on 10-Sep-2017 (Sun)

Fearon et al. [41] found that when participants reported pain reproduction at the greater trochanter on the FABER test, in the absence of difficulty manipulating shoes and socks (which will be difficult if limited in FABER), this formed a strong basis for diagnosis of greater trochanteric pain syndrome, together with pain on palpation of the greater trochanter.

What a man wishes, he also believes. Similarly, what we believe is what we choose to see. This is commonly referred to as the confirmation bias.

The modern scientific enterprise operates under the principle of falsification: A method is termed scientific if it can be stated in such a way that a certain defined result would cause it to be proved false. Pseudo-knowledge and pseudo-science operate and propagate by being unfalsifiable – as with astrology, we are unable to prove them either correct or incorrect because the conditions under which they would be shown false are never stated.

The desire to be right and the desire to have been right are two desires, and the sooner we separate them the better off we are. The desire to be right is the thirst for truth. On all counts, both practical and theoretical, there is nothing but good to be said for it. The desire to have been right, on the other hand, is the pride that goeth before a fall. It stands in the way of our seeing we were wrong, and thus blocks the progress of our knowledge.

The modern scientific enterprise operates under the principle of falsification: A method is termed scientific if it can be stated in such a way that a certain defined result would cause it to be proved false

R 62 Pharmacokinetics is a term used to describe the study of the changes in the concentration of a drug during the processes of absorption, distribution, metabolism or biotransformation, and elimination from the body.

Essentially, it is the study of what the body does to a drug once the agent has been introduced into the system.

This transfer of drug to various sites depends on several intrinsic proper- ties of the agent, such as molecular size, degree of ionization, lipid solubility, and protein binding.

molecules with molecular weights greater than 100 to 200 do not cross the cell membranes.

Pas- sive transport does not require energy and involves transfer of a drug from an area of high concentration to an area of lower concentra- tion. Active transport mechanisms are generally faster and require energy.

It may involve exchange of one molecule for another called antiport or transport of two molecules together in the same direction referred to as symport

The charged (ionized) form is water soluble, and the uncharged (nonionized) form is lipophilic.

nonionized molecules are lipid soluble, they can diffuse across cell membranes such as the blood-brain, gastric, and placental barriers to reach the effect site.

The higher the degree of ionization, the less access the drug has across tissues such as the gastrointestinal tract, the blood-brain and placental barriers, and liver hepatocytes

This is important in that ionized drugs are not absorbed well when taken orally and may not be metabolized by the liver to a significant extent. Instead, they commonly are excreted via the renal system

the degree of ionization of an agent at a particular site is determined by the dissociation constant (pK a ) of the agent and its pH gradient across the membrane

The pK a is the negative log of the equilibrium constant for the dissociation of the acid or base.

Acids are usually defined as proton donors, whereas bases are made up of molecules that can accept a proton.

When the pH is equal to the pK a , the two species exist in equal amounts; for example, because phenobarbital has a pK a of 7.4 and blood has a pH of 7.4, in the bloodstream the drug is pres- ent in equal proportions of charged and uncharged forms

If a drug is a weak acid and if the pH of the fluid environment is below the pK a , most of the drug’s protons are associated with the drug molecule, and the predominant species is uncharged and therefore lipid soluble

if the pH is below the pK a for a drug that is a weak base, an abundance of protons exists, and most of the drug tends to ion- ize as the proton is donated by the drug molecule, which results in a species that is highly charged and therefore lipid insoluble

The degree of ionization for a specific agent can vary across a membrane that separates fluids with different pH values.

