THE SECOND MIDTERM Flashcards
What are the nine major causes of death in order?
- Heart disease - 28% 2. Malignancies - 23% 3. Stroke 4. Emphysema 5. Accidents 6. Diabetes 7. Pneumonia 8. Alzheimer’s 9. Renal diseases - 1.7%
Definition of hypertrophy and hyperplasia:
It is the increase in the volume of an organ or tissue due to the enlargement of its component cells. It is distinguished from hyperplasia, in which the cells remain approximately the same size but increase in number. You are born with about all of the cardiac myocytes that you will get, but they can get bigger, this is hypertrophy.
Definition of metaplasia:
It is the reversible replacement of one differentiated cell type with another mature differentiated cell type. The change from one type of cell to another may generally be a part of normal maturation process or caused by some sort of abnormal stimulus. In simplistic terms, it is as if the original cells are not robust enough to withstand the new environment, and so they change into another type more suited to the new environment.
Definition of dysplasia:
It is an ambiguous term used in pathology to refer to an abnormality of development or an epithelial anomaly of growth and differentiation. It is disordered hyperplasia without maturation.
Definition of atrophy:
Cell shrinkage or loss, caused by lack of hormonal signals, loss of innervation, lack of use, loss of blood supply, starvation, individual cell death
Definition of cachexia:
The formal definition of cachexia is the loss of body mass that cannot be reversed nutritionally: Even if the affected patient eats more calories, lean body mass will be lost, indicating a primary pathology is in place.
At what percent of normal body weight is cachexia fatal?
Fatal at 68% of normal body weight
What type of cell change is the uterine cervix, bowel in IBS, esophagus with Barrett’s?
Dysplasia
What are the main eight causes of cell injury and death
- Trauma - force, heat, cold 2. Ischemia - inadequate circulation 3. Toxins & radiation 4. Infection 5. Inflammation 6. Genetic diseases 7. Nutritional problems 8. Tumors
Which cells are most prone to injury?
Those that have a high metabolic activity and those that proliferate rapidly
What are three examples of cells that have a high metabolic activity?
- Cardiac myocytes 2. Renal tubular cells 3. Hepatocytes
What are three examples of cells that proliferate rapidly?
- Testicular germ cells 2. Intestinal epithelium 3. Hematopoietic cells
What are the two degrees of cell injury and what are examples of each?
Reversible and Irreversible (cell death). An example of reversible is mild acute tubular necrosis of kidney, toxic livery injury, severe exercise. An example of irreversible is holes in cell membrane, long Ca++ influx, mitochondrial loss, and the two types of irreversible are necrosis and apoptosis.
What happens during severe exercise to our cells in the body?
You get hypoxia because of loss of ATP, anaerobic glycolysis with acidosis, and cell swelling because loss of Na pump.
Apoptosis involves inflammation. True or False?
False, it happens in normal cell turnover, viral infections, normal embryology, damaged cells.
What are the early events of necrosis?
Cell membrane disruption, Ca++ signal, energy loss.
Necrosis happens more often to individual cells rather than cell clusters. True or False?
False, it is the opposite
Necrosis involves inflammation. True or False?
True, it incites acute inflammation from leakage of cell contents
What is kariolysis?
It is the complete dissolution of the chromatin of a dying cell due to the enzymatic degradation by endonucleases. We get a digested, pale nucleus
What is nuclear pyknosis?
Is when the nucleus becomes shriveled and dark.
What is karyorrhexis?
It is when the nucleus becomes fragmented.
What is coagulative necrosis?
Coagulative -See this in infarcts in any tissue (except brain) -Due to loss of blood -Gross: tissue is firm -Micro: Cell outlines are preserved (cells look ghostly), and everything looks red
What is liquefactive necrosis?
Liquefactive -See this in infections and, for some unknown reason, in brain infarcts -Due to lots of neutrophils around releasing their toxic contents, “liquefying” the tissue -Gross: tissue is liquidy and creamy yellow (pus) -Micro: lots of neutrophils and cell debris
What is caseous necrosis?
Caseous -See this in tuberculosis -Due to the body trying to wall off and kill the bug with macrophages -Gross: White, soft, cheesy-looking (“caseous”) material -Micro: fragmented cells and debris surrounded by a collar of lymphocytes and macrophages (granuloma)
What is fat necrosis?
Fat necrosis -See this in acute pancreatitis -Damaged cells release lipases, which split the triglyceride esters within fat cells -Gross: chalky, white areas from the combination of the newly-formed free fatty acids with calcium (saponification) -Micro: shadowy outlines of dead fat cells (see image above); sometimes there is a bluish cast from the calcium deposits, which are basophilic
What is gangrenous necrosis?
Gangrenous necrosis -See this when an entire limb loses blood supply and dies (usually the lower leg) -This isn’t really a different kind of necrosis, but people use the term clinically so it’s worth knowing about -Gross: skin looks black and dead; underlying tissue is in varying stages of decomposition -Micro: initially there is coagulative necrosis from the loss of blood supply (this stage is called “dry gangrene”); if bacterial infection is superimposed, there is liquefactive necrosis (this stage is called “wet gangrene”)
What are the six main abnormal storage products? And details about them?
- Fatty change of liver (common with alcoholism, obesity, starvation, toxins. 2. Glycogen accumulation (in liver in diabetes, in glycogen storage disease, in certain tumors) 3. Lipid (lipid storage disease -Fabry’s-Gaucher’s, lysosomal accumulation of lipid, in vessels in atherosclerosis) 4. Brown storage (lipofuscin is degraded lipid in lysosomes, increases with age and free radical damage, bilirubin is a hemoglobin breakdown product, normally present in bile, increased with biliary obstruction & hepatocyte disorders, too much causes jaundice, Hemosiderin is an iron containing pigment that is increased with excessive iron absorption, you get bleeding into tissues) 5. Protein storage (alpha-1 antitrypsin deficiency and russell bodies in plasma cells are intracellular examples, whereas amyloid is an extracellular example and is a beta pleated sheet protein accumulation. 6. Calcification (you can get dystrophic or metastatic calcification (into damaged or normal tissue), an example of metastatic is disorder of calcium metabolism, renal failure, hyperparathyroidism)
What is the name for Coal Worker’s lung?
Anthracosis, abormal storage products in lung
What is edema?
Too much extravascular fluid in tissues. Hormonal fluid retention, heart failure, and inflammation are common causes for edema. Dependent edema is when fluid accumulates in lower part of body. A common cause of pulmonary edema is heart failure.
What is effusion?
Too much fluid in body cavity, examples are ascites, excess fluid in peritoneal space, pleural effusion, and hydrocephalus, excess cerebrospinal fluid.
