hypertension
Hypertension:
Based on data of the National Health and Nutrition Examination Survey (NHANES), about 29% of US adults corresponding to about 58 million individuals (age-adjusted prevalence) are hypertensive.269
This definition is based on the following criteria: systolic blood pressure >= 140 mmHg; diastolic pressure >= 90 mmHg; taking antihypertensive drugs.
Distribution of hypertension prevalence among groups: 33.5% in non-Hispanic blacks, 28.9% in non-Hispanic whites, and 20.7% in Mexican-Americans.
The likelihood of hypertension increases with age and in those individuals 60 years or older, hypertension prevalence is about 65%.
There may be a trend towards increasing hypertension prevalence in the United States that could be associated with increasing obesity.
Among regions within the United States, the southeastern region appears to have the highest prevalence of hypertension and stroke mortality rates.
Among the African-American group, hypertension tends to occur earlier, is more severe, and results in higher morbidity and mortality rates from stroke, left ventricular hypertrophy, congestive heart failure as well as and-stage renal disease compared to Caucasian Americans.269
Regional and racial differences in blood pressure and hypertension likelihood appear to depend on both environmental and genetic factors.
Moreover, obesity and weight gain appear as strong and independent risk factors.
About 60% of hypertensive are >20% overweight.269
A direct positive relationship associating blood pressure and cardiovascular disease risk has been described independent of gender, age, race, ethnic groups, and countries existing independently of other cardiovascular disease risk factors.271
Deaths from cardiovascular disease increases linearly and progressively as blood pressure increases above 115 mmHg systolic and 75 mmHg diastolic.271
A doubling of mortality due to both stroke and ischemic myocardial disease in age groups from 40 to 89 years of age correlates with every 20 mmHg systolic and 10 mmHg diastolic increment. Categorization of blood pressure for adults (18 years and older) has been specified (JNC 7 Seventh Report of the United States Joint National Committee on Prevention Detection, Evaluation, and Treatment of High Blood Pressure).270,271
Aortic pressure (red line) and left ventricular pressure (blue line) over two cardiac cycles noting systolic and diastolic pressures.
"What's New in Adult Hypertension": Nov. 2012
Southern Medical Association: JNC8
Primary Hypertension:271
Primary hypertension accounts for almost all cases of hypertension in is defined by high blood pressure absent a definable secondary cause.271
Examples of secondary causes include pheochromocytoma (discussed earlier), renovascular disease, aldosteronism, or gene mutations.
Factors which may predispose to high blood pressure in primary hypertension include:271
Overweight condition and obesity, accounting for about 70% of risk
Excessive salt or alcohol intake
Reduced K+ intake, and
Sedentary lifestyle.
An important consideration in normotensive and hypertensive physiological states is a relationship between cardiac output and tissue blood flow homeostasis.
Several mechanisms influence tissue blood flow.271Local blood flow regulation includes both short-term and long-term mechanisms.271
Acute local control can be modulated very quickly, within seconds or minutes, by changes in vasomotor tone (vascular constriction or dilitation).
Accompanying localized vasoconstriction is compensatory, delayed vasodilation, which facilitates local metabolic waste removal.
In the kidney, a vasoconstrictor e.g. angiotensin II causes a sustained blood flow reduction, given absence of a metabolic compensatory component.
Another type of short-term control involves altering vascular resistance secondary to blood pressure changes.
Long-term blood flow regulation, occurring in a several days to weeks timeframe, is associated with vessel wall thickening and a reduction in capillary number in some tissues.
Both local tissue control affecting local vasomotor tone and broader circulatory effects including modulation of cardiac pumping and overall vascular tone are required to insure appropriate tissue perfusion.271
In one example, with intense exercise, local skeletal muscle metabolic factors cause vasodilation, thus matching blood flow to increased local metabolic requirements.
Associated with this activity, moreover, is a generalized reduction in peripheral vascular resistance which tends to reduce blood pressure.
This blood pressure reduction tendency is offset by compensatory release of vasoconstrictive neurohumoral factors.
