Choose the correct answer: If I lived in the country, ...

I would ride my bike to school.

I would rode my bike to school.

If clause (Second condtional)

Etymology explains the origin of the word itself. Example: Using the example term “arbitration”: Arbitration comes from the Latin judicium which means “judgment”. 2. History discusses the history of the term, its use, and controversies associated with it. Example: The use of arbitration as third-party mediation dates from the 1630s. 3. Cause and Effect discusses how the situation came about and what effects it may have. Example: An arbitration clause is considered to be ambiguous when the parties do not express clearly, that in case of conflict, the method to use to settle the disagreements will be arbitration. Hence, parties are compelled to refrain from signing confusing agreements to arbitrate, because the general rule is that arbitration is prompted out of the contract, and if there is not an explicit arbitration clause within the contract it would not be an agreement to arbitrate. 4. Description lists and defines the term. Example: Arbitration is the process of solving an argument between people by helping them to agree to an acceptable solution. It is the formal process of having an outside person, chosen by both sides to a disagreement to end the disagreement. 5. Principles of Operation discusses how something functions, including any special materials or conditions required. Example: Arbitration is conducted by a trained arbiter who sets down the rules that the parties must abide by. The object of arbitration is to obtain a fair resolution of disputes by an impartial third party without unnecessary expense or delay. Parties should be free to agree on how their disputes are resolved, subject only to such safeguards as are necessary for the public interest. Courts should not interfere. 5 6. Classification shows how the topic fits into a larger category. Example: Arbitration is one of the alternatives to going into a formal court to settle disputes. 7. Contrast shows how the topic differs from others in the same class. Example: In an arbitration proceeding, no lawyers are present. The main difference between arbitration and litigation law is that the court is involved in the case of litigation, as it is a lawsuit, whereas, in arbitration, a settlement between the parties is done outside of court. 8. Comparison shows how the topic is similar to others in the class. Example: As with lawsuits or other court proceedings, the decision in an arbitration proceeding is legally binding on the parties. 9. Analogy explains and compares two dissimilar topics, where the second is familiar to the audience. Example: An arbiter is like a referee–he or she listens to both sides and decides as to who is at fault, without the intervention of outside parties. 10.Examples represent other things because they have all the main qualities or characteristics that the thing they represent also have. Examples: Arbitration was used to settle the dispute between the labor union and management. Two people who are divorcing cannot agree on terms and allow a third party to come in to help them negotiate

Name: Marco Ramirez - “I Am Not Batman” TW: language It’s the middle of the night. And the sky is glowing like mad radioactive red. And if you squint, you could maybe see the moon through a thick layer of cigarette smoke and airplane exhaust that covers the entire city like mosquito net that won’t let the angels in. And if you look up high enough you could see me-standing on the edge of a eighty seven story building. And up there-a place for gargoyles and broken clock towers that have stayed still and dead for maybe like a hundred years-up there is me. And I’m freakin Batman. And I gots Bat-mobiles and Bat-a-rangs and freakin Bat-caves like for real, and all it takes is a broom closet or a back room or a fire escape and Danny’s hand-me-down jeans are gone. And my navy blue polo shirt? – The one that looks kinda good on me but has a hole on it near the butt from when it got snagged on the chain linked fence behind Arturo’s but it isn’t even a big deal cause I tuck that part in and its like all good? –that blue polo shirt? – It’s gone too. And I get like, like transformational. And nobody pulls out a belt and whips Batman for talking back –-Or for not talking back –And nobody calls Batman simple –- Or stupid –- Or skinny –- And nobody fires Batman’s brother from the Eastern Taxi Company ‘cause they was making cutbacks, neither, ‘cause they got nothing but respect, and not like afraid-respect. Just like respect-respect. ‘Cause nobody’s afraid of you. Cause Batman doesn’t mean nobody harm. Ever. Cause all Batman really wants to do is save people and maybe pay Abuela’s bills one day and die happy and maybe get like mad famous. For real.…And kill the Joker. Tonight, like most nights, I’m all alone. And I’m watching…And I’m waiting… Like a eagle. Or like a –no, yea, like a eagle. And my cape is flappin’ in the wind (‘cause it’s freakin’ long), and my pointy ears are on, and that mask that covers like half my face is on too, and I got like bulletproof stuff all in my chest so no one could hurt me and nobody – nobody – is gonna come between Batman, And Justice. From where I am I could hear everything. Somewhere in the city there’s a old lady picking Styrofoam leftovers up outta a trash can and she’s putting a piece of sesame chicken someone spit out into her own mouth. And somewhere there’s a doctor with a whack haircut in a black lab coat trying to find a cure for the diseases that are gonna make us all extinct for real one day. And somewhere there’s a man, a man in a janitor’s uniform, stumbling home drunk and dizzy after spending half his paycheck on forty-ounce bottles of twist-off beer and the other half on a four hour visit to some lady’s house on a street where the lights have all been shot out by people who’d rather do what they do, in this city, in the dark. And half a block away from JanitorMan there’s a group of good-for-nothings who don’t know no better waiting to beat JanitorMan with rusted bicycle chains and imitation Lousiville Sluggers, and if they don’t find a cent on him – which they won’t – they’ll just pound at him till the muscles in their arms start burning, till there’s no more teeth to crack out. But they don’t count on me. They don’t count on no dark night (with a stomach full of grocery store brand macaroni-and-cheese and cut up Vienna sausages), Cause they’d rather believe I don’t exist, And from eighty-seven stories up I could hear one of the good-for-nothings say “Gimmethecash” real fast (like that) just “Gimmethefuckingcash” and I see JAnitorMan mumble something in drunk language and turn pale and from eighty-seven stories up I could hear his stomach trying to hurl its way out of his Dickies. So I swoop down like and fast and I’m like darkness. I’m like SWOOSH –- And I throw a Bat-a-rang at the one naked lightbulb –- And they’re all like “whoa-motherfucker-who-just-turned-out-the-lights?” –“What’s that over there?” –-“What?” –- “Gimme whatchou got old man” –- “Did anybody hear that?!” –- “No, really” –- “There ain’t. No. Bat.” – But then –- One out of three good-for-nothings gets it to the head! And number Two swings blindly into the dark cape before him but before his fist hits anything I grab a trash can lid and –-- Right into the gut, and number One comes back with a jump-kick but I know judo-karate too so I’m like –-- Twice –-- but before I can do any more damage suddenly we all hear a CLIC – CLIC –And suddenly everything gets quiet And the one good-for-nothing left standing grips a handgun and aims straight up, like he’s holding Jesus hostage, like he’s threatening maybe to blow a hole in the moon. And the good-for-nothing who got it to the head who tried to jump-kick me and the other good-for-nothing who got it in the gut is both scrambling back away from the dark figure before him. And the drunk man the JanitorMan is huddled in a corner, praying to Saint Anthony ‘cause that’s the only one he could remember. And there’s me, Eyes glowing white, cape blowing softly in the wind. Bulletporoof chest heaving. My heart beating right through it in a Morse code for “fuck with me, just once, come on, just try.” And the one good-for-nothing left standing, the one with the handgun, he laughs he lowers his arm, and he points it at me and gives the moon a break, and he aims it right between my pointy ears, like goalposts and he’s special teams. And JanitorMan is still calling Saint Anthony but he ain’t pickin’ up, And for a second it seems like…maybe I’m gonna lose. Naw. SHOO – SHOO! FUACATA! --“Don’t kill me man!” –“SNAP! – Wrist CRACK – Neck – SLASH! – Skin – meets – acid – “AHH!!” –And he’s on the floor. And I’m standing over him. And I got the gun in MY hands now. And I hate guns, I hate holding ‘em cause I’m Batman, and –Batman don’t like guns ‘cause his parents got iced by guns a long time ago – but for just a second, my eyes glow white, and I hold this thing, for I could speak to the good-for-nothing in a language he maybe understands…CLIC – CLIC…And the good-for-nothings become good-for-disappearing into whatever toxic-waste-chemical-sludge-shit-hole they crawled out of. And it’s just me and JanitorMan. And I pick him up. And I wipe sweat and cheap perfume off his forehead. And he begs me not to hurt him and I grab him tight by his JanitorMan shirt collar and I pull him to my face, and he’s taller than me, but the cape helps so he listens when I look him straight in the eyes and I say two words to him: “Go home.” And he does, checking behind his shoulder every ten feet. And I SWOOSH from building to building on his way there, ‘cause I know where he lives. And I watch his hands where he lives. And I watch his hands tremble as he pulls out his keychain and opens the door to his building. And I’m back in bed before he even walks in through the front door. And I hear him turn on the faucet and pour himself a glass of warm tap water And he puts the glass back in the sink. And I hear his footsteps, And they get slower as they get to my room. And he creaks my door open like mad slow. And he takes a step in, which he never does. And he’s staring off into nowhere, his face the color of sidewalks in summer, and I act like I’m just waking up, and I say, “What’s up, Pop?” And JanitorMan says nothing to me. But I see, in the dark, I see his arms go limp and his head turns back, like towards me, and he lifts it for I could see his face, For I could see his eyes, And his cheeks is dripping but not with sweat. And he just stands there, breathing, like he remembers my eyes glowing white. Like he remembers my bulletproof chest. Like he remembers he’s my pop. And for a long time I don’t say nothing. And he turns around, hand on the doorknob, and he ain’t looking up my way but I hear him mumble two words to me. “I’m sorry.” And I lean over and open my window just a crack.… If you look up high enough you could see me. And from where I am? I could hear everything.

Chapter 22 Antihypertensive Drugs Hypertension Defined (JNC-8) Pharmacology Overview 7 main categories of drugs to treat HTN Adrenergic drugs (old friend) Angiotensin-converting enzyme (ACE) inhibitors Angiotensin II receptor blockers (ARBs) Calcium channel blockers (CCBs) Diuretics Vasodilators Direct renin inhibitors A. Adrenergic Drugs: 5 Subcategories and where they act A1. Adrenergic neuron blockers (central and peripheral)- we won’t talk about this A2. Alpha1 receptor blockers (peripheral) A3. Alpha2 receptor agonists (central) A4. Beta receptor blockers (peripheral) A5. Combined α and β receptor blockers (peripheral) A2. Peripherally Acting Adrenergic DrugAlpha1 Blockers (we’ve met these) Doxazosin, prazosin, alfuzosin Block alpha1-receptors which causes BP to decrease Reduces peripheral vascular resistance and BP by dilating both arterial and venous blood vessels Main Use: benign prostatic hyperplasia (BPH) Alpha1 Blockers REMEMBER Tamsulosin (Flomax)* is an α1 blocker BUT *Tamsulosin is not used to control BP, just for BPH. A3. Centrally Acting Adrenergic DrugsAlpha 2 agonist Clonidine and methyldopa 1- Stimulate alpha2-adrenergic receptors. in the brain Decreases sympathetic outflow from the CNS which decreases NE production 2. Stimulate alpha2-adrenergic receptors in kidneys remember alpha 2 opposes alpha 1 Dilates peripheral blood vessels → lowers peripheral resistance → Results in decreased BP So ….Clonidine (Catapres) Used primarily for its ability to decrease blood pressure in an urgent setting Also use in opioid withdrawal as previously discussed Oral (multiple times a day), and topical patch formulations Do not stop abruptly as it may lead to rebound hypertension In reality, Clonidine and methyldopa Not prescribed as first-line home antiHTN drugs High incidence of unwanted adverse effects: orthostatic hypotension, fatigue, and dizziness MIGHT be uses as adjunct drugs after other drugs have failed, in conjunction with other antiHTN such as diuretics A4. Adrenergic Drugs Selective Beta 1 Blockers Metoprolol, Atenolol Reduction of HR through β1 receptor blockade (remember adrenergic blocking of this receptor???) HR results in BP Cause reduced secretion of renin = BP A4. Adrenergic Drugs Selective Beta1 Blockers Nebivolol (Bystolic) Uses: hypertension and HF Action: blocks β1 receptors and produces vasodilatation, which results in a decrease in SVR High doses loses selectivity and blocks both β1 and β2 Less sexual dysfunction All BB- Do not stop abruptly; must be tapered over 1 to 2 weeks A4. Adrenergic Drugs NONSelective Beta Blockers Propranolol Acts equally on β1 and β2 Other uses include situational anxiety associated with public speaking, test taking As mentioned on previous slide, nebivolol at high doses becomes beta nonselective A5. Dual-Action Adrenergic Drugs α1 and β Receptor Blockers Dual antihypertensive effects