What is ascites?
Massive peritoneal space fluid in a liver failure patient.
Tumors often grow into veins and embolize. True or False?
False, they rarely do. But foreign material, amniotic fluid, and air can embolize and cause infarcts by blocking blood flow.
If left heart isn’t doing its job, what would you get?
It would back up and it would cause pulmonary edema
If right heart isn’t doing its job, what would you get?
It would back up in the veins and you would get edema throughout the whole body.
What are the three common causes of hypotension?
- Hypovolemic (low blood volume, blood flows mainly to vital organs) 2. Cardiogenic (heart infarct or failure, arrhythmia, pulmonary emboli 3. Septic shock (overwhelming infection, vasodilation and high permeability, poor cardiac pumping, patient often febrile, flushed, chills, poor prognosis unless infection is rapidly controlled.
What is congestive heart failure?
It is when the cardiac output is insufficient for metabolic needs of the body. You can get systolic dysfunction, which is decreased myocardial contractility (heart pumps weakly), diastolic dysfunction, which is insufficient expansion (heart does not fill with blood between beats). And problems are accentuated by increased demand.
What are the body’s five main methods to compensate for congestive heart failure?
- Tachycardia 2. Frank-Starling (increased end diastolic volume results in increased stroke volume) 3. Myocardial hypertrophy 4. Increased catecholamine activity leading to positive ionotropic effect (they tell the myocytes to keep contracting the best you can), as well as renin-angiotensin-aldosterone system 5. Redistribution of blood flow
How does left-sided heart failure occur and what are the consequences?
It is caused by ischemic heart disease, hypertension, aortic and mitral valve disease, myocardial disease like cardiomyopathy. You get pulmonary edema and breathing problems, dyspnea (breathlessness), orthopnea (dyspnea while lying down due to vascular congestion and it develops within minutes), paroxysmal nocturnal dyspnea (extreme dyspnea, develops over a few hours, due to pulmonary edema from heart failure while lying down). You also get reduced perfusion to organs like kidneys, ending up with prerenal azotemia (high BUN with less high or normal creatinine) or ischemic tubular necrosis.
How does right-sided heart failure occur and what are the consequences?
Can be caused by right-sided heart disease or cor pulmonale (abnormal enlargement of right side), and can be a consequence of left-sided failure, or due to myocarditis, cardiomyopathy. You end up getting chronic passive congestion to the liver, congestive splenomegaly, congestion and hypoxia to the kidneys, peripheral edema and anasarca (extreme edema), pleural effusions, venous congestion and hypoxia, and ascites.
What are the main symptoms of a myocardial infarct?
Retrosternal chest pain, dyspnea, diaphoresis (sweating), nausea/vomiting, palpitations, anxiety, or can be asymptomatic or present as sudden death.
What is the diagnostic criteria for a myocardial infarct?
You need at least 2 of the following: -Ischemic type chest pain for more than 20 minutes -Acute EKG changes -Rising, then falling serum cardiac biomarkers (troponin, CK) -Documentation of an infarct at autopsy
What is a transmural infarct?
It is due to an anuerysm in the heart wall and it has full thickness, endocardium to epicardium. Usually involving left ventricle anterior and posterior free wall or septum with extension into right ventricle wall in 15-30% of cases. More severe than MI, correlates with ST segment elevation myocardial infarct on EKG.
What is a subendocardial infarct?
It is due to hypotension, global ischemia, and is multifocal or diffuse areas of necrosis confined to inner 1/3 to 1/2 of left ventricular wall. Infarct is not necessarily in distribution of one coronary artery. Correlates with Non-ST segment elevation myocardial infarct on EKG, less severe but still potentially lethal.
What are the main complications of myocardial infarcts, and which are most common?
Most to least common 1. Arrhythmias 2. Congestive heart failure and pulmonary edema 3. Pericarditis 4. Mural thrombosis 5. None 6. Cardiogenic shock 7. Rupture of ventricle or papillary muscle
In referring to valvular heart disease, what is stenosis?
A failure to open, prevents forward flow
In referring to valvular heart disease, what is regurgitation?
A failure to close, allows reverse flow
What are the main two causes of calcific aortic valve stenosis?
Post infective endocarditis or rheumatic fever. It is also common in congenital bicuspid valves or normal valves of elderly people.
What are the main causes of aortic regurgitation?
Postinflammatory scarring, syphilitic aortitis, ankylosing spondylitis, rheumatoid arthritis, Marfan’s syndrome
What is a mitral valve prolapse, and who usually gets it?
It is excessively large leaflets in the mitral valve, long chordae tendineae, or myxomatous change within valve leaflets especially posterior leaflet. Could be hereditary or associated with Marfan’s syndrome, happens with 2-3% of population, mostly women, susceptible to endocarditis and psychiatric disorders.
What are the systemic symptoms of rheumatic fever?
Polyarthritis of large joints, carditis, subcutaneous nodules, sydenham’s chorea, used to be very common but due to antibiotic treatment for strep throat, not very common anymore.
Where does infective endocarditis usually take place in the heart?
Mitral valve and aortic valve - 25-35% of time Tricuspid valve, valve prosthesis, congenital defect - 10% of time. It consists of friable vegetations containing RBCs, fibrin, inflammatory cells and organisms.
What are the main causative agents of infective endoarditis?
Staph aureus, strep, pseudomonas, HACEK, polymicrobial. Fever and murmur are common, and mortality is as high as 70% if staphylococcal.
What re the main complications of infective endocarditis?
Cardiac complications, which are coronary artery emboli, abscesses, erosion of valve or chordae tenineae. Non-cardiac complications, which are septic emboli, immune complex diseases in vessels or kidneys.
What are the complications of artificial valves?
Thrombosis, can cause thromboembolism, anticoagulant related hemorrhage, increased risk of infective endocarditis, structural or biological deterioration, nonstructural dysfunction-tissue entrapment, paravalvular leaks, anemia, wears out valves and leaks.
What is an arrhythmia?
Palpitations, irregular heartbeat, premature atrial or ventricular contractions, the most common kind are normal EKG, infrequent, no other heart disease. Can have tachyarrhythmia, which is more serious.
What is syncope?
Fainting, due to hypotension or low cardiac output, arrhythmias happen to about 1/3 of patients with syncope, often serious, need EKG and evaluation. Presyncope if feeling lightheaded.
How do you differentiate a seizure from syncope?
Look for postictal changes with seizures, confusion for 2-10 minutes after seizures.
What are the usual cause of sudden cardiac death?
Arrhythmias, most often from coronary atherosclerosis, although infarct is not needed.
What is bradycardia?
Heart rate of less than 60 beats per minute
What is tachycardia?
