Pseudoephedrine

Pseudoephedrine Misuse and Regulation

Vince Buttrick, Jinender Kumar, Sami Musleh, Angela Nikolakis, Ahmad Sayed, Shawn Smith

These people are addicted to Methamphetamine- also known asCrank, speed, crystal meth, ice Methamphetamine is illicitly

manufactured from pseudoephedrine, the active ingredient in many over-the-counter cold medications

ChemistryChemistry

Pseudoephedrine Pseudoephedrine

-a phenethylamine -a phenethylamine

ChemistryChemistry

– Pseudoephedrine is a diastereomer of Pseudoephedrine is a diastereomer of ephedrineephedrine

– Diastereomers: stereoisomers that are not Diastereomers: stereoisomers that are not enantiomers; not mirror imagesenantiomers; not mirror images

Ephedrine:Ephedrine: Pseudoephedrine:Pseudoephedrine:

Chemistry Chemistry

As a sympathomimetic amine, As a sympathomimetic amine, pseudoephedrine relies on its indirect pseudoephedrine relies on its indirect stimulation of the adrenergic receptor stimulation of the adrenergic receptor system to produce its effectssystem 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) displacing noradrenaline (norepinephrine) from storage vesicles in presynaptic neuronsfrom storage vesicles in presynaptic neurons

ChemistryChemistry

Once the norepinephrine is displaced from storage Once the norepinephrine is displaced from storage vesicles, it is released into the neuronal synapsevesicles, it is released into the neuronal synapse

At the neuronal synapse, the norepninephrine At the neuronal synapse, the norepninephrine becomes available to activate the alpha and beta becomes available to activate the alpha and beta postsynaptic adrenergic receptorspostsynaptic adrenergic receptors

ChemistryChemistry

The alpha and beta receptors are located on the The alpha and beta receptors are located on the muscles lining the walls of blood vesselsmuscles lining the walls of blood vessels

Activation of the receptors by pseudoephedrine Activation of the receptors by pseudoephedrine causes muscle contraction, resulting in causes muscle contraction, resulting in vasoconstriction of the blood vesselsvasoconstriction of the blood vessels

ChemistryChemistry

By constricting the blood vessels, less fluid is By constricting the blood vessels, less fluid is capable of leaving the blood vessels and capable of leaving the blood vessels and entering the nose, throat, and sinus liningsentering the nose, throat, and sinus linings

ChemistryChemistry

The end result of pseudoephedrine The end result of pseudoephedrine results in decreased inflammation of results in decreased inflammation of nasal membranes, as well as nasal membranes, as well as decreased mucous productiondecreased mucous production

Chemistry

Methamphetamine

Pseudoephedrine

Chemistry

Methamphetamine is a central nervous system stimulant

– Meth Mechanism of Action

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.

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 Rare adverse effect could be hallucination, arrhythmia, seizure, hallucination, arrhythmia, seizure, ischemic colitis, recurrent pseudo scar ischemic colitis, recurrent pseudo scar Latina, systemic contract dermatitis, Latina, systemic contract dermatitis, stroke.stroke.

PrecautionsPrecautions

Should be used with caution in patients Should be used with caution in patients with diabetes mellitus, cardiovascular with diabetes mellitus, cardiovascular disease, hypertension, Prostatic disease, hypertension, Prostatic hypertrophy, hyperthyroidism, closed hypertrophy, hyperthyroidism, closed angle glaucoma and/or pregnancy.angle glaucoma 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.

ContraindicationContraindication

Concomitant or recent (previous Concomitant or recent (previous 14 days) use of monoamine 14 days) use of monoamine oxidase inhibitor.oxidase inhibitor.

Severe/uncontrolled Severe/uncontrolled hypertension, and /or severe hypertension, and /or severe coronary artery disease.coronary artery disease.

People with bipolar disorder as it People with bipolar disorder as it can cause insomnia and thus can can cause insomnia and thus can trigger a manic episode.trigger a manic episode.

ManufactureManufacture

pseudoephedrine occurs naturally as an pseudoephedrine occurs naturally as an alkaloid in certain plant species for alkaloid in certain plant species for example, as a constituent of extracts example, as a constituent of extracts from the ephedra species, also known from the ephedra species, also known as Ma Huang in which it occurs together as Ma Huang in which it occurs together with other isomers of ephedrine with other isomers of ephedrine

Ma Huang has been used in traditional Ma Huang has been used in traditional Chinese medicine for 5,000 years for Chinese medicine for 5,000 years for the treatment of asthma and hay fever, the treatment of asthma and hay fever, as well as for the common cold.as well as for the common cold.


