Pseudoephedrine

1. Pseudoephedrine
Misuse and
Regulation
Vince Buttrick, Jinender Kumar, Sami Musleh, Angela
Nikolakis, Ahmad Sayed, Shawn Smith

5. These people are addicted to
Methamphetamine- also known as
Crank, speed, crystal meth, ice
Methamphetamine is illicitly
manufactured from pseudoephedrine,
the active ingredient in many over-
the-counter cold medications

6. ChemistryChemistry
Pseudoephedrine Pseudoephedrine
-a phenethylamine -a phenethylamine

7. ChemistryChemistry
–Pseudoephedrine is a diastereomer of ephedrinePseudoephedrine is a diastereomer of ephedrine
–Diastereomers: stereoisomers that are not Diastereomers: stereoisomers that are not
enantiomers; not mirror imagesenantiomers; not mirror images
Ephedrine:Ephedrine: Pseudoephedrine:Pseudoephedrine:

8. Chemistry Chemistry
As a sympathomimetic amine, pseudoephedrine As a sympathomimetic amine, pseudoephedrine
relies on its indirect stimulation of the adrenergic relies on its indirect stimulation of the adrenergic
receptor system to produce its effectsreceptor system to produce its effects
The principal mechanism by which The principal mechanism by which
pseudoephedrine achieves its effects is by pseudoephedrine achieves its effects is by
displacing noradrenaline (norepinephrine) from displacing noradrenaline (norepinephrine) from
storage vesicles in presynaptic neuronsstorage vesicles in presynaptic neurons

9. ChemistryChemistry
Once the norepinephrine is displaced from storage vesicles, it Once the norepinephrine is displaced from storage vesicles, it
is released into the neuronal synapseis released into the neuronal synapse
At the neuronal synapse, the norepninephrine becomes At the neuronal synapse, the norepninephrine becomes
available to activate the alpha and beta postsynaptic available to activate the alpha and beta postsynaptic
adrenergic receptorsadrenergic receptors

10. ChemistryChemistry
The alpha and beta receptors are located on the muscles The alpha and beta receptors are located on the muscles
lining the walls of blood vesselslining the walls of blood vessels
Activation of the receptors by pseudoephedrine causes muscle Activation of the receptors by pseudoephedrine causes muscle
contraction, resulting in vasoconstriction of the blood vesselscontraction, resulting in vasoconstriction of the blood vessels

11. ChemistryChemistry
By constricting the blood vessels, less fluid is By constricting the blood vessels, less fluid is
capable of leaving the blood vessels and entering capable of leaving the blood vessels and entering
the nose, throat, and sinus liningsthe nose, throat, and sinus linings

12. ChemistryChemistry
The end result of pseudoephedrine results The end result of pseudoephedrine results
in decreased inflammation of nasal in decreased inflammation of nasal
membranes, as well as decreased mucous membranes, as well as decreased mucous
productionproduction

13. Chemistry
Methamphetamine Pseudoephedrine

14. Chemistry
Methamphetamine is a central nervous system
stimulant
–Meth Mechanism of Action

15. Indications:Indications:
For treatment of Nasal, Sinus and For treatment of Nasal, Sinus and
eustachian tube congestion.eustachian tube congestion.
For treatment of vasomotor Rhinitis.For treatment of vasomotor Rhinitis.
As an adjunct to other agents in optimum As an adjunct to other agents in optimum
treatment of allergic rhinitis, sinusitis,otitis treatment of allergic rhinitis, sinusitis,otitis
media and tracheobronchitis.media and tracheobronchitis.
Could also be used as first line therapy for Could also be used as first line therapy for
priapism.priapism.
Used as off label indication for urinary Used as off label indication for urinary
incontinence.incontinence.

16. Adverse effectAdverse effect
Common adverse effects include CNS Common adverse effects include CNS
stimulation, sleeplessness, nervousness, stimulation, sleeplessness, nervousness,
excitability, dizziness, anxiety.excitability, dizziness, anxiety.
Infrequent adverse effect include Infrequent adverse effect include
tachycardia and/or palpitation.tachycardia and/or palpitation.
Rare adverse effect could be hallucination, Rare adverse effect could be hallucination,
arrhythmia, seizure, ischemic colitis, arrhythmia, seizure, ischemic colitis,
recurrent pseudo scar Latina, systemic recurrent pseudo scar Latina, systemic
contract dermatitis, stroke.contract dermatitis, stroke.