Heart rate of more than 100 beats per minute
What can contribute to bradycardia?
Disturbances in impulse generation to the sinus node, impulse propagation from the sinus node to the atria, impulse propagation through the AV node/His-Purkinje system. Bradycardia due to abnormal impulse propagation is known as a conduction block.
What are the main causes of conduction disturbances?
Ischemic heart disease and cardiomyopathic scarring, degenerative changes in the conduction system, antiarrhythmic drugs, hyperkalemia, myocardial infection (lyme disease), trauma, congenital abnormality.
What is a first degree heart block?
It is a slow but reliable impulse propagation to ventricles, generally not symptomatic, no treatment.
What is a second degree heart block?
It is when impulse propagation to ventricles sometimes fails. You get irregular ventricular contractions, sometimes causes syncope, pacemaker sometimes needed.
What is a complete or third degree heart block?
No conduction of any atrial electrical impulses to the ventricles, ventricles resort to latent pacemakers, result is more P waves than QRS complexes, QRS complexes are regular as determined by latent pacemaker, no relationship between P and QRS complexes, and you get syncope and risk for sudden cardiac death.
What is an ectopic beat?
It is an increased rate of depolarization, at any site, to a rate faster than the sinus node which results in a premature depolarization. It is called ectopic because it originates from a site other than the sinus node.
What are the three main places where ectopic beats usually originate form?
- The atria (APDs, atrial premature depolarization) 2. Specialized conduction system - usually the AV node or His bundle (Junctional premature depolarizations) 3. The ventricles (VPDs, ventricular premature depolarizations)
What can an ectopic focus that is firing rapidly or multiple ectopic foci collectively causing a fast rhythym end up causing?
Tachycardia and Tachy-arrhythmias
What is a re-entrant arrhythmia?
Normally, electrical waves stop propagating when they encounter unexcitable tissue, re-entry occurs when the wave form does not extinguish as it continues to find excitable tissue.
How does re-entrant tachycardia persist?
For re-entry tachycardia to persist, the leading edge of the electrical wave front must always meet excitable (repolarized) tissue that is ready to depolarization, if it meets refractory tissue, the wave front will be extinguished and re-entry will stop. Conduction delay within the re-entrant circuit is crucial in maintaining the re-entry as it creates an excitable gap between the head of the wave front and refractory tissue at its tail.
What is atrial fibrillation?
It is the most common sustained arrhythmia in adult clinical cardiology. Atrial flutter is different and involves very rapid atrial contractions, and can turn into atrial fibrillation. AF increases with age and often co-exists with other cardiovascular diseases like congestive heart failure, valvular heart disease, and hypertension. 10% of Americans older than 65 years old have AF. It is associated with electrical and structural changes of the atrium. You get electrical remodeling, meaning shorter atrial action potentials, loss of rate of adaptation to action potential duration, and loss of myocytes and replacement with collagen and fibroblasts. AF causes inefficient atrial contraction, which causes decrease in cardiac output, due to loss of atrial contribution to ventricular filling, and is also involved with a high risk of thrombosis and embolization.
What is ventricular fibrillation?
It is a condition in which there is uncoordinated contraction of the cardiac muscle of the ventricles in the heart, making them quiver rather than contract properly. P waves are absent here, and can quickly lead to sudden cardiac arrest or death.
When does sudden cardiac arrest occur?
When there is an abrupt cessation of ventricular function due to rapid ventricular tachycardia or ventricular fibrillation. It is fatal 90% of the time.
Who is the population at risk of sudden cardiac arrest?
Patients with coronary artery disease, patients with heart failure, patients with inherited channelopathies causing ventricular arrhythmias.
How fast does brain damage and brain death occur within sudden cardiac arrest start?
Within 4-6 minutes, and it is reversible in most individuals if it is treated within minutes with CPR and defibrillator. A victim’s chances of survival are reduced by 7-10% per minute without CPR and defibrillator.
What is the main cause of cardiovascular mortality?
Sudden cardiac arrest, it is due to fast ventricular tachycardia and ventricular fibrillation.
What is unique about atrial fibrillation and atrial flutter and their risk associations?
They are both associated with a thrombo-embolic risk, while other arrhythmias are typically not associated with this risk.
What is sudden cardiac arrest?
Cardiac arrest, also known as cardiopulmonary arrest or circulatory arrest, is a sudden stop in effective blood circulation due to the failure of the heart to contract effectively or at all. A cardiac arrest is different from (but may be caused by) a myocardial infarction, where blood flow to the muscle of the heart is impaired. It is different from congestive heart failure, where circulation is substandard, but the heart is still pumping sufficient blood to sustain life. Arrested blood circulation prevents delivery of oxygen and glucose to the body. Lack of oxygen and glucose to the brain causes loss of consciousness, which then results in abnormal or absent breathing. Brain injury is likely to happen if cardiac arrest goes untreated for more than five minutes. For the best chance of survival and neurological recovery immediate treatment is important. Cardiac arrest is a medical emergency that, in certain situations, is potentially reversible if treated early. Unexpected cardiac arrest can lead to death within minutes: this is called sudden cardiac death (SCD). The treatment for cardiac arrest is immediate defibrillation if a “shockable” rhythm is present, while cardiopulmonary resuscitation (CPR) is used to provide circulatory support and/or to induce a “shockable” rhythm. A number of heart conditions and non-heart-related events can cause cardiac arrest; the most common cause is coronary artery disease.
What is considered a hypertensive emergency or crisis?
Direct acute organ damage, often with a BP greater than 180/110. It causes severe vessel damage.
What is essential hypertension?
No obvious cause, very common, nearly 50 million in US, 95% of all hypertensive patients. Possible causes include increased sodium retention & intravascular volume, narrowing of arteries, high TPR lowers blood pressure in kidneys, kidneys sense lower pressure and signal to retain sodium to increase BP, vicious cycle.
What is secondary hypertension?
Uncommon, 5% of all hypertensive patients, possible causes include endocrine (steroid, pheochromocytoma), drugs, pregnancy, renal failure, sleep apnea, pain, stress.
What are the main hypertension-induced problems?
Accelerated atherosclerosis due to endothelial injury, myocardial infarcts, stroke, peripheral vascular disease, aneurysms, heart failure, renal failure, retinal and brain damage, hemorrhages.
Which side of the heart gets bigger when body has systemic hypertension?
Left side has to pump harder so it undergoes hypertrophy.
What happens to the kidneys with extreme hypertensive changes?
Arterionephrosclerosis, the kidneys become smaller and have a finely pitted surface, very common in black people.
What percent of US adults have hypercholesterolemia levels above 200 mg/dl? 240 mg/dl?
