Path and Pharmacology Exam 2 

  • Blood pressure readings normal, elevated, stage 1 and stage 2 Normal - systolic <120 and diastolic less than 80, Elevated/Prehypertensive - 120-139 systolic OR 80-89 diastolic, Hypertension stage 1 - 140-159 systolic or 90-99 diastolic, Hypertension stage 2 - 160+ systolic or 100+ diastolic
  • Hypertension incidence→1 in 3 adult americans, twice as prevalent and more severe among African Americans(genetics and environmental stress), greater salt intake and higher salt sensitivity. Fluid always follows salt, so more salt means higher plasma volume, which means higher blood pressure. Blood pressure control rates vary among minority groups and more prevalent in obese
  • Primary vs secondary hypertension- Primary hypertension- Known as essential hypertension, 95% of hypertensive people are categorized as essential, Cause in most people: unknown(genetics/environment), most likely caused by combo of overactivity of sympathetic nervous system, Reduction in baroreceptor reflex sensitivity (aortic/carotid), Associated with metabolic abnormalities (diabetes, calcium anomalies), adaptive responses to diet/lifestyles .Blood pressure = Cardiac Output x stroke volume, Initially if someone was diagnosed with hypertension→treat it through the heart or at the vasculature, Secondary Hypertension- Accounts for 5-10% of hypertensive individuals, Results from an identifiable cause, Chronic renal failure (CNF), renal artery stenosis, endocrine disease, etc.
  • Risk factors for hypertension- Genetics, smoking, obesity, diabetes, kidney disease, age, more often in men under 50 years, after 50 years, higher in women, sodium sensitivity, being of african american or latin descent, high cholesterol levels, sedentary nature, alcohol consumption, continuous emotional stress, oral contraceptives(tricks body into thinking it's pregnant, so increases plasma volume), corticosteroids(increase plasma volume), risk of moribidity/mortality - increase of 20mmHg SBP/10mmHg DBP; each associated with doubling risk of death from stroke, heart disease, or other vascular disease; 30 or older increased SBP/DBP associated with risk for CVD, angina, myocardial infarction, heart failure, cerebral vascular accident, peripheral arterial disease, abdominal aortic aneurysm, modifiable risk factors:cigarette smoking, second hand smoking, diabetes, dyslipidemia, overweight/obesity, physical inactivity/low fitness, unhealthy diet, relatively fixed risk factors: Kidney disease, family history, increased age, low socioeconomic /educational status, male sex, obstructive sleep apnea, psychosocial stress
  • Stepped care approach for HTN treatment- Monotherapy (where hypertension is not that high), Desired effect is not achieved through drug 1, second added, third drug added, fourth drug added, Initial first line pharmacological therapy for stage 1 HTN - Calcium channel blockers second, ACE inhibitors or angiotensin II receptor blockers third, two first line drugs of different classes are recommended for stage 2 HTN
  • Baroreceptor hyper/or hypostimulation- Direct mechanism - has baroreceptors in body, at the kidneys, they monitor the pressure of blood getting to the capillaries, If pressure is high, arteriole dilation where more blood to kidneys and more blood is filtered. More blood filters means plasma volume reduced and this reduces blood pressure, If baroreceptors are understimulated/pressure is low at kidneys, arteriole constriction occurs, less blood to kidneys, which causes plasma volume to be maintained., If baroreceptors are under stimulated, they increase sympathetic nervous system, understimulation means low pressure, so they want to increase pressure, Negative feedback because elevated BP causes the HR to decrease and causes BP to decrease, decreased BP decreased baroreflex activation and causes HR to increase and restore BP levels
  • Mechanism of action for drugs- Beta-adrenergic blockers- block beta 1 receptors(reduces contractility and rate of contraction), decrease total cardiac workload, normalizes HR, decrease general sympathetic tone, limit extend of cardiac damage after MI, decrease the risk of fatality after MI, beta 1 selective predominantly affects beta 1 receptors, known as cardioselective, beta nonselective - equal affinity for beta 1 and beta 2 receptors(located in bronchioles), Alpha blockers - blocks the alpha 1 adrenergic receptors or vascular smooth muscle if selective , reduction of intra-cellular Ca++, Results in vaso-smooth muscle relaxation, Decreases peripheral vascular resistance, used in autonomic crisis (hypertensive crisis), promotes vasodilation in conditions of vascular insufficiency such as peripheral vascular disease and raynauds disease, calcium channel blockers - drugs that selectively block calcium entry into vascular smooth muscle cells, inhibits cross bridging of smooth muscle actin and myosin, vasodilation, reduced vascular resistance so better blood flow and lower pressure, reduces HR, decreases myocardial contraction force, inhibits Ca++ channels at the zona glomerulosa of the adrenal gland, Calcium channel blockers directly reduce the biosynthesis of aldosterone, diuretics - Increase formation and excretion of urine(reduce plasma volume), first line pharmacological approach to HTN, mild-moderate HTN, often