Psychopharmacology

From Nicotine to Opiates

What is the leading cause of preventable death in the world?

Smoking

Fill in the blank: Nicotine is _______ and is _______ by animal models in a manner that is similar to human smoking.

reinforcing; self-administered

T/F: There are a wide range of products that contain nicotine but only some are abused and cause physical dependence

F; There are a wide range of products that contain nicotine—all are abused and all cause physical dependence

What is the one major factor that reduces use of nicotine?

Price

How is nicotine most rapidly absorbed?

Through the lungs

What triggers nicotine cravings?

Low Plasma concentration

T/F: All states have their own laws that allow flavored pods

T; The Commonwealth of Massachusetts only allows tobacco flavored nicotine pods to be sold. All fruit and unique flavors are banned.

circa WWII, what was nicotine a prime ingredient of?

Insecticides

Y/N: Can you develop tolerance to nicotine?

Y

Y/N: Is abrupt termination of nicotine use life threatening?

N; Abrupt termination causes rapid withdrawal signs and symptoms but non life-threatening.

What triggers relapse of nicotine use?

Cue exposure

T/F: There are no pharmacological and behavioral therapies to treat tobacco dependence

F; There are several pharmacological and behavioral therapies to treat tobacco dependence

Describe what is happening in these graphs

Shows 1. Teenagers are still most at risk, 2. use of other drugs correlates with increased use

What are the constituents of a cigarette? The pyrolysis products?

1. Cigarette constituents: organics, nicotine, additives

2. Pyrolysis products: CO, CO₂ , tar

What factors affect absorption in the lungs?

inhalation volume, inhalation depth, inhalation duration, and pH of smoke

What are the 3 types of cigarette smoke?

mainstream, sidestream, secondhand

Compare the detection & euphoria latency of a nicotine cigarette compared to I.V. nicotine?

Cigarette: Detection latency-- 12 sec Euphoria latency-- 44 sec

I.V.: Detection latency-- 27 sec Euphoria latency-- 74 sec —> LONGER

T/F: Nicotine only has euphoric effects?

F; Nicotine cause both euphoria and dysphoria

What are other sites for nicotine absorption (other than the lungs)?

buccal cavity, nasal mucosa, skin, GI tract

What version of nicotine is the active agent?

Unmetabolized nicotine

Where is nicotine metabolized? What is metabolized to?

Liver; cotinine (90%), nicotine-N-oxide (10%)

What are the 3 fastest modes of absorption for nicotine?

Inhalation, buccal, and then transdermal patch

What is Dr. Lukas’ favorite route of administration?

The patch due to sustained release

Where are nicotine receptors found and what do they lead to?

Found on presynaptic sites, which explains how nicotine can cause release of DA and 5-HT (Acetylcholine sensitive located in both CNS and PNS (brain, ganglia and striated muscle), CNS sites include the substantia nigra and ventral tegmentum (associated with DA neurons)).

How do the nicotine cholinergic receptors work?

Acetylcholine produces an influx of sodium (a positively charged ion) INTO the cell which results in less negative potential and increases the firing rate of neurons.

How can nicotinic cholinergic receptors mediate the reinforcing effects of nicotine and cause relapse?

Abnormally high concentrations of these receptors (due to upregulation after chronic nicotine exposure) can cause relapse

What are the central nervous system effects for novice smokers?

• Dizziness, lightheadedness and vertigo

• Nausea and vomiting, secondary to stimulation of the chemoreceptor trigger zone (CTZ)

• Reduces the tremor of Parkinson’s Disease, but elicits physiologic tremor secondary to NE & DA release and sympathetic stimulation.

T/F: Depending on dose, has both stimulant- and depressant-like effects.

T

Why are low-yield, menthol or additive-free cigarettes not actually “safer”?

because many switch to these brands instead of quitting

What are cigars?

A roll of tobacco wrapped in leaf tobacco or in any substance containing tobacco

• Cigar wrappers are not porous, causing poor burning and higher nitrogen oxides, ammonia, CO and tar

• Cigar packaging is not required to have warning labels

• Some large cigars contain as much tobacco as a pack of cigarettes

What is smokeless tobacco or snuff?

Raw tobacco that is placed between cheek and gum. Nicotine is absorbed directly into bloodstream

• Lead and cadmium (heavy metals) also found and can lead to birth defects.