50% and 13%
What are the secondary causes of hyperlipidemia?
These are far more common than familial by the way, but they are diabetes, sedentary lifestyle, poor diet, obesity, heavy alcohol. Familial is primary hyperlipidemia and has to do with genetics.
What are the four major lipoprotein classes?
- High density - HDL 2. Low density - LDL 3. Very low density - VLDL 4. Chylo-microns
Where do HDL’s deliver lipids to?
They deliver lipids periphery to liver
Where do LDL’s and VLDL’s deliver lipids to?
They deliver lipids liver to periphery
Where do chylo-microns deliver lipids to?
They deliver lipids gut to liver
What kind of lipoproteins are apo-B associated with?
LDLs and VLDLs, the bad ones, lipids induce atherosclerosis, they leak into vessel intima, induce macrophage response/inflammation, the inflammatory response induces smooth muscle cells in intima, fibrosis, calcification, and an atheroma can rupture into lumen and cause a thrombus.
What is the leading cause of death in America, and what causes 80% of that?
Heart disease, and Atherosclerosis does. Atherosclerosis can also be main cause of stroke, main cause of peripheral vascular disease.
What is arteriosclerosis vs atherosclerosis?
Arteriosclerosis is the hardening of the arteries. Atherosclerosis is lipid deposits, plaques in arteries, and can cause arteriosclerosis.
What is the mechanism behind atherosclerosis?
Endothelial dysfunction (smoking, hypertension, diabetes, lipids, inflammation) then lipids deposit in vessel wall intima, then inflammation/foamy macrophages, which all can do 1 of 2 things, either go to intimal smooth muscle, cause fibrosis, cause fibroatheroma with stenosis, which can lead to angina, claudication, etc, or it can cause plaque ulcer or rupture, which can lead to thrombosis (ruptured or ulcerated plaques), which causes most infarcts and sudden death.
How does atherosclerosis cause stenosis and disease?
Resistance to flow is inversely proportional to diameter^4 (i.e. inversely proportional to cross sectional area^2). You must have 75% stenosis (decreased cross sectional area) to clinically impede flow. This increases resistance 16-fold. Slow stenosis causes stable angina while abrupt stenosis or occlusion can cause infarcts/sudden death and is associated with a thrombus or embolus. A rupture/erosion causes a complicated lesion, and is the most common cause of most infarcts.
Where does arteriosclerosis usually happen?
Aorta, coronary arteries, iliac/femoral/and politeal arteries, carotids/circle of willis arteries, kidney, and pulmonary arteries.
What are the consequences of atherosclerosis in the aorta?
Very common in the aorta, most often below the renal arteries, the aorta is usually never occluded complete, but damage to media can cause aneurysm, and can rupture. Abdominal Aortic Aneurysm risk factors include family history, smoking, hypertension, but lipids do not matter for AAA. Ulcerated plaques can embolize.
What are the consequences of atherosclerosis in coronary arteries?
It causes 80% of heart disease:angina, infarct, chronic ischemic heart disease. Common sites are proximal 2-3 cm of LAD and LCX, and entire length of right coronary artery. Ruptured plaque with thrombus and erosion on a plaque with thrombus is most common, and rarely a hematoma in the plaque will happen. But you can’t predict well with an angiogram who is most at risk for an infarct.
What are the consequences of atherosclerosis in the peripheral arteries like iliac, femoral, and popliteal arteries?
Causes claudication (ache, pain, fatigue with exertion), then ulcers and ultimately gangrene.
What are the consequences of atherosclerosis in the carotid and circle of willis?
Erosions (not rupture) of a plaque is the more common cause of a thrombus here, and these are closely associated with hypertension, hypercoaguability, and old age, but less with hyperlipidemias and other risk factors.
What is a stroke?
Defined as an abrupt onset of focal or global neurological symptoms caused by ischemia or hemorrhage. Symptoms must continue for >24 hours and are usually associated with permanent damage to brain tissue. If symptoms resolve within 24 hours, the episode is called a transient ischemic attack - TIA. Also called CVA, cerebrovascular accident, or brain ttack.
What is the most common cause of strokes?
Cerebral infarct, 60-80%. then intracerebral hemorrhage, 10-30%, then subarachnoid hemorrhage, 5-10%
What is Cor pulmonale?
It is enlargement and failure of the right ventricle due to pulmonary hypertension and RV hypertrophy.
What are the ten main risk factors associated with atherosclerosis?
- Inreasing age (>45 male, >55 female) 2. Smoking (endothelial injury, increased coagulation and free radials) 3. Diabetes and metabolic syndrome 4. Hypertension (endothelial injury) 5. Dyslipidemia (promotes deposition in vessels) 6. Family history/genetics 7. Male or postmenopausal female (lack estrogenic protective effects like HDL) 8. Lifestyle factors (obesity, inactivity, poor diet) 9. Inflammatory markers (local or systemic inflammation) 10. Periodontal disease
What are the atherosclerosis main key points?
Exremely common cause of death. Due to endothelial damage, lipid deposits, inflammation, fibrosis/smooth muscle, and rupture or erosion causing thrombosis. Thrombosis (not stenosis) is the main cause of infarcts. Often happens in areas of only mild/moderate stenosis. Stenosis (not thrombosis) is the main cause of predictable pain with exertion, like angina and claudication (leg pain).
What percentage of heart disease deaths does Ischemic heart disease cause in US? (also known as coronary artery disease, or atherosclerotic heart disase)
Causes 70% of US heart disease-deaths and 30% of total mortality.
When we get severe stenosis in coronary arteries, in what layer of the vessels do most changes take place?
Tunica Intima
Why can slow stenosis be asymptomatic sometimes and not cause angina or claudication?
Because of good collateral circulation
What is the process of atherosclerosis?
Endothelial injury, then lipid deposits, then inflammation, then fibrosis, then calcification, and this is all mostly in the tunica intima. Then because of this we get slow stenosis which can cause angina and claudication, and then we can get a thrombus/disrupted plaque, where blood flow abruptly stops, we get a myocardial infarct, arrhythmia, sudden cardiac death, and gangrene.
What is an atheroma?
It is an accumulation of degenerative material in the tunica intima (inner layer) of artery walls. The material consists of (mostly) macrophage cells, or debris, containing lipids (cholesterol and fatty acids), calcium and a variable amount of fibrous connective tissue. The accumulated material forms a swelling in the artery wall, which may intrude into the channel of the artery, narrowing it and restricting blood flow. Atheroma occurs in atherosclerosis, which is one of the three subtypes of arteriosclerosis.
What are the main three types of angina?
- Stable angina 2. Variant angina 3. Unstable angina (most dangerous, prolonged pain)
What is stable angina?