of reduction in heart rate (beta1 receptor blockade) and vasodilation (alpha1 receptor blockade) Examples are carvedilol (common) and labetalol (not as common) A5. Dual-Action Adrenergic Drugs α1 and β Receptor Blockers Carvedilol (Coreg) Widely used drug that is well tolerated Uses: HTN, mild to moderate HF in conjunction with digoxin, diuretics, and ACE inhibitors Contraindications: severe bradycardia or unstable HF, bronchospastic conditions such as asthma, and various cardiac conduction problems Adrenergic Drugs Indications - HTN But also for Glaucoma (topical) BPH: doxazosin, prazosin, and terazosin (2 for 1) Management of severe HF when used with cardiac glycosides and diuretics Contraindications Acute HF- have to stabilize first MOAIs- yeah doesn’t everything interact with MAOIs? Peptic ulcers Severe liver/kidney disease Asthma (with beta blockers) Adrenergic Drugs: Adverse Effects Orthostatic hypotension 1st-dose syncope Rebound hypertension with abrupt discontinuation Most common: Dry mouth, drowsiness, constipation, sedation Interactions- always check for specific drug interactions Can cause additive CNS depression with alcohol, benzodiazepines, opioids Question #1 When administering an alpha-adrenergic drug for hypertension, it is most important for the nurse to assess the patient for the development of what response? Hypotension Hyperkalemia Oliguria Respiratory distress Answer A Hypotension This is a key point in patient education These drugs have strong vasodilating properties and may cause severe hypotension, especially at the beginning of therapy. B. Angiotensin-Converting Enzyme Inhibitorsaka ACE Inhibitors or ACEi Large group of safe and effective drugs Currently are 10 ACEi Often used as first-line drugs for HF and hypertension May be combined with a thiazide diuretic, loop diuretic, or Calcium Channel Blocker (CCB) You need to understand the basics ACE Inhibitors: Review RAAS ACE converts angiotensin I, formed through the action of renin, to angiotensin II Angiotensin 2 is a potent vasoconstrictor and also induces aldosterone secretion by the adrenal glands Aldosterone stimulates sodium resorption (H20 follows Na Both act to raise BP which causes kidneys to reduce renin production ACEi= Great drug to treat HTN BUT contraindicated in pregnancy (2nd,3rd trimester due to fetal renal damage) and breastfeeding first few weeks after birth B. ACE Inhibitors - PRIL Lisinopril (Prinivil) super common, often the 1st drug Enalapril (Vasotec) also common Captopril (Capoten) great if liver disease present Benazepril (Lotensin) Fosinopril (Monopril) Perindopril (Aceon) Quinapril (Accupril) Ramipril (Altace) Trandolapril (Mavik) Primary Effects of the ACE Inhibitors Prevent Na (and H2O) resorption by inhibiting aldosterone secretion (volume reduction) (GO BACK TO RAAS DIAGRAM) blood volume decreases work of the heart preload, or the left ventricular end-diastolic volume which is important in HF ACE SUMMARY OF ACTIVITY 1) Prevent vasoconstriction caused by angiotensin 2 (2) Prevent aldosterone secretion  less sodium and water resorption Cardioprotective Effects of ACEi They slow progression of left ventricular hypertrophy (ventricular remodeling) after MI so considered cardioprotective ACE inhibitors have been shown to decrease morbidity and mortality in patients with HF Renal Protective Effects of ACEi ACE inhibitors: reduce glomerular filtration pressure by volume reduction Cardiovascular drug of choice for patients with diabetes since it helps protect kidneys by reducing pressure. Sometimes used low dose for kidney protection with DM without HTN B. ACEi Enalapril (Vasotec) Only ACEi available in both oral and IV Enalapril IV does not require cardiac monitoring Oral enalapril: prodrug (metabolized in liver) Improves patient’s chances of survival after an MI Reduces the incidence of HF B. ACEi Captopril (Capoten) Uses: prevention of ventricular remodeling after MI; reduce the risk of HF after MI Shortest half-life Must be administered multiple times throughout the day so this limits its use Not a prodrug so good for patient with liver disease Question #2 A patient with diabetes has a new prescription for the ACE inhibitor lisinopril. She questions this order because her provider has never told her that she has hypertension. What is the best explanation for this order? The doctor knows best The patient is confused This medication has cardioprotective properties This medication has a protective effect on the kidneys for patients with diabetes Answer D ACE inhibitors have been shown to have a protective effect on the kidneys because they reduce glomerular filtration pressure. This property makes them the cardiovascular drug of choice for patients with diabetes. Question #3 A patient with a history of pancreatitis and cirrhosis is also being treated for hypertension. Which drug will most likely be ordered for this patient? Clonidine Prazosin Diltiazem Captopril Answer D Captopril Captopril is not a prodrug; therefore, it does not need to be metabolized by the liver to be effective. This is an advantage in patients with liver disease. ACE Inhibitors: Adverse Effects *Dry, nonproductive cough, which reverses when therapy is stopped. This is a class effect Dizziness- Note: First-dose hypotensive effect may occur Headache & Fatigue Possible hyperkalemia ** Angioedema: rare but potentially fatal Not safe in pregnancy-are contraindicated during the second and third trimesters of pregnancy because of increased risk of fetal renal damage C. Angiotensin II Receptor Blockers(ARB) Considered an alternative to ACEi Less likely to cause a dry cough and hyper K+ that is common with ACE inhibitors Angiotensin II Receptor Blockers: Mechanism of Action Go back to RAAS diagram! ARBs affect primarily 2 places 1. Vascular smooth muscle - blocks vasoconstriction 2. Adrenal gland -Selectively blocks the binding of Ang 2 to certain Ang 2 receptors inhibiting secretion of aldosterone Lowers volume retention and BP Angiotensin II Receptor Blockers -ARTAN Losartan (Cozaar)- very common Eprosartan (Teveten) Valsartan (Diovan) Irbesartan (Avapro) Candesartan (Atacand) Olmesartan (Benicar) Telmisartan (Micardis) Azilsartan (Edarbi) C. ARB Losartan (Cozaar) Beneficial in patients with HTN and HF Used with caution in patients with kidney or liver dysfunction and in patients with renal artery stenosis ***Not safe for breastfeeding women and should not be used in pregnancy (Cat C 1st trimester, Cat D 2nd-3rd trimester), potential fetal toxicity Appear to be equally effective for the treatment of hypertension and well tolerated ARBs less likely to cause cough and hyperK+ but can still happen Evidence that ARBs are associated with lower mortality after MI than ACE inhibitors Never take ACEi and ARBs at the same time* 5. Calcium Channel Blockers (CCB) Primary use: HTN, angina, some dysrhythmias Cause smooth muscle relaxation by blocking the binding of calcium to its receptors, preventing muscle