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Nicotine Use in Pregnant Women and its Effect on Offspring Jessica Kozlowski, Pak Kei Chan Alan Lu, Shunzhi Chang 2014 Nov 25 PHM142 Fall 2014 Coordinator:

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Presentation on theme: "Nicotine Use in Pregnant Women and its Effect on Offspring Jessica Kozlowski, Pak Kei Chan Alan Lu, Shunzhi Chang 2014 Nov 25 PHM142 Fall 2014 Coordinator:"— Presentation transcript:

1 Nicotine Use in Pregnant Women and its Effect on Offspring Jessica Kozlowski, Pak Kei Chan Alan Lu, Shunzhi Chang 2014 Nov 25 PHM142 Fall 2014 Coordinator: Dr. Jeffrey Henderson Instructor: Dr. David Hampson

2 1. Introduction Negative effects of smoking on mother and fetus: Negative effects of smoking on mother and fetus: Neurobehavioral effects Neurobehavioral effects Cardiovascular effects Cardiovascular effects Reduced infant birth weight Reduced infant birth weight Premature delivery Premature delivery Infant death Infant death

3 15-25% of mothers smoking during pregnancy 15-25% of mothers smoking during pregnancy Majority of women who quit for pregnancy start again after their child’s birth Majority of women who quit for pregnancy start again after their child’s birth 45% of fathers smoking at the time of their child’s birth 45% of fathers smoking at the time of their child’s birth Why not quit? Start smoking cessation? - nicotine addiction Why not quit? Start smoking cessation? - nicotine addiction Nicotine replacement therapy (NRT) better alternative for the fetus. Nicotine replacement therapy (NRT) better alternative for the fetus. Is it safe? Is it safe? Minimal human data about effect of direct nicotine exposure in pregnant women, but a lot about tobacco smoke exposure. Minimal human data about effect of direct nicotine exposure in pregnant women, but a lot about tobacco smoke exposure. 1. Introduction

4 2. Pharmacokinetics of Nicotine Clear liquid b.p.247 °C Clear liquid b.p.247 °C Small molecule Mw = 162 Small molecule Mw = 162 Miscible in water logP = 1.2, amphiphilic Miscible in water logP = 1.2, amphiphilic Fast absorption Fast absorption Cross Blood-brain barrier (10~20s) and placenta barrier Cross Blood-brain barrier (10~20s) and placenta barrier

5 2. Pharmacokinetics of Nicotine

6 Few studies to accurately evaluate effects in pregnant women using nicotine replacement therapy (NRT). Most effects studied in rodents. Few studies to accurately evaluate effects in pregnant women using nicotine replacement therapy (NRT). Most effects studied in rodents. Short term effects: low birth weight and sudden infant death syndrome. Short term effects: low birth weight and sudden infant death syndrome. Long-term effects: Long-term effects: 1. Neurobehavioral problems. 2. Hypertension. 3. Obesity and type 2 diabetes. 4. Respiratory dysfunction. 5. Childhood cancers (leukemia/lymphoma). 6. Impaired fertility. - Effects on offspring 3. Cigarette Smoking during Pregnancy

7 - Neurobehavioural problems Attention-deficit hyperactivity disorder, learning disabilities, behavioral problems, increased anxiety. Attention-deficit hyperactivity disorder, learning disabilities, behavioral problems, increased anxiety. In rats, nicotine is a neuroteratogen, which compromises development of critical neural pathways. In rats, nicotine is a neuroteratogen, which compromises development of critical neural pathways. 10 uM100 uM

8 Associated with in utero exposure to cigarette smoking. Associated with in utero exposure to cigarette smoking. AT1: Angiotensin II receptor type 1. AT2: Angiotensin II receptor type 2. Perinatal nicotine exposure AT1/AT2 ratio ↑ ↑ Ca 2+ sensitivity of myofilaments ↑ Vasoconstriction Hypertension 3. Cigarette Smoking during Pregnancy - Hypertension In rats, perinatal nicotine exposure: In rats, perinatal nicotine exposure: Enhances AT1 and attenuates AT2 gene expression. Enhances AT1 and attenuates AT2 gene expression. Increases Ca 2+ sensitivity of myofilaments leading to vasoconstriction and development of hypertensive phenotype in adulthood. Increases Ca 2+ sensitivity of myofilaments leading to vasoconstriction and development of hypertensive phenotype in adulthood.