Pain that feels like pressure for 2-5 minutes and associated with exertion. Relieved by rest or vasodilators (nitroglycerine). It is subendocardial ischemia, and you get a ST-segment depression. Usulaly due to fixed coronary stenosis.
What is variant or prinzmetal’s angina?
It classically occurs at rest. Brief, like stable angina. Reversible spasm, ST-segment elevation (instead of depression with stable angina).
What is unstable angina?
New or worsening angina, prolonged pain or pain at rest. You get an ST-segment depression, and often due to acute plaque change. Most dangerous.
What is sudden cardiac death, how many people per year die because of it?
It is unexpected death within 1 hour of cardiac event, usually due to a high grade coronary stenosis, ventricular electrical instability, and arrhythmia. 300–400,000 people every year.
What are the four major classes of antihypertensives?
- Diuretics (deplete sodium, reduce blood volume) 2. Sympathoplegics (reduce peripheral vascular resistance) 3. Direct vasodilators (relax vascular smooth muscle, dilating vessels) 4. Anti-angiotensin agents (inhibit action/production of angiotensin and thus reduce peripheral vascular resistance)
Mannitol
It is an osmotic agent. It draws free water out of tissues (including the brain) and into the intravascular space, and can transiently decrease cerebral edema (until excreted by the kidneys). Mannitol is freely filtered in the glomerulus, but cannot be reabsorbed. Thus, it remains in the lumen of the nephron and lowers osmotic pressure. Water then “follows” mannitol into the lumen due to the osmotic pressure.
Acetazolamide
It is a carbonic anhydrase inhibitor, which will decrease the reabsorption of NaCO3 in the end, because the proton pump isn’t working because CA was blocked, so without that proton pump, less NaCO3 is reabsorbed, and more is secreted, and water will follow. Works in the primary convoluted tubule. It also changes the pH to make urine more basic because not as much acid is being secreted. This drug is used for treating glaucoma, epilepsy.
Furosemide
It is a loop diuretic. It inhibits the luminal Na/K/2Cl transporters in the thick ascending limb of the loop of Henle, thus reducing NaCL reabsorption and increasing its secretion. Can also cause hypokalemia, because it increases luminal sodium and thus stimulates the aldosterone-sensitive sodium pump to increase sodium reabsorption in exchange for potassium and hydrogen ions, which are lost to the urine. Also this drug can be inhibited by NSAIDs under certain conditions. Diuretics, especially furosemide, can also be used to treat heart failure. Does not have positive ionotropic effect, but you are getting fluid accumulation because heart is not working very well, which will cause problems to whole body so you use a potent diuretic like furosemide.
Bumetanide
It is a loop diuretic. It inhibits the luminal Na/K/2Cl transporters in the thick ascending limb of the loop of Henle, thus reducing NaCL reabsorption and increasing its secretion. Can also cause hypokalemia, because it increases luminal sodium and thus stimulates the aldosterone-sensitive sodium pump to increase sodium reabsorption in exchange for potassium and hydrogen ions, which are lost to the urine. Also this drug can be inhibited by NSAIDs under certain conditions.
Hydrochlorothiazide
It is a loop diuretic and it is a thiazide. It inhibits NaCl reabsorption from the luminal side of epithelial cells in the distal convoluted tubule by blocking the Na/Cl transporter. Can also cause hypokalemia, and this is a problem because of cardiac arrhythmias, because it increases luminal sodium and thus stimulates the aldosterone-sensitive sodium pump to increase sodium reabsorption in exchange for potassium and hydrogen ions, which are lost to the urine. Also this drug can be inhibited by NSAIDs under certain conditions.
Chlorthalidone
It is a loop diuretic and it is a thiazide. It inhibits NaCl reabsorption from the luminal side of epithelial cells in the distal convoluted tubule by blocking the Na/Cl transporter. Can also cause hypokalemia, because it increases luminal sodium and thus stimulates the aldosterone-sensitive sodium pump to increase sodium reabsorption in exchange for potassium and hydrogen ions, which are lost to the urine. Also this drug can be inhibited by NSAIDs under certain conditions.
Spironolactone
This drug is a potassium-sparing diuretic. Most diuretics cause us to lose potassium through urine, sometimes people who take those drugs will also be given a potassium-sparing drug to take with it. This drug prevents K secretion by antagonizing the effects of aldosterone in collecting tubules (via blockade of mineralocorticoid receptors).
Amiloride
This drug is a potassium-sparing diuretic. Most diuretics cause us to lose potassium through urine, sometimes people who take those drugs will also be given a potassium-sparing drug to take with it. This drug prevents K secretion by antagonizing effects of aldosterone in collecting tubules via Na influx through ion channels in the luminal membrane.
Clonidine
Is an alpha-2 agonist in the medulla that reduces sympathetic tone, resulting in decreased blood pressure. Remember that alpha-2 can be an autoreceptor. Dry mouth, sedation are common. Both effects are centrally mediated and dose-dependent.
Mecamylamine
Rarely used, but is a nicoticic neuronal receptor antagonist. It competitively blocks nicotinic cholinoceptors on postganglionic neurons in both sympathetic and parasympathetic ganglia. Causes excessive orthostatic hypotension and constipation, urinary retention, blurred vision, dry mouth, so it has sympathoplegic and parasympathoplegic effects.
Guanethidine
This is an adrenergic blocking agent, it inhibits the release of norepinephrine from sympathetic nerve endings by entering the nerve, then replacing norepinephrine, thus gradually depleting NE stores in the nerve ending. Side effects include orthostatic hypotension and diarrhea.
Atenolol
Beta-1 antagonist that is also used to lower blood pressure, angina, glaucoma. Effects include decreased HR and contractility, increased TPR because of beta-2 blockage in skeletal muscle (seems counterintuitive, what decreased HR is more important factor), decreased renin release, bronchial constriction, decreased glycogenolysis in response to hypoglycemia, decreased aqueous humor production.
Metoprolol
Beta-1 antagonist used to lower blood pressure, angina, glaucoma. Effects include decreased HR and contractility, increased TPR because of beta-2 blockage in skeletal muscle (seems counterintuitive, what decreased HR is more important factor), decreased renin release, bronchial constriction, decreased glycogenolysis in response to hypoglycemia, decreased aqueous humor production. Also used to treat heart failure.
Propranolol
Non-selective beta antagonist used to lower blood pressure, and also inhibits the stimulation of renin production by catecholamines (mediated by beta-1 receptors) and thus, it is likely that propranolol’s effect is due in part to depression of the renin-angiotensin-aldosterone system. Effects include decreased HR and contractility, increased TPR because of beta-2 blockage in skeletal muscle (seems counterintuitive, what decreased HR is more important factor), decreased renin release, bronchial constriction, decreased glycogenolysis in response to hypoglycemia, decreased aqueous humor production.