If peripheral vasodilation is prolonged, other compensatory systems are activated which expand systemic blood volume by changing salt and water retention. Additionally, cardiac hypertrophy may occur with persistant vasodilation.
In summary, many systems are involved in circulatory control and these systems affect cardiac output, blood pressure, and circulatory blood volume.271
In hypertension, the same control mechanisms are also in place, although hypertension is usually accompanied by elevated total vascular resistance.
This change is not usually associated with inadequate tissue perfusion, except in individuals with heart failure or with substantial target-organ pathology.
At least in non-obese, primary hypertensive individuals, the likely physiological pattern is one of normal blood flow, normal oxygen consumption and elevated vascular resistance.275
Abnormal renal pressure natriuresis appears central in human hypertension.271
Disorders of pressure natriuresis usually originate within the kidneys.
However, abnormal activation of multiple antinatriuretic hormones (e.g. aldosterone, angiotensin II) which usually regulate sodium excretion or a deficiency of natriuretic effects (mediated by e.g. nitric oxide or atrial natriuretic peptide) on the kidney may damage renal pressure natriuresis resulting in chronic hypertension.
"Blue and red dashed arrows indicate stimulatory or inhibitory signals, which is also indicated by the +/-.
In the tubule and collecting duct graphics, the grey dashed arrows indicate passive transport processes, contrary to the active transport processes which are indicated by the solid grey arrows.
The other solid arrows either indicate a secretion from an organ (blue, with a starting Spot) or a reaction (black). These 2 processes can be stimulated or inhibited by other factors."277
Abnormal activation of the sympathetic nervous system may also play an important role in elevated blood pressure observed in the hypertensive patient.
With respect to the autonomic nervous system (ANS), the sympathetic nervous system (SNS) is important in both short-term and long-term blood pressure regulation.271
Postganglionic sympathetic fibers mediate vascular vasoconstriction and can cause blood pressure elevation very rapidly not only by vasoconstriction but also by increasing myocardial contractility and rate.
Reduction of sympathetic outflow can, by contrast, rapidly reduce blood pressure. Accordingly, regulation of sympathetic outflow is an important factor in blood pressure regulation.
With respect to long-term blood pressure regulation and hypertension pathogenesis, activation of renal sympathetic nerves may play an important role.271
Excessive activation of the system results in sodium retention, increased renin secretion and impaired renal pressure natriuresis. (Note that the sympathetic system prominently innervates renal vasculature, juxtaglomerular apparatus, and renal tubules.)
Relatively small increases in renal sympathetic nerve activity results in increased renin secretion and increased sodium reabsorption at various nephron sites, including proximal tubule, loop of Henle, and distal sites.
courtesy of Robert H. Parsons, Ph.D., Rensselaer Polytechnic Institute, used with permission
Human primary hypertension, particularly in the obese population subset, appears associated with elevated renal sympathetic nervous system activity.
The underlying mechanism that causes renal sympathetic activation in primary hypertension remains to be elucidated.271
Clinical Assessment:272
Three principal objectives in initial evaluation of hypertensive patients have been identified.272
The first is the identification of possible target-organ (end-organ) damage secondary to hypertension; some of these possible findings might influence therapeutic approaches.
Another issue is the identification of the presence of cardiovascular disease and assessment of existing cardiovascular risk factors.
Finally, early assessment requires identification of possible secondary causes of hypertension. Fulfilling these objectives usually require medical history, physical examination, and some laboratory testing.
Within the history, several especially important issues are addressed.272
These include age of onset, duration and possible previous levels of high blood pressure.
Effectiveness of possible previous antihypertensive treatment should be determined, along with any adverse effects associated with medication.
Identification of symptoms consistent with secondary hypertension causes is important.
Factors that predispose to hypertension, i.e. lifestyle factors such as dietary fat consumption, salt, alcohol, smoking, level of physical activity as well as weight gain should be assessed.
Possible symptoms that may identify presence of neurological pathologies, heart failure, coronary vascular disease or peripheral arterial and-organ pathology must be assessed.
