Autonomic pharmacology

Therapeutic Uses: β-Adrenergic Receptor Antagonists

Heart Failure, (Congestive Heart Failure, CHF):³⁰⁴

Introduction: Clinical presentations of heart failure (HF) include fatigue and dyspnea (symptoms) and edema and rales (signs).
- Heart Failure Lecture^304a
- HF may require hospitalization; furthermore, patients may exhibit both reduced life expectancy and a poor quality of life.
- The likelihood of the patient developing heart failure increases in the presence of left ventricular structural or functional pathologies.
- Heart failure may present in patients with either reduced left ventricular ejection fraction (<40%) or with preserved ejection fraction (>40%-50%).
  - About half of patients with heart failure fall in the group of preserved ejection fraction and half in the group of depressed ejection fraction.
    - The former condition (preserved ejection fraction group) defines "diastolic failure"; whereas, the latter group (presenting with reduced or depressed ejection fraction) exhibits "systolic failure."
  - Heart Failure Animation³⁰⁶
  - In industrialized countries coronary artery disease (CAD) defines the predominant heart failure cause in both men and women, responsible for about 60%-75% of cases.
    - Hypertension is often a contributing factor in heart failure development; moreover, the combination of both coronary artery disease and hypertension increases heart failure risk with diabetes further increasing risk.³⁰⁴
  - A number of conditions are associated with or cause heart failure with depressed ejection fraction (<40%).³⁰⁴
    - For example, coronary artery disease resulting in myocardial infarction or ischemia may be associated with heart failure.
    - Hypertension or obstructive valve disease which results in chronic pressure overload also predisposes to heart failure.
    - Chronic volume overload associated with valvular disease (regurgitant), intra- or extracardiac shunting can manifest as heart failure.
    - Nonischemic dilated cardiomyopathy (e.g. toxic/drug-induced pathology, viral etiology, Chagas' disease, familial/genetic disorders, or metabolic disorder) may be associated with heart failure.
      - Chagas disease (American trypanosomiasis) is a tropical parasitic disorder caused by the protozoan Trypanosoma cruzi. Chronic Chagas disease is associated with cardiac, digestive system and nervous system pathologies.
      - Dilated cardiomyopathy may occur in chronically afflicted patients.
        
        Cardiac Pathology: Chagas Disease³⁰⁷
    - Certain myocardial arrhythmias may also result in heart failure; examples of these arrhythmias include both bradyarrhythmias and tachyarrhythmias.³⁰⁴
  - Heart failure may also occur with preserved ejection fraction (> 40%-50%).³⁰⁴
    - Pathological hypertrophy of a primary type (hypertrophic cardiomyopathy) or of a secondary type (hypertension) may be associated with heart failure.
    - Restrictive cardiomyopathy due to amyloidosis or sarcoidosis (infiltrative disorder) or hemochromatosis (storage disease) also may result in heart failure.
    - Endomyocardial pathologies, aging, or fibrosis also predisposes to heart failure.
  - High-output heart failure may be due to metabolic disorders, such as thyrotoxicosis or beriberi (the nutritional disorder). High-output heart failure may also occur secondary to chronic anemia.³⁰⁴

Classification of Heart Failure:³⁰⁸

Heart failure may be avoided by management of risk factors or by intervention following diagnosis of asymptomatic left ventricular dysfunction.

Guidelines of the American College of Cardiology/American Heart Association describe heart failure as a "continuum" with the range initially exhibiting risk factors and may progress to refractory, end-stage failure.³⁰⁹

Stage A defines risk factors that may be associated with heart failure development.
Stage B describes myocardial structural changes that may lead to heart failure; however, at stage B only asymptomatic heart failure is present.
Characteristics of stage C include verification of not only cardiac structural pathologies but also clinical presentations. Stage C defines symptomatic heart failure.
Finally, stage D or end-stage heart failure is characterized by symptoms at rest even if maximum medical treatment is being employed.³⁰⁹

Heart Failure: Classification³⁰⁹
Stage	Definition	Clinical Description
A	"High risk for developing heart failure"	Coronary Artery Disease (CAD) Diabetes mellitus Familial history of cardiomyopathy Hypertension
B	Asymptomatic heart failure	Previous myocardial infarction (heart attack) Left ventricular hypertrophy or systolic dysfunction Valvular disease (asymptomatic)
C	Symptomatic heart failure	Verified structural heart pathology Decrease exercise tolerance Fatigue Shortness of breath
D	Refractory end-stage heart failure	"Marked symptoms at rest despite maximal medical therapy"

= severity

Routine Assessments Establishing Presence and Probable Heart Failure Cause^308,310
Assessments	Heart Failure Diagnosis			Possible Alternative or Additional Diagnosis
	Necessary For	Supports	Opposes
Appropriate Symptoms			if not present
Appropriate Signs			if not present
Myocardial Abnormality as Evidenced by Imaging			if not present
Symptoms or Signs Respond to Treatment			if not present
ECG			if Normal
Chest X-Ray		If findings indicate cardiac enlargement or pulmonary congestion	if Normal	Pulmonary Disease
Full Blood Count				Anemia/secondary polycythemia
Biochemistry and Urinalysis				Kidney or liver disease/diabetes
Plasma concentration of natriuretic peptides in untreated patients		, if elevated	if Normal	May be normal in treated patients

= of some weight; = of substantial weight

Additional Tests in Support of either a Heart Failure Diagnosis or an Alternative^308,310
Medical Tests	Heart Failure Diagnosis		Possible Alternative or Additional Diagnosis
	Supports	Opposes
Exercise Test	if impaired	if normal
Pulmonary Function Test			Pulmonary Disease
Thyroid Function Test			Thyroid Disease
Invasive Testing and Angiography			Coronary Artery Disease
Cardiac Output	if depressed at rest	if normal, particularly during exercise
Left Atrial Pressure (pulmonary capillary wedge pressure)	if elevated at rest	if normal in the absence of therapy

Functional capacity is an important assessment in heart failure patient evaluations.³⁰⁸

Classifications are based on four categories:
- Class I: absence of physical activity limitations with no symptoms associated with routine day-to-day activities.
- Class II: only minimal limitation but symptoms do appear when the patient engages in ordinary day-to-day activities.
- Class III: patients in this category exhibit more significant limitations ("marked limitations") and exhibit diminished functional capacity symptoms at less than ordinary day-to-day activities.
- Class IV: this class describes patients with severe limitation; these patients exhibit heart failure symptoms at rest.
Individuals who can walk several blocks without symptoms but exhibit difficulty when climbing two flights of stairs would fall into class II heart failure.
Class III patients are not able to walk several blocks readily and might become short of breath while walking up only a short flight of stairs.³⁰⁸

Accurate assessment by patient history of functional capacity depends on the question asked.
For example, if the patient is asked "do you become short of breath?"
- The response may well be "no."
  - In actuality what has been happening is that the patient progressively reduces their level of exercise because of shortness of breath to the point that the symptom is not present.
An alternative way of asking this question may be more useful, such as "are you able to walk three blocks without feeling short of breath?"

A relatively new clinical evaluation method that may be useful in determining both diagnosis and prognosis of heart failure is plasma B-type natriuretic peptide (BNP) levels.^308,312
- In the "B-type Natriuretic Peptide for Acute Shortness of Breath Evaluation" study, some emergency department patients presenting with acute shortness of breath underwent a single measurement of BNP.
- From the study, it appears that a plasma BNP concentration of <100 pg/ml made a diagnosis of congestive heart failure unlikely; by contrast, the level of >500 pg/ml made such a diagnosis quite likely.³¹²
- In this patient population (those presenting to the emergency department with acute shortness of breath (dyspnea), having a BNP level determination was found cost-effective during both initial hospitalization and at 180 days.³¹¹
Fluid retention assessment in potential congestive heart failure patients may be accomplished by jugular venous pressure, evaluation of possible lung congestion, and presence/absence of peripheral edema.³⁰⁸
- Mild congestive indicators may suggest volume excess even absent direct evidence by physical examination. New onset heart failure may be especially sensitive to chest radiographic imaging as an indicator of volume overload.

Elevated Jugular Venous Pressure³⁰⁵

"A person with congestive heart failure who presented with an exceedingly elevated JVP (marked by the arrow)"³⁰⁵

Chest Radiograph: Pulmonary Edema³¹³

"Acute pulmonary edema. Note enlarged heart size, apical vascular redistribution ( circle ), and small bilateral pleural effusions ( arrow )."³¹³

Pedal, Pitting Edema³¹⁴
"Pedal edema before and after the application of pressure to the shin."³¹⁴