contraction Results in: Relaxed blood vessels to the heart Decreased peripheral smooth muscle tone Decreased SVResistance Decreased BP E. Diuretics First-line antiHTN in JNC 8 guidelines Decreases fluid volume The results from diuresis: preload, Peripheral resistance Overall effect  Decreased workload of the heart and decreased BP Thiazide diuretics are the most commonly used diuretics for HTN Ie hydrochlorothiazide (HCTZ), chlorthalidone We will discuss diuretics further in the chapter on diuretics F. Vasodilators Directly relax arterial or venous smooth muscle (or both) Results in: Decreased SVR Decreased afterload Peripheral vasodilation Indicated for treatment of HTN May be used in combination with other drugs F. Vasodilators Hydralazine (Apresoline) Orally: routine cases of essential hypertension Injectable: hypertensive emergencies BiDil: specifically indicated as an adjunct for treatment of HF in African-American patients F. Vasodilators Sodium Nitroprusside (Nitropress) *Sodium nitroprusside and IV diazoxide are reserved for the management of hypertensive emergencies. Contraindications: severe HF, known inadequate cerebral perfusion (especially during neurosurgical procedures) F. Vasodilators Adverse Effects Hydralazine: dizziness, headache, tachycardia, edema, dyspnea, N/V/D, vitamin B6 deficiency, rash Sodium nitroprusside: hypotension, bradycardia, decreased platelet aggregation, rash G. Direct Renin Inhibitors Aliskirin (Tekturna) Blocks the RAS pathway at the point of activation. Inhibiting renin production prevents the downstream production of Ang II (potent vasoconstrictor) Adverse effects: N/V, severe hypotension, hyponatremia, hyperkalemia… Contraindicated in patients with DM taking ACEi or ARB Miscellaneous Antihypertensives Eplerenone (Inspra) Newer class of drugs called selective aldosterone blockers (remember RAAS?) Reduces BP by blocking the actions of aldosterone at its corresponding receptors in the kidney, heart, blood vessels, and brain Indications: routine treatment of hypertension and for post-MI HF Contraindicated if serum potassium levels are high (above 5.6 mEq/L) A Special Form of HTNTreatment of Pulmonary Hypertension Sildenafil and Tadalafil Commonly used for erectile dysfunction Used for pulmonary hypertension but with different trade names Sildenafil: Revatio* (Viagra for ED) Tadalafil: Adcirca* (Cialis for ED)

Fed. 51: To the People of the State of New York: TO WHAT expedient, then, shall we finally resort, for maintaining in practice the necessary partition of power among the several departments, as laid down in the Constitution? The only answer that can be given is, that as all these exterior provisions are found to be inadequate, the defect must be supplied, by so contriving the interior structure of the government as that its several constituent parts may, by their mutual relations, be the means of keeping each other in their proper places. Without presuming to undertake a full development of this important idea, I will hazard a few general observations, which may perhaps place it in a clearer light, and enable us to form a more correct judgment of the principles and structure of the government planned by the convention. In order to lay a due foundation for that separate and distinct exercise of the different powers of government, which to a certain extent is admitted on all hands to be essential to the preservation of liberty, it is evident that each department should have a will of its own; and consequently should be so constituted that the members of each should have as little agency as possible in the appointment of the members of the others. Were this principle rigorously adhered to, it would require that all the appointments for the supreme executive, legislative, and judiciary magistracies should be drawn from the same fountain of authority, the people, through channels having no communication whatever with one another. Perhaps such a plan of constructing the several departments would be less difficult in practice than it may in contemplation appear. Some difficulties, however, and some additional expense would attend the execution of it. Some deviations, therefore, from the principle must be admitted. In the constitution of the judiciary department in particular, it might be inexpedient to insist rigorously on the principle: first, because peculiar qualifications being essential in the members, the primary consideration ought to be to select that mode of choice which best secures these qualifications; secondly, because the permanent tenure by which the appointments are held in that department, must soon destroy all sense of dependence on the authority conferring them. It is equally evident, that the members of each department should be as little dependent as possible on those of the others, for the emoluments annexed to their offices. Were the executive magistrate, or the judges, not independent of the legislature in this particular, their independence in every other would be merely nominal. But the great security against a gradual concentration of the several powers in the same department, consists in giving to those who administer each department the necessary constitutional means and personal motives to resist encroachments of the others. The provision for defense must in this, as in all other cases, be made commensurate to the danger of attack. Ambition must be made to counteract ambition. The interest of the man must be connected with the constitutional rights of the place. It may be a reflection on human nature, that such devices should be necessary to control the abuses of government. But what is government itself, but the greatest of all reflections on human nature? If men were angels, no government would be necessary. If angels were to govern men, neither external nor internal controls on government would be necessary. In framing a government which is to be administered by men over men, the great difficulty lies in this: you must first enable the government to control the governed; and in the next place oblige it to control itself. A dependence on the people is, no doubt, the primary control on the government; but experience has taught mankind the necessity of auxiliary precautions. This policy of supplying, by opposite and rival interests, the defect of better motives, might be traced through the whole system of human affairs, private as well as public. We see it particularly displayed in all the subordinate distributions of power, where the constant aim is to divide and arrange the several offices in such a manner as that each may be a check on the other that the private interest of every individual may be a sentinel over the public rights. These inventions of prudence cannot be less requisite in the distribution of the supreme powers of the State. But it is not possible to give to each department an equal power of self-defense. In republican government, the legislative authority necessarily predominates. The