Use of drugs that affect blood pressure such as oral contraceptives, nasal drops, cocaine, amphetamine, steroids, nonsteroidal anti-inflammatory agents (NSAIDS), erythropoietin, cyclosporine, and carbenoxolone should be documented.272,278
Risk Assessment:272
The extent to which hypertension is associated with especially prominent cardiovascular risk is suggested by:272
Presence of multiple risk factors
Diabetes
and Prior cardiovascular events.
Important specific risk factors include:272
Age (>55 years for males; >65 years for females)
Ramily history of premature cardiovascular disease presentations (<55 years in males; <65 years in females)
Cigarette smoking
Abnormal lipid profile
Diabetes
Obesity (body mass index >30 kg/m2)
Decreased glomerular filtration rate (GFR; <60 mL/min)
Glomerular filtration rates (GFR) <60 mL/min/1.73 m2 for three months defined chronic renal disease independent of presence or absence of apparent renal damage. This GFR level indicates at least a loss of 50% or more of the adult level normal kidney function and is related to various health complications.280
Patients with kidney damage exhibit elevated risk for two major consequences of renal disease: (1) loss of kidney function and (2) cardiovascular disease development.
Proteinuria is considered an independent marker for declining renal function and cardiovascular disease.
Stages of renal dysfunction:280
Stage 1 renal disease: slightly reduced renal function; kidney damage abnormal relatively high GFR (>= 90 mL/min/1.73 m2).
Kidney damage is defined on the basis of pathological abnormalities or other markers of pathology including abnormal blood or urine tests or abnormal findings upon imaging studies.
Stage 2 renal disease: mild reduction in GFR (60-89 mL/min/1.73 m2) with renal damage as defined above.
Stage 3 renal disease: moderate reduction in GFR (30-59 mL/min/1.73 m2).
Stage 4 renal disease: severe GFR reduction (15-29 mL/min/1.73 m2).
This level of renal dysfunction necessitates preparation for kidney transplant treatment.
Stage 5 renal disease: clear evidence of kidney failure (GFR <15 mL/min/1.73 m2); permanent renal replacement treatment considered
or the presence of Microalbuminuria.
Secondary Hypertension:272
Whereas primary or essential hypertension may not be attributable to a specific cause, secondary hypertension is associated with a particular direct cause.272
The most common pathologies which result in secondary hypertension include:
Renal artery stenosis
Renal parenchymal disease
Sleep apnea
Primary aldosteronism
Cushing's syndrome and
Pheochromocytoma.
Renovascular hypertension may be suggested by:272
Either abrupt hypertension onset before age 30 or worsening after age 55
Renal artery diastolic or lateralizing bruit
Relatively resistance to drug treatment
Sustained creatinine increase after initiation of angiotensin-converting enzyme inhibitor medications (ACE inhibitors)
Retinal hemorrhage, exudates, or papilledema and
"Flash" pulmonary edema.
Renovascular hypertension, although only accounting for 1%-2% in the hypertensive population in general, may account for up to 10% in resistant hypertension and even a higher percentage in patients with accelerated/malignant hypertension.272
In younger patients, fibromuscular dysplasia appears to be a common cause of renovascular hypertension.
Atherosclerotic renal artery stenosis is more likely to account for this presentation in older patients and may occur bilaterally up to half the time.
Atherosclerotic-induced renovascular hypertension is also associated with coronary and carotid artery vascular atherosclerosis as well as atherosclerotic disease in lower extremity vasculature.
Standard therapy is often less efficacious in this type of hypertension.
Various invasive and noninvasive tests are available for both screening and assessment of renal artery stenosis.272
Some tests might be less appropriate in those cases when patients are not judged to be ultimately a candidate for surgery or angioplastic intervention.
A reliable method for detection and grading of renal artery stenosis is three-dimensional MRI imaging (gadolinium enhanced).
Sensitivity and specificity of this imaging technique for renovascular stenosis appears >90% with appropriate post-acquisition image processing.
