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Muscles review
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Muscles We Eat Exam ReviewHuman Bones, Muscles, and Nerves ReviewMuscle ReviewThe Muscle System ReviewMuscle strength: do and review (non-statutory)The cytoskeleton is a network of thin tubes and filaments that crisscrosses the cytosol. The tubes and filaments give shape to the cell from the inside in the same way that tent poles support the shape of a tent. The cytoskeleton also acts as a system of internal tracks, shown in Figure 4-18, on which items move around inside the cell. The cytoskeleton’s functions are based on several struc- tural elements. Three of these are microtubules, microfilaments, and intermediate filaments, shown and described in Table 4-2. Microtubules Microtubules are hollow tubes made of a protein called tubulin. Each tubulin molecule consists of two slightly different subunits. Microtubules radiate outward from a central point called the centrosome near the nucleus. Microtubules hold organelles in place, maintain a cell’s shape, and act as tracks that guide organelles and molecules as they move within the cell. Microfilaments Finer than microtubules, microfilaments are long threads of the beadlike protein actin and are linked end to end and wrapped around each other like two strands of a rope. Microfilaments con- tribute to cell movement, including the crawling of white blood cells and the contraction of muscle cells. Intermediate Filaments Intermediate filaments are rods that anchor the nucleus and some other organelles to their places in the cell. They maintain the inter- nal shape of the nucleus. Hair-follicle cells produce large quantities of intermediate filament proteins. These proteins make up most of the hair shaft. 84 CHAPTER 4 TABLE 4-2 The Structure of the Cytoskeleton Property Microtubules Microfilaments Intermediate filaments Structure hollow tubes made of two strands of intertwined protein fibers coiled into coiled protein protein cables Protein subunits tubulin, with two subunits: å actin one of several types of and ∫ tubulin fibrous proteins Main function maintenance of cell shape; cell maintenance and changing of maintenance of cell shape; motility (in cilia and flagella); cell shape; muscle contraction; anchor nucleus and other chromosome movement; movement of cytoplasm; cell organelles; maintenance of organelle movement motility; cell division shape of nucleus Shape Microtubules provide a path for organelles and molecules as they move throughout the cell. FIGURE 4-18 Microtubules Nucleus Endoplasmic reticulum Mitochondrion Ribosomes Copyright © by Holt, Rinehart and Winston. All rights reserved. Copyright © by Holt, Rinehart and Winston. All rights reserved. CELL STRUCTURE AND FUNCTION 85 1. Explain how the fluid mosaic model describes the plasma membrane. 2. List three cellular functions that occur in the nucleus. 3. Describe the organelles that are found in a eukaryotic cell. 4. Identify two characteristics that make mitochon- dria different from other organelles. 5. Contrast three types of cytoskeletal fibers. CRITICAL THINKING 6. Relating Concepts If a cell has a high energy requirement, would you expect the cell to have many mitochondria or few mitochondria? Why? 7. Analyzing Information How do scientists think that mitochondria originated? Why? 8. Analyzing Statements It is not completely accurate to say that organelles are floating freely in the cytosol. Why not? SECTION 3 REVIEW During cell division, centrioles organize microtubules that pull the chromosomes (orange) apart. The centrioles are at the center of rays of microtubules, which have been stained green with a fluorescent dye. FIGURE 4-20 Cilia and Flagella Cilia (SIL-ee-uh) and flagella (fluh-JEL-uh) are hairlike structures that extend from the surface of the cell, where they assist in movement. Cilia are short and are present in large numbers on certain cells, whereas flagella are longer and are far less numerous on the cells where they occur. Cilia and flagella have a membrane on their outer surface and an internal structure of nine pairs of micro- tubules around two central tubules, as Figure 4-19 shows. Cilia on cells in the inner ear vibrate and help detect sound. Cilia cover the surfaces of many protists and “row” the protists through water like thousands of oars. On other protists, cilia sweep water and food particles into a mouthlike opening. Many kinds of protists use flagella to propel themselves, as do human sperm cells. Centrioles Centrioles consist of two short cylinders of microtubules at right angles to each other and are situated in the cytoplasm near the nuclear envelope. Centrioles occur in animal cells, where they organize the microtubules of the cytoskeleton