CHAPTER XVI PDL 101 HUMAN ANATOMY & PHYSIOLOGY. Ms. K. GOWRI. M.Pharm., Lecturer.
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1 CHAPTER XVI PDL 101 HUMAN ANATOMY & PHYSIOLOGY Ms. K. GOWRI. M.Pharm., Lecturer.
2 Muscle Cell Metabolism Muscle Cells Provide ATP to Drive the Crossbridge Cycle The sources of ATP: Available ATP in the sarcoplasm Creatine phosphate Glucose
3 Muscle Cell Metabolism Available ATP There is a limited supply of readily available ATP A small amount of ATP is stored in the myosin crossbridges immediately available when the muscle begins to contract. Contraction uses up this source of ATP in about 6 seconds making it necessary to have other sources of ATP available
4 Muscle Cell Metabolism Creatine Phosphate (CP) When the ATP stores in the myosin crossbridges are exhausted, ADP and CP are used to regenerate ATP. CP + ADP = ATP + Creatine. The energy available from stored ATP and from the reaction of joining ADP with CP provides only about 20 seconds worth of energy The muscles could contract only long enough to run a 100 m dash on the energy from these sources
5 Glucose Muscle Cell Metabolism Cellular respiration of glucose is an energy source utilized to generate ATP Muscle contractions that are longer than seconds depend on cellular respiration of glucose as a source of ATP
6 Muscle Cell Metabolism Recall Cells store glucose in the sarcoplasm in the form of glycogen The cell must break apart the glycogen molecules to release the individual glucose molecules this is called glycogenolysis The breakdown of glucose, called glycolysis, occurs in the sarcoplasm of the muscle cell and does not require oxygen, it is anaerobic Glycolysis produces pyruvic acid, and a small amount of ATP. The majority of the ATP used by muscles is formed by aerobic processes in the mitochondria. At low intensities, the muscle cell depends on aerobic glycolysis during which oxidative phosphorylation becomes more important
7 Muscle Cell Metabolism Changes with Anerobic Metabolism Exercise Intensity Oxygen is not readily available During intense exercise, when the supply of oxygen cannot keep up with metabolic demand of the cells, pyruvic acid produced during glycolysis is converted to lactic acid. Lactic acid accumulates in the muscle resulting in the burning sensation during short duration, high intensity muscular exercise such as lifting weights Lactic acid is quickly removed from the muscle and taken to the liver where it is converted to glucose
8 Muscle Cell Metabolism Changes with Exercise Intensity Aerobic Metabolism Oxygen is readily available During prolonged, low intensity exercise, the muscles are supplied with adequate oxygen by the protein myoglobin Myoglobin Similar to hemoglobin (oxygen binding protein in the blood) Myoglobin has a high affinity for oxygen and binds to it loosely inside muscle cells Myoglobin brings oxygen into the muscle cell and stores it temporarily This provides a continuous supply of oxygen even when blood flow to the muscle is reduced
9 Muscle Cell Metabolism Changes with Exercise Intensity When exercise stops, the body's need for oxygen continues for a period of time The body responds to this need by continuing to breathing heavily until all the sources of ATP have been replenished Oxygen Debt The amount of oxygen necessary to restore the resting metabolic state of the body A better, and more currently accepted, term to describe the events following exercise is recovery oxygen consumption
10 Muscle Cell Metabolism Changes with Exercise Intensity Recovery oxygen consumption Includes the oxygen needed to: Restore muscles to their resting metabolic condition Convert lactic acid to pyruvic acid in the liver Replenish cellular stores of glycogen, creatine phosphate, and ATP Return resting body temperature to normal Return the heart muscle and the muscles of respiration to normal, which need repair from the minor tissue damage that occurs due to exercise The amount of oxygen needed to meet recovery oxygen consumption demands depends on an individual's physical condition and the duration and intensity of the exercise session.