Drawbacks of MR imaging methods include false-positive conclusions based on respiratory artifacts, peristalsis, and complex vessel geometry.
The "gold standard" diagnostic technique is renal angiography; limited usefulness of this method in some patients with impaired renal function is due to the requirement for contrast and associated complications.
Spiral computed tomography (spiral CT) with angiography allows high sensitivity and specificity.
Treatment of renal artery stenosis appears controversial.272
Antihypertensive drug treatment often allows reasonable blood pressure control even in renovascular hypertensive disease.
Another approach involves correcting the stenosis itself using renal artery angioplasty with stenting.
The treatment approach in an individual patient must take into account relative risks associated with invasive methods compared to possible benefits of renal vascularization relative to blood pressure control and reducing progressive renal injury.283
Risk factors which may make revascularization approaches less likely beneficial include:
Urinary protein excretion of >= 1 g/day
Hyperuricemia
Creatinine clearance <40 mL/min
Age >65
Coronary artery disease
Arterial occlusive disease in the legs
Cerebrovascular disease
Resistance index of >80 and segmental arteries of both kidneys by Doppler ultrasonography.282
Hypertension Treatment:
ß-receptor antagonists:272
Use of ß-adrenergic antagonists (a.k.a. beta blockers) are effective in reducing blood pressure.272
The primary mechanism is by antagonism at ß1-adrenergic receptors.
Reduced adrenergic receptor activity manifests, in part, as a reduction in both heart rate and myocardial contractility.
Moreover, ß-adrenergic receptor blockade also decreases renin release and angiotensin II levels.294
Additional actions of ß-antagonists include downregulation (reduction in number) of adrenergic receptors, increased prostacyclin synthesis and changes in baroreceptor sensitivity.
In black and elderly patients ß-adrenergic receptor blockers may be less efficacious as monotherapy.
However, effectiveness improves if ß-adrenergic antagonists are administered in combination with diuretics or Ca2+ channel antagonists.
As described earlier, some ß-adrenergic antagonists also possess intrinsic sympathomimetic properties and as such may be useful in those patients who require ß-adrenergic blockade but exhibit bradycardia or vasoconstriction.
Agents which exhibit both α- and ß-adrenergic antagonism show faster onset of antihypertensive effects with reduced actions on blood lipids and glucose levels.295
Most ß-adrenergic antagonists exhibit comparable clinical antihypertensive effectiveness.272
Abbreviations:276
ACEI: Angiotensin Converting Enzyme Inhibitor
ARB: Angiotensin Receptor Blocker
BB: Beta Blocker
CCB: Calcium Channel Blocker
ß-antagonists Trade Name
Atenolol Tenormin
Betaxolol Kerlone
Bisoprolol Zebeta
Metoprolol Lopressor
Metoprolol extended-release Toprol XL
Nadolol Corgard
Propranolol Inderal
Propranolol long-acting Inderal LA
Timolol Blocadren
ß-antagonists with sympathomimetic activity Trade Name
Acebutalol Sectral
Penbutolol Levatol
Pindolol (generic)
Combined α- and ß-adrenergic receptor antagonism Trade Name
Carvedilol Coreg
Labetalol Normodyne, Trandate
Combined ß-adrenergic receptor antagonism and diuretic Trade Name
Atenolol-chlorothalidone Tenoretic
Bisoprolol-hydrochlorothiazide Ziac
Metoprolol-hydrochlorothiazide Lopressor HCT
Nadolol-bendroflumethiazide Corzide
Propranolol LA-hydrochlorothiazide Inderide LA
Timolol-hydrochlorothiazide Timolide
Adverse effects associated with β-adrenergic receptor agonists:152
Adverse effects associated with β2-adrenergic receptor agonists are directly related to β-receptor activation. Patients with cardiovascular disease perhaps especially myocardial disease may be particularly sensitive to adrenergic activation.
Administration of adrenergic receptor agonist by inhalation reduces systemic absorption and accordingly decreases systemic toxicities.β2-adrenergic agonist administration may induce tremor, which, over time, often diminishes.