References
Hoffman, B.B and Lefkowitz, R.J, Catecholamines, Sympathomimetic Drugs, and Adrenergic Receptor Antagonists, In Goodman and Gillman's The Pharmacologial Basis of Therapeutics,(Hardman, J.G, Limbird, L.E, Molinoff, P.B., Ruddon, R.W, and Gilman, A.G.,eds) The McGraw-Hill Companies, Inc.,1996, pp.199-242 Stoelting, R.K., "Sympathomimetics", in Pharmacology and Physiology in Anesthetic Practice, Lippincott-Raven Publishers, 1999, p. 260 Carotic Baroreceptors: CRRx: Mediine ReEnvisioned http://www.cvrx.com/patients/index.php?id=41 Westfall, TC and Westfall DP Adrenergic Agonists and Antagonists in Goodman and Gilman's The Pharmacological Basis of Therapeutics, eleventh editions, (Brunton LL, Lazo JS and Parker KL, eds), McGraw-Hill Medical Publishing Division, New York, 237-295, 2006. Catecholamine Biosynthesis: The Interactive Library; Edinformatics.com: http://www.edinformatics.com/interactive_molecules/info/adrenaline.htm . Standaert DG and Young AB Treatment of Central Nervous System Degenerative Disorders In Goodman and Gillman's The Pharmacologial Basis of Therapeutics,(Hardman, J.G, Limbird, L.E, Molinoff, P.B., Ruddon, R.W, and Gilman, A.G.,eds) TheMcGraw-Hill Companies, Inc.,1996, pp536-537. Adrenergic Neuronal Diagram adapted from http://www.drugabuse.gov/pubs/teaching/Teaching4/Teaching.html Guanetidine (Ismelin™, brand name not available in the U.S.) pharmacology: Clinical Pharmacology, RxList: The Internet Drug Index, http://www.rxlist.com/ismelin-drug.htm . Williams FM and Turner TJ Adrenergic Pharmacology in Principles of Pharmacology: The Pathophysiologic Basis of Drug Therapy, 2nd Edition (Golan DE, Tashijan Jr AH, Armstrong EJ and Armstrong AW, eds) Wolters Kluwer-Lippincott Williams & Wilkins, Philadelphia, 129-144, 2008. Moss J and Glick D Autonomic Function in Anesthetic Pharmacology: Physiological Principles and Clinical Practice: A Companion to Miller's Anesthesia (Evers AS and Maze M, eds) Churchill Livingstone, Philadelphia, Chapter 14, 209-226, 2004. Presynaptic Proteins, Synaptic Vesicle Docking and Membrane Fusion, http://neuromuscular.wustl.edu/pathol/snare.htm#cachan, Neuromuscular Disease Center, Washington University, St. Louis, MO USA (http://neuromuscular.wustl.edu/index.html) Sudhof TC The Synaptic Vesicle Cycle, Annual Review of Neuroscience, July 200, Vol. 27, pp 509-547. Phenochomocytoma picture (http://health-pictures.com/pheochromocytoma.htm); Geneva Foundation of Medical Education and Research, Pheochromocytoma, http://www.gfmer.ch/selected_images_v2/detail_list.php?cat1=1&cat2=113&cat3=22&cat4=2&stype=n . Brown H, Goldberg PA, Selter JG, Cabin HS, Marieb NJ, Udelsman R and Setaro JF Hemorrhagic Pheochromocytoma Associated with Systemic Corticosteroid Therapy and Presenting as Myocardial Infarction with Severe Hypertension. Clinical Case Seminar, J Clin Endocrinol Metab 2005 90: 563-569. (http://jcem.endojournals.org/cgi/content/full/90/1/563). "Clevidine (Cleviprex) for IV Treatment of Severe Hypertension", Table 1. Some Parenteral Drugs for Hypertensive Emergencies. The Medical Letter^® on Drugs and Therapeutics, Volume 50 (Issue 1295) September 22, 2008. Katzung, BG Introduction to Autonomic Pharmacology (Section II: Autonomic Drugs) in: Basic and Clinical Pharmacology (10th edition), (Katzung BG, ed) McGraw-Hill Medical , New York, pp. 75-92, 2007. Sympathetic Nerve Pathway: Neuroeffector Junction ("Simplified diagram of a sympathetic neuroeffector junction displaying genes which may be involved"); PharmGKb modified slightly to highlight uptake1, uptake-2, uptake 1 block, and location of intravesicular norephinephrine synthesis. (Pharmacogenomics Knowledge Base). http://www.pharmgkb.org/search/pathway/neurotransmitter/neuroeffector.jsp . T.E. Klein, J.T. Chang, M.K. Cho, K.L. Easton, R. Fergerson, M. Hewett, Z. Lin, Y. Liu, S. Liu, D.E. Oliver, D.L. Rubin, F. Shafa, J.M. Stuart and R.B. Altman, "Integrating Genotype and Phenotype Information: An Overview of the PharmGKB Project" (220k PDF), The Pharmacogenomics Journal (2001) 1, 167-170. Tellioglu T, Robertson D (November 2001). "Genetic or acquired deficits in the norepinephrine transporter: current understanding of clinical implications". Expert Rev Mol Med 2001: 1–10. Kekuda R, Prasad PD, Wu X, Wang H, Fei YJ, Leibach FH, Ganapathy V (Aug 1998). "Cloning and functional characterization of a potential-sensitive, polyspecific organic cation transporter (OCT3) most abundantly expressed in placenta". J Biol Chem 273 (26): 15971–9. Amphoux A, Vialou V, Drescher E, Brüss M, Mannoury La Cour C, Rochat C, Millan MJ, Giros B, Bönisch H, Gautron S. (Jun 2006). "Differential pharmacological in vitro properties of organic cation transporters and regional distribution in rat brain.". Neuropharmacology 50 (8): 941–952. Bourne HR and von Zastrow M "Drug Receptors and Pharmacodyamics" Chapter 2 in Basic and Clinical Pharmacology (10th edition), (Katzung BG, ed) McGraw-Hill Medical , New York, pp. 17-27, 2007. Muller M Lecture Material Online: Lecture 6: "Cellular Communication" http://www.uic.edu/classes/bios/bios100/summer2003/lect06.htm. Bowman T and Jove R STAT Proteins and Cancer: From the Molecular Oncology Program at the H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida http://www.moffitt.org/moffittapps/ccj/v6n6/dept6h.htm . Tong L, Warren TC, King J, Betageri R, Rose J, Jakes S (March 1996). "Crystal structures of the human p56lck SH2 domain in complex with two short phosphotyrosyl peptides at 1.0 A and 1.8 A resolution". J. Mol. Biol. 256 (3): 601–10. Sadowski I, Stone JC, Pawson T (December 1986). "A noncatalytic domain conserved among cytoplasmic protein-tyrosine kinases modifies the kinase function and transforming activity of Fujinami sarcoma virus P130gag-fps". Mol. Cell. Biol. 6 (12): 4396–4408. Russell RB, Breed J, Barton GJ (June 1992). "Conservation analysis and structure prediction of the SH2 family of phosphotyrosine binding domains". FEBS Lett. 304 (1): 15–20. von Zastrow M and Bourne HR "Drug Receptors and Pharmacodynamics" Chapter 2 in Basic and Clinical Pharmacology (11th edition), (Katzung BG, Masters, SB and Trevor AJ, eds) McGraw-Hill Medical , New York, on-line version (Access Medicine) 2009. Powledge TM (2004) Nicotine as Therapy. PLoS Biol 2(11): e404. doi:10.1371/journal.pbio.0020404 (http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0020404) Green T, Heinemann SF and Gusella JF Molecular Neurobiology and Genetics: Investigation of Neuron Function and Dysfunction (Review) Neuron, Vol. 20, 427-444, March, 1998 (Cell Press (c), 1998). Unwin N Nicotinic acetylcholine receptor at 9 Å resolution. J. Mol. Biol. 229, 1101-1124. Eyford, T Adenylyl cyclase http://proteopedia.org/wiki/index.php/Adenylyl_cyclase . 31 a. Hurley JH. Structure, mechanism, and regulation of mammalian adenylyl cyclase. J Biol Chem. 1999 Mar 19;274(12):7599-602. 31 b, Zhang G, Liu Y, Ruoho AE, Hurley JH. Structure of the adenylyl cyclase catalytic core. Nature. 1997 Mar 20;386(6622):247-53. Goodsell DS illustrator, The Scrips Research Institute, public domain work, http://en.wikipedia.org/wiki/Adenylate_cyclase . Ranganathan R, Ross E (1997). "PDZ domain proteins: scaffolds for signaling complexes.". Curr Biol 7 (12): R770–3 PDZ domain http://en.wikipedia.org/wiki/PDZ_domain Biaggioni I and Robertson D Adrenoceptor Agonists & Sympathomimetic Drugs (Chapter 9) in in Basic and Clinical Pharmacology (11th edition), (Katzung BG, Masters, SB and Trevor AJ, eds) McGraw-Hill Medical , New York, on-line version (Access Medicine) 2009. Korte E "PIP2 cleavage by PLC to release IP3 and DAG", public domain, http://en.wikipedia.org/wiki/File:PIP2_cleavage_to_IP3_and_DAG.jpg . McVary KT A review of combination therapy in patients with benign prostatic hyperplasia, Clinical Therapeutics 2007 29 (3): 387-398. Caine M The present role of alpha-adrenergic blockers in the treatment of benign prostatic hypertrophy. J Urol. 1986; 136: 1-4. Shapiro E Hartanto V and Lepor H. The response to alpha blockade in benign prostatic hyperplasia is related to the percent area density of prostate smooth muscle. Prostate. 1992; 21: 297-307. Brittsan AG and Kranias EG Review: Phosphlakmban and Cardiac Contractile Function. J. Mol Cell Cardiol 32. 2131-2139. Lomize A Phospholamban Pentamer, protein image from OPM database, public domain media (http://en.wikipedia.org/wiki/File:1zll_opm.gif) Foex P and Highan H. Myocardial Performance: Physiological Principles and Clinical Practice: A Companion to Miller's Anesthesia (Evers AS and Maze M, eds) Churchill Livingstone, Philadelphia, Chapter 14, 284-2285, 2004. 