This claim seems implausible and lacks sufficient evidence. While the MMP may have had positive impact, making historical claims would require comprehensive analysis across many prevention programs over long periods. A more modest evaluation of the survey data is warranted
This document discusses adrenergic agonists and antagonists that affect the sympathetic and parasympathetic nervous systems. It describes the main uses and adverse effects of selective and non-selective adrenergic agonists as well as adrenergic antagonists. Specifically, it discusses drugs like epinephrine, phenylephrine, clonidine, isoproterenol, dobutamine, albuterol, salmeterol, formoterol, yohimbine, reserpine, cocaine, methamphetamine, amphetamine, and various beta blockers. It provides information on their mechanisms of action, locations of adrenergic receptors, and controversies regarding their use and safety.
Autonomic Nervous System Pharmacology and Cholinergics (updated 2016) - drdhr...
Similar to This claim seems implausible and lacks sufficient evidence. While the MMP may have had positive impact, making historical claims would require comprehensive analysis across many prevention programs over long periods. A more modest evaluation of the survey data is warranted
Targets for the treatment of Alzheimer's diseaseBSAppleby
Similar to This claim seems implausible and lacks sufficient evidence. While the MMP may have had positive impact, making historical claims would require comprehensive analysis across many prevention programs over long periods. A more modest evaluation of the survey data is warranted (20)
Wessex Health Partners Wessex Integrated Care, Population Health, Research & ...
This claim seems implausible and lacks sufficient evidence. While the MMP may have had positive impact, making historical claims would require comprehensive analysis across many prevention programs over long periods. A more modest evaluation of the survey data is warranted
2. Objective
• Describe the main uses and adverse effects of
selective & non-selective adrenergic agonists
• Describe the main uses and adverse effects of
adrenergic antagonists
David Westfall Tom Westfall
5. *
* Acetylcholine & muscarinic receptors for sweat glands
Howland & Mycek (2006). Lippincott’s Illustrated Reviews: Pharmacology, p. 56.
6. Jargon
sympathomimetic: drug that activates
sympathetic nervous system
parasympathomimetic: drug that activates
parasympathetic nervous system
sympatholytic: drug that decreases or blocks
sympathetic response
parasympatholytic: drug that decreases or
blocks parasympathetic response
adrenaline = epinephrine
20. Safety of Long-Acting β-agonists for
Asthma
• A large trial (N=26,000) found a 4-fold elevation
in asthma related deaths with salmeterol1.
• Deaths are uncommon (2/1000 patient-years)
• Prior research on more frequent outcomes has
been revealed inconsistent results
• What to do?
– Tally studies (worst)
– Authority (ok)
1Salmeterol Multi-center Asthma Research Trial (SMART)
21. Meta-Analysis of LABA Asthma Related
Hospitalizations
->
Odds Ratio = 1 means probability of event is equal in both groups
Odds Ratio <> 1 means probability of event differs in each group
OR salmeterol = 1.7, OR formoterol = 3.2; OR children = 3.9, OR adults = 2.0
Salpeter et al. (2006). Annals of Internal Medicine, 144, 904-912.
22. Long Acting B Agonists FDA Warning
http://www.pdr.net/drugpages/concisemonograph.aspx?concise=1691
23. Neuroanatomy of Food Intake
1 2
Hypothalamus
1) Lateral: hunger center “gas”
2) Ventro-medial: satiety center “brakes”
Meyer & Quezner (2005). Psychopharmacology. p. 135.
25. α1 & β12 Agonists & Arousal
30 Minute Blocks
Phenylephrine (10 x 10-9 mol), isoproterenol (4 x 10-9 mol) or both
injected into the medial septum. Behavior based on EEG/EMG.
Meyer & Quezner (2005). Psychopharmacology. p. 134; from Berridge et al. (2004). Brain Research Review, 42, 33-84.
26. Ephedrine
• Ephedra sinica (má huáng) used in traditional
Chinese medicine
• Contains ephedrine and pseudoephedrine
• Mixed: α1 α2 β1 β2 agonist, NE releaser
• 2002: FDA withdrawal from OTC diet agents
over concerns of strokes & arrhythmias (but
gone?)
Kaplan (2011). Gastroenterology Clinics North America, 39(1), 69-79.
27. Ephedra & Weight Loss: Example
Randomized Controlled Trial
• Overweight (BMI > 25) participants were
randomized to placebo or ma
huang/kola pills (tid)
• Analytical chemistry revealed 33 mg
ephedrine & 14 mg caffeine
• Ambulatory monitoring revealed slight
changes (BP: Placebo -3; Herbal +4)
• Adverse effects: insomnia & anxiety
• Weight loss but:
– placebo response
– drop-out
Boozer et al. (2002). International J Obesity, 26, 593-604.
28. History of Methamphetamine
• 1893: Synthesized by Nagai Nagayoshi in Japan
• 1940s- : Popular with military
• 1960s- : used for short-term treatment of obesity, narcolepsy,
and, later, ADHD
• 1983-2005 : state and federal laws attempt to reduce use by
decreasing availability of ephedrine and pseudoephedrine
• 2000s- : several aggressive (factually correct?) advertising
campaigns are aimed at reducing demand
29. History of Methamphetamine
• 1960s- : used for short-term treatment of obesity, narcolepsy,
and, later, ADHD
• 1983-2005 : state and federal laws attempt to reduce use by
decreasing availability of ephedrine and pseudoephedrine
• 2000s- : several aggressive (factually correct?) advertising
campaigns are aimed at reducing demand
Starts slow (3 min): http://montana.methproject.org/Our-Work/brain-and-behavior.php
30. True or False:
“the MMP results in Montana have
been more significant than any other drug
prevention program in history”?