Nadolol
Non-selective beta antagonist used to lower blood pressure, and also inhibits the stimulation of renin production by catecholamines (mediated by beta-1 receptors) and thus, it is likely that propranolol’s effect is due in part to depression of the renin-angiotensin-aldosterone system.
Labetalol
This drug is a beta and alpha-1 antagonist used to treat high blood pressure, angina, glaucoma.
Carvedilol
This drug is a beta and alpha-1 antagonist used to treat high blood pressure, angina, open-angle glaucoma.
Prazosin
This drug is an alpha-1 antagonist. Causes vasodilation and thus decreased TPR and decreased BP. Used to treat hypertension, benign prostatic hypertrophy. Side effects include orthostatic hypotension, nasal congestion.
Terazosin
This drug is an alpha-1 antagonist. Causes vasodilation and thus decreased TPR and decreased BP. Used to treat hypertension, benign prostatic hypertrophy. Side effects include orthostatic hypotension, nasal congestion.
Phentolamine
This drug is a non-selective alpha antagonist
Phenoxybenzamine
This drug is a non-selective alpha antagonist.
Tamsulosin
A adrenergic alpha blocker used to treat benign prostatic hypertrophy.
Hydralazine
This drug is a direct vasodilator that releases nitric oxide from the drug or from endothelium. All the vasodilators that are useful in hypertension relax smooth muscle of arterioles, thereby decreasing systemic vascular resistance. Decreased arterial resistance and decreased mean arterial blood pressure elicit compensatory responses, mediated by baroreceptors and the sympathetic nervous system, and because these are still intact, vasodilator therapies generally do not cause orthostatic hypotension. Also used to treat heart failure.
Verapamil
This drug is a direct vasodilator that reduces calcium influx, is a calcium channel blocker. All the vasodilators that are useful in hypertension relax smooth muscle of arterioles, thereby decreasing systemic vascular resistance. Decreased arterial resistance and decreased mean arterial blood pressure elicit compensatory responses, mediated by baroreceptors and the sympathetic nervous system, and because these are still intact, vasodilator therapies generally do not cause orthostatic hypotension. This drug is also used to treat angina by prevent Ca influx through L-type channels and blocking contraction of smooth and cardiac muscles while reducing O2 demand. Can cause cardiac depression, bradycardia, flushing. This drug is also considered a class IV anti-arrhythmia drug.
Diltiazem
This drug is a direct vasodilator that reduces calcium influx, is a calcium channel blocker. All the vasodilators that are useful in hypertension relax smooth muscle of arterioles, thereby decreasing systemic vascular resistance. Decreased arterial resistance and decreased mean arterial blood pressure elicit compensatory responses, mediated by baroreceptors and the sympathetic nervous system, and because these are still intact, vasodilator therapies generally do not cause orthostatic hypotension. This drug is also used to treat angina by prevent Ca influx through L-type channels and blocking contraction of smooth and cardiac muscles while reducing O2 demand. Can cause cardiac depression, bradycardia, flushing. This drug is also considered a class IV anti-arrhythmia drug.
Nifedipine
This drug is a direct vasodilator that reduces calcium influx, is a calcium channel blocker. All the vasodilators that are useful in hypertension relax smooth muscle of arterioles, thereby decreasing systemic vascular resistance. Decreased arterial resistance and decreased mean arterial blood pressure elicit compensatory responses, mediated by baroreceptors and the sympathetic nervous system, and because these are still intact, vasodilator therapies generally do not cause orthostatic hypotension. This drug is also used to treat angina by prevent Ca influx through L-type channels and blocking contraction of smooth and cardiac muscles while reducing O2 demand. Can cause cardiac depression, bradycardia, flushing.
Minoxidil
This drug is a direct vasodilator that hyperpolarizes smooth muscle membrane through opening of potassium channels. All the vasodilators that are useful in hypertension relax smooth muscle of arterioles, thereby decreasing systemic vascular resistance. Decreased arterial resistance and decreased mean arterial blood pressure elicit compensatory responses, mediated by baroreceptors and the sympathetic nervous system, and because these are still intact, vasodilator therapies generally do not cause orthostatic hypotension.
Captopril
This drug is an ACE inhibitor (any drug that ends with pril, is usually an ACE inhibitor). It inhibits the converting enzyme (peptidyl dipeptidase) that hydrolyzes angiotensin I to angiotensin II, so you can’t get increased blood pressure through the ACE pathway. This also allows bradykinin to stay active (because ACE turns it off usually), which is a potent vasodilator that stimulates the release of nitric oxide and prostaglandins. You also get major hyperkalemia with these drugs. Also used to treat heart failure.
Losartan
This drug is an angiotensin II inhibitor (ACE helps convert angiotensin I to angiotensin II). It decreases peripheral vascular resistance, but has no effect on bradykinin (a potent vasodilator) metabolism and is therefore a more selective blocker of angiotensin effects than ACE inhibitors.
What are the mediators that actually cause angina pectoris?
It is due to ischemia-related metabolites like glucose and other factors.
What are the best ways to treat angina?
Vasodilation, decreased O2 consumption via beta blockers and calcium channel blockers, nitrates and nitrites (which are metabolized to nitric oxide), which increase smooth muscle relaxation.
Nitroglycerin
Allows nitric oxide to float around in the body causing vasodilation to the arteries of the heart, treating angina and chest pain, it also decreases myocardial O2 consumption. They have long-lasting patches for 8 hours, and it is volatile, needs to be stored in closed glass container. Side effects include orthostatic hypotension, tachycardia (reflex), throbbing headache. Tolerance develops rapidly.
Amyl nitrate
Used to treat angina, and this is used for someone who can only breath in the drug instead of swallow. Ampule is crushed and fumes inhaled, it is short acting.
Why can atenolol be more helpful in treating angina than propranolol?
Because atenolol is a selective blocker, you have a smaller risk for bronchospasms. And beta blockers are used to treat angina prophylactically.
What habit has been shown to lower HDL values?
Cigarette smoking
What is primary hypercholesterolemia?
Also called familial, and it is an autosomal dominant gene. LDL ranges from 260-500 mg/dl, but triglycerides are usually normal. Coronary disease is often premature, and you have defects in LDL receptors.
How do you treat familial hypercholesterolemia?
You don’t use drugs, you improve diet first, if no coronary involvement, include complex carbohydrates and fiber, avoid alcohol if VLDL elevated.
