. It is a high-potency and an intermediate-acting benzodiazepine, and its
uniqueness advantages, and disadvantages are largely explained by its pharmacokinetic
properties (poor water and lipid solubility, high protein binding and anoxidative metabolism
to a pharmacologically inactive glucuronide form) and by its high relative potency
(lorazepam 1–2 mg is equal in effect to diazepam 10 to 20 mg). The biological half-life of
lorazepam is 10–20 hours.

Pharmacokinetics

Lorazepam is highly protein bound and is extensively metabolised into pharmacologically

inactive metabolites. Due to its poor lipid solubility, lorazepam is absorbed relatively slowly
by mouth and is unsuitable for rectal administration. However, its poor lipid solubility and
high degree of protein binding (85-90%) mean its volume of distribution is mainly the
vascular compartment, causing relatively prolonged peak effects. This contrasts with the
highly lipid-soluble diazepam, which, although rapidly absorbed orally or rectally, soon
redistributes from the serum to other parts of the body, in particular body fat. This explains
why one lorazepam dose, despite its shorter serum half-life, has more prolonged peak
effects than an equivalent diazepam dose. Lorazepam is rapidly conjugated at its 3-hydroxy
group into lorazepam glucuronide which is then excreted in the urine. Lorazepam
glucuronide has no demonstrable CNS activity in animals. The plasma levels of lorazepam
are proportional to the dose given. There is no evidence of accumulation of lorazepam on

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administration up to six months. On regular administration, diazepam will accumulate, since
it has a longer half-life and active metabolites, these metabolites also have long half-lives.

Pharmacodynamics

Relative to other benzodiazepines, lorazepam is thought to have high affinity for GABA
receptors, which may also explain its marked amnesic effects. Its main pharmacological
effects are the enhancement of the effects of GABA at the GABAA receptor.
Benzodiazepines, such as lorazepam, enhance the effects of GABA at the GABA A receptor via
increasing the frequency of opening of the chloride ion channel on the GABA A receptors;
which results in the therapeutic actions of benzodiazepines. They, however, do not on their
own enhance the GABAA receptors, but require the neurotransmitter GABA to be present.
Thus, the effect of benzodiazepines is to enhance the effects of the neurotransmitter GABA.

The magnitude and duration of lorazepam effects are dose-related, meaning larger doses
have stronger and longer-lasting effects, because the brain has spare benzodiazepine drug
receptor capacity, with single, clinical doses leading only to an occupancy of some 3% of the
available receptors.

The anticonvulsant properties of lorazepam and other benzodiazepines may be, in part or
entirely, due to binding to voltage-dependent sodium channels rather than benzodiazepine
receptors. Sustained repetitive firing seems to get limited, by the benzodiazepine effect of
slowing recovery of sodium channels from inactivation in mouse spinal cord cell cultures.

Recreational use

Lorazepam is also used for other purposes, such as recreational use, wherein the drug is
taken to achieve a high, or when the drug is continued long-term against medical advice.

In addition to recreational use, benzodiazepines may be diverted and used to facilitate

crime: Criminals may take them to deliberately seek disinhibition before committing crimes
(which increases their potential for violence). The anterograde amnesia and sedative-
hypnotic effects of benzodiazepines such as lorazepam are sometimes used by predators on
unwitting victims as date rape drugs, or for the purpose of robbery.

Contraindications

Before taking lorazepam, tell your doctor if you are allergic to any drugs, or if you have:

 Glaucoma;
 Asthma, emphysema, bronchitis, chronic obstructive pulmonary disorder (copd), or
other breathing problems;
 Kidney or liver disease;
 A history of depression or suicidal thoughts or behavior; or
 A history of drug or alcohol addiction.

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Usual Adult Dose for Anxiety

Tablets:
Initial dose: 1 mg orally 2 to 3 times a day.
Maintenance dose: 1 to 2 mg orally 2 to 3 times a day
Parenteral:
IV: 2 mg total, or 0.044 mg/kg, whichever is smaller

Usual Adult Dose for Light Anesthesia

IM: 0.05 mg/kg up to a maximum of 4 mg

IV: 2 mg total, or 0.044 mg/kg, whichever is smaller

Usual Adult Dose for Status Epilepticus

4 mg/dose slow IV (2 mg/minute); may repeat in 10 to 15 minutes

Maximum dose: 8 mg

Usual Adult Dose for Insomnia

2 to 4 mg orally administered at bedtime

Usual Geriatric Dose for Anxiety

Elderly or debilitated patients:

1 to 2 mg orally per day in divided doses

Usual Pediatric Dose for Anxiety

12 years or older:
Initial dose: 1 mg orally 2 to 3 times a day.
Maintenance dose: 1 to 2 mg orally 2 to 3 times a day

Usual Pediatric Dose for Insomnia

12 years or older:
2 to 4 mg orally administered at bedtime

Common medications checked in combination with lorazepam

 Abilify (aripiprazole)
 Advair Diskus (fluticasone / salmeterol)
 Ambien (zolpidem)
 Aspirin Low Strength (aspirin)
 Crestor (rosuvastatin)

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  Cymbalta (duloxetine)
 Fish Oil (omega-3 polyunsaturated fatty acids)
 Lexapro (escitalopram)
 Lipitor (atorvastatin)
 Lyrica (pregabalin)
 Nexium (esomeprazole)
 Norco (acetaminophen / hydrocodone)
 Plavix (clopidogrel)
 Seroquel (quetiapine)
 Synthroid (levothyroxine)
 Tylenol (acetaminophen)
 Vitamin B12 (cyanocobalamin)
 Vitamin C (ascorbic acid)
 Vitamin D3 (cholecalciferol)
 Zoloft (sertraline)

Drug Interaction Classification

The classifications below are a general guideline only. It is difficult to determine the
relevance of a particular drug interaction to any individual given the large number of
variables.

Major Highly clinically significant. Avoid combinations; the risk of the interaction
outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only
under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an
alternative drug, take steps to circumvent the interaction risk and/or institute
a monitoring plan.

Side effects

 Anxiety
 Cervical Dystonia
 Dysautonomia
 ICU Agitation
 Insomnia
 Light Anesthesia
 Nausea/Vomiting
 Nausea/Vomiting, Chemotherapy Induced
 Panic Disorder
 Sedation
 Status Epilepticus

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