42(a) Weiss HR Effect of coronary artery occlusion on regional arterial and venous O₂ saturation, O₂ extraction, blood flow and O₂ consumption in the dog heart. Circulation Research 47(3) 400-407, September 1980. Khouri EM Gregg DE and Rayford CR Effect of exercise on cardiac output, left coronary flow and myocardial metabolism in the unanesthetized dog. Circulation Research 17(5) 327-437, November 1965. Epicardial Vessels: Gray's Anatomy, 20th U.S. edition of Gray's Anatomy of the Human Body, originally publishedin 1918, public domain. Beta-2 Adrenergic Receptor, figure public domain (http://en.wikipedia.org/wiki/File:2RH1.png); original crystallographic citations: 45 (a) Cherezov V, Rosenbaum DM, Hanson MA, Rasmussen SG, Thian FS, Kobilka TS, Choi HJ, Kuhn P, Weis WI, Kobilka BK, Stevens RC (2007). "High-resolution crystal structure of an engineered human β₂-adrenergic G protein-coupled receptor". Science 318 (5854): 1258–65. 45 (b) Rosenbaum DM, Cherezov V, Hanson MA, Rasmussen SG, Thian FS, Kobilka TS, Choi HJ, Yao XJ, Weis WI, Stevens RC, Kobilka BK (2007). "GPCR engineering yields high-resolution structural insights into β₂-adrenergic receptor function". Science 318 (5854): 1266–73. Westfall, TC and Westfall DP Neurotransmission: The Autonomic and Somatic Motor Nervous System in Goodman and Gilman's The Pharmacological Basis of Therapeutics, eleventh editions, (Brunton LL, Lazo JS and Parker KL, eds), McGraw-Hill Medical Publishing Division, New York, 137-181, 2006. Emorine LJ Marullo S Briend-Sutren MM Patey G Tate K Delavier-Klutchko C Strosberg AD Molecular characterization of the human β₃-adrenergic receptor. Science, Vol. 245, No. 4922, Sep. 8, 1989, pp. 1118-1121. Walston J Silver K Bogardus C Knowler W Celi FS Austin S Manning B Strosberg AD Stern MP Raben N Sorkin JD Roth J Shuldiner AR Time of onset of non-insulin-dependent diabetes mellitus and genetic variation in the β₃-adrenergic receptor gene. New England J. of Medicine, Vol. 333 No. 6, August 10, 1995, pp. 343-347. Hoffman BB Adrenoceptor-Activating & Other Sympathomimetic Drugs in: Basic and Clinical Pharmacology (10th edition), (Katzung BG, ed) McGraw-Hill Medical , New York, pp. 121-140, 2007. Goodsell, DS, Tyrosine Hydroxylase, The Scripps Research Institute, public domain image, http://en.wikipedia.org/wiki/File:Tyrosine_Hydroxylase.png . Chemical Synapse, http://schools-wikipedia.org/wp/c/Chemical_synapse.htm . Frang H Cockcroft V Karskela T Scheinin M Marjamaki A Phenoxybenzamine binding reveals the helical orientation of the third transmembrane domain of adrenergic receptors JBC, 276, 31279-31284, June 6, 2001. http://www.jbc.org/content/276/33/31279.full Barrett KE Barman SM Boitano S Brooks H "The Adrenal Medulla & Adrenal Cortex" in: Ganong's Review of Medical Physiology, 23e, Chapter 22, on-line version, 2010. Achermann JC and Jameson JL "Disorders of Sex Development" in Harrison's Principles of Internal Medicine (eds, Fauci AS Braunwald E Kasper DL Hauser SL Longo DL Jameson JL Loscalzo J), 17th edition, pp 2345-2346, 2008, McGraw-Hill Medical, New York. Goldenberg M Aranow H Jr Smith AA Faber M Pheochromocytoma and essential hypertensive vascular disease. Arch. Intern. Med. 86: 823-826, 1950. Carrim YO "The Cardiovascular system, heart muscle; The heart as a pump." http://samedical.blogspot.com/2010/08/heart-muscle-heart-as-pump.html . "Madhero88" "A graphical representation of the electrical conduction system of the heart showing the sinoatrial node, atrioventricular none, bundle of His, Purkinje fibers and Bachmann's bundle, http://en.wikipedia.org/wiki/File:ConductionsystemoftheheartwithouttheHeart.png . Ewy GA Cardiopulmonary and Cardiocerebral Resuscitation, Chapter 50, in Hurst's The Heart, 12th edition (eds, Fuster V O'Rourke RA Wash RA Poole-Wilson P; associate eds: King II SB Roberts R Nash IS Prystowsky EN; Editors of the online edition: senior editors: Walsh RA and Simon DI; associate Editors; Hoit BD Fang JC Costa M), 2008, on-line edition. 58a. American Heart Association. 2005 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation, 2005; 112 (Suppl IV): IV-1-IV-211. Mohrman DE and Heller LJ "Vascular Control" Chapter 7, in Cardiovascular Physiology, 6th edition, The McGraw-Hill Companies, Inc, 2006, on-line edition. Stoelting, RK and Dierdorf, SF, "Asthma" in Anesthesia and Co-Existing Disease, 4th edition, Chapter 14, pp 194-204, Churchill-Livingstone, Philadelphia, 2002 60a. Kingston, HGG, Hirshman, CA Perioperative management of the patient with asthma. Anesth Analg 1984; 63: 844-55. (second sourced from reference 1) Roisen, MF, "Anesthetic Implications of Concurrent Diseases" in Anesthesia, 5th edition, (Miller, R.D, editor), Chapter 25, pp 996-997, Churchill-Livingstone, Philadephia 2000. Barrett KE Barman SM Boitano S Brooks H "Endocrine Functions of the Pancreas & Regulation of Carbohydrate Metabolism" in: Ganong's Review of Medical Physiology, 23e, Chapter 21, on-line version, 2010. Narayanese and YassineMrabet, Citric acid cycle (Tricarboxylic acid cycle), public domain, GNUU Free Documentation License, http://en.wikipedia.org/wiki/Citric_acid_cycle . Elayat AA, el-Naggar MM, Tahir M (1995). "An immunocytochemical and morphometric study of the rat pancreatic islets". Journal of Anatomy 186 (Pt 3): 629–37. (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1167020/pdf/janat00134-0170.pdf) 64a. Islets of Langerhans; http://en.wikipedia.org/wiki/Islets_of_Langerhans Süß C Sukale J Solima M "light microscopy of a paraffin embedded mouse islet; labels: insulin green, glucagon red, nuclei blue" Solimena Lab, Med. Fac., University of Technology, Dresden, Germany. http://en.wikipedia.org/wiki/File:Mouse_islet_LM_SolimenaLab.jpg . http://en.wikipedia.org/wiki/File:PDB_3tgl_EBI.jpg courtesy: http://www.ebi.ac.uk/ Chapus C, Rovery M, Sarda L, Verger R (1988). "Minireview on pancreatic lipase and colipase". Biochimie 70 (9): 1223–1234. Barrett KE Barman SM Boitano S Brooks H "General Principles & Energy Production in Medical Physiology in: Ganong's Review of Medical Physiology, 23e, Chapter 1, on-line version, 2010. Austgen L and Bowen R "Brown Adipose Tissue" http://www.vivo.colostate.edu/hbooks/pathphys/misc_topics/brownfat.html . Ropper AH and Samuels MA "Ion Channel Disorders: The periodic paralyses and hereditary nondystrophic mytonias (Channelopathies) in Adams & Victor's Principles of Neurology, 9e, 2009, online edition. Estelle F Simons R Gu X and Simons KJ Epinephrine absorption in adults: Intramuscular versus subcutaneous injection J Allergy Clin Immunol 2001; 108: 871-873. Flavine Adenine Dinucleotide (FAD) public domain images http://en.wikipedia.org/wiki/Flavin_adenine_dinucleotide . Axelrod J (August 1957). "O-Methylation of Epinephrine and Other Catechols in vitro and in vivo". Science 126 (3270): 400–1. Entacapone PubMed Health http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0000168 . Dopamine Degradation by "Neurotiker", public domain image, http://en.wikipedia.org/wiki/File:Dopamine_degradation.svg . Haggstrom M Breakdown of norepinephrine, public domain inkscape http://en.wikipedia.org/wiki/File:Noradrenaline_breakdown.svg . Fvasconcellos "Cartoon diagram of human catechol-O-methyl transferase (COMT) in complex with S-adenosyl methionine and 3,5-dinitrocatechol; public domain drawing. 77a. Rutherford K, Le Trong I, Stenkamp RE, Parson WW (June 2008). "Crystal structures of human 108V and 108M catechol O-methyltransferase". J Mol Biol 380 (1): 120–30, http://www.rcsb.org/pdb/explore/explore.do?structureId=3BWM . Stoelting, R.K., "Local Anesthetics", in Pharmacology and Physiology in Anesthetic Practice, Lippincott-Raven Publishers, 1999, pp 158-181. Parrmann C Decision Making and Local Anesthesia Dimensions of Dental Hygiene, October 2008; 6(10): 24. http://www.dimensionsofdentalhygiene.com/ddhright.aspx?id=2384 . Allwood MJ Cobbold AF and Ginsberg J. Peripheral vascular effects of noradrenaline, isopropylnoradrenaline, and dopamine. Br. Med. Bull., 1963, 19: 132-136. Bloom FE Neurotransmission and the Central Nervous System in Goodman and Gilman's The Pharmacological Basis of Therapeutics, eleventh editions, (Brunton LL, Lazo JS and Parker KL,eds)McGraw-Hill Medical Publishing Division, New York, 317-340 2006. The dopamine pathways in the brain, Lundbeck Institute, CNSforum, Educational Resources, Image Bank, http://www.cnsforum.com/imagebank/item/Neuro_path_DA/default.aspx . Diseases associated with abnormalities in the basal ganglia, Lundbeck Institute, CNSforum, Educational Resources, Image Bank, http://www.cnsforum.com/imagebank/item/brain_struc_bagang_ALZ/default.aspx . Factor SA and Weiner WJ Molecular Characterization of Dopamine Receptors in Parkinson's Disease: Diagnosis and Management http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=parkinsons&part=A2249 . Dopamine receptors-7- transmembrane spanning, G-protein coupled receptors, Lundbeck Institute, CNSforum, Educational Resources, Image Bank, http://www.cnsforum.com/imagebank/item/D_struc_level2/default.aspx . Standaert DG and Galanter JM Pharmacology of Dopaminergic Neurotransmission in Principles