17. PrecautionsPrecautions
Should be used with caution in patients with Should be used with caution in patients with
diabetes mellitus, cardiovascular disease, diabetes mellitus, cardiovascular disease,
hypertension, Prostatic hypertrophy, hypertension, Prostatic hypertrophy,
hyperthyroidism, closed angle glaucoma hyperthyroidism, closed angle glaucoma
and/or pregnancy.and/or pregnancy.
When used for nasal congestion, try When used for nasal congestion, try
appropriate alternative like topical appropriate alternative like topical
decongestant, saline spray/instillations decongestant, saline spray/instillations
depending on patient condition.depending on patient condition.

18. ContraindicationContraindication
Concomitant or recent (previous 14 Concomitant or recent (previous 14
days) use of monoamine oxidase days) use of monoamine oxidase
inhibitor.inhibitor.
Severe/uncontrolled hypertension, and Severe/uncontrolled hypertension, and
/or severe coronary artery disease./or severe coronary artery disease.
People with bipolar disorder as it can People with bipolar disorder as it can
cause insomnia and thus can trigger a cause insomnia and thus can trigger a
manic episode.manic episode.

19. ManufactureManufacture
 pseudoephedrine occurs naturally as an pseudoephedrine occurs naturally as an
alkaloid in certain plant species for example, alkaloid in certain plant species for example,
as a constituent of extracts from the as a constituent of extracts from the
ephedra species, also known as Ma Huang ephedra species, also known as Ma Huang
in which it occurs together with other in which it occurs together with other
isomers of ephedrine isomers of ephedrine
Ma Huang has been used in traditional Ma Huang has been used in traditional
Chinese medicine for 5,000 years for the Chinese medicine for 5,000 years for the
treatment of asthma and hay fever, as well treatment of asthma and hay fever, as well
as for the common cold.as for the common cold.

20. ManufactureManufacture
The majority of pseudoephedrine produced for The majority of pseudoephedrine produced for
commercial use is derived from yeast fermentation commercial use is derived from yeast fermentation
of dextrose in the presence of benzaldehyde. of dextrose in the presence of benzaldehyde.
In this process, specialized strains of yeast In this process, specialized strains of yeast
typically a variety of typically a variety of Candida utilis Candida utilis oror
Saccharomyces cerevisiaeSaccharomyces cerevisiae are added to are added to
large vats containing water, dextose, and large vats containing water, dextose, and
the enzyme pyruvate decarboxylasethe enzyme pyruvate decarboxylase

21. ManufactureManufacture
After the yeast has begun fermenting the After the yeast has begun fermenting the
dextrose, the benzaldehyde is added to the dextrose, the benzaldehyde is added to the
vats. vats.
In this environment, the yeast converts the In this environment, the yeast converts the
chemical precursor ingredients to 1-chemical precursor ingredients to 1-
phenylacetylcarbinol (L-PAC)phenylacetylcarbinol (L-PAC)
In the final step of the synthesis, the L-PAC In the final step of the synthesis, the L-PAC
undergoes reductive amination to produce undergoes reductive amination to produce
pseudoephedrinepseudoephedrine

22. ManufactureManufacture
The countries which contribute to the The countries which contribute to the
bulk production of PSE include India bulk production of PSE include India
and China, due to their optimum and China, due to their optimum
economic and industrial conditions economic and industrial conditions

23. Why Pseudoephedrine is
Misused
Very similar to chemical structure of
amphetamines which is used to make
methamphetamines
Previously easy to obtain; over the
counter

24. Ways of Obtaining PSE
Smurfing: multiple purchases at one
location
Shelf-Sweeping: theft of all
medications containing
pseudoephedrine from a shelf stock
Shoplifting
Theft from wholesalers

25. Ingredients to Make
Methamphetamies

26. Ingredients to Make
Methamphetamines
Cold
Medicines/Decongestan
ts that contain PSE
Iodine
Distilled Water
Red Phosphorus
(matches and road
flares)
Ether (camping fuel,
brake cleaner, starting
fluid, paint thinner,
toluene, or acetone)
Coffee Filters
Rock Salts
Lithium (batteries)
Denatured Alcohol
(gasoline additives)
Muratic Acid
Kitty Litter
Anhydrous Ammonia
Foil, Funnels, and
Tubing