during cell division, as shown in Figure 4-20. Plant cells lack centrioles. Basal bodies have the same structure that centrioles do. Basal bodies are found at the base of cilia and flagella and appear to organize the devel- opment of cilia and flagella.Some substances, such as macromolecules and nutrients, are too large to pass through the cell membrane by the transport processes you have studied so far. Cells employ two other transport mecha- nisms—endocytosis and exocytosis—to move such substances into or out of cells. Endocytosis and exocytosis are also used to transport large quantities of small molecules into or out of cells at a single time. Both endocytosis and exocytosis require cells to expend energy. Therefore, they are types of active transport. Endocytosis Endocytosis (EN-doh-sie-TOH-sis) is the process by which cells ingest external fluid, macromolecules, and large particles, including other cells. As you can see in Figure 5-7, these external materials are enclosed by a portion of the cell’s membrane, which folds into itself and forms a pouch. The pouch then pinches off from the cell membrane and becomes a membrane-bound organelle called a vesicle. Some of the vesicles fuse with lysosomes, and their con- tents are digested by lysosomal enzymes. Other vesicles that form during endocytosis fuse with other membrane-bound organelles. Two main types of endocytosis are based on the kind of material that is taken into the cell: pinocytosis (PIEN-oh-sie-TOH-sis) involves the transport of solutes or fluids, and phagocytosis (FAG-oh-sie-TOH-sis) is the movement of large particles or whole cells. Many unicellular organisms feed by phagocytosis. In addition, certain cells in animals use phagocytosis to ingest bacteria and viruses that invade the body. These cells, known as phagocytes, allow lysosomes to fuse with the vesicles that contain the ingested bacteria and viruses. Lysosomal enzymes then destroy the bacteria and viruses before they can harm the animal. CYTOSOL EXTERNAL ENVIRONMENT During endocytosis, the cell membrane folds around food or liquid and forms a small pouch. The pouch then pinches off from the cell membrane to become a vesicle. FIGURE 5-7 vesicle from the Latin vesicula, meaning “bladder” or “sac” Word Roots and Origins www.scilinks.org Topic: Endocytosis Keyword: HM60505 mb06se_homs02.qxd 5/18/07 11:03 AM Page 105 106 CHAPTER 5 1. Explain the difference between passive trans- port and active transport. 2. What functions do carrier proteins perform in active transport? 3. What provides the energy that drives the sodium-potassium pump? 4. Explain the difference between pinocytosis and phagocytosis. 5. Describe the steps involved in exocytosis. 6. How do endocytosis and exocytosis differ? How can that difference be seen? CRITICAL THINKING 7. Analyzing Information During intense exercise, potassium tends to accumulate in the fluid surrounding muscle cells. What membrane protein helps muscle cells counteract this tendency? Explain your answer. 8. Evaluating Differences How does the sodium- potassium pump differ from facilitated diffusion? 9. Relating Concepts The vesicles formed during pinocytosis are much smaller than those formed during phagocytosis. Explain. SECTION 2 REVIEW Vesicle Cell membrane EXTERNAL ENVIRONMENT CYTOSOL During exocytosis, a vesicle moves to the cell membrane, fuses with it, and then releases its contents to the outside of the cell. FIGURE 5-8 INSIDE OF CELL Vesicle OUTSIDE OF CELL Exocytosis Exocytosis (EK-soh-sie-TOH-sis) is the process by which a substance is released from the cell through a vesicle that transports the sub- stance to the cell surface and then fuses with the membrane to let the substance out of the cell. This process, illustrated in Figure 5-8, is basically the reverse of endocytosis. During exocytosis, vesi- cles release their contents into the cell’s external environment. Figure 5-8 also shows a photo of a vesicle during exocytosis. Cells may use exocytosis to release large molecules such as pro- teins, waste products, or toxins that would damage the cell if they were released within the cytosol. Recall that proteins are made on ribosomes and packaged into vesicles by the Golgi apparatus. The vesicles then move to the cell membrane and fuse with it, deliver- ing the proteins outside the cell. Cells in the nervous and endocrine systems also use exocytosis to release small molecules that control the activities of other cells.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 Drug Alpha1 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 Drugs Alpha 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 Inhibitors aka 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 HTN Treatment 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)