The majority of pseudoephedrine produced The majority of pseudoephedrine produced for commercial use is derived from yeast for commercial use is derived from yeast fermentation of dextrose in the presence of fermentation of dextrose in the presence of benzaldehyde. benzaldehyde.

In this process, specialized strains of In this process, specialized strains of yeast typically a variety of yeast typically a variety of Candida Candida utilis utilis oror Saccharomyces cerevisiae Saccharomyces cerevisiae are are added to large vats containing water, added to large vats containing water, dextose, and the enzyme pyruvate dextose, and the enzyme pyruvate decarboxylasedecarboxylase


After the yeast has begun fermenting After the yeast has begun fermenting the dextrose, the benzaldehyde is the dextrose, the benzaldehyde is added to the vats. added to the vats.

In this environment, the yeast converts In this environment, the yeast converts the chemical precursor ingredients to the chemical precursor ingredients to 1-phenylacetylcarbinol (L-PAC)1-phenylacetylcarbinol (L-PAC)

In the final step of the synthesis, the L-In the final step of the synthesis, the L-PAC undergoes reductive amination to PAC undergoes reductive amination to produce pseudoephedrineproduce pseudoephedrine


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

Why Pseudoephedrine is Misused Very similar to chemical structure

of amphetamines which is used to make methamphetamines

Previously easy to obtain; over the counter

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

Ingredients to Make Methamphetamies

Ingredients to Make Methamphetamines Cold

Medicines/Decongestants 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

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

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

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.

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

Dangers of Misusing

Meth labs cause 194 fires, 117 explosions, and 22 deaths in 2002.

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.

Pseudoephedrine LawsPseudoephedrine Laws

In 2005, the Committee on Education & Workforce In 2005, the Committee on Education & Workforce heard testimony regarding rising methamphetamine heard testimony regarding rising methamphetamine productionproduction

Combat Methamphetimine Epidemic Act (CMEA) passed Combat Methamphetimine Epidemic Act (CMEA) passed by Congress as an amendment to the Patriot Actby Congress as an amendment to the Patriot Act

Signed into law March 6Signed into law March 6thth, 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

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.

2)2) Address of the person purchasing, receiving or Address of the person purchasing, receiving or otherwise acquiring the ephedrine, pseudoephedrine, otherwise acquiring the ephedrine, pseudoephedrine, or PPA be properly recorded by the seller in the log. or PPA be properly recorded by the seller in the log.

3)3) Date and time of saleDate and time of sale

4)4) 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


The pharmacy may not sell The pharmacy may not sell the product unless the the product unless the customer provides an ID even customer provides an ID even if you know the person if you 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 sold behind the counter or in a locked cabinet in such a a locked cabinet in such a way as to restrict public way as to restrict public access access

A retrievable record of all A retrievable record of all purchases identifying the purchases identifying the name and address of each name and address of each party to be kept for two years party to 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 regulated product may only be sold in unit dose blister be sold in unit dose blister packs 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 U.S. Government is subject to criminal penalties. to criminal penalties. Penalties may include a fine Penalties may include a fine of up to $250,000 and or of up to $250,000 and or imprisonment for up to five imprisonment for up to five yearsyears

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

Now What?

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

Drug ReformulationDrug Reformulation

Phenylephrine is a recent reformulated Phenylephrine is a recent reformulated compound that has been marketed as compound that has been marketed as a substitute for Pseudoephedrine. a substitute for Pseudoephedrine.

It is used as decongestant orally or as It is used as decongestant orally or as a nasal spray. a nasal spray.

Phenylephrine uses the same pathway Phenylephrine uses the same pathway as PSE but does not release as PSE but does not release noradrenaline. Therefore it is less likely noradrenaline. Therefore it is less likely to cause CNS stimulation like PSE. to cause CNS stimulation like PSE.

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 the isomer used to produce methamphetamine. methamphetamine.

Currently, Pfizer/Warner-Lambert holds this Currently, Pfizer/Warner-Lambert holds this patent but it is not yet approved for public patent but it is not yet approved for public sale. sale.

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

ConclusionConclusion

Critical ingredient in the Critical ingredient in the manufacturing of methamphetamine. manufacturing 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

Questions?

Pseudoephedrine

Health & Medicine

Transcript of Pseudoephedrine