27. Ways PSE is Misused in The
Manufacture of
Methamphetamines
Made by reduction of PSE
Involves hydrogenation of the hydroxyl
group on the PSE molecule
Most common way is called “Red, White,
and Blue Process” because it involves red
phosphorus, PSE (white), and blue iodine
Increasingly common method is Birch
reduction which uses anhydrous ammonia
and lithium to reduce PSE

28. Ways to Misuse
Smoking: not really smoking because it is
actually vaporizing to produce fumes. Also
called “Clucking”; fastest and most potent
effect.
Injection: a.k.a. “Slamming”. Biggest Risk-
easier to overdose (anywhere from 125 mg
to 1 gram can fit through a small needle),
infection, skin rashes, and HIV.
Less Common Ways: Snorting, Swallowing,
and Anal Insertion

29. Effects of Misusing
Immediate Effects: Inc. energy, euphoria, excessive
swelling, loss of appetite, insomnia, agitation,
tremor, panic attacks, inc. libido, dilated pupils,
nausea, diarrhea.
Chronic Use Effects: addiction, weight loss,
withdrawal-related depression, tooth decay (“meth
mouth”), high blood pressure, seizures, skin ulcers,
and amphetamine psychosis (mild craziness)
Tolerance occurs rapidly. Repeated over stimulation
of dopamine receptors cause down regulation of
the receptors.

30. Dangers of Misusing
Overdose can cause: brain damage,
Meningitis (lead poisoning), meth bugs
( sensation of bugs crawling under the skin),
paranoia, delusions, hallucinations,
Rhabdomyolysis (muscle breakdown), and
death.
Meth labs cause 194 fires, 117 explosions,
and 22 deaths in 2002.
Dump sites cause death in livestock,
contaminated streams, and dead vegetation

31. Dangers of Misusing
Meth labs cause 194 fires, 117
explosions, and 22 deaths in 2002.

32. Ways to Stop PSE From
Being Misused
Many stores and pharmacies have
policies where the drug must be kept
behind a counter, limiting purchase
sales, a minimum age requirement
with identification, and some require a
signature.

33. Pseudoephedrine LawsPseudoephedrine Laws
In 2005, the Committee on Education & Workforce heard In 2005, the Committee on Education & Workforce heard
testimony regarding rising methamphetamine productiontestimony regarding rising methamphetamine production
Combat Methamphetimine Epidemic Act (CMEA) passed by Combat Methamphetimine Epidemic Act (CMEA) passed by
Congress as an amendment to the Patriot ActCongress as an amendment to the Patriot Act
Signed into law March 6Signed into law March 6
thth
, 2006 by President Bush, 2006 by President Bush
Regulate over-the-counter sales of ephedrine and Regulate over-the-counter sales of ephedrine and
pseudoephedrinepseudoephedrine

34. Pseudoephedrine LawsPseudoephedrine Laws
Each pharmacy Each pharmacy mustmust keep a copy or electronic keep a copy or electronic
logbook which contains:logbook which contains:
1)1)Name of person purchasing, receiving or acquiring the Name of person purchasing, receiving or acquiring the
ephedrine, pseudoephedrine, or PPA. ephedrine, pseudoephedrine, or PPA.
3)3)Address of the person purchasing, receiving or otherwise Address of the person purchasing, receiving or otherwise
acquiring the ephedrine, pseudoephedrine, or PPA be properly acquiring the ephedrine, pseudoephedrine, or PPA be properly
recorded by the seller in the log. recorded by the seller in the log.
5)5)Date and time of saleDate and time of sale
7)7)Name and quantity of the controlled substance sold Name and quantity of the controlled substance sold
5) Purchaser must sign the logbook5) Purchaser must sign the logbook