9 4. Methods of Smoking Cessation Bupropion (Zyban) Nicotine Replacement Therapy Other (Hypnosis, acupuncture, quitting gradually, quitting “Cold Turkey”)

10 Initially prescribed to treat various forms of depression. Initially prescribed to treat various forms of depression. It was discovered that smoking cravings and withdrawal effects were reduced. It was discovered that smoking cravings and withdrawal effects were reduced. Inhibition of neurotransmitter uptake Inhibition of neurotransmitter uptake Study conducted showed no increased risk of congenital malformation in fetal development. Study conducted showed no increased risk of congenital malformation in fetal development. 4. Preventative Methods - Bupropion

11 Summary Slide Nicotine can readily cross the blood-brain barrier and the placental barrier. It is also an ingredient found in tobacco and it’s primary responsible for sustaining addictive effects. Smoking during pregnancy has been shown to cause neurobehavioral and cardiovascular abnormalities. Nicotine acts as a neuroteratogen and induce neurobehavioral problems which include: Attention deficit hyperactivity disorder (ADHD), learning disabilities, or increased risk of nicotine addiction. An example of a cardiovascular problem is hypertension. Studies conducted in rats have shown that perinatal nicotine exposure : - Alters the gene expression of AT1 and AT2 - Myofilaments are more sensitive to Ca 2+ - Vasoconstriction occurs easily, thus causing hypertension The bottom line: Absentia > Bupropion > NRT > cigarette smoking, with the best alternative to smoking being quitting prior to pregnancy.

12 Thank You Very Much!

13 References Bruin JE, Gerstein HC, Holloway AC (2010) Long-term consequences of fetal and neonatal nicotine exposure: a critical review. Toxicol Sci 116: Ho MK, Tyndale RF (2007) Overview of the pharmacogenomics of cigarette smoking. Pharmacogenomics J 7: Horst WD, Preskorn SH (1998) Mechanisms of action and clinical characteristics of three atypical antidepressants: venlafaxine, nefazodone, bupropion. J Affect Disord 51: Rose JE, Behm FM, Westman EC, Coleman RE (1999) Arterial nicotine kinetics during cigarette smoking and intravenous nicotine administration: implications for addiction. Drug Alcohol Depend 56: Slotkin TA (2004) Cholinergic systems in brain development and disruption by neurotoxicants: nicotine, environmental tobacco smoke, organophosphates. Toxicol Appl Pharmacol 198: Wickstrom R (2007) Effects of nicotine during pregnancy: human and experimental evidence. Curr Neuropharmacol 5: Wu P, Wilson K, Dimoulas P, Mills EJ (2006) Effectiveness of smoking cessation therapies: a systematic review and meta-analysis. BMC Public Health 6: 300. Xiao D, Dasgupta C, Li Y, Huang X, Zhang L (2014) Perinatal nicotine exposure increases Angiotensin II receptor-mediated vascular contractility in adult offspring. PLoS One 9: e Zyban 150 mg prolonged release film-coated tablets – Summary of Product Characteristics (SPC)". electronic Medicines Compendium. GlaxoSmithKline UK. 1 August Retrieved 22 October 2013.

14 4. Preventative Methods - Nicotine Replacement Therapy (NRT) Nicotine is given during therapy, but in low and controlled doses. Nicotine is given during therapy, but in low and controlled doses. The purpose NRT help the person quit smoking while minimizing the withdrawal effects. The purpose NRT help the person quit smoking while minimizing the withdrawal effects. A study suggests that NRT may be ineffective: A study suggests that NRT may be ineffective: Many pregnant mothers did not adhere after 2-4 weeks of therapy. Many pregnant mothers did not adhere after 2-4 weeks of therapy. The safety is unknown due to insufficient research. The safety is unknown due to insufficient research.

