Beta-Blockers, Sodium bicarbonate, & Diuretics in Sport Flashcards
What suffix of most beta blockers end with?
-lol
What are beta blockers?
Beta adrenergic antagonists.
Competitive antagonism of sympathetic receptors
What are the classes of beta blockers?
Cardioselective/Non-cardioselective
Intrinsic sympathomimetic activity (ISA)/Non-ISA
Intrinsic sympathomimetic activity (ISA)
-Exerts low level agonism/stimulation on receptor, while simultaneously blocking endogenous catecholamines (e.g. epinephrine)
-Less potent than those without ISA
-**In sport - the ISA property may benefit some athletes who have low resting HR and require BB therapy, or in cases where high doses of BB are needed and severe bradycardia is not desirable
Cardioselectivity
Preferentially affects B1>B2 receptors
B1 predominate in the heart, vs B2 in the lungs/arterioles
What is the mechanism of action for beta blockers?
BBs block the effects of epinephrine/adrenaline
- Cardiac effects
-Decrease contractility
-Decrease BP
-Decrease HR
-Decrease conduction velocity
-Vascular effects
-Smooth muscle contraction & mild vasoconstriction
-“Blunting of the fight or flight response” (Mossberg & Peel, 2002)
What is Renin?
Hormone that regulates BP and tissue fluid balance…block renin=reduced angiotensin=decreased BP
Pharmacodynamics (propranolol - ‘pro-pran-o-lol’)
Normal dose ranges:
10-30 mg, 3-4 times/day for arrhythmia
80-160 mg daily for migraine
Peak plasma concentration:
60-90 min
Half Life:
2-3 hrs
Duration of effects is much longer!
Steady levels reported after several days
What are diuretics?
Substances that increase the clearance of water from the body via kidney output
Reasons for athletic use/abuse of diuretics?
-Weight loss
-Maintenance of low body weight
-Accentuation of muscle definition
-Mask detection of other banned substances (!)
What are diuretics typically used to treat?
hypertension
Types of diuretics
Loop diuretics - most potent, very rapid effects
K+ sparing diuretics - similar, but preserve electrolyte losses commonly seen in loop diuretics
Thiazide diuretics - milder, used primarily in treatment of hypertension
Carbonic anhydrase inhibitors - used in treatment of glaucoma, high altitude mountain sickness
Is caffeine a diuretic?
It’s not a true diuretic, but it has similar diuretic effects
Are diuretics ergogenic?
Not ergogenic. Useful for making weight, aesthetic purposes, etc.
Will decrease your performance!!
Will decrease body weight
You’ll basically be really dehydrated
What are the side effects of diuretics?
-Hyperthermia
-Heat exhaustion/stroke
-Photosensitivity (thiazide family)
-Muscle cramps
-Cardiac arrhythmia (due to electrolyte imbalance)
-Impaired performance:
-Reduced endurance
-Reduced VO2
-Potential for neuromuscular dis-coordination
What should you be aware of as a practitioner about diuretic use?
-Diuretics are banned by all major groups
-Rapid dehydration, even if corrected prior to event, has severe negative effects on performance
-If you do work with pts with high BP, and who are taking diuretics, they tend to have significantly impaired exercise tolerance and thus you should set realistic expectations for exercise
-Fatal outcomes are common when used in concert with sweat rooms, rubber suits, etc.
-Beware of early signs suggesting thermoregulatory decline/electrolyte imbalance, etc.
What is the mechanism of action for caffeine?
-Caffeine hits adenosine receptor which transmits it to the cell itself, blocks body’s ability to calm itself down chemically (you feel more awake and alert if you can’t bind the adenosine receptor with other chemicals)
-Won’t let you relax
What are the desirable effects of caffeine?
CNS stimulant, increased alertness, increased concentration, increased energy, bronchodilation
What are the undesirable effects of caffeine?
Restlessness, jitters, anxiety, insomnia, elevated or irregular heart rate
What are the withdrawal effects of caffeine?
Transient but persistent headache, low energy, inability to concentrate
What is the half life of caffeine?
Average adult - 3-5 hours
Child <6 months - 24 hrs
Pregnant - 7-8 hrs
Smoker - 2-3 hrs
High inter-individual variability
Pharmacokinetics of caffeine?