of Pharmacology: The Pathophysiologic Basis of Drug Therapy, 2nd Edition (Golan DE, Tashijan Jr AH, Armstrong EJ and Armstrong AW, eds) Wolters Kluwer-Lippincott Williams & Wilkins, Philadelphia, 185-206, 2008. Dopamine receptor subtypes, Lundbeck Institute, CNSforum, Educational Resources, Image Bank, http://www.cnsforum.com/imagebank/item/DA_rcpt_subtypes/default.aspx . D2 receptor antagonist, Lundbeck Institute, CNSforum, Educational Resources, Image Bank, http://www.cnsforum.com/imagebank/item/hrl_rcpt_sys_DA2_antag/default.aspx . Henkel J Structure of the basal ganglia, including thalamus, globus paladus, substantia nigra and cerebellum, http://en.wikipedia.org/wiki/File:Basal_Ganglia_and_Related_Structures.svg . Dopamine and Serotonin pathways, http://en.wikipedia.org/wiki/File:Dopamineseratonin.png . Valeryns G-protein receptor http://en.wikipedia.org/wiki/File:7TM4_(GPCR).png Bensaccount G-protein coupled receptor http://en.wikipedia.org/wiki/File:7TM4_(GPCR).png . Jahnichen S Activation cycle of G-proteins by G-protein-coupled receptors, http://en.wikipedia.org/wiki/File:GPCR-Zyklus.png . Raashid AS So CH Kong MMC Furtak T El-Ghundi M Cheng R O'Dowd BF George SR D₁-D₂ dopamine receptor heterooligomers with unique pharmacology are couple to rapid activation of Gq/11 in the striatum. PNAM, January 9, 2007, 104(2): 654-659. Dopamine Pathways, NIDA Research Report Series--Methamphetamine Abuse and Adiction, http://en.wikipedia.org/wiki/File:Dopamine_Pathways.png . Davie CA (2008). "A review of Parkinson's disease". Br. Med. Bull. 86: 109–27. 96a."Madhero88" Midbrain Section http://commons.wikimedia.org/wiki/File:Midbrainsection.svg . 96b Hauser RA Parkinson's Disease: Early Diagnosis and Treatment http://www.youtube.com/watch?v=T8lXjNUMaWA . Haggstrom M (images by Gillies A, (Araru) and Lynch PJ Basal Ganglia Circuits, http://en.wikipedia.org/wiki/File:Basal_ganglia_circuits.svg . Gillies A Classic connectivity diagram of the basal ganglia, showing glutamatergic pathways as red, dopaminergic as magenta and GABA pathways as blue. http://en.wikipedia.org/wiki/File:Basal-ganglia-classic.png . Gillies A (Araru) basal-ganglia-coronal-sections, http://commons.wikimedia.org/wiki/File:Basal-ganglia-coronal-sections-large.png . 99a Fisch A Basal Ganglia- Drawit to Know it- Neuroantomy Tutorial, http://www.youtube.com/watch?v=-5PXAUdWDgU . Draw it to know it site: http://www.drawittoknowit.com/ . Burns JM Wilkinson S Kieltyka J Overman J Lundsgaarde T Tollefson T Koller WC Pahwa R Troster AI Lyons KE Batnitzky S Wetzel L and Gordon MA Analysis of pallidotomy lesion positions using three-dimensional reconstruction of pallidal lesions, the basal ganglia, and the optic tract. Neurosurgery 41(6), December 1997, pp 1303-1318. 100a. Thomas BG, Insertion of an electrode during deep brain stimulation for Parkinson's disease. http://en.wikipedia.org/wiki/File:Parkinson_surgery.jpg . 100b. Deep brain simulation for Parkinson's Disease, http://www.youtube.com/watch?v=IOHtUzW02cg . Standaert DG and Young AB Treatment of Central Nervous System Degenerative Disorders: In Goodman and Gillman's The Pharmacological Basis of Therapeutics, (Brunton LL, Lazo JS and Parker KL,eds) The McGraw-Hill Companies, Inc., 2006, pp.527-538. Cotzias GC Papavasilious PS Gellene R Modification of Parkinsonism: Chornic treatment with L-DOPA. New Engl. J. Med., 19769, 280: 337-345. (cited by primary reference 101) Hornykiewicz O. Dopamine in the basal ganglia: Its role and therapeutic indictions (including the clinical use of L-DOPA). Br. Med. Bull., 1973, 29: 172-178. (cited by primary reference 101) "Marvin 101" Immunohistochemistry for alpha-synuclein showing positive staining (brown of an intraneural Lewy-body in the Substantia nigra in Parkinson disease. August 2009, http://en.wikipedia.org/wiki/File:Lewy_Body_alphaSynuclein.jpg . Beal JA Frontal (Coronal) section of the brain http://en.wikipedia.org/wiki/File:Human_brain_frontal_(coronal)_section_description_2.JPG . Sudarsky Lewis, "Chapter 24. Gait and Balance Disorders" (Chapter). Fauci AS, Braunwald E, Kasper DL, Hauser SL, Longo DL, Jameson JL, Loscalzo J: Harrison's Principles of Internal Medicine, 17e, 2008, on-line edition. 106a. Parkinsonian Gait Demonstration http://www.youtube.com/watch?v=j86omOwx0Hk . Sir William Richard Gowers, neurologist, researcher and artist, drew this illustration in 1886 as part of his documentation of Parkinson's Disease. The image appeared in his book, A Manual of Diseases of the Nervous System, still used today by medical professionals as a primary reference for this disease. (public domain due to copyright expiration). http://commons.wikimedia.org/wiki/File:Sir_William_Richard_Gowers_Parkinson_Disease_sketch_1886.svg . DeLong Mahlon R, Juncos Jorge L, "Chapter 366. Parkinson’s Disease and Other Extrapyramidal Movement Disorders" (Chapter). Fauci AS, Braunwald E, Kasper DL, Hauser SL, Longo DL, Jameson JL, Loscalzo J: Harrison's Principles of Internal Medicine, 17e,2008, on-line edition. 108a Silver D Parkinson's Disease Dementia MDTV http://www.youtube.com/watch?v=ZPnpmVWU0Hk . UCtelevision, January 31, 2008. Alpha-synuclein http://en.wikipedia.org/wiki/Alpha-synuclein . 109a. Uéda K, Fukushima H, Masliah E, Xia Y, Iwai A, Yoshimoto M, Otero DA, Kondo J, Ihara Y, Saitoh T (December 1993). "Molecular cloning of cDNA encoding an unrecognized component of amyloid in Alzheimer disease". Proc. Natl. Acad. Sci. U.S.A. 90 (23): 11282–6. 109b. Xia Y, Saitoh T, Uéda K, Tanaka S, Chen X, Hashimoto M, Hsu L, Conrad C, Sundsmo M, Yoshimoto M, Thal L, Katzman R, Masliah E (October 2001). "Characterization of the human alpha-synuclein gene: Genomic structure, transcription start site, promoter region and polymorphisms". J. Alzheimers Dis. 3 (5): 485–494. 109c. Xia Y, Saitoh T, Uéda K, Tanaka S, Chen X, Hashimoto M, Hsu L, Conrad C, Sundsmo M, Yoshimoto M, Thal L, Katzman R, Masliah E (2002). "Characterization of the human alpha-synuclein gene: Genomic structure, transcription start site, promoter region and polymorphisms: Erratum p489 Fig 3". J. Alzheimers Dis. 4 (4): 337. Cookson MR Events in alpha synuclein toxicty http://en.wikipedia.org/wiki/File:Events_in_alpha_synuclein_toxicity.jpg . (Cookson Molecular Neurodegeneration 2009 4:9) . Kitada T, Asakawa S, Hattori N, Matsumine H, Yamamura Y, Minoshima S, Yokochi M, Mizuno Y, Shimizu N (April 1998). "Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism". Nature 392 (6676): 605–8. Matsumine H, Yamamura Y, Hattori N, Kobayashi T, Kitada T, Yoritaka A, Mizuno Y (April 1998). "A microdeletion of D6S305 in a family of autosomal recessive juvenile parkinsonism (PARK2)". Genomics 49 (1): 143–6 ENW Structure of the PARK2 protein http://en.wikipedia.org/wiki/File:Protein_PARK2_PDB_1iyf.png . 113a. Parkin (ligase) http://en.wikipedia.org/wiki/Parkin_(ligase) . Lohmann E, Periquet M, Bonifati V, Wood NW, De Michele G, Bonnet AM, Fraix V, Broussolle E, Horstink MW, Vidailhet M, Verpillat P, Gasser T, Nicholl D, Teive H, Raskin S, Rascol O, Destée A, Ruberg M, Gasparini F, Meco G, Agid Y, Durr A, Brice A (2003). "How much phenotypic variation can be attributed to parkin genotype?". Ann. Neurol. 54 (2): 176–85. PARK7 Gene, NIH Genetic home reference: http://ghr.nlm.nih.gov/gene/PARK7 . UCHL1 gene (PARK5), NIH Genetic home reference: http://ghr.nlm.nih.gov/gene/UCHL1 . LRRK2 gene (PARK8), NIH Genetic home reference: http://ghr.nlm.nih.gov/gene/LRRK2 . Aminoff MJ and Kerchner GA Nervous System Disorders, Chapter 24 in Current Medical Diagnosis & Treatment 2011 (McPhee SJ, Papadakis MA, eds. Rabow MW, Associate Ed) McGraw-Hill, Fiftieth edition, 2011, on-line edition. Kayser-Fleischer Ring http://en.wikipedia.org/wiki/Kayser%E2%80%93Fleischer_ring . Mattheis E Kayser-Fleicher Ring http://www.gourmandizer.com/wilsons/kf2.html . Finkbeiner S Gladstone Institute of Neurological Disease, The Taube-Koret Center for Huntington's Disease Research, and the University of California San Francisco, http://en.wikipedia.org/wiki/File:Neuron_with_mHtt_inclusion.jpg and http://www.ninds.nih.gov/news_and_events/news_articles/pressrelease_huntington's_inclusion_bodies_101304.htm . Collinge J, UCL Insitute of Neurology, Department of Neurodegenerative Disease, National Hospital for Neurology & Neurosurgery, London (http://www.ion.ucl.ac.uk/departments/neurodegeneration) Creutzfeldt-Jakob disease (CJD) http://www.youtube.com/watch?v=vKGXnwXrPCQ . Silver D Dopamine Agonist Patch for Treatment of Parkinson's MDTV http://www.youtube.com/watch?v=OlF_ysmzVYo . UCtelevision, January 22, 2008. Beal JA Department of Cellular Biology & Anatomy, Louisiana State University Health Sciences Center, "Human caudal brainstem posterior view description", http://en.wikipedia.org/wiki/File:Human_caudal_brainstem_posterior_view_description.JPG . Ferguson, Alastair V., Ted D. Hoyda, and Christopher J. Price. “The Area Postrema: A Brain Monitor and Integrator of Systemic Autonomic State.” The Neuroscientist, Vol. 14, No. 2, 182-194 (2008). 