remedy for this inconveniency is to divide the legislature into different branches; and to render them, by different modes of election and different principles of action, as little connected with each other as the nature of their common functions and their common dependence on the society will admit. It may even be necessary to guard against dangerous encroachments by still further precautions. As the weight of the legislative authority requires that it should be thus divided, the weakness of the executive may require, on the other hand, that it should be fortified. An absolute negative on the legislature appears, at first view, to be the natural defense with which the executive magistrate should be armed. But perhaps it would be neither altogether safe nor alone sufficient. On ordinary occasions it might not be exerted with the requisite firmness, and on extraordinary occasions it might be perfidiously abused. May not this defect of an absolute negative be supplied by some qualified connection between this weaker department and the weaker branch of the stronger department, by which the latter may be led to support the constitutional rights of the former, without being too much detached from the rights of its own department? If the principles on which these observations are founded be just, as I persuade myself they are, and they be applied as a criterion to the several State constitutions, and to the federal Constitution it will be found that if the latter does not perfectly correspond with them, the former are infinitely less able to bear such a test. There are, moreover, two considerations particularly applicable to the federal system of America, which place that system in a very interesting point of view. First. In a single republic, all the power surrendered by the people is submitted to the administration of a single government; and the usurpations are guarded against by a division of the government into distinct and separate departments. In the compound republic of America, the power surrendered by the people is first divided between two distinct governments, and then the portion allotted to each subdivided among distinct and separate departments. Hence a double security arises to the rights of the people. The different governments will control each other, at the same time that each will be controlled by itself. Second. It is of great importance in a republic not only to guard the society against the oppression of its rulers, but to guard one part of the society against the injustice of the other part. Different interests necessarily exist in different classes of citizens. If a majority be united by a common interest, the rights of the minority will be insecure. There are but two methods of providing against this evil: the one by creating a will in the community independent of the majority that is, of the society itself; the other, by comprehending in the society so many separate descriptions of citizens as will render an unjust combination of a majority of the whole very improbable, if not impracticable. The first method prevails in all governments possessing an hereditary or self-appointed authority. This, at best, is but a precarious security; because a power independent of the society may as well espouse the unjust views of the major, as the rightful interests of the minor party, and may possibly be turned against both parties. The second method will be exemplified in the federal republic of the United States. Whilst all authority in it will be derived from and dependent on the society, the society itself will be broken into so many parts, interests, and classes of citizens, that the rights of individuals, or of the minority, will be in little danger from interested combinations of the majority. In a free government the security for civil rights must be the same as that for religious rights. It consists in the one case in the multiplicity of interests, and in the other in the multiplicity of sects. The degree of security in both cases will depend on the number of interests and sects; and this may be presumed to depend on the extent of country and number of people comprehended under the same government. This view of the subject must particularly recommend a proper federal system to all the sincere and considerate friends of republican government, since it shows that in exact proportion as the territory of the Union may be formed into more circumscribed Confederacies, or States oppressive combinations of a majority will be facilitated: the best security, under the republican forms, for the rights of every class of citizens, will be diminished: and consequently the stability and independence of some member of the government, the only other security, must be proportionately increased. Justice is the end of government. It is the end of civil society. It ever has been and ever will be pursued until it be obtained, or until liberty be lost in the pursuit. In a society under the forms of which the stronger faction can readily unite and oppress the weaker, anarchy may as truly be said to reign as in a state of nature, where the weaker individual is not secured against the violence of the stronger; and as, in the latter state, even the stronger individuals are prompted, by the uncertainty of their condition, to submit to a government which may protect the weak as well as themselves; so, in the former state, will the more powerful factions or parties be gradnally induced, by a like motive, to wish for a government which will protect all parties, the weaker as well as the more powerful. It can be little doubted that if the State of Rhode Island was separated from the Confederacy and left to itself, the insecurity of rights under the popular form of government within such narrow limits would be displayed by such reiterated oppressions of factious majorities that some power altogether independent of the people would soon be called for by the voice of the very factions whose misrule had proved the necessity of it. In the extended republic of the United States, and among the great variety of interests, parties, and sects which it embraces, a coalition of a majority of the whole society could seldom take place on any other principles than those of justice and the general good; whilst there being thus less danger to a minor from the will of a major party, there must be less pretext, also, to provide for the security of the former, by introducing into the government a will not dependent on the latter, or, in other words, a will independent of the society itself. It is no less certain than it is important, notwithstanding the contrary opinions which have been entertained, that the larger the society, provided it lie within a practical sphere, the more duly capable it will be of self-government. And happily for the REPUBLICAN CAUSE, the practicable sphere may be carried to a very great extent, by a judicious modification and mixture of the FEDERAL PRINCIPLE. PUBLIUS.