The likelihood of tremor following oral administration is reduced if a lower drug dose is administered at first, followed by increasing drug dosages as tolerance to tremor develops.
Anxiety, apprehension, and restlessness, sometimes therapy limiting, are also noted with these drugs.
Tachycardia is commonly observed with administration of β-adrenergic receptor agonists, possibly a consequence of direct receptor activation (β1-adrenergic receptor subtype).
Another possibility is that agents with β2-adrenergic agonist activity may produce peripheral vasodilation which, by autonomic reflex mechanisms, cause tachycardia.
Tachycardia associated with an ongoing severe asthma attack may be reduced following administration of a β-receptor agonist, because of improved pulmonary function on one hand and resultant reduced anxiety, which reduces circulating catecholamines, on the other.
If tachycardia is considered a relatively benign arrhythmia, more serious arrhythmias may develop associated with β-adrenergic stimulation in patients with pre-existing coronary vascular disease or pre-existing arrhythmia.
Adverse cardiovascular incidents are more likely in patients receiving monoamine oxidase inhibitors (MAO inhibitors), presumably administered as part of management of endogenous depression
Thiazide diuretics:272
Thiazide diuretics inhibit the distal tubular Na+-Cl- renal cotransporter and therefore decrease extracellular volume in reduced cardiac output.272
Diuresis is central to the antihypertensive effect of thiazide agents, although diuresis by itself is inadequate to fully account for thiazide-mediated long-term antihypertensive effects.
Thiazide-type agents result in some vasodilation.
Possible other pharmacological mechanisms which may explain more completely thiazide-antihypertensive effects include effects on the Ca2+-activated K+ channels and actions at vascular smooth muscle.
The most commonly prescribed thiazide drugs are hydrochlorothiazide (HydroDIURIL) and chlorthalidone (Hygroton), the latter being about 1.5-2 times more potent.272
Indapamide (Lozol) is less likely to produce hypokalemia, an effect of thiazide-type diuretics.
Thiazide diuretics tend to be less effective as antihypertensive drugs when glomerular filtration rate (GFR) becomes <30-40 mL/min; metolazone and indapamide represents an exception to this finding.272
Diuretics have been found essentially unsurpassed in limiting cardiovascular complications associated with hypertension.296
The ALLHAT study involved following 40,000 hypertensive patients.296
Analysis of the ALLHAT study, when considering the primary coronary heart disease (CHD) outcome or mortality, no difference was found between a thiazide-type diuretic, chlorthalidone (Hygroton), and angiotensin-converting enzyme inhibitor, lisinopril (Prinivil) or a calcium channel blocker, amlodipine (Norvasc) .
Elevation of stroke incidence was greater with lisinopril compared to chlorthalidone; however, this difference was localized mainly in African-American patients who exhibited reduced blood pressure response to lisinopril, compared to diuretics.
The likelihood of heart failure was found greater in calcium channel blocker-treated and ACE inhibitor-treated patients compared to patients receiving the diuretic in both white and African-American groups.296
Most clinical trial results suggest that diuretics are typically well-tolerated and appear efficacious at "low-dose" levels [equivalent of 25-50 mg hydrochlorothiazide or 12.5-25 mg chlorthalidone].296
Higher thiazide doses appear to confer limited additional antihypertensive effect but are more likely to cause hypokalemia along with other undesirable effects.
Uric acid levels tend to increase in patients on a diuretic although gout is unlikely at dosages = <50 mg/day of hydrochlorothiazide or = <25 mg chlorthalidone.
High dose thiazide administration may cause hypokalemia, a predisposing factor for ventricular ectopy and even possible sudden death.
Use of the potassium-sparing agent along with a thiazide may be considered.296
Thiazide Diuretic Trade Name
Chlorothiazide Diuril
Chlorthalidone (generic)
Hydrochlorothiazide Microzide, HydroDIURIL
Polythiazide Renese
Indapamide Lozol
Metolazone Mykrox
Metolazone Zaroxolyn
Loop Diuretics:272
Loop diuretics inhibit Na+-K+-2Cl- at the thick ascending limb of the loop of Henle
Loop of Henle: Ascending Limb, site of action of "loop" diuretics.