1 April 2008. http://nro.sagepub.com/content/14/2/182.abstract . [http://en.wikipedia.org/wiki/Area_postrema] . Dyskinesia http://en.wikipedia.org/wiki/Dyskinesia . Parkinson's Disease Video: Dyskinesia http://www.youtube.com/watch?v=d1jJyk_poqE . Uploaded by LloydTanTrustFund, http://www.lloydtan-trust.com/ , May 18, 2009. Aminoff MJ "Pharmacologic Management of Parkinsonism & Other Movement Disorders" Chapter 28 in Basic and Clinical Pharmacology (11th edition), (Katzung BG, Masters, SB and Trevor AJ, eds) McGraw-Hill Medical , New York, on-line version (Access Medicine) 2009. Atkielski A Schematic diagram of normal sinus rhythm for a human heart as seen on ECG, public domain image, http://en.wikipedia.org/wiki/File:SinusRhythmLabels.svg . Fred HL and Dijk HA Erythomelalgia http://en.wikipedia.org/wiki/File:Erythromelalgia.jpg . Waxman, Stephan G.; Dib-Hajj, Sulayman D. (June 2005). "Erythromelalgia: A hereditary pain syndrome enters the molecular era". Annals of Neurology 57 (6): 785–788. Ormond JK (1948). "Bilateral ureteral obstruction due to envelopment and compression by an inflammatory retroperitoneal process". J Urol. 59 (6): 1072–9; Ormond JK (October 1965). "Idiopathic retroperitoneal fibrosis: a discussion of the etiology". J Urol. 94 (4): 385–90; http://en.wikipedia.org/wiki/Retroperitoneal_fibrosis . Binda C, Hubálek F, Li M, et al. (2005). "Binding of rasagiline-related inhibitors to human monoamine oxidases: a kinetic and crystallographic analysis". Journal of medicinal chemistry 48 (26): 8148–54. Chen JJ and Swope DM Clinical pharmacology of rasagiline: A novel, second-generation propargyline for the treatment of Parkinson Disease, J Clin Pharmacol 2005 45: 878-894, on-line version. Chen JJ Swope DM and Dashtiour K Comprehensive review of rasagiline, a second-generation monoamine oxidase inhibitor, for the treatment of Parkinson's disease. Clinical Therapeutics, 29(9), 1825-1849, 2007. 135a. Riederer P and Youdim MB, Monoamine oxidase activity and monoamine metabolism in brains ofparkinsonian patients treated with I-deprenyl, J Neurochem 46 (1986), pp. 1359–1365. 135b Youdim MB and Finberg JP, Monoamine oxidase In:. In: A Lajtha, Editor, Handbook of Neurochemistry, Enzymes in the Nervous System 4, Plenum Press, New York, NY (1983), pp. 293–313. 135c Saura Marti J Kettler R, Da Prada M and Richards JG, Molecular neuroanatomy of MAO-A and MAO-B, J Neural Transm Suppl. 32 (1990), pp. 49–53. Meltzer H "Antipsychotic Agents & Lithium" Chapter 29 in Basic and Clinical Pharmacology (11th edition), (Katzung BG, Masters, SB and Trevor AJ, eds) McGraw-Hill Medical , New York, on-line version (Access Medicine) 2009. Potter WZ and Hollister LE "Antipsychotic Agents & Lithium" Chapter 29 in Basic and Clinical Pharmacology (10th edition), (Katzung BG, editor) McGraw-Hill Medical , New York, 2007. Reus VI "Chapter 386. Mental Disorders" (Chapter). Fauci AS, Braunwald E, Kasper DL, Hauser SL, Longo DL, Jameson JL, Loscalzo J: Harrison's Principles of Internal Medicine, 17e,2008, on-line edition. Meyer-Lindenberg A Schizophrenia PET scan, http://en.wikipedia.org/wiki/File:Schizophrenia_PET_scan.jpg public domain. Meyer-Lindenberg A Miletich RS Kohn PD Esposito G Carson RE Quarantelli M Weinberger DR Berman KF Reduced prefrontal activity predicts exaggerated striatal dopaminergic function in schizophrenia Nat Neurosci. 2002 Mar; 5(3): 267-271. Wisconsin card sort http://en.wikipedia.org/wiki/Wisconsin_card_sort . 141a. Berg EA. (1948). A simple objective technique for measuring flexibility in thinking J. Gen. Psychol. 39: 15-22. 141b. Psychological Assessment Resources. Computerised Wisconsin Card Sort Task Version 4 (WCST). Psychological Assessment Resources; 2003. 141c. Milner B. Effect of Different Brain Lesions on Card Sorting. Archives of Neurology 1963; 9: 90-100. 141d Greve KW, Stickle TR, Love J, Bianchini KJ, Stanford MS. Latent structure of the Wisconsin Card Sorting Test: a confirmatory factor analytic study. Archives of Clinical Neuropsychology 2005; 20: 355-364. 141e. Berman KF, Ostrem JL, Randolph C et al. Physiological activation of a cortical network during performance of the Wisconsin Card Sorting Test: a positron emission tomography study. Neuropsychologia 1995; 33: 1027-1046. 141f Cabeza R, Nyberg L. Imaging cognition II: An empirical review of 275 PET and fMRI studies. J Cogn Neurosci 2000; 12: 1-47. 141g Cannon TD, Glahn DC, Kim J, Van Erp TG, Karlsgodt K, Cohen MS, Nuechterlein KH, Bava S, Shirinyan D., Dorsolateral Prefrontal Cortex Activity During Maintenance and Manipulation of Information in Working Memory in Patients With Schizophrenia, Arch Gen Psychiatry 2005;62:1071-1080. 141h Rossi A, Daneluzzo E, Tomassini A, Struglia F, Cavallaro R, Smeraldi E, Stratta P., The effect of verbalization strategy on Wisconsin Card Sorting Test performance in schizophrenic patients receiving classical or atypical antipsychotics. BMC Psychiatry. 1290 Jan 26;6:3. Criteria for Schizophrenia: Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Text Revision Laube, B; Hirai H, Sturgess M, Betz H, and Kuhse J (1997). "Molecular determinants of antagonists discrimination by NMDA receptor subunits: Analysis of the glutamate binding site on the NR2B subunit". Neuron 18 (3): 493–503. http://www.cell.com/neuron/retrieve/pii/S0896627300812490 . User.Delldot (http://en.wikipedia.org/wiki/User:Delldot) Activated NMDAR http://en.wikipedia.org/wiki/File:Activated_NMDAR.PNG .. NMDA Receptor http://en.wikipedia.org/wiki/NMDA_receptor . The Pleasure Centres: Reward Circuit figure, http://thebrain.mcgill.ca/flash/a/a_03/a_03_cr/a_03_cr_que/a_03_cr_que.html . Tisch S, Silberstein P, Limousin-Dowsey P, Jahanshahi M. 2004. The basal ganglia: anatomy, physiology, and pharmacology. Psychiatric clinics of North America 27:757-799. Pierce RC, Kumaresan V. 2006. The mesolimbic dopamine system: The final common pathway for the reinforcing effect of drugs of abuse? Neuroscience and Biobehavioral Reviews 30:215-38. Gray's Anatomy: Dissection of brain-stem, lateral view, public domain as a result of its 1918 publication date http://en.wikipedia.org/wiki/File:Gray683.png . Beal JA, Department of Cellular Biology & Anatomy, Louisiana State University Health Sciences Center Shreveport, Human brain left dissected-midsagittal view http://en.wikipedia.org/wiki/File:Human_brain_left_dissected_midsagittal_view_description_2.JPG . Baldessarini RJ and Tarazi FI : Pharmacotherapy of Psychosis and Mania In Goodman and Gillman's The Pharmacological Basis of Therapeutics, (Brunton LL, Lazo JS and Parker KL,eds) The McGraw-Hill Companies, Inc.,2006, pp.461-500. Westfall TC and Westfall DP Adrenergic Agonists and Antagonists, Chapter 12, in Goodman & Gilman's The Pharmacological Basis of Therapeutics (Brunton LL, editor; Chabner BA and Knollmann BC, associate editors), 12th edition, McGraw Hill Medical, 2011, 277-333. Rippe, James M.; Irwin, Richard S. (2003). Irwin and Rippe's intensive care medicine. Philadelphia: Lippincott Williams & Wilkins. "Madhero88" Ventricular assist device, http://en.wikipedia.org/wiki/File:Ventricular_assist_device.png . Ventricular Assist Device http://en.wikipedia.org/wiki/Ventricular_assist_device . Kotchen TA, "Chapter 241. Hypertensive Vascular Disease". Fauci AS, Braunwald E, Kasper DL, Hauser SL, Longo DL, Jameson JL, Loscalzo J: Harrison's Principles of Internal Medicine, 17e,2008, on-line edition. Wood F, Hypertensive Retinopathy, http://en.wikipedia.org/wiki/File:Hypertensiveretinopathy.jpg . Wong TY, Mcintosh R (2005). "Hypertensive retinopathy signs as risk indicators of cardiovascular morbidity and mortality". British Medical Bulletin 73-74: 57–70. 158a. Hypertensive retinopathy http://en.wikipedia.org/wiki/Hypertensive_retinopathy . Public Domain, "Lead II (2) ECG EKG strip of an AICD ICD converting a patient back into thier baseline cardiac ryhthm. The AICD fires near the end of the strip, where the straight line is seen." http://en.wikipedia.org/wiki/File:Torsades_converted_by_AICD_ECG_strip_Lead_II.JPG . Torsade de Pointes from "HeartStartSkills" http://www.youtube.com/watch?v=1ccTO6fNobU . 