CARBOHYDRATES Carbohydrates are organic compounds composed of carbon, hydrogen, and oxygen in a ratio of about one carbon atom to two hydrogen atoms to one oxygen atom. The number of carbon atoms in a carbohydrate varies. Some carbohydrates serve as a source of energy. Other carbohydrates are used as structural materials. Carbohydrates can exist as monosaccharides, disaccharides, or polysaccharides. Monosaccharides A monomer of a carbohydrate is called a monosaccharide (MAHN-oh-SAK-uh-RIED). A monosaccharide—or simple sugar— contains carbon, hydrogen, and oxygen in a ratio of 1:2:1. The gen- eral formula for a monosaccharide is written as (CH2O)n, where n is any whole number from 3 to 8. For example, a six-carbon mono- saccharide, (CH2O)6, would have the formula C6H12O6. The most common monosaccharides are glucose, fructose, and galactose, as shown in Figure 3-6. Glucose is a main source of energy for cells. Fructose is found in fruits and is the sweetest of the monosaccharides. Galactose is found in milk. Notice in Figure 3-6 that glucose, fructose, and galactose have the same molecular formula, C6H12O6, but differing structures. The different structures determine the slightly different properties of the three compounds. Compounds like these sugars, with a single chemical formula but different structural forms, are called isomers (IE-soh-muhrz). SECTION 2 OBJECTIVES ● Distinguish between monosaccharides, disaccharides, and polysaccharides. ● Explain the relationship between amino acids and protein structure. ● Describe the induced fit model of enzyme action. ● Compare the structure and function of each of the different types of lipids. ● Compare the nucleic acids DNA and RNA. VOCABULARY carbohydrate monosaccharide disaccharide polysaccharide protein amino acid peptide bond polypeptide enzyme substrate active site lipid fatty acid phospholipid wax steroid nucleic acid deoxyribonucleic acid (DNA) ribonucleic acid (RNA) nucleotide C HO H C H OH C OH H C CH2OH H C H OH O Glucose C OH C O H OH C OH H CH2OH C H CH2OH Fructose C H HO C OH H C OH H C CH2OH H C H OH O Galactose Glucose, fructose, and galactose have the same chemical formula, but their structural differences result in different properties among the three compounds. FIGURE 3-6 Copyright © by Holt, Rinehart and Winston. All rights reserved. 56 CHAPTER 3 Disaccharides and Polysaccharides In living things, two monosaccharides can combine in a condensa- tion reaction to form a double sugar, or disaccharide (die-SAK-e-RIED). For example in Figure 3-4, the monosaccharides fructose and glu- cose can combine to form the disaccharide sucrose. A polysaccharide is a complex molecule composed of three or more monosaccharides. Animals store glucose in the form of the polysaccharide glycogen. Glycogen consists of hundreds of glucose molecules strung together in a highly branched chain. Much of the glucose that comes from food is ultimately stored in your liver and muscles as glycogen and is ready to be used for quick energy. Plants store glucose molecules in the form of the polysaccha- ride starch. Starch molecules have two basic forms—highly branched chains that are similar to glycogen and long, coiled, unbranched chains. Plants also make a large polysaccharide called cellulose. Cellulose, which gives strength and rigidity to plant cells, makes up about 50 percent of wood. In a single cellu- lose molecule, thousands of glucose monomers are linked in long, straight chains. These chains tend to form hydrogen bonds with each other. The resulting structure is strong and can be broken down by hydrolysis only under certain conditions. PROTEINS Proteins are organic compounds composed mainly of carbon, hydrogen, oxygen, and nitrogen. Like most of the other biological macromolecules, proteins are formed from the linkage of monomers called amino acids. Hair and horns, as shown in Figure 3-7a, are made mostly of proteins, as are skin, muscles and many biological catalysts (enzymes). Amino Acids There are 20 different amino acids, and all share a basic structure. As Figure 3-7b shows, each amino acid contains a central carbon atom covalently bonded to four other atoms or functional groups. A single hydrogen atom, highlighted in blue in the illustration, bonds at one site. A carboxyl group, —COOH, highlighted in green, bonds at a second site. An amino group, —NH2, highlighted in yel- low, bonds at a third site. A side chain called the R group, high- lighted in red, bonds at the fourth site. The main difference among the different amino acids is in their R groups. The R group can be complex or it can be simple, such as the CH3 group shown in the amino acid alanine in Figure 3-7b. The differences among the amino acid R groups gives different proteins very different shapes. The different shapes allow pro- teins to carry out many different activities in living things. Amino acids are commonly shown in a simplified way such as balls, as shown in Figure 3-7c. (a) Many structures, such as hair and horns are made of proteins. (b) Proteins are made up of amino acids. Amino acids differ only in the type of R group (shown in red) they carry. Polar R groups can dissolve in water, but nonpolar R groups cannot. (c) Amino acids have complex structures, so, in this and other textbooks, they are often simplified into balls. FIGURE 3-7 (b) Alanine (an amino acid) (c) Simplified version of amino acid CH3 H N OH C C H O H (a) Copyright © by Holt, Rinehart and Winston. All rights reserved. BIOCHEMISTRY 57 H H N C C OH H O H CH3 H2O Glycine Alanine H N OH C C H O H H H N C C H O H CH3 N OH C C H O H (a) (b) (a) The peptide bond (shaded blue) that binds amino acids together to form a polypeptide results from a condensation reaction that produces water. (b) Poly- peptides are commonly shown as a string of balls in this textbook and elsewhere. Each ball represents an amino acid. FIGURE 3-8 Substrate Products Enzyme 1 2 3 In the induced fit model of enzyme action, the enzyme can attach only to a substrate (reactant) with a specific shape. The enzyme then changes and reduces the activation energy of the reaction so reactants can become products. The enzyme is unchanged and is available to be used again. 3 2 1 FIGURE 3-9 Dipeptides and Polypeptides Figure 3-8a shows how two amino acids bond to form a dipeptide (die-PEP-TIED). In this condensation reaction, the two amino acids form a covalent bond, called a peptide bond (shaded in blue in Figure 3-8a) and release a water molecule. Amino acids often form very long chains called polypeptides (PAHL-i-PEP-TIEDZ). Proteins are composed of one or more polypep- tides. Some proteins are very large molecules, containing hun- dreds of amino acids. Often, these long proteins are bent and folded upon themselves as a result of interactions—such as hydrogen bonding—between individual amino acids. Protein shape can also be influenced by conditions such as temperature and the type of solvent in which a protein is dissolved. For exam- ple, cooking an egg changes the shape of proteins in the egg white. The firm, opaque result is very different from the initial clear, runny material. Enzymes Enzymes—RNA or protein molecules that act as biological catalysts—are essential for the functioning of any cell. Many enzymes are proteins. Figure 3-9 shows an induced fit model of enzyme action. Enzyme reactions depend on a physical fit between the enzyme molecule and its specific substrate, the reactant being catalyzed. Notice that the enzyme has folds, or an active site, with a shape that allows the substrate to fit into the active site. An enzyme acts only on a specific substrate because only that substrate fits into its active site. The linkage of the enzyme and substrate causes a slight change in the enzyme’s shape. The change in the enzyme’s shape weakens some chemical bonds in the substrate, which is one way that enzymes reduce activation energy, the energy needed to start the reaction. After the reaction, the enzyme releases the products. Like any catalyst, the enzyme itself is unchanged, so it can be used many times. An enzyme may not work if its environment is changed. For example, change in temperature or pH can cause a change in the shape of the enzyme or the substrate. If such a change happens, the reaction that the enzyme would have catalyzed cannot occur.