Bioavailability - complete absorption within 60 min; no splanchnic first-pass effect
Peak plasma concentration (PPC) - 5-10uM for each 1 mg/kg oral dose
Time for PPC - 60 (15-120) min
Volume of distribution - 700 (500-800) mL/kg
Half-life for elimination - 5 (2.5-10) h
Clearance rate - 1.5 (1-3) mL/kg/min
Peak urine concentration (PUC) - 0.5-1.5 ug/mL for each 1 mg/kg oral dose
Time for PUC - 120 (60-180) min
EXERCISE DOES NOT INFLUENCE CAFFEINE PHARMACOKINETICS
What are the primary hypotheses in ergogenic mechanisms of caffeine?
Glycogen Sparing
Skeletal Muscle Ion Handling
CNS Effects
Adenosine Antagonism
RPE
Central Fatigue Hypothesis
Caffeine: Glycogen Sparing
-Increased Ca release during latter stages of exercise
-Increase release of Ca from SR
-Increased troponin/myosin Ca sensitivity
-Decreased Ca reuptake by SR
Caffeine: Skeletal Muscle Ion Handling
-Increased Na/K ATPase activity
-Increased K uptake and Na flux
-This attenuates the increase in K with exercise = maintenance of membrane potential
Increased force production!
Caffeine: CNS Effects
-Increased wakefulness
-Increased vigilance
-Many suggest ergogenic effect due to increased alertness or improved mood
Caffeine: Adenosine Antagonism
-Caffeine readily passes through blood-brain barrier
-Rapid rise in brain/CNS after ingestion
-Also increased serotonin, dopamine, acetylcholine, NE, glutamate (all inhibited by adenosine)
= increased locomotor activity & neuronal firing rates
Caffeine: RPE
Caffeine =
- Decreased RPE at given power output
- Increased power work when RPE constant
- Decreased RPE thought to be due to decreased firing thresholds of motor neurons or changes in contraction force
= decreased afferent feedback from working muscles due to a) more motor unit recruitment and b) greater force/stimulus
Caffeine: Central Fatigue Hypothesis
Premise:
Fatigue = increased serotonin in brain due to increases in tryptophan (S precursor)
However:
Caffeine increased S, and
Caffeine pre-exercise = increased plasma FFA, which should increase TRP
In summary, results not clear at this time
Is caffeine a banned substance?
Yes! But only at a certain urinary concentration
NCAA: urinary concentration > 15 ug/mL
Equivalent to ~8 cups of coffee in 2-3 hours
IOC/USDA/WADA: Caffeine not prohibited???
Taken off list in 2004, now it is “restricted/controlled”
Still monitoring in testing (>12ug/ml)
What are the limitations to testing for caffeine use?
-Optimal dose for PE = 3-6 mg/kg
-Thus, lower than banned/restricted limits
-Only 0.5-3% ingested caffeine reaches the urine!
-Majority metabolized by liver and excreted in forms not measured by doping tests
-Half life? Time of test?
-Habitual use?
-Those that “use” caffeine regularly have dampened response
Caffeine Myths
High CHO diet negates FFA increases due to caffeine
Creatine benefits?
-Large research base, with general agreement
-Supports increased focus and memory
-Promotes musculoskeletal health in older adults
-Encourages healthy blood sugar levels
Creatine Mechanism
Creatine is a nitrogenous amino acid both endogenously synthesized and consumed in the diet
-Synthesized primarily in the pancreas and liver
-Absorption occurs in the intestine, and is actively transported into the blood stream
-Most creatine is stored in skeletal muscle (~95%), ~70% of which is found inside the cell as phosphocreatine (PCr)
-PCr + ADP + H^+
-Cr + ATP
-Mechanism not entirely clear
-Most consider creatine/PCr as “phosphate shuttle” between cytosol and mitochondria
-Some evidence of a buffering effect of PCr
-PCr is a major source of skeletal muscle energy during short term high intensity bouts lasting from ~2-30 secs
Creatine in the body?
Cr degradation rate is ~1.6% (2g)/day
Thus, to maintain normal stores, it is necessary to synthesize ~2g Cr per day
~50% is achieved via nutritional intake
Remainder is synthesized endogenously
What are some dietary sources of creatine?
Meat, fish, and other animal products
Creatine administration?
-Commercially available in powder, gel, tablet, liquid, and gum forms
-Most recommendations from the literature support a dose of 20-30g Cr/day for ~14 days
-Typical regimen includes both a “loading phase” and a “maintenance phase”
-I.e. 5-7g/dose, 4 X per day for 5-7 days, followed by a maintenance phase of ~2g/day
-Uptake is enhanced when Cr taken with CH20
-Some evidence that uptake is greater in humans with low levels of TCr (Greenhaff, et al, 1994)
Where is creatine primarily synthesized?
pancreas and liver
PCr is a major source of skeletal
muscle energy during what type of exercise?
Short-term, high-intensity bouts (~2-30 sec)