35. Pseudoephedrine LawsPseudoephedrine Laws

36. Pseudoephedrine LawsPseudoephedrine Laws

37. Pseudoephedrine LawsPseudoephedrine Laws

38. Pseudoephedrine LawsPseudoephedrine Laws
The pharmacy may not sell the The pharmacy may not sell the
product unless the customer product unless the customer
provides an ID even if you provides an ID even if you
know the person know the person
Must be 18 years or older to Must be 18 years or older to
purchase purchase
Regulated products are to be Regulated products are to be
sold behind the counter or in a sold behind the counter or in a
locked cabinet in such a way locked cabinet in such a way
as to restrict public access as to restrict public access
A retrievable record of all A retrievable record of all
purchases identifying the name purchases identifying the name
and address of each party to and address of each party to
be kept for two years be kept for two years
Daily sales of regulated Daily sales of regulated
products not to exceed 3.6 products not to exceed 3.6
grams or 9 grams per month grams or 9 grams per month
Non-liquid dose form of Non-liquid dose form of
regulated product may only be regulated product may only be
sold in unit dose blister packs sold in unit dose blister packs
Anyone who makes a Anyone who makes a
materially false, fictitious, or materially false, fictitious, or
fraudulent statement to the fraudulent statement to the
U.S. Government is subject to U.S. Government is subject to
criminal penalties. Penalties criminal penalties. Penalties
may include a fine of up to may include a fine of up to
$250,000 and or imprisonment $250,000 and or imprisonment
for up to five yearsfor up to five years

39. Methamphetamine Lab Seizures in the US
Year Seizures
1999 7,438
2000 9,902
2001 13,357
2002 16,212
2003 17,356
2004 17,710
2005 12,484
2006 6,435
Effect of Laws
Since the Combat Methamphetamine Epidemic Act of 2005,
methamphetamine lab seizures have decline by nearly 50%.
*2006 study by the Drug Enforcement Agency

40. Now What?

41. Additional Measures of
Prevention
Stricter Regulations
–Hong Kong and Canada
–Life imprisonment
Schedule III drug
–Oregon & Kansas by prescription only
Montana Meth Project
–Ads to horrify addicts or anyone
considering use

42. Drug ReformulationDrug Reformulation
Phenylephrine is a recent reformulated Phenylephrine is a recent reformulated
compound that has been marketed as a compound that has been marketed as a
substitute for Pseudoephedrine. substitute for Pseudoephedrine.
It is used as decongestant orally or as a It is used as decongestant orally or as a
nasal spray. nasal spray.
Phenylephrine uses the same pathway as Phenylephrine uses the same pathway as
PSE but does not release noradrenaline. PSE but does not release noradrenaline.
Therefore it is less likely to cause CNS Therefore it is less likely to cause CNS
stimulation like PSE. stimulation like PSE.

43. Optical IsomerOptical Isomer
Optical isomer used in PSE products are Optical isomer used in PSE products are
–D-pseudoephedrine (L-PSE)D-pseudoephedrine (L-PSE)
–L-pseudoephedrine (D-PSE)L-pseudoephedrine (D-PSE)
L-PSE has fewer side effects and fewer CNS L-PSE has fewer side effects and fewer CNS
stimulations yet remains a good decongestant.stimulations yet remains a good decongestant.
L-PSE isomer does not reduce to D-PSE which is L-PSE isomer does not reduce to D-PSE which is
the isomer used to produce methamphetamine. the isomer used to produce methamphetamine.
Currently, Pfizer/Warner-Lambert holds this patent Currently, Pfizer/Warner-Lambert holds this patent
but it is not yet approved for public sale. but it is not yet approved for public sale.

44. ConclusionConclusion
What is Pseudoephedrine?What is Pseudoephedrine?
common decongestant used to relieve symptoms common decongestant used to relieve symptoms
associated with colds or respiratory allergies, such associated with colds or respiratory allergies, such
as nasal, sinus, and Eustachian tube congestion. as nasal, sinus, and Eustachian tube congestion.
Effects are achieved by indirect stimulation of the Effects are achieved by indirect stimulation of the
adrenergic receptor system in the SNS. adrenergic receptor system in the SNS.
Adverse effects include: CNS stimulation, Adverse effects include: CNS stimulation,
sleeplessness, nervousness, excitability and anxietysleeplessness, nervousness, excitability and anxiety

45. ConclusionConclusion
Critical ingredient in the manufacturing Critical ingredient in the manufacturing
of methamphetamine. of methamphetamine.
The Combat Methamphetamine The Combat Methamphetamine
Epidemic Act of 2005 regulates and Epidemic Act of 2005 regulates and
restricts the sale and distribution of restricts the sale and distribution of
PSE. PSE.
This act was passed to help control This act was passed to help control
the production of methamphetaminethe production of methamphetamine

46. Questions?