[t comes from the GREEK name "Epilepsia" which means "taking hold of or seizing". - It is a disorder characterized by: recurrent seizures. SEIZURES R ectment transient attacks of: R epresent: R esult from: ASSOCIATED WITH: somatic, psychic, or, autonomic clinical featmes. clinical features of abnormally hyperexcitable cortical neurons. paroxvsmal and excessive electrical neuronal discharges. EEG changes & may be disturbance of consciousness. same causes of convulsions 1. Idiopathic epile~ • It is the commonest cause. no cause can be detected ( 65 % ) • It may be associated with positive family history in some cases. • It starts in the l st & 2nd decades in the form of: -- Grand ma! epilepsy. Petit mal epilepsy. Myoclonic epilepsy. Atonic seizures. 2. Secondary epilepsy A. Local causes in the brain: l. Congenital: 2. Traumatic: cerebral palsy. a cause can be detected cerebral contusion or laceration. 3. Inflammatory: 4. Neoplastic: 5. Degenerative: 6. Vascular: encephalitis, brain tumours. mening1t1s, presenile dementia. brain abscess. stroke (especially hemon-hagic), hypertensive encephalopathy. B. General causes with secondary effects on the brain: I. Toxic: 2. Iatrogenic: 3. Metabolic: 4. Endocrinal: 5. Organ failure: 6. Heart disease: 7. Nutritional: - Alcohol, cocaine, lead. - Lidocaine, INH. - j glucose & ! glucose. - Hypoparathyroidism. - Hepatic failme. - Adam's Stoke's attacks. - Pellagra. - Botulism, tetanus. - Ambilhar, Amphetamine, Aminophylline. - j Ca & ! Ca. - Hype1thyroid crisis. - Renal failure. - Fallot's tetralogy. - j Na & ! Na. - Vitamin B6 deficiency. 8. Physical: 9. HYSTERICAL. - High fevers. - Heat stroke. 136 137 CLINICAL PICTURE 1. GENERALISED SEIZURES " Excessive electrical discharges from cortical neurons in BOTH hemispheres simultaneously " I. II. 1. Grand Mal Epile~: 1. Pre-ictal stage "attacks of tonic-clonic convulsions " (aura) It is a warning sign of a coming attack. It may be: • Somatic: • Psychic: • Autonomic: 2. Ictal stage Myoclonus, Hallucinations. Tachycardia, (seizure) Sudden loss of consciousness: Parasthesias. Sweating. for seconds to minutes. -- Tonic phase (few seconds) o The UL & LL: o o o o The HEAD: The JAWS: CYANOSIS: are extended. is retracted to one side & the eye balls rolled up. are firmly clenched, with biting of the TONGUE. due to impaired respiration. There may be incontinence of urine. Clonic phase (few minutes) o The UL & LL: o The HEAD: 3. Post-ictal stage - It may be: • Somatic: • Psychic: • Autonomic: Drug of choice: contract & relax repeatedly & rapidly. jerks forcibly. (sequelae) Todd's paralysis(< 24 hours, due to neuronal exhaustion). Confusion. Vomiting. Carbamazepine (Tegretol) or Phenytoin (Epanutin) Petit Mal Epilepsy: "attacks of loss of consciousness " " Absence " It starts in childhood & improves at puberty & usually disappears at the age of 20. 2. It is NOT PRECEEDED by aura & NOT FOLLOWED by sequelae. 3. It is usually PRECIPITATED by: hyperventilation 4. It is characterized by: or photic stimulation. sudden loss of consciousness of short duration (few seconds). 5. It may be associated with: • High frequency ( 50 attacks / day). • Falling to the ground without warning. • Jerky movements of the head & UL Drug of choice: (myoclonic petit mal). Valproate (Depakine) or Succinimide (Zarontin) 137 138 Ill. M oclonic Seizures: "attacks of involuntary clonic movements " - It is characterized by: sudden, jerky, shock-like INVOLUNTARY muscle contraction. • The jerks are bilateral contractions, mainly of the shoulders and arms. • However, some patients repmtjerking in the lower limbs, trunk, or head. - It may be of 2 types: - Occurs singly • Simple: • As a pait of: I Drug of choice: IV. Atonic seizures: (no loss of consciousness). - Grand mal epilepsy (aura). - Petit mal epilepsy. Valproate (Depakine) or Clonazepam (Rivotril) I - Transient attacks of brief loss of postural tone, often resulting in falls and injuries. 2. PARTIAL SEIZURES "Excessive electrical discharges from cmtical neurons in a ce1tain area in ONE hemisphere" A. Simple seizures: " No disturbance in consciousness " - The CP depends on the site of the hyperexcitable neurones in the cerebral cortex, whether in: "Motor area or Senso,y areas". 