used in combination with other HTN meds, ACE inhibitor - inhibits the enzyme that converts the angiotensin I to angiotensin II (this enzyme narrows blood vessels- makes the heart pump harder/work hard, therefore increasing BP), Renin-angiotensin-aldosterone system- Reduction in arteriole pressure, aortic and carotid baroreceptors are understimulated, a sequence of stimulation are sent to the cardioavasulcar control system that is very low and this increases sympathetic nervous system activity, Nor and epi are released into bloodstream and this binds with beta receptors and this releases renin, When renin is released, it goes into bloodstream. Liver is producing peptide angiotensinogen, when they come together, a reaction occurs and this forms angiotensin I., During this event, the lungs are making angiotensin converter enzyme(ACE), when angiotensin I and ACE combine, angiotensin II is made. Angiotensin II leads to vasoconstriction(blood vessels constrict), stimulate hypothalamus for the thirst reflex so we get very thirsty, stimulates the release of anti-diuretic hormone from the posterior pituitary and this creates aquaporins at the kidneys(This allows us to preserve water volume and extract water from what's filtered from the collecting ducts and puts it back into the reserves and this enhances plasma volume), Adrenal cortex stimulates production of peptide aldosterone. Serves to preserve our sodium concentration so we hold on to more sodium. Fluid follows sodium so this causes sodium to be maintained and increases our plasma volume, Angiotensin II stimulates production of vascular endothelial growth factor, this promotes conversion of simple epithelia(single layer cells) to stratified epithelia(more than one cell layer thick)(When this happens, the epithelia run into problems. It produces chemicals such as nitric oxide and it can no longer do that as well when it goes from simple to stratified epithelia), Centrally acting agents- inhibits the sympathetic discharge from the brainstem(working on alpha 2 receptors)
  • Using selective or nonselective alpha blockers and beta blockers↓ selective - has an affinity/selection for the specific receptor, whereas nonselective means it can block/inhibit any of the alpha receptors, Alpha-1 receptor - in smooth muscle(vascular), epinephrine and norepinepherine receptors, raises BP, intestinal relaxation(if receptor is blocked, BP drops and intestinal tightening), Alpha II: CNS (brainstem), reduces sympathetic flow(cholinergic neurons nerves to the sweat glands and adrenergic neurons provide nerves to the blood vessels and hair follicles, reduces stress., Beta-1: heart and kidneys, increased HR and heart contractility, Beta-II: bronchiole smooth muscle (breathing), smooth muscle relaxation, dilates bronchioles, Beta-III: adipose tissue, release triglyceride/fatty acids into the bloodstream (lipolysis)
  • Enzyme secreted by kidneys when recognized reduced blood flow or pressure→renin
  • renin-angiotensin aldosterone system and Angiotensin Converting Enzyme(ACE) - Renin-angiotensin aldosterone system, Reduction in arteriole pressure, aortic and carotid baroreceptors are understimulated, a sequence of stimulation are sent to the cardioavasulcar control system that is very low and this increases sympathetic nervous system activity, Nor and epi are released into bloodstream and this binds with beta receptors and this releases renin, When renin is released, it goes into bloodstream. Liver is producing peptide angiotensinogen, when they come together, a reaction occurs and this forms angiotensin I., During this event, the lungs are making angiotensin converter enzyme(ACE), when angiotensin I and ACE combine, angiotensin II is made. Angiotensin II leads to vasoconstriction(blood vessels constrict), stimulate hypothalamus for the thirst reflex so we get very thirsty, stimulates the release of anti-diuretic hormone from the posterior pituitary and this creates aquaporins at the kidneys, This allows us to preserve water volume and extract water from what's filtered from the collecting ducts and puts it back into the reserves and this enhances plasma volume, Adrenal cortex stimulates production of peptide aldosterone. Serves to preserve our sodium concentration so we hold on to more sodium. Fluid follows sodium so this causes sodium to be maintained and increases our plasma volume, Angiotensin II stimulates production of vascular endothelial growth factor, this promotes conversion of simple epithelia(single layer cells) to stratified epithelia(more than one cell layer thick), When this happens, the epithelia run into problems. It produces chemicals such as nitric oxide and it can no longer do that as well when it goes from simple to stratified epithelia, Stress and low blood volume/pressure at the kidneys stimulate the release of renin as well
  • ACE inhibitors adverse reactions/side effects→skin rash, persistent dry cough from ACE inhibitors, continuations of aldosterone mechanism
  • contraindications for people taking vasodilators→if people have orthostatic hypotension do not take it, someone who cannot tolerate nitrates should not be on them