3rd Degree Atrioventriular Block from "HeartStartSkills" http://www.youtube.com/watch?v=NEGnCKC0Mrk . Saucerman J "Automated contractility measurements of cardiac myocytes" http://www.youtube.com/watch?v=EuciGjPwqtc and http://bme.virginia.edu/saucerman/index.php?n=Main.People . Kauczuk Cultured skin mast cells, stained with Tol Blue, http://en.wikipedia.org/wiki/File:SMCpolyhydroxysmall.jpg . Prussin C, Metcalfe DD (2003). "IgE, mast cells, basophils, and eosinophils". J Allergy Clin Immunol 111 (2 Suppl): S486–94; http://en.wikipedia.org/wiki/Mast_cell . A Levalbuterol Metered-Dose Inhaler (Xopenex HFA) for Asthma: The Medical Letter on Drugs and Therapeutics, March 13, 2006, Issue 1230 p. 21. Lotval J Palmqvist M Arvidsson P Maloney A Ventresca GP Ward J The therapeutic ratio of R-albuterol is comparable with that of RS-albuterol in asthmatic patients. J. Allergy Clin Immunol 2001 Nov; 108(5): 726-731. Mills B Ball-and-stick model of the (R)-salbutamol (top) and (S)-salbutamol (bottom) molecules, both C₁₃H₂₁NO₃ . http://en.wikipedia.org/wiki/File:RS-salbutamol-from-xtal-3D-balls.png 3M Autohaler™ http://solutions.3m.com/wps/portal/3M/en_WW/DrugDeliverySystems/DDSD/technology-solutions/inhalation-technology/systems/autohaler/ . FDA Drug Safety Communication: New safety requirements for long-acting inhaled asthma medications called Long-Acting Beta-Agonists (LABAs) . Fanta CH Drug Therapy: Asthma N Engl J Med March 5, 2009 1002-1014. Mometasone/Formoterol (Dulera) for Asthma The Medial Letter on Drugs and Therapeutics October 18, 2010, issue 1349, p. 83. Arformoterol (Brovana) for COPD The Medical Letter Online, July 2, 2007 Issue 1264, p. 53. Morgan Jr GE Mikhail MS Murray MJ Clinical Anesthesiology, Chapter 12, Adrenergic Agonists & Antagonists, on-line edition, 2006. Flach AJ and Fraunfelder FW Opthalmic Therapeutics, Chapter 3 in (Vaughan & Asbury's General Ophthalmology, Riordan-Eva P and Whitcher JP, eds, 17th edition (on-line version), 2008. Orlando G Animation that illustrates the pupillary light reflex. When the light is turned on, the pupil reacts by constricting. http://en.wikipedia.org/wiki/File:Eye_dilate.gif . Manske M Dilated pupils after an optometrist appointment. http://en.wikipedia.org/wiki/File:Dilated_pupils_2006.jpg . HeartStartSkills, "Sinus Tachycardia with Bundle Branch Block" http://www.youtube.com/watch?v=Df7c7eppIJs . Midodrine for Orthostatic Hypotension, The Medical Letter on Drugs and Therapeutics, June 20, 1997, issue 1003, p. 59. 178a. Robertson D and Davis TL, Nurology, 45 suppl 5: S26, 1995. Midodrine Update, FDA U.S. Food and Drug Administration, http://www.fda.gov/Drugs/DrugSafety/ucm225444.htm . Galanter JM and Lowenstein DH "Principles of Nervous System Physiology and Pharmacology" Chapter 7 in in Principles of Pharmacology: The Pathophysiologic Basis of Drug Therapy, 2nd Edition (Golan DE, Tashijan Jr AH, Armstrong EJ and Armstrong AW, eds) Wolters Kluwer-Lippincott Williams & Wilkins, Philadelphia, 91-106, 2008. Lee JY and DeBernardis JF Alpha 2-adrenergic receptors an calcium: alpha 2-receptor blockade in vascular smooth muscle as a approach to the treatment of hypertension, Methods Find Exp Exp Clin Pharmacol. 1990, Apr; 12(3) 213-215. http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=Retrieve&list_uids=1972206 . Maksim Diagram showing the location of vascular smooth muscle cells http://en.wikipedia.org/wiki/File:Anatomy_artery.png . Benowitz NL Chapter 11. Antihypertensive agents, in in Basic and Clinical Pharmacology (11th edition), (Katzung BG, Masters, SB and Trevor AJ, eds) McGraw-Hill Medical , New York, on-line version (Access Medicine) 2009. Head GA Mayorov DN Imidazoline receptors, novel agents and therapeutic potential Cardiovasc Hematol Agents Med Chem 4(1): 17-32, 2006. Ernsberger P The I1-imidazoline receptor and its cellular signaling pathways Ann.N .Y. Acad Sci 881: 35-53 1999. Zhu QM Lesnick JD Jasper JR MacALennan SJ Dillon MP Eglen RM and Blue Jr DR Cardiovascular effects of rilmenidine, moxonidine and clonidine in conscious wild-type and D79N α_2A-adrenoceptor transgenic mice. British Journal of Pharmacology (1998) 126, 1522-1530. MacMillan LB Lakhlani PP Hein L Piascik M Limbird LE Central hypotensive effects of the α_2A-adrenergic receptor subtype. Science, 273, 801-803,1996. Yu A and Frishman WH Imidazoline receptor agonist drugs: a new approach to the treatment of systemic hypotension. J. Clin. Pharmacol. 36, 98-111, 1996. Bousquet P Identification and characterization of I1 imadazoline receptors: their role in blood pressure regulation. American Journal of Hypertension, 2000; 12: 84S-88S. Fabi F Argiolas L Ruvolo G del Basso P Neuropeptide Y-induced potentiation of noradrenergic vasoconstriction in the human saphenous vein: involvement of endothelium generated thromboxane. British Journal of Pharmacology (1994) 124, 101-110. Jahnichen S NMR solution structure of Neuropeptide Y. http://en.wikipedia.org/wiki/File:Neuropeptide_Y.png . 191a. Monks SA Karagianis G Howlett GJ Notrton RS Solution structure of human neuropeptide Y J. Biomol NMR 1996 Dec; 8(4): 379-390. Olson KR Clonidine and related drugs in Poisoning & Drug Overdosage, 5th edition, on-line edition, McGraw-Hill Companies, 2007. Stafford B Child & Adolescent Psychiatric Disorders & Psychosocial Aspects of Pediatrics, Chapter 6, in Current Diagnosis & Treatment: Pediatrics, 20th edition (Hay Jr WH Levin MJ Sondheimer JM and Deterding RR, eds) on-line edition, McGraw-Hill Companies, 2011. Multiple endocring neoplasia type 2; Bilateral pheochromocytomas associated with multiple endocrine neoplasia type 2 http://en.wikipedia.org/wiki/Multiple_endocrine_neoplasia_type_2 ; http://en.wikipedia.org/wiki/File:Bilateral_pheo_MEN2.jpg . public domain image. Pheochromocytoma, public domain, http://en.wikipedia.org/wiki/File:Pheochromocytoma.jpg . (Choyke PL Glenn GM Walther W Patronas NJ Linehan WM Zbar B, Radiology (March) 146: 629-642, 1995, http://www.cc.nih.gov/ccc/papers/vonhip/adrenal.html .) Fitzgerald PA Adrenal Medulla & Paraganglia (Chapter 12) in Greenspan's Basic & Clinical Endocrinology, 8th edition, Gardner DB and Shoback D, eds, on-line edition, The McGraw-Hill Companies, 2007. Salmon JF Glaucoma, Chapter 11 in in (Vaughan & Asbury's General Ophthalmology, Riordan-Eva P and Whitcher JP, eds, 17th edition (on-line version), 2008. Shoy, Methamphetamines, http://en.wikipedia.org/wiki/File:Methamphetamines.PNG . Ropper AH and Samuels MA Disorders of the Nervous System Caused by Drugs, Toxins, and Other Chemical Agents (Chapter 43) in Adams & Victor's Principles of Neurology, 9th edition. The McGraw-Hill Companies, 2009, on-line edition. Apartmento2 A rational scale to assess the harm of drugs, public domain (as explained in the figure legend), http://en.wikipedia.org/wiki/File:Rational_scale_to_assess_the_harm_of_drugs_(mean_physical_harm_and_mean_dependence).svg . Drug classification:making a hash of it? House of Commons Science and Technology Committee, Fifth Report of Session 2005-2006, http://news.bbc.co.uk/2/shared/bsp/hi/pdfs/31_07_06_drugsreport.pdf , appendex 14. Deep brain stem dissection: This faithful reproduction of a lithograph plate from Gray's Anatomy, This image is in the public domain because its copyright has expired. http://en.wikipedia.org/wiki/File:Gray690.png . 202a. Brain: Reticular Activating System http://en.wikipedia.org/wiki/Reticular_activating_system . Steriade, M "Neuromodulatory systems of thalamus and neocortex." Seminars in the Neurosciences 7 (5): 361–370, 1995. Steriade, M "Arousal: Revisiting the reticular activating system". Science 272 (5259): 225–226, 1996. Rothballer, AB "Studies on the adrenaline-sensitive component of the reticular activating system". Electroencephalography and Clinical Neurophysiology 8 (4): 603–621 (1956). Kinomura S Larsson,J Gulyas B & Roland PE. "Activation by attention of the human reticular formation and thalamic intralaminar nuclei". Science 271 (5248): 512–515 (1996). Hsieh Y-S Yang S-F Kuo D-Y Amphetamine, an appetite suppressant, decreases neuropeptide Y immunoreactivity in rat hypothalamic paraventriculum. Regulatory Peptides 127: issues 1-3, 169-176, 2005. Seiden LS Sabol KE and Ricaurte GA Amphetamine: effects on catecholamine systems and behavior, Annu. Rev. Pharmacol. Toxicol. 23 (1993), pp. 639–677. Uramura K Yada T Muroya,S Shioda S Shiratani T and Takigawa M Methamphetamine induces cytosolic Ca²⁺ oscillations in the VTA dopamine neurons, NeuroReport 11 (2000), pp. 1057–1061. Mackler SA and Eberwine JH The molecular biology of additive drugs, Mol. Neurobiol. 