These agents are usually highly effective in inducing profound diuresis.
Prominent "loop" diuretics include furosemide (Lasix), bumetanide (Bumex), ethacrynic acid (Edecrin) and torsemide (Demadex).272
Due to their limited half-life, loop diuretics are less effective compared to thiazides in reducing blood pressure in patients with normal renal function, when prescribed once or twice per day.272
However, in patients with reduced GFR (glomerular filtration rate) <30-40 mL/min/1.73m2, loop diuretics are important for blood pressure reduction.
Loop diuretics also may be used to achieve volume control in patients receiving vasodilators, particularly minoxidil which promotes fluid retention.
Adverse effects are related to electrolyte abnormalities and include:
Hypokalemia
Hyponatremic
Hypochloremic alkalosis
Hyperuricemia, and
Hyperglycemia.
Hypomagnesemia and hypokalemia occur as a result of enhanced Mg2+ and Ca2+ excretion.
Thiazide diuretics and loop diuretics act in a synergistic manner; however, nonsteroidal anti-inflammatory drugs (NSAIDS) and probenecid attenuate loop diuretic activity.272
Loop Diuretics Trade Name
Furosemide Lasix
Bumetanide Bumex
Torsemide Demadex
Reduction in blood pressure is initially due to a reduction in extracellular volume and cardiac output.
Long-term antihypertensive effects of thiazides appear due to reduced vascular resistance.
The exact mechanism responsible for the reduction in vascular resistance is not known.
Thiazides, due to their inhibition of the Na+-Cl- symport system, increase sodium and chloride excretion: renal synport diagram
Distal Convoluted Tubule: From: Goodman and Gilman's "The Pharmacological Basis of Therapeutics, Ninth Edition
Potassium-Sparing Diuretics:272
Potassium-sparing diuretics act by inhibiting renal epithelial Na+, promoting an increase in NaCl excretion.
These agents are not suitable as monotherapy in management of peripheral edema or hypertension; however, potassium-sparing agents are helpful in preventing or limiting diuretic-caused hypokalemia.
Accordingly, potassium-sparing drugs may be prescribed along with other diuretics.
Hyperkalemia is a serious adverse effect associated with these agents.
The risk of hyperkalemia is increased when potassium-sparing drugs are used with:
Nonsteroidal anti-inflammatory agents (NSAIDs)
Angiotensin-converting enzyme (ACE) inhibitors
Angiotensin receptor antagonist
ß-adrenergic receptor antagonists, and
In diabetic hypertensives.
Triamterine (Dyrenium) and amiloride (Midamor) are classical potassium-sparing diuretics.272
Note that amiloride (Midamor) and probably triamterene (Dyrenium) blocks sodium channels in the luminal membrane in the late distal tubule and collecting duct.
Such action inhibits the normal movement of Na+ into the cell.
Normally, Na+ entry create the net negative luminal charge that results in K+ efflux.
By reducing the net negative luminal charge, amiloride (Midamor)/triamterene (Dyrenium) administration help conserve potassium. Therefore, they are called "potassium sparing".
Figure adapted from "Goodman and Gillman's The Pharmacological Basis of Therapeutics" Ninth Edition, p. 705
Mineralocorticoid Receptor Antagonists:272
Mineralocorticoid antagonists represent another group of potassium-sparing diuretics.
Mineralcorticoids bind to the mineralcorticoid receptors, causing both water and salt retention and K+ and H+ excretion.
Antagonism of this process reduces K+ excretion.
Mineralcorticoid antagonists include spirolactone (Aldactone) and eplerenone (Inspra).
Mineralcorticoid antagonists are typically combined with thiazide diuretics for hypertension management.
Also, these agents are helpful in treating primary aldosteronism.
Prominent adverse effects include:
Hyperkalemia
Anti-androgen effects (breast pain, gynecomastia, sexual dysfunction in males) and
Hypertriglyceridemia.