Lovastatin
This drug is a competitive inhibitor of HMG-COA reductase, which helps form cholesterol. These should be avoided during pregnancy. Statins reduce synthesis of cholesterol and have most effect on LDL. These drugs have liver toxicity, and give weakness in skeletal muscles because of increased creatine kinase. If you use them for months, you can have permanent damage to skeletal muscle. This drug is a competitive inhibitor of HMG-COA reductase, which helps form cholesterol. These should be avoided during pregnancy. Statins reduce synthesis of cholesterol and have most effect on LDL. These drugs have liver toxicity, and give weakness in skeletal muscles because of increased creatine kinase. If you use them for months, you can have permanent damage to skeletal muscle.
Atorvastatin
This drug is a competitive inhibitor of HMG-COA reductase, which helps form cholesterol. These should be avoided during pregnancy. Statins reduce synthesis of cholesterol and have most effect on LDL. These drugs have liver toxicity, and give weakness in skeletal muscles because of increased creatine kinase. If you use them for months, you can have permanent damage to skeletal muscle.
Simvastatin
This drug is a competitive inhibitor of HMG-COA reductase, which helps form cholesterol. These should be avoided during pregnancy. Statins reduce synthesis of cholesterol and have most effect on LDL. These drugs have liver toxicity, and give weakness in skeletal muscles because of increased creatine kinase. If you use them for months, you can have permanent damage to skeletal muscle.
Fenobrate
This drug, used to treat hypercholesterolemia, is a fibrate that increases oxidation of fatty acids in liver and muscles (causes lipolysis). It reduces VLDL and has modest effect on LDL, and a moderate increase in HDL while reducing triglycerides. It’s main side effects are GI symptoms.
Niacin
Nicotinic Acid, it helps decrease triglyceride and LDL, used to treat hypercholesterolemia, always causes flushing though, and tolerance develops.
Cholesteramine
This drug is used to treat hypercholesterolemia and it is a bile acid-binding agent. It reduces absorption of bile acids and metabolites. It all goes to the stool though so you end up getting constipation and bloating.
Ezetimibe
This drug is used to treat hypercholesterolemia and it is an inhibitor of intestinal sterol absorption. It inhibits intestinal absorption of cholesterol and reduces LDL. If you have a genetic problem though, this won’t do much good. This is great if you have a diet problem.
If you are a younger patient and have heart failure, is it more likely a systolic or diastolic problem?
Systolic, reduced contractility and reduced ejection. Diastolic likelihood increases with age and we get a reduced filling to the ventricles.
Digitalis
This drug is a positive ionotropic drug, and digitalis is a genus plant name that provides cardiac glycosides such as digoxin. It increases intracellular Ca and cardiac contractility, only temporarily though. It helps treat heart failure. It increases blood ejection. It is not just selective for cardiac calcium channels so its side effects are that it affects all excitable tissues. Can cause premature depolarizations and ectopic beats.
Milrinone
This drug is a Bipyridine that works like digitalis, helps treat heart failure. It increases contractility and Ca flux. But unlike digitalis, this is synthetic and not naturally-occurring.
Dobutamine
This drug is a beta-1 agonist that is used to treat heart failure. Can cause arrhythmias.
What percentage of patients with a history of myocardial infarctions have arrhythmias?
80%, because of all of the scar tissue there.
What are the four classes of drugs used to treat heart arrhythmias?
Class I - Sodium channel blockade Class II - Block sympathetic autonomic effects on heart (beta blocker = Propanolol) Class III - Prolong refractory period Class IV - Ca channel blockade (Verapamil and Diltiazem)
Procainamide
Class I anti-arrhythmic drug. It blocks sodium channels. Involved with cocaine, and local anesthetics, so if you inject it into an artery, can cause problems. Usually not first choice drug because it can precipitate new arrhythmias. It slows action potential conduction.
Quinidine
Class I anti-arrhythmic drug. Has similar actions to procainamide. It blocks sodium channels. Involved with cocaine, and local anesthetics, so if you inject it into an artery, can cause problems. Usually not first choice drug because it can precipitate new arrhythmias. It slows action potential conduction.
Lidocaine
Class I anti-arrhythmic drug. Effective against infarct-related arrhythmias. Is the first choice for ventricular arrhythmias, which are the worst kind!
Amiodarone
Class III anti-arrhythmic drug. It helps prolong the refractory period, treats ventricular arrhythmias and atrial fibrillation. A side effect is pulmonary fibrosis.
Which two organisms that cause pneumonia in the immunocompromised often demonstrate blood vessel invasions?
Aspergillus and Mucormycosis. Aspergillus histo has acute angled branching/septa.
What greater risk number do smokers have of developing lung cancer?
10-55X, squamous cell and small cell most closely tied to smoking.
What is the definition of Atelectasis? What can cause it?
Collapse, caused by inadequate expansion of airspaces. Gives rise to hypoxia, can be caused by airway obstruction, compression, pleural effusion, pneumothorax, aspiration, pleural fibrosis.
What is dyspnea?
Acute shortness of breathe, difficulty breathing.
What is ARDS?
Acute Respiratory Distress Syndrome - and it is progression of acute injury and damage from activated neutrophils.
What is COPD?
Chronic Obstructive Pulmonary Disease. Includes emphysema, chronic bronchitis, asthma, bronchiectasis, and the main cause is cigarette smoke.
What is emphysema?
It is destruction of alveolar walls leading to permanent enlargement of airspaces. Caused by smoking, alpha-1 antitrypsin deficiency (imbalance of proteases and antiproteases), air pollution. You get a barrel chest with hyperinflation, low Forced Extrctory Volume.
What is alpha-1-antitrypsin?
-it is rare, but their liver doesn’t produce antitrypsin, which helps control trypsin, which destroys particles in lungs that would do bad, but we need to be able to control trypsin.
What does smoking do to alpha-1-antitrypsin?
It inhibits it, so trypsin goes uncontrolled and destroys particles in lungs and good tissue in lungs.
What is the difference between centrilobular emphysema and panacinar emphysema?
Cintrolobular is smoking-related, and panacinar is alpha-1-antitrypsin related.
What are the requirements for chronic bronchitis?
Persistent productive cough for 3 months in 2 consecutive years, and it is caused by smoking, air pollution and has hypersecretion of mucus by airways and infections are often secondarily present. If the mucus glands get expanded and reach greater than 40$ to the epithelium, than it suggests chronic bronchitis - Reid index.
What is bronchiectasis?
Results from obstruction of the bronchi and persistent necrotizing infections. You get destruction of elastin and muscles in bronchial walls-congenital expression often caused by cystic fibrosis. You get persistent productive cough, and the infection which causes the suppurative pneumonia is usually caused by TB, Staph, Klebsiella (Alcoholics).