11 IOC prohibited substances 1. Anabolic agents 2. Peptide hormones, mimetics, and analogues 3. Stimulants 4. Diuretics 5. Narcotics
12 Anabolic Agents Enhance muscle mass gained from strength training Anabolic steriods Testosterone precursors
13 Anabolic Steroids Testosterone derivatives modified to increase anabolic effects while decreasing androgenic effects Doses may reach 100X medical replacement dose Efficacy in numerous studies since the 1970 s
14 Anabolic steroid side effects Acne Alopecia Testicular atrophy Masculinization Gynecomastia Infertility Mood alterations Adverse lipid profile Hypertension Glucose intolerance Premature epiphyseal closure
15 Testosterone precursors Cholesterol Pregnenolone 17 hydroxypregnenolone DHEA Androstenedione Testosterone
16 Androstenedione / DHEA Excess quantities theoretically are metabolized to testosterone, thereby increasing serum levels. Early studies showed promise, but a recent randomized, double blinded study of 30 men by King (1999) demonstrated no gains over placebo in testosterone levels or strength.
17 Androstenedione / DHEA Potential side effects similar to anabolic steroids Excessive precursors shown to be aromatized to form estrogen
18 Human Growth Hormone Manufactured by recombinant technology for replacement in deficient patients Promotes protein anabolism Intramuscular delivery No virilizing effects attractive to women
19 Human Growth Hormone Studies suggest increases in muscle size, but not strength (increased collagen in muscles without an increase in contractile tissue) Excess may lead to SxS of acromegaly
20 Insulin like Growth Factor Newer; poor in vivo data Potential anabolic and growth promoting effects similar to human growth hormone without the lipid side effects More prone to cause hypoglycemia
21 Creatine Intrinsic fuel for anaerobic activity After ingestion, creatine readily binds to phosphorus Phosphocreatine mediates the regeneration of ATP from ADP P Cr + ADP + H + Cr + ATP
22 Creatine Supplementation aimed at maximizing stores of phosphocreatine in muscle tissue Potentially decreases fatigue and increases recovery time Enhances training, but no direct anabolic effect Still legal for most competitions
23 Creatine Some equivocal studies Others demonstrate positive effect on short, high intensity activity Dawson (1995), repeated short sprints Earnest (1995) & Hamilton Ward (1997), bench press weight
24 Creatine side effects Muscle cramps at recommended doses Potential for renal insult at high doses, with a few anecdoctal reports of interstitial nephritis
25 Stimulants Promote CNS and muscular excitation Caffeine Amphetamines Ephedrine (and pseudoephedrine)
26 Caffeine The most used and abused drug in the world Variety of effects from adenosine receptor antagonism increased catecholamines increased lipolysis CNS activation improved respiratory function
27 Caffeine Many studies of varying quality Review by Sinclair and Geiger; studies selecting only those using highly trained athletes (for reproducibility of performance) with caffeine washout period 11 studies, 115 participants cycling/running significant increases in time to exhaustion and decreased perception of effort
28 Caffeine Tolerance develops to repeated dosing Excess may cause increased anxiety, insomnia, and cardiovascular strain
29 Amphetamines Abused since 1920 s Increase alertness and produce euphoria by central modulation of dopamine and noradrenaline Side effects: psychosis, hyperthermia, cardiovascular strain Several deaths from heat stroke
30 Ephedrine Ma Haung, ephedra Increases myocardial contraction and blood pressure, decreases perception of fatigue, decreases appetite Similar side effects of hyperthermia and cardiovascular strain
31 Caffeine and Ephedrine Randomized, blinded, placebo study by Bell (2001) with 24 healthy, untrained men cycling to exhaustion Significant increase in power by ephedrine Significant increase in endurance by caffeine Synergistic effect
32 Other Agents Erythropoietin increases hematocrit to increase oxygencarrying capacity, and thus stamina increases blood vicosity posing risk for vascular occlusion, especially when concurrent with dehydration during exercise
33 Other Agents Beta Blocker reduce anxiety and tremor, but also reduces energy Diuretics transient weight loss (e.g. wrestlers and boxers seeking a lower weight class) risk for dehydration
34 Conclusions Sports doping is widespread Lack strong data on safety and efficacy Potential benefits in amateur athletes (our patients) probably negligible Unclear risks, especially on long term use and mega dosing First, do no harm.
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