  • Side effects of Diuretic→fluid depletion, electrolyte imbalance(lose a lot), hyponatremia or hypokalemia (low sodium or potassium), baroreflex activation (plasma volume reduced significantly, means wont be stimulated as often and can yield significant sympathetic reaction by the body), GI disturbances, weakness and fatigue from electrolyte imbalance, orthostatic hypotension, confusion, mood changes, plasma volume compensation
  • regular aerobic exercise can help reduce hypertension
  • The enzyme to look for in the blood when someone has a MI→troponin
  • Know about the process of having a MI(what's happening, inflammatory response, thrombogenic response, role of each thrombus Pathogenesis of atherosclerosis→Progression of Atherosclerosis, Under normal conditions, leukocytes do not adhere to endothelial cells, injury provokes inflammatory response, cellular apoptosis occurs with loss of SM cells, Rupture ‒> Thrombogenicity(how thrombus generates), cytokines attract monocytes, monocytes adhere to damaged area due to cell surface adhesion molecules vascular cellular adhesion molecules(VCAM-1), Migrate into intima between endothelial junctions, Junctions between endothelial cells become weakened, destabilization of vessel, contributes to increase in thrombus, connective tissue and plaque calcification, Plaque with deep injury/defect or gap in the fibrous cap, scap in the region of the damaged endothelial tissue is the cap, plaque/connective scar tissue exposed when there is a breach of the cap and this is plaque rupture, 76% of MI fatalities are from rupture of the plaque, further increases immune response, Chronic or mild plaque ruptures with healing inducing platelet accumulation, Increased permeability of tunica intima, lipoproteins enter intima and undergo oxidation, mineralization begins at site of injury, monocytes differentiate into macrophages, macrophages take up oxidized ldl and minerals and turn into foam cells, smooth muscle cells proliferate into tunica intima and further destabilize the vessel, platelets limit blood flow, thrombogenic occlusion derived from fibrin formation in conjunction with platelet aggregation(activation of proteolytic enzyme created by liver, these help build up or break down clots, blood vessel damage initiates a cascade effect of enzyme activation based on the inflammatory response called thromboplastin and that is released from the damaged vessel wall causing prothrombin. This is catalyzed to thrombin and thrombin is an enzyme that converts inactive fibrinogen to fibrin. STrands of fibrin bind together to form a meshwork structure/netting, phosphate is toxic to elastic, damaged elastin has high affinity for calcium/mineralization, This structure allows platelets to accumulate on it and this forms the clot, this causes vascular mineralization
  • calcium channel blockers can be provided to inhibit an adverse reaction, Long acting agents don't rapidly decrease BP and tend not to demonstrate the adverse reactions associated with short acting calcium channel blockers, Progression of Atherosclerosis, cellular apoptosis occurs with loss of SM cells, destabilization of vessel, contributres to increase in thromb
    • cellular apoptosis occurs with loss of SM cells
    • destabilization of vessel, contributes to increase in thrombus
    • connective tissue and plaque calcification
    • Rupture
    • Plaque with deep injury/defect or gap in the fibrous cap, scap in the region of the damaged endothelial tissue is the cap, plaque/connective scar tissue exposed when there is a breach of the cap and this is plaque rupture
    • 76% of MI fatalities are from rupture of the plaque
    • further increases immune response
    • Thrombogenicity(how thrombus generates)
    • Chronic or mild plaque ruptures with healing inducing platelet accumulation
      • platelets limit blood floow
      • thrombogenic occlusion derived from fibrin formation in conjunction with platelet aggregation(activation of proteolytic enzyme created by liver, these help build up or break down clots, blood vessel damage initiates a cascade effect of enzyme activation based on the inflammatory response called thromboplastin and that is released from the damaged vessel wall causing prothrombin. This is catalyzed to thrombin and thrombin is an enzyme that converts inactive fibrinogen to fibrin. STrands of fibrin bind together to form a meshwork structure/netting
      • This structure allows platelets to accumulate on it and this forms the clot
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  • Why heart attacks happen in the morning→early morning(when you first get out of bed, catecholamine levels are very high, vasoconstriction, HR and BP is very high, thicker blood so less enzyme searing proteases that break down blood clots. They find most people dead from MI on toilet or fallen off toilet due to pushing while going to the bathroom, this creates significant valsalva, yields a rise in BP, and if there's a susceptible fibrous cap so far, it can begin the cascade of a thrombotic event)
  • akinetic and dyskinetic issues with the heart and necrosis - know which one is worse and which would lead to CHF, If the area of the transmural infarction is small, the necrotic wall may be, dyskinetic meaning difficulty moving, If the damage to the myocardial tissue is more extensive, the myocardial muscle may become akinetic (doesnt move at all, if it doesnt move at all, that will completely limit the contractile capacity of the heart and is very dangerous), akinetic worse than dyskinetic