5 (1991), pp. 45–58. Yoshihiro T Honma S Mitome M and Honma KI, Methamphetamine stimulates the release of neuropeptide Y and noradrenaline from the paraventricular nucleus in rats, Brain Res. 707 (1993), pp. 119–121. The Mechanism of Action of amphetamine (low-dose) , Lundbeck Institute, CNSforum, Educational Resources, Image Bank, http://www.cnsforum.com/imagebank/item/Drug_amphet_low/default.aspx . The Mechanism of Action of amphetamine (high-dose) , Lundbeck Institute, CNSforum, Educational Resources, Image Bank, http://www.cnsforum.com/imagebank/item/Drug_amphet_high/default.aspx . Albertson TE Amphetamines in Poisoning & Drug Overdose, 5th edition (Olson KR, ed) The McGraw-Hill Companies, 2007, on-line edition. Mendelson JA and Mello NK "Chapter 389 Cocaine and other commonly abused drugs.".Fauci AS, Braunwald E, Kasper DL, Hauser SL, Longo DL, Jameson JL, Loscalzo J: Harrison's Principles of Internal Medicine, 17e,2008, on-line edition. Editor 182, Crystal methamphetamine, public doman, http://en.wikipedia.org/wiki/File:Blue_Crystal_Meth_.jpg . "Meth Mouth Damage" METH Awareness and Prevention Project of South Dakota, picture attribution: Robert D. Thomas, DDS, Savannah, TN, Other image attribution: USD Dental Hygiene, http://www.mappsd.org/Meth Mouth Photo Gallery.htm . "Meth Mouth Video--The Effects of Methamphetamine on Teeth." http://www.youtube.com/watch?v=j5SXjgrJITY . Crystal Meth / Methamphetamine / Ice - Educational Video PSA http://www.youtube.com/watch?v=70nMQ9Fbjhw . Pollock BG Semla TP and Forsyth CE "Chapter 63. Psychoactive Drug Therapy" in Hazzard's Geriatic Medicien and Gerontology, 6th edition (Halter JB Ouslander JG Tinetti ME Studenski S High KP and Asthana S, eds) The McGraw-Hill Companies, 2009, on-line edition. Drugs for Treatment of ADHD, The Medical Letter Online: Treatment Guidelines from the Medical Letter, November 1, 2006, issue 51, p. 77. Focalin XR for ADHA, The Medical Letter on Drugs and Therapeutics, March 23, 2009, issue 1308, p. 22. Robertson D and Biaggioni I Adrenoceptor Antagonist Drugs (Chapter 10) in in Basic and Clinical Pharmacology (11th edition), (Katzung BG, Masters, SB and Trevor AJ, eds) McGraw-Hill Medical , New York, on-line version (Access Medicine) 2009. Prostate Enlargement: Benign Prostatic Hyperplasia, National Kidney and Urologic Diseases Information Clearinghouse (NKUDIC) (A service of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK, NIH), http://www.kidney.niddk.nih.gov/kudiseases/pubs/prostateenlargement/index.htm . Alpha 1 acid glycoprotein (a1AGP) Uscn Life Sciences http://www.uscnk.com/directory/Alpha-1-Acid-glycoprotein-orosomucoid(a1AGP-ORM)-0816.htm . Evaluation of Biological Function and Pharmacokinetics of Alpha1-Acid Glycoprotein (AGP) http://www.pharm.kumamoto-u.ac.jp/Labs/Yakuzai/AGP.eng.html . ALLHAT Collaborative Research Group. Diuretic versus alpha-block as first-step antihypertensive therapy: final results from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Hypertension Sept; 42(3) 239-246, 2003. http://www.ncbi.nlm.nih.gov/pubmed/12925554?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum . Kirby RS, Pool JL. α-Adrenoceptor blockade in the treatment of benign prostatic hyperplasia: past, present and future. Br J Urol 1997;80:521–32. Kyprianou N. Doxazosin and terazosin suppress prostate growth by inducing apoptosis: clinical significance.J Urol 2003;169:1520–5. Benning CM, Kyprianou N. Quinazoline-derived a1-adrenoceptor antagonists induce prostate cancer cell apoptosis via an a1-adrenoceptor-independent action. Cancer Res 2002;62:597–603. Partin JV, Anglin IE, Kyprianou N. Quinazoline-based α1-adrenoceptor antagonists induce prostate cancer cell apoptosis via TGF-h1 signaling InBa induction. Br J Cancer 2003;88:1615–21. Keledjian K, Kyprianou N. Anoikis induction by quinazoline based α1-adrenoceptor antagonists in prostate cancer cells: antagonistic effect of bcl-2. J Urol 2003;169:1150–6. Garrison JB Kyprianou N Doxazosin induces apoptosis of benign and malignant prostate cells via a death receptor-mediated pathway. Cancer Res 66:464-472, 2006. Rajaratnam, Relief from BPH, http://www.youtube.com/watch?v=Loit7-wCOAQ . Donabel, PDB 206l EBI, public domain image, http://en.wikipedia.org/wiki/UGT2B7 . Haggstrom M Adrenoceptor-Signal Transduction http://en.wikipedia.org/wiki/File:Adrenoceptor-Signal_transduktion.PNG . 236a. Adrenergic Receptor: http://en.wikipedia.org/wiki/Adrenergic_receptor . Prakash GB Baroreceptors (www.gims-org.com); http://www.youtube.com/watch?v=zqcnExm3xdY . Hoffman BB Adrenoceptor Antagonist Drugs in: Basic and Clinical Pharmacology (10th edition), (Katzung BG, ed) McGraw-Hill Medical , New York, pp. 141-148, 2007. Veverka A and Salinas JL Nebivolol in the treatment of chronic heart failure Vasc Health Risk Manag. 2007 October 3(5): 647-654 2007. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2291309/ . Murray KT Reilly CR Koshakji RP Roden DM Lineberry MD Wood AJJ Siddoway LA Barbey JT Woosley RL Suppression of ventricular arrhythmias in man by d-propranolol independent of beta-adrenergic receptor blockade. J. Clin. Invest. 85: March, 836-842, 1990. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC296501/pdf/jcinvest00069-0230.pdf . Diberri Pacemaker Potential http://en.wikipedia.org/wiki/File:Pacemaker_potential_annotated.gif . Swarminathan J and MSD staff (European Bioinformatics Institute), Renin dimer http://en.wikipedia.org/wiki/File:PDB_2ren_EBI.jpg . Haggstrom M Overview of the renin-angiotensin system, 2009, http://en.wikipedia.org/wiki/File:Renin-angiotensin_system_in_man_shadow.png ; http://en.wikipedia.org/wiki/Renin . Renin: http://en.wikipedia.org/wiki/Renin . Toda N Vasodilating ß-adrenoceptor b lockers as cardiovascular therapeutics Pharmacology & Therapeutics 100: 2145-234, 2003. Iridos ANP-structure http://en.wikipedia.org/wiki/File:ANP-structure.jpg . Widmaier, Eric P.; Hershel Raff, Kevin T. Strang (2008). Vander's Human Physiology, 11th Ed.. McGraw-Hill. pp. 291, 509–10. Potter LR, Yoder AR, Flora DR, Antos LK, Dickey DM (2009). "Natriuretic peptides: their structures, receptors, physiologic functions and therapeutic applications". Handb Exp Pharmacol 191 (191): 341–66. http://www.springerlink.com/content/u648j605872u4360/ . de Bold A (1985). "Atrial natriuretic factor: a hormone produced by the heart". Science 230 (4727): 767–70. http://www.sciencemag.org/content/230/4727/767 , Atrial natriuretic peptide: http://en.wikipedia.org/wiki/Atrial_natriuretic_peptide . Ishida H Hirota Y Higashijima N Ishiwata K Chokoh G Matsuyama S Murakami Eiichi Nakazawa H Direct nitric oxide release from nipradilol in human coronary arterial smooth muscle cells observed with flurorescent NO probe and NO-electrode. Pathophysiology 11: 77-80, 2004. Murad F The Nitric Oxide Signaling Pathway http://www.youtube.com/watch?v=6mKwbAyhBPQ . Schiller E Kriz W Bartsch H Free radicals and inhalation pathology: respiratory system: 6.1 The Respiratory Burst, Springer-Verlag, Berlin, p113, 2004 Jakov Schematic diagram of the human eye. http://en.wikipedia.org/wiki/File:Schematic_diagram_of_the_human_eye_en.svg . Ske Retinography http://en.wikipedia.org/wiki/File:Retinography.jpg . Heilman, J Wheeze respirations. http://en.wikipedia.org/wiki/File:Wheeze2O.ogg . Cryer PE Hypoglycemia Chapter 339 in in Harrison's Principles of Internal Medicine (eds, Fauci AS Braunwald E Kasper DL Hauser SL Longo DL Jameson JL Loscalzo J), 17th edition, 2008, McGraw-Hill Medical, New York, on-line edition. Hypoglycemia Signs and Symptoms: "dinoLomedico" http://www.youtube.com/watch?v=D7yDfk3Q-8g . Rfch HDL, public domain image, http://en.wikipedia.org/wiki/File:Hdl1.svg . Tcai Raynaud's Syndrome, http://en.wikipedia.org/wiki/File:Raynaud%27s_Syndrome.jpg . Hellmann DB and Imboden Jr JB Musculoskleta & Immunologic Disorders, Raynaud Phenomenon, Chapter 20 in Current Medical Diagnosis & Treatment 2011 (McPhee SJ, Papadakis MA, eds. Rabow MW, Associate Ed) McGraw-Hill, Fiftieth edition, 2011, on-line edition. Moneta, Society for Vascular Surgery briefing: Raynaud's Syndrome, http://www.youtube.com/watch?v=9aaOgJEUy8E . Benowitz NL Beta-adrenergic blockers in Poisoning & Drug Overdose, 5th edition (Olson KR, ed.) The McGraw-Hill Companies, 2007, on-line edition. Snubcube Action potential Class III (public domain) http://en.wikipedia.org/wiki/File:Action_potential_Class_III.svg . Lenz TL, Hilleman DE Dofetilide, a New Class III Antiarrhythmic Agent. Pharmacotherapy 20(7):776-786, 2000. http://www.ncbi.nlm.nih.gov/pubmed/10907968?dopt=Abstract . Gordon M Medical Pharmacology http://www.pharmacology2000.com/Cardio/antiarr/antiarrtable.htm . Dellegrottaglie S Gershlick AH Chiariello M Gersh BJ Chapter 61. Pharmacologic Therapy for Acute Coronary Syndrome in Hurst's The Heart, 12th edition (eds, Fuster V O'Rourke RA Wash RA Poole-Wilson P; associate eds: King II SB Roberts R Nash IS Prystowsky EN; Editors of the online edition: senior editors: Walsh RA and Simon DI; associate Editors; Hoit BD Fang JC Costa M), 2008, on-line edition. Maask S Scheme of different terms surrounding myocardial infarction: ACS scheme http://en.wikipedia.org/wiki/File:ACS_scheme.jpg . http://en.wikipedia.org/wiki/Acute_coronary_syndrome . Kotchen TA Chapter 241. Hypertensive Vascular Disease Fauci AS, Braunwald E, Kasper DL, Hauser SL, Longo DL, Jameson JL, Loscalzo J, eds : Harrison's Principles of Internal Medicine, 17e, 2008, on-line edition. Chobanian AV, Bakris GL, Black HR, et al. Seventh report of the joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension 2003;42:1206–1252. Hall JE Granger JP Hall ME Jones DW Pathophysiology of Hypertension Chapter 69 in Hurst's The Heart, 12th edition (eds, Fuster V O'Rourke