Youth Risk Behavior Survey
• High School students were
asked about lifetime
methamphetamine use
before and after the
Montana
Methamphetamine Project.
Anderson (2010) J Health Econ, 29, 732-742.
32. Montana Meth Project
• Businessman Thomas
Siebel supported
graphic advertising in
2005
• Goal was to reach each
teenager 3+
times/week (TV, radio,
print).
To View Ads:
http://www.montanameth.org/View_Ads/index.php
33. Similarities & Differences of Exposed &
Unexposed Children
Unexposed (N=35) Exposed (N=31)
Trimesters of Methamphetamine 0 (0) 2.5 (0.3)***
Income while pregnant : <15,000 17.1% 76.2*
Income currently : >35,000 51.4% 60.0%
Maternal Age at Birth (years) 26.9 (1.1) 29.8 (1.5)
Nicotine 17.1% 76.2***
Alcohol 11.4% 71.4%***
Marijuana 11.4% 58.8%*
Biological father involved 85.7% 44.8%***
Number of other children 2.7 (0.3) 1.3 (0.3)**
In home
p < *.05, **.01, or ***.005
Piper et al. (2011). Pharmacol Biochem Behav, 98, 432-439.
34. Behavioral Rating Inventory of Executive
Function (BRIEF)
• Please rate whether the following behaviors are never, sometimes, or often a problem (1-3 points):
– Emotional Control (EC) : overreacts to small problems
– Inhibit (INH): interrupts others
– Shift (SHI): becomes upset with new situations
– Working Memory (WM): when given three things to do, remembers only the first or last
– Initiate (INI): has trouble coming up with ideas for what to do in play time
– Plan/Organize (PO): gets caught up in details and misses the big picture
– Organization of Materials (OM): cannot find things in room
– Monitor (MON): does not check work for mistakes
– Behavioral Regulation Index + Metacognition Index =
Global Executive Composite (Mean= 50.0, SD = 10)
Gioia GA, Isquith PK, Guy SC, et al. (2000). Behavioral Rating Inventory of Executive Function: Professional Manual. Psychological Assessment Resources: Lutz.
35. “Clinically Significant” Behavioral Problems in Children Exposed
Prenatally to Methamphetamine & Other Drugs
*** p < .0005, ** p < .005, * p < .05 Piper et al. (2011). Pharmacol Biochem Behav, 98, 432-439.
36. Common Sympathomimetic Drugs
Drug Schedule FDA Approved Acute High-Dose
For Mechanisms
methamphetamine II ADHD Per: αβ agonist ↓DAT
(Desoxyn) obesity Cen: DA, NE, 5-HT ↓ SERT
amphetamine II ADHD Per: αβ agonist ↓DAT
(Adderall) narcolepsy Cen: DA, NE, 5-HT
Methylphenidate II ADHD Per: αβ agonist
(Ritalin) narcolepsy Cen: DA, NE
Cen = central nervous system; Per = peripheral nervous system
37. Top Drug Molecules Dispensed to the Pediatric Population From US Retail
Pharmacies According to Patient Age in 2010
Chai et al. (2012). Pediatrics, 131(1), 23-31. Grace Chai, PharmD
38. Weight, Growth, & Psychostimulants
• statistically but clinically
significant?
• height ≈ 0.5 cm/year
• weight ≈ 2 kg/year
• tolerance
• catch-up?
Faraone et al. (2008). Journal of the American Academy of Child & Adolesclent Psychiatry, 47(9), 994-1009.
39. Cocaine
• Mechanism:
– Central: block DAT, NET & SERT
– Peripheral: αβ agonist
• Schedule II (nasal surgery)
Erythroxylon coca powder crack
41. Why is cocaine reinforcing?
Meyer & Quenzer (2008). Psychopharmacology. p. 283; Rocha (2003). Eur J Pharmacol, 479, 107-115.
42. Drug Abuse Warning Network
• Tracks number of time drug is
Boston 2010
implicated in (urban) ER visits
Drug N
• poly-substance use
alcohol 17,796
cocaine 11,431
heroin 10,493
opiates (oxycontin) 8,525
antidepressants 1,875
stimulants (meth, amph) 739
<- Thalamic hemorrhage in crack smoker (CT)
http://www.samhsa.gov/data/DAWN.aspx#DAWN%202010%20ED%20Excel%20Files%20%E2%80%93%20Metro%20Tables
44. Goodman & Gilman (2011). Pharmacological Basis of Therapeutics. p. 304.
45. Yohimbine
• Content of African tree bark
• Pre-synaptic α2 antagonist
• Inconsistent bioavailability (5 to 80%)
• Purported male aphrodisiac (ED)
Pausinystalia yohimbe
46. β Blockers Overview
• End in “olol”
• Contraindications: asthma
• Heart, eyes, kidneys (β1 predominate)
• Lungs, smooth muscle, uterine muscle (β2 predominate)
O to 4:00 (skip add): http://www.youtube.com/watch?v=h2QR8HxxY1I
47. Controversy Over Phenylephrine
Hendeles, L. (2006) Oral phenylephrine: An ineffective replacement for pseudoephedrine?
J Allergy Clin Immunology, 118(1), 279-280.
48. Terminology Refresher
positive ionotropic action (p. 282): increased strength of ventricular contraction
positive chronotropic action (p. 282): increased rate of heart contraction
hyperhidrosis (p. 296): excessive sweating
General Refresher 0 to 31:50: http://www.youtube.com/watch?v=bMnz7dgHztg&feature=related