15 0 introduction symbol 0 introduction symbol 1outline of presentation 1outline of presentation 2 epidemiology data % of people smoking 2 epidemiology data % of people smoking 3 effect of tobacco smoking in human 3 effect of tobacco smoking in human 4 nicotine pharmacology & effect of nicotine in animal model at cellular / molecular level 4 nicotine pharmacology & effect of nicotine in animal model at cellular / molecular level 5 Intervention smoking cessation Rx 5 Intervention smoking cessation Rx Conclusion further study…… Conclusion further study…… Reference Reference Summary slide Summary slide

16 Some where….Nicotine is the primary substance that sustains the powerful addictive effects of tobacco products. Some where….Nicotine is the primary substance that sustains the powerful addictive effects of tobacco products. 1. Introduction

17 Altered state of awareness Altered state of awareness It is believed that during hypnosis, you are more relaxed and are more willing to hear suggestions (ex. Quitting) It is believed that during hypnosis, you are more relaxed and are more willing to hear suggestions (ex. Quitting) Hypnotherapist may associate the smell cigarette smoke and the smell of truck exhaust. Hypnotherapist may associate the smell cigarette smoke and the smell of truck exhaust. Research is still needed (not recognized by medical associations) Research is still needed (not recognized by medical associations) 4. Preventative Methods - Hypnosis

18 - Neurobehavioural abnormality Neuroteratogen Neuroteratogen Attention-deficit hyperactivitiy disorder, learning disabilities, increased risk of nicotine addiction Attention-deficit hyperactivitiy disorder, learning disabilities, increased risk of nicotine addiction Development of critical neural pathways in the developing brain (animal) Development of critical neural pathways in the developing brain (animal) Cognitive impairment, increased axiety, persistent neruochemical alterations, changes in sensitivity of nictoine and nicotine self-administration. (animal) Cognitive impairment, increased axiety, persistent neruochemical alterations, changes in sensitivity of nictoine and nicotine self-administration. (animal) 3. Cigarette Smoking during Pregnancy

19 Spontaneous abortion, placental abruption, stillbirth, fetal growth restriction, low birthweight, sudden infant death syndrome Spontaneous abortion, placental abruption, stillbirth, fetal growth restriction, low birthweight, sudden infant death syndrome Neurobehavioural abnormality Neurobehavioural abnormality Cardiovascular abnormality Cardiovascular abnormality Childhood Cancer Childhood Cancer Type II Diabetes Type II Diabetes Obesity Obesity ………… …………

20 - Cardiovascular abnormality Hypertension Hypertension Cardiac dysfunction (animal) Cardiac dysfunction (animal) Perivascular adipose tissue function,enothelial dysfunction, renal function ???? (animal) Perivascular adipose tissue function,enothelial dysfunction, renal function ???? (animal) Sudden infant death syndrome (SIDS) Sudden infant death syndrome (SIDS) 3. Cigarette Smoking during Pregnancy

21 Summary Do NOT smoke! Do NOT smoke! If you do, try not have babies, because cigarette smoking can have various negative effects on the developing fetus. If you do, try not have babies, because cigarette smoking can have various negative effects on the developing fetus. If you still can not quit, try NRT, Bupropion, available in pharmacies, which will significantly reduce the daily consumption of cigarettes! If you still can not quit, try NRT, Bupropion, available in pharmacies, which will significantly reduce the daily consumption of cigarettes! The bottom line: The bottom line: Absentia > NRT / Bupropion > cigarette smoking Absentia > NRT / Bupropion > cigarette smoking

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23 Which method is the best for the fetus? Nicotine Replacement Therapy Vs Bupropion Timing is more important than the type of method.


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