RA Wash RA Poole-Wilson P; associate eds: King II SB Roberts R Nash IS Prystowsky EN; Editors of the online edition: senior editors: Walsh RA and Simon DI; associate Editors; Hoit BD Fang JC Costa M), 2008, on-line edition. Rashidi A Rahman M Wright Jr JI Chapter 70. Diagnosis and Treatment of Hypertension in Hurst's The Heart, 12th edition (eds, Fuster V O'Rourke RA Wash RA Poole-Wilson P; associate eds: King II SB Roberts R Nash IS Prystowsky EN; Editors of the online edition: senior editors: Walsh RA and Simon DI; associate Editors; Hoit BD Fang JC Costa M), 2008, on-line edition. Madhere88 Arterial Pressure (public domain) http://en.wikipedia.org/wiki/File:Arterial_pressure_diagram.png . DestinQX/PhyChim62 (talk) (public domain) http://en.wikipedia.org/wiki/File:Cardiac_cycle_pressure_only.png . Coleman TG Hall JE System hemodynamics and regional blood flow regulation. In Izzo JL Black HR, eds Hypertension Primer: The Essentials of High Blood Pressure, 2nd ed. American Heart Assocation, 1999: 92-94. Reference Card from the Seventh report of the joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC7), U.S. Department of Health and Human Services, National Institutes of Health, National Heart, Lung and Blood Institute. http://www.nhlbi.nih.gov/guidelines/hypertension/phycard.pdf . Rad A The renin-angiotensin-aldosterone system (RAS) http://en.wikipedia.org/wiki/File:Renin-angiotensin-aldosterone_system.png . 2003 European Society of Hypertension-European Society of Cardiology guidelines for the management of arterial hypertension J. Hypertens 21(6): 1011-1053, 2003. Definition and Diagnosis of Diabetes Mellitus and Intermediate Hyperglycaemia, World Health Organization 2006; http://www.who.int/diabetes/publications/Definition and diagnosis of diabetes_new.pdf . National Kidney Foundation K/DOQI clincial practice guidelines for chronic kidney diesease (2002); http://www.kidney.org/professionals/KDOQI/guidelines_ckd/toc.htm . Madhero88 Physiology of Nephron (public domain) http://en.wikipedia.org/wiki/File:Physiology_of_Nephron.png . Radermacher J Chavan A Bleck J Vitzthum A Stoess B Gebel MJ Galanski M Koch KM Haller. Use of Doppler ultrasonography to predict the outcome of therapy for renal-artery stenosis. N Engl J Med 344(6): 410–417,2001. Radermacher J, Haller H. The right diagnostic work-up: investigating renal and renovascular disorders. J Hypertens Suppl 21(2): S19–S24, 2003. Venkatesan S Bilateral Renal Arterial Stenosis http://www.youtube.com/watch?v=xeV3lmYi1Hk ; http://www.onlineheartcare.co.in/ . Interventional Radiology in Action: Renal artery stenosis, http://www.lakeridgehealth.on.ca/patient_care/interventional_radiology/presentations/interventional/slide34.htm . Pimenta E Calhous DA Oparil S Sleep apnea, aldosterone, and resistant hypertension. Prog. in Cardiovascular Diseases, 51(5) (March/April) 371-380, 2009. M'henni H Obstructive sleep apnea (public domain) http://en.wikipedia.org/wiki/File:Obstruction_ventilation_apn%C3%A9e_sommeil.svg . Pilz S Tomaschitz A Stepan V Obermayer-Pietsch B Fahrleitner-Pammer A Schweighofer N Portugaller HR Sourij H Dobnig H Meinitzer A Pieber TR Graz Endocrine causes of hypertension (GECOH) study: a diagnostic accuracy study of aldosterone to active renin ratio in screening for primary aldosteronism. BMC Endocrine Disorders 9:11 2009 http://www.biomedcentral.com/1472-6823/9/11 . Feldman M (University of Pennsylvania School of Medicine) Adrenal Adenoma in Clinical Conn's Syndrome. http://commons.wikimedia.org/wiki/File:Adrenal_gland_Conn_syndrome4.jpg Williams GH Dluhy RG Chapter 336. Disorders of the Adrenal Cortex. Fauci AS, Braunwald E, Kasper DL, Hauser SL, Longo DL, Jameson JL, Loscalzo J: Harrison's Principles of Internal Medicine, 17e,2008, on-line edition. Arcadian, "Adrenal Gland" public domain, U.S. Government publication: http://en.wikipedia.org/wiki/File:Illu_adrenal_gland.jpg . Pituitary Gland SEER Training Modules National Cancer Institute U.S. National Institutes of Health, http://training.seer.cancer.gov/anatomy/endocrine/glands/pituitary.html . StudyWithSubstanceP "Cushing's Disease and Syndrome-USMLEntertainment http://www.youtube.com/watch?v=JpcA6JFzP0M ; http://www.youtube.com/user/StudyWithSubstanceP . http://sites.google.com/site/studywithsubstancep/ . Hoffman BB. Therapy of hypertension. In: Brunton LL, Lazo JS, Parker KL, eds. The Pharmacological Basis of Therapeutics. New York: McGraw-Hill, 2006:845–868. Bakris GL, Fonseca V, Katholi RE, et al. Metabolic effects of carvedilol vs metoprolol in patients with type 2 diabetes mellitus and hypertension: a randomized controlled trial. JAMA 2004;292(18):2227–2236. Seventh report of the joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC7), U.S. Department of Health and Human Services, National Institutes of Health, National Heart, Lung and Blood Institute. 2004 http://www.nhlbi.nih.gov/guidelines/hypertension/jnc7full.htm . Nephron Anatomy: Loop of Henle 20th U.S. edition of Gray's Anatomy of the Human Body, originally published in 1918, public domain, http://en.wikipedia.org/wiki/File:Gray1128.png . URIanimation (developed by University of Rhode Island pharmacy students) http://www.youtube.com/watch?v=6Wc4f2KnbYo . GeneEd "Ion Channel Coupled Receptors" http://www.youtube.com/watch?v=4zzedEDQ6AU . Brette F Leroy J Le Guennec JY Salle L Review: Ca2+ currents in cardiac myocytes: Old story, new insights, slightly modified from Fig. 6, Progress in Biophysics and Molecular Biology 91: 1-82, 2006. Bodi I Mikala G Koch SE Akhter SA Schwartz A The L-type calcium channel in the heart: the beat goes on. J. Clin Invest. 115(12) 3306-3317, 2005. Williams TD Renal Hormone Regulation, http://en.wikipedia.org/wiki/File:RenalHormoneRegulation.png . Higuchi S, Ohtsu H, Suzuki H, Shirai H, Frank GD, Eguchi S . "Angiotensin II signal transduction through the AT1 receptor: novel insights into mechanisms and pathophysiology". Clin. Sci. 112 (8): 417–28, 2007. http://www.clinsci.org/cs/112/cs1120417.htm . Mann DL Heart Failure and Cor Pulmonale Chapter 227 Fauci AS, Braunwald E, Kasper DL, Hauser SL, Longo DL, Jameson JL, Loscalzo J: Harrison's Principles of Internal Medicine, 17e, 2008, on-line edition. 304a Fowler MB Ashley E. Heart Failure: Stanford Health Video Library, Stanford University School of Medicine: Research Channel http://www.youtube.com/watch?v=Iyb8okxrMbU . Research Channel: Adrenergic-44.htm . Hellman J "A person with congestive heart failure who presented with an exceedingly elevated JVP (marked by the arrow)." http://en.wikipedia.org/wiki/File:Elevated_JVP.JPG . ASKVisualScience "Congestive Heart Failure Animation" http://www.youtube.com/watch?v=3YddwXPWVSc ; http://www.ask-visual.com/Main.html . Heart Pathology Chagas Disease, CDC document ftp://ftp.cdc.gov/pub/infectious_diseases/iceid/2002/pdf/schmunis.pdf ; http://en.wikipedia.org/wiki/File:Heart_pathology_Chagas_disease.JPG . Abraham WT Hasan A Poole-Wilson P Diagnosis and Management of Heart Failure Chapter 26 in Hurst's The Heart, 12th edition (eds, Fuster V O'Rourke RA Wash RA Poole-Wilson P; associate eds: King II SB Roberts R Nash IS Prystowsky EN; Editors of the online edition: senior editors: Walsh RA and Simon DI; associate Editors; Hoit BD Fang JC Costa M), 2008, on-line edition. Hunt SA Abraham WT Chin MH Fledman AM Francis GS Ganiats TG Jessup M Konstam MA Mancini DM Michl K Oates JA Rahko PS Silver MA Stevenson LW Yancy CW 2005 guideline update for the diagnosis and management of chronic heart failure in the adult: summary article. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to revise the 2001 Guidelines for the Evaluation and Management of Heart Failure). J Am Coll Cardiol 2005;46:1116–1143. Swedberg K Cleland H Dargie H Drexler H Follath F Komajda M Tavazzi L Smiseth OA Guidelines for the diagnosis and treatment of chronic heart failure: executive summary (update 2005) The Task Force for the Diagnosis and Treatment of Chronic Heart Failure of the European Society of Cardiology European Heart Journal 26, 1115-1140, 2005. Mueller C Laule-Kilian K Schindler C Klima T Frana B Rodriguez D Scholer A Christ M Perruchoud AP Cost-effectiveness of B-type natriuretic peptide testing in patients with acute dyspnea Arch Intern Med 166: 1081-1087, 2006. Mueller C Scholer A Laule-Kilian K Martina B Schindler C Buser P Pfisterer M Perruchoud AP Use of B-type natriuretic peptide in the evaluation and managemnt of acute dyspnea. New England Journal of Medicine 350: (7) 647-657, 2004. Hellman J Pulmonary Edema: "Acute pulmonary edema. Note enlarged heart size, apical vascular redistribution ( circle ), and small bilateral pleural effusions ( arrow )." http://en.wikipedia.org/wiki/File:Pulmonaryedema09.JPG . Hellman J Pedal Edema: "Pedal edema before and after the application of pressure to the shin." http://en.wikipedia.org/wiki/File:Combinpedal.jpg .