• Contains high sodium levels--> hypertension

• Contains 10X the amount of nitrosamines in cigarettes-- leading cause of oral cancers (Carcinogenic & destroys teeth and gums)

What is Camel Snus “snoose”?

• smokeless pouch product that is spit-less, contains less moisture and salt than the moist smokeless tobacco products

• Requites spitting

• Very popular in Sweden, but not very popular in America

What are Zyn, On! and VELO?

• Tobacco-free pouches that contain synthetic nicotine, flavorings and plant-based fillers

• Various nicotine strengths

• Placed between the gum and lip so nicotine is dissolved and then absorbed

• Dripless and requires very little, if any, spitting

• Generally considered to be safer than vaping due to lack of lung irritation

• Considered safer than Snus as lack nitrosamines

• Since they contain nicotine, they are reinforcing and can produce tolerance and dependence

• They are not absolutely safe

• Can elevate blood pressure and heartrate

• Gum and mouth problems—irritation

• Nausea, headaches, dizziness

What is the principle of operation for Electronic Nicotine Delivery Systems (ENDS) or electronic cigarettes?

Battery driven device delivers vapor containing nicotine and flavors to simulate the sensation and appearance of smoking

Use heat or ultrasonic waves to vaporize a propylene glycol or glycerin-based liquid.

What are the four parts of an electronic cigarette?

Battery, Atomizer, Tank, and mouthpiece

Electronic cigarettes come in varying strengths- what are the strengths and what is the level of nicotine in the highest and lowest?

Sold in 4 strengths: nicotine free, light, medium and full flavor

• Full flavor: 16-24 mg nicotine

• Light: 4-8 mg nicotine

T/F: The “smoke” in e-cigarettes contains combustion products and is much safer than that of regular cigarettes.

F; The “smoke” is really vapor and does not contain combustion products, so it is touted as being “safer” than real cigarettes—but still contains many chemicals

What is menthol and its significance?

Menthol was the first and most common additive/flavor to be added to tobacco products. Mentholated cigarettes reduce the harshness of tobacco smoke and so may assist in the initiation of smoking — addictive impact

“Are e-cigarettes safer than tobacco cigarettes?”

Likely yes, but safer does not mean that they are safe.

What is the best treatment for nicotine use disorder?

No proven methods for matching a specific patient to a particular treatment but Nicotine replacement treatment (NRT) relieves withdrawal and craving and Combined behavioral techniques with pharmacotherapy has increased success rate to 40-50%

What are some Nicotine replacement treatments (NRT)?

• Nicotine Polacrilex (gum): Nicorette™- 2 mg

• Nicotine polacrilex (lozenge)- 2 and 4 mg

• Transdermal (patch): Nicoderm™- 7, 14 and 21 mg

• Inhalation: Nicotrol® Inhaler- 10 mg/cartridge*, Nicotrol® Nasal Spray - 10 mg/mL

• Vapor (oral/smoked): e-cigarettes (but not really used this way)

Y/N: Nicotine and pregnancy okay?

N; Tobacco smoking is extremely dangerous to the developing fetus and to a pregnant mother

What is Prof. Lukas’ opinion on NRT while pregnant?

NRT use during pregnancy is advised if the product is used to eliminate tobacco smoking but other medications like varenicline and bupropion are not recommended during pregnancy

What are non-nicotine treatments for nicotine use disorder?

Bupropion (Zyban®) (antidepressant): reduces withdrawal, helps cessation

Clonidine (antihypertensive): approved for use alleviates w/d

Buspirone (antianxiety): encouraging initial studies

Mecamylamine (antihypertensive that is no longer available): nicotine receptor blocker

Nicotine vaccine: Body creates antibodies that are specific for the nicotine molecule. The antibodies bind up the nicotine making it too large to cross the BBB.

What is varenicline?

Varenicline (Chantix®) is a nicotine receptor partial agonist that reduces craving for nicotine, decreases pleasurable effects of nicotine, typically treat for 12 weeks, 1 year success rate is about 23%

How does treatment affect weight gain?

• Sense of taste and smell returns—food tastes better!

• Cravings for sweets and calorie increases

• Bodies need 100-200 fewer calories per day

• Choose to place food in mouth instead of a cigarette