What is asthma?
It is a reactive airway disease and narrowing of airways-hyperreactivity: hyperinflated lungs, thick mucus plugs in airways, smooth muscle hypertrophy • Types: • Atopic- childhood onset often with allergic rhinitis, type I hypersensitiviy response. • Non-atopic- non-immune, occupational exposures, like aspirin or viral infections.
What are signs of restrictive lung diseases?
Reduced lung compliance, more effort required to expand lungs, leading to dyspnea, “ground-glass” infiltrates, fibrosis is common.
What are fibrosing lung diseases?
Associated with collagen vascular diseases such as rheumatoid arthritis-restrictive lung disease: stiff lung and hard to expand lungs. Usual Interstitial Pneumonitis is UIP and is idiopathic pulmonary fibrosis and this type has the worst prognosis. RB-ILD and DIP is common in smokers, but good prognosis if they quit.
What are the types and what can cause occupational lung diseases?
They are restrictive, and are mineral dust induced lung injury and fibrosis (restrictive), e.g., mineral dust-induced, silicosis [inhalation of crysalline silica by sandlblasters and miners], asbestosis [mesothelioma].
What is sarcoidosis?
It is also a restrictive lung disease, believed to be driven by anormally stimulated CD4+ helper T cells. Abnormal connective tissue and reduced elastic properties; multi-organ involvement.
What is a pulmonary embolus?
Can cause sudden death if in pulmonary artery. Origin from deep veins in legs. Cause: prolonged bed rest, surgery, congestive heart failure. Small emboli can cause pulmonary hypertension.
What causes pulmonary hypertension and what are the consequences?
Causes: heart disease, recurrent thromboemboli, and it can cause cor pulmonale- right ventricular failure.
What are the three main types of lung diseases and a summary of each?
- Restrictive: caused by fibrosis or chest wall abnormalities; gas exchange impaired; difficulty inhaling and expanding lungs 2. Vascular: gas exchange impaired by obstruction or hemorrhage; may be abrupt or insidious 3. Obstruction: blocked airways; gas exchange through septal walls not impaired; unable to exhale
What are the main organisms that cause Community Acquired Pneumonia?
S. pneumoniae, H, influenzae, S. aureus.
What are the main organisms that cause Community Acquired Atypical Pneumonia (“walking pneumonia”)?
Mycoplasma pneumoniae, viruses like influenza
What are the main organisms that cause Hospital Acquired Pneumonia?
Enterbocteriaceae, Pseudomonas, S. aureus
What lobe is usually involved with aspiration pneumonia?
Right lower lobe - caustic gastric contents
What are the characteristics of Tuberculosis?
D. Tuberculosis-caused by mycobacterium tuberculosis 1. Usually lungs but can affect other organs 2. Flourishes in crowded, impoverished areas 3. Non-contagious during long periods of dormancy 4. Problems with multidrug antibiotic resistance 5. Forms necrotizing granulomas
What are the common organisms that cause pulmonary fungal infections?
Histoplasma (Ohio River Valley), Coccidiodes (Valley fever, Utah), Blastomycoses
What causes pneumonia in the immunocompromised?
Pneumonia in immunocompromised (e.g., AIDS) -Can be caused by micro-organisms including from normal flora -CMV (cytomegalo virus-common infection) causes ‘owl’s eye’ histology -Pneumocystis jiroveci is also an opportunistic fungus
What is the leading cause of cancer deaths in the world for both men and women?
Lung tumors. 95% of primary lung cancers are carcinomas.
What are the subtypes of lung carcinoma?
- Non-small cell carcinomas include adenocarcinoma and squamous cell carcinoma. (adeno and squamous cell [contains keratin] types most common) - Large cell neuroendocrine carcinoma - Small cell carcinoma
In which population is asthma the greatest?
In children, especially women.
In terms of pulmonary pharmacology, what are relievers?
They are rapid bronchodilators (Beta-2 agonists), used at minimum dose and frequency. They are short-acting, for less severe cases. Drugs include albuterol and salmaterol.
Albuterol
Fast acting reliever, the only true “rescue” reliever, acts within 15 minutes and is effective for 4-6 hours. directly relax airway smooth muscle and bronchodilate.
Salmeterol
Pulmonary reliever, slower onset, longer-acting reliever than albuterol, effective 12 or more hours. directly relax airway smooth muscle and bronchodilate.
What kind of drugs are considered asthma controllers?
]Take regularly for long-term stable control-often more side effects Inhaled: corticosteroids/drug of choice for moderate to severe asthma -often combine with β 2 agonists, e.g., fluticasone + salmeterol (Advair Diskus) -chronic management, not for rescue
Fluticasone
Inhaled steroid for controlled asthma, prevents transcription of inflammatory mediators in the nucleus, resulting in a decrease in inflammation. Side effects: nose bleeds, sores in nose, mouth, tongue that don’t heal, oropharyngeal candidiasis (thrush), interfere with growth in children.
What are two antifungal treatments that help with candidiasis associated with using steroids for asthma?
- Fluconazole 2. Clotrimazole
What class does methylxanthine drugs fall into?
Add-on controllers for Asthma.
Theophylline
Is a type of methylxanthine drug used as an add-on controller for asthma, it is a phosphodiesterase inhibitor and increases cAMP and relaxes airway smooth muscle. Available as tablet or inhaler through tea. Monotherapy for mild asthma. Combine with corticosteroids to reduce steroid doses and side effects. Also helps relax diaphragmatic fatigue in COPD. Toxicity: nausea, headache and anxiety. Requires plasma level monitoring.
What do antimuscarinics do for Asthma?
During an asthma attack, ACh is released from the vagus nerve. Antimuscarinics like ipatroprium bromide reverses the contraction of airway smooth muscles and production of mucus caused in response to this vagal activity.
Ipatroprium Bromide
Is an antimuscarinic used to treat Asthma and specifically bronchospasms, related to Tiotropium Bromide-(Spriva)-which is not approved for asthma, but is approved to treat COPD) –reverses contraction of smooth muscle from vagal activity-usually backup for beta 2 agonists-sometimes combine antimuscarinics with β2 agonists (eg, albuterol). Reversible blockade of acetylcholine by antimuscarinics prevents the release of IP3 and prevents the inhibition of ACh at postganglionic muscarinic receptors. • Side effect of dry mouth • Used as an inhalant for bronchospasms
What do leukotriene modifiers do for Asthma?
Use is for prophylaxis and chronic treatment-for patients who have trouble with inhaled therapies (e.g., nasal bleeding)-can take orally-especially good for aspirin-induced asthma. Montelukast is an example drug. Mechanism: block leukotriene-binding to receptor.