Anti-androgenic effects are less likely observed with eplerenone which is more selective for mineralcorticoid receptors compared to spirolactone.272
Spironolactone is an antagonist of mineralocorticoid receptors (aldosterone-antagonist) .
Normally, aldosterone interactions with mineralocoricoid receptors result in synthesis of aldosterone-induced proteins (AIPs).
These proteins appear to increase the number or activity of Na+ channels and cause an increase in Na+ conductance.
Increased Na+ conductance (with inward movement of Na+) results in a net negative luminal charge favoring K+ loss.
Antagonism of the interaction between aldosterone and its receptor by spironolactone conserves K+ (potassium sparing).
Figure from Goodman and Gilman's "The Pharmacological Basis of Therapeutics" Ninth Edition, p. 708
Calcium Channel Antagonists:272
Calcium channel antagonists limit Ca2+ entry into vascular smooth muscle through voltage-sensitive L-type Ca2+ channels.
"Schematic representation of cardiac L-type Ca2+ channel CaV1.2 (a1C) subunit with accessory subunits (b and a2d). AID, alpha interacting domain; PKA, cAMP-dependent protein kinase; PKC, protein kinase C, PKG, cGMPdependent protein kinase; CaM, calmodulin, AKAP, A-kinase anchoring protein."300 ;
"Structural organization of L-VDCCs.
The predicted membrane topological organization of the core subunits, their interactions, and structural domains of the auxiliary subunits, which are common to all VDCC types, are shown.
The primary structure of the pore-forming α1 subunit is composed of 4 homologous repeating motifs (I–IV), each of which consists of 6 putative transmembrane segments (S1–S6)."300
Reduced Ca2+ entry results in coronary and peripheral arterial vasodilation.Calcium channel blockers may be classified as dihydropyridines and non-dihydropyridines.
An example of a dihydropyridine calcium channel antagonist is nifedipine (Procardia); whereas, examples of non-dihydropyridines include diltiazem
(Cardizem) and verapamil (Calan).
Agents belonging to these classes exhibit comparable antihypertensive effectiveness but differ in terms of actions on AV (atrioventricular) impulse conduction, vasodilation, and myocardial contractility.
For example, non-dihydropyridines decrease myocardial contractility and AV nodal conduction.
Because they may reduce cardiac contractility, non-dihydropyridine-type calcium channel blockers are relatively contraindicated in patients with substantial left ventricular dysfunction (poor contractility) or AV block.
Dihydropyridine calcium channel antagonists are effective arteriolar vasodilators while exhibiting limited suppression of cardiac impulse conduction or contractility.
Examples of dihydropyridine calcium channel antagonists with demonstrated relative safety in hypertensive patients with heart failure include amlodipine and felodipine.
Common side effects of dihydropyridine-calcium channel antagonists include flushing, headache, and a dose-dependent peripheral edema caused by precapillary arteriolar dilatation with fluid moving from vascular compartments into tissue.
This type of edema may be less readily managed by diuretics.272
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_LangerhansSüß 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/ .
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 α2A-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 α2A-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 .
This Web-based pharmacology and disease-based integrated teaching site is based on reference materials, that are believed reliable and consistent with standards accepted at the time of development. Possibility of human error and on-going research and development in medical sciences do not allow assurance that the information contained herein is in every respect accurate or complete. Users should confirm the information contained herein with other sources. This site should only be considered as a teaching aid for undergraduate and graduate biomedical education and is intended only as a teaching site. Information contained here should not be used for patient management and should not be used as a substitute for consultation with practicing medical professionals. Users of this website should check the product information sheet included in the package of any drug they plan to administer to be certain that the information contained in this site is accurate and that changes have not been made in the recommended dose or in the contraindications for administration. Advertisements that appear on this site are not reviewed for content accuracy and it is the responsibility of users of this website to make individual assessments concerning this information. Medical or other information thus obtained should not be used as a substitute for consultation with practicing medical or scientific or other professionals.