1. Motor fits: • Focal fits: • Motor jacksonian fits: 2. General Sensory fits: • Focal fits: • Sensory jacksonian fits: 3. Special Senso1y fits: • Visual hallucinations: • Auditory hallucinations: • Olfactory hallucinations: B. Complex seizures: - SITE: movement of part of a limb or the whole limb. movement of one side of the body (see before). parasthesia of part of a limb or the whole limb. parasthesia of one side of the body (see before). irritation of the visual sensory area. irritation of the auditory sensory area. initation of the uncus. " disturbance in consciousness " The hyperexcitable neurons are in the Temporal lobe "Temporal lobe epilepsy". - DURATION: The seizure lasts few seconds to few minutes. - The seizure starts with A ura, followed by A bsence, Automatism, Amnesia: 1. 2. 3. 4. A ura: A bsence: Automatism: A mnesia: Olfactory hallucinations, Deja-vu phenomenon, Sensation of fear. Absent patient with staring eyes (with no response to conversation). Involuntary Purposeless acts: motor ( eg, lip smacking, chewing) or verbal. No recalling of the seizure. 138 139 3. PARTIAL SEIZURES ~ GENERALISED SEIZURES " Partial seizures may spread to involve the whole brain .- secondarily generalised seizures " . HY-sterical epilepsY • Usually: • The cause: • Incidence: young neurotic Sj2 . psychological & there is no organic lesion. usually occurs in the presence of people. • It is associated with: • EEG: • It is not associated with: normal. • Missed ttt. • Menses. • Alkalosis. anxiety, palpitaion & hyperventilation. tongue biting or incontinence of urine. • Alcohol use & Drug abuse ( e.g. cocaine ). • S timulation by photons & Hyperventilation. • S leep deprivation & Stress & sudden withdrawal of antiepileptic drngs. INVESTIGATIONS 1. EEG: • It is the most specific test for epilepsy because it records the electrical activity of the brain. • It shows specific pattern: 2. LOCAL INVESTIGATIONS: "Epilepsy waves". "CT & MRI of the brain" • To identify or exclude a LOCAL CAUSE of seizures in the brain. 3. GENERAL INVESTIGATIONS: "Laboratory investigations" • To search for a GENERAL CAUSE of seizures, e.g. blood glucose. 139 140 TREATMENT A. General Measures: 1. 2. Moderation of the patient's physical activity. A void the precipitating factors ( Alcohol, hyperventilation, photic stimulation ...... ). 3. A ketogenic diet is encouraged because it will induce acidosis: - Acidosis is beneficial as it raises the threshold of stimulation of the brain cells. B. Specific Treatment: 2. 1. Treatment of the cause in secondary epilepsy. Anti-epileptic drugs: a) Always sta1t with one drug, then add another drug if there is no response. b) Always stop the drugs ONLY if: • The patient stays free of symptoms for at least 2 years. • The patient has a normal EEG. 3. Side effects of Anti-epileptic drugs: I . Skin rash. 2. 3. Bone marrow depression. Ataxia. Drug 1. Barbiturates (Pbenonobarbitone) 2. Hydantoin (Epanutin) 3. Carbamazepine 4. Clonazepam 5. Valproate 6. Succinamide ANTI-EPILEPTIC DRUGS NEW ANTI-EPILEPTIC DRUGS - These drugs are new dtugs that may be used in resistant seizures. 1. Lamotrigine: 200 - 400 mg/ day. 2. Felbamate: 3. Gabapentin: 400- 800 mg/ day. 600 - 1200 mg/ day. \ " General rules for use ": Dose 100-600 mg I day 100-600 mg / day 200-600 mg I day 2-6 mg I day 500-1500 mg I day 500-1000 mg / day Best indicated - Broad spectrum. - Not for petit mal. - Grand mal. - Motor Jacksonian fits. - Grand mal. - Motor Jacksonian fits. - Complex seizures. - Not for petit ma!. - Myoclonic. - Grand mat. - Broad spectrum. - Petit mat. 140 141 STATUS EPILEPTICUS DEFINITION - A medical emergency: 1. Repeated attacks of generalized convulsions, with lack of recove,y of consciousness, 2. Persistent attack of seizure lasting for at least 30 minutes. OR, - If the convulsions are not stopped rapidly, coma deepens & death may occur due to: heart failure or respiratory failure or brain damage or hyperpyrexia. - The most common causes are: sudden withdrawal of anti-epileptic drugs & stroke. TREATMENT A. General Measures: l. Take care of: " ABC " • Place the patient on the ground, to guard against falling from bed. • Mouth gag & 02 inhalation ( endo-tracheal intubation may be needed). • Record the vital signs regularly. 2. Take a sample of: - Venous blood: for the level of: - A.tierial blood: for the level of: 3. a nti-epileptic drugs, a lcohol. pH, p0 2, pC02, HC0 3. Give cerebral dehydrating measures: e.g. Frusemide, cone. Mannitol, Dexamethazone. B. Specific Treatment: - Phenytoin with diazepam (or clonazepam) immediately: 1. Phenytoin: 2. Diazepam: Clonazepam: seizures recur: 15 mg I Kg slow infusion. 5 mg slowly IV, to be repeated after 5 minutes if seizures recur: maximum dose: 20 mg. OR: 2 mg slowly IV, to be repeated after 5 minutes if maximum dose: 6 mg. - If seizures persist after 20 min. of Phenytoin & diazepam: 3. PHENOBARBITONE: - In resistant cases: 200 mg infusion. 4. GENERAL ANAESTHESIA: may be used.

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