  • know primary mechanisms of actions behind reperfusion injuries after a heart attack, why is it so critical to use early on set breathing exercises after heart attack, cellular changes with a MI can be followed by development of infarct extension(new myocardial necrosis), reperfusion injuries where the surrounding tissue is damaged by inflammatory reaction, Infarct expansion(disproportionate thinning and dilation at that zone of tissue, susceptible to rupture), ventricular remodeling(become thin and dilated, they become extended/elongated and lose their ability to contract, breathing exercises/coughing(people dont want to expand their chest because of pain and it causes shallow breathing, this limits amount of oxygen saturation in the blood and this limits the body's ability to get rid of the fluid accumulating in the lungs and this can causes pneumonia)
  • Why people see a backflow of blood after a left ventricular ischemic event or necrotic event, what else aside from the ventricular walls get damaged that could cause a backflow of blood, left sided heart failure - when the left ventricle can no longer maintain a normal cardiac output(when left side fails, blood backs up into the lungs), Right sided heart failure- right ventricular dysfunction secondary to either left sided heart failure or related to pulmonary disease(if right side fails, blood backs into extremities like abdominal cavities)
  • know which side of the heart failure is strictly classified as congestive heart failure→the left side, specifically the left ventricle- the heart's main pumping chamber
  • Know the neural humoral compensations associated with CHF and focus time on first one/step/part→3 neurohumoral(based on nervous and endocrine system) compensations to the decreased cardiac conractile capacity - lack of oxygen and nutrient supply, 1). increase in cardiac output through ventricular enlargement and muscle fiber distention(presents initially as SOB, progresses to peripheral or visceral edema)
  • Peripheral edema, know what happens to it as the day goes on, worse or better? will it be observed in one or both lower extremities, Right sided heart failure presents with inadequate pumping capacity into the pulmonary circulation resulting in venous backup, leading to accumulation of fluid in the peripheral/extracellular spaces(ankles, and pelvic girdle), peripheral edema worsens as the day goes on, fluid has a harder time making it's way back up from the heart from the lower extremeties
  • know about digitalis, medication used for CHF, increases strength of contraction
  • Digitalis- increase the force and velocity of myocardial systolic contraction, reducing HR and AV node conduction velocity, Through mediation of Sodium/potassium ATPase mechanism, Results in increased intracellular Na+ concentration, so increased Ca++ concentration, results in increased baroreceptor sensitivity with decreased sympathetic activity (slows HR)
  • Know about different forms of angina, exertional or stable angina, angina that occurs at a certain time of the day, know unstable and acute angina, Angina
    • When cardiac workload exceeds oxygen supply to myocardial tissue, ischemia occurs and results in temporary chest pain or disscomfort, referred to as angina pectoralis
    • imbalance between myocardial oxygen supply and demand
    • common in individuals 65 or older, more common in men
    • Stable angina
    • usually lasts less than 20 minutes (>20 is a heart attack)
    • precipitated by exertion
    • relieved by rest or nitrates
    • why are symptoms relieved by rest? (when you rest, you reduce the metabolic requirement of the heart, so symptoms reduce)
    • Acute coronary syndrome(unstable angina)
      • usually lasts more than 20 minutes
      • sudden onset usually at rest and not relieved by rest, means someone is about to have a heart attack/MI
    • Nocturnal Angina- same symptoms as exertional angina, but occurs at night and wakes the person from sleep
    • increased HR in dreams/underlying CHF/sleep apnea
  • Know how someone with angina who is taking medication in the form of a nitrate, how would they ingest it and why is it ingested that way
    • Sublingually, takes effect in about 2 minutes, extended release form in buccal administration route, transdermal route for prophylaxis which results in drug tolerance and occurs at the enzymatic level
    • if taken orally, 99.9% destroyed in first pass effect, sublingually, it gets to where it has to go before it gets to the liver and is broken down in second pass effect
  • Know on an ekg what would be most indicative of ischemic heart disease or angina→ECG- ST segment changes/arrhythmias, typically depression
    • Detects ventricular wall motion abnormalities(contractile) and H+ build up
    • leads to clinical angina
    • chest pain and compression/tightness in the chest
  • Know on an ekg what would be most indicative of ischemic heart disease or angina→imbalance between myocardial oxygen supply and demand
  • Prinzmetal's, vasopastic, or variant angina
    • symptoms similar in nature to typical angina, but caused by coronary artery vaso-spasms
    • more common in women younger than 50 years
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