As the drug enters the stomach, a very acidic environment with a pH of 1.9, morphine accepts protons and becomes ionized, and ion trapping occurs

CHAPTER 6    Pharmacokinetics 63 t From these equations an estimate of the degree of drug absorp- tion can be developed. 4,5 Acids are usually defined as proton donors, whereas bases are made up of molecules that can accept a proton. When the pH is equal to the pK a , the two species exist in equal amounts; for example, because phenobarbital has a pK a of 7.4 and blood has a pH of 7.4, in the bloodstream the drug is pres- ent in equal proportions of charged and uncharged forms. It is of importance to note that relatively modest changes in the pH of the environment, when it is close to the pK a , are more significant in changing the ratio of charged to uncharged forms than the same change in pH at some value far removed from the pK a . For example, phenobarbital, with a pK a of 7.4, is for the most part nondissociated and therefore is nonionized at a pH of 1.4. This results from the fact that the pH is well below the pK a , and when phenobarbital is in a relatively strongly acidic envi- ronment with an abundance of protons, it does not give up its protons readily. If a drug is a weak acid and if the pH of the fluid environment is below the pK a , most of the drug’s protons are associated with the drug molecule, and the predominant species is uncharged and therefore lipid soluble (Figure 6-2). Conversely, if the pH is below the pK a for a drug that is a weak base, an abundance of protons exists, and most of the drug tends to ion- ize as the proton is donated by the drug molecule, which results in a species that is highly charged and therefore lipid insoluble 4 (Figure 6-3). The effects of pK a and pH on ionization are sum- marized in Box 6-1. 6 Ion Trapping Ion trapping has several anesthesia-related applications. Influ- ences on oral absorption of drugs, maternal-fetal transfer, and central nervous system toxicity of local anesthetics are commonly cited. The degree of ionization for a specific agent can vary across a membrane that separates fluids with different pH values. For example, morphine sulfate, a base with a pK a of 7.9 when pres- ent in the blood (pH 7.4), exists in appreciable amounts in both ionized and nonionized forms. The uncharged drug fraction moves freely across tissue membranes, and the charged fraction does not. As the drug enters the stomach, a very acidic environment with a pH of 1.9, morphine accepts protons and becomes ionized, and ion trapping occurs 4 (Figure 6-4 illustrates this phenomenon using diazepam as an example). The drug, however, will be absorbed later, as stomach contents move farther down the gastrointestinal tract to the more basic and favorable environment of the small intestine. A similar scenario occurs when agents are transferred between a mother and a fetus, where the placenta is the membrane separat- ing fluids with varying pH values—that of the fetus is more acidic than that of the mother. Again, the lipid-soluble fraction of basic agents such as lidocaine (pK a 7.9) crosses to the placenta easily. However, once there, because of the lower pH of the fetus, the drug becomes more ionized and cannot easily cross the lipid bilayer of placenta, resulting in accumulation of drug in the fetus. Finally, ion trapping may occur in a local anesthetic overdose situation in which high concentrations of a basic local anesthetic agent have entered the central nervous system and caused toxicity. If the patient experiences respiratory arrest and hypoxia, the resulting EXTRACELLULAR MEMBRANE INTRACELLULAR Carrier Diffusion through aqueous channel Diffusion through lipid FIGURE 6-1 Routes by which solutes can traverse cell membranes. (From Rang HP, et al. Rang and Dale’s Pharmacology. 7th ed. Edin- burgh: Churchill Livingstone; 2012:100.) FIGURE 6-2

Intravenous injections completely bypass the process of absorption

Increasing cadence by 10 % has also been shown to result in increased activity of GMed during the late swing phase but not during the stance phase [71].

Conclusion: The evidence consistently demonstrated that both hip strengthening and neuromuscular exercise has a beneficial effect on pain and function in people with PFP. Strengthening exercise pre- dominantly addressed abductor and external rotator muscle groups

Potential clinical changes are conceptualized by the follow- ing phenomena. Some drugs are bound extensively to proteins in the plasma because of their innate affinity for circulating and tissue proteins.

Paired cartilages � arytenoids, corniculate and cuneiform

EPIGLOTTIS Functionally separates larynx from trachea

Epiglottis

Like a lid that prevents solids and liquids from entering the trachea while swallowing

THYROID CARTILAGE
Largest cartilage of the larynx

CRICOID CARTILAGE
Ring shaped cartilage connected to the thyroid cartilage by the cricothyroid ligament at the level of the 6th vertebrae

ARYTENOID CARTILAGES
Attached to the cricoid cartilage by the cricoarytenoid muscles Attached to vocal cords and span across larynx to part of the thyroid cartilage

CORNICULATE CARTILAGES “Horn -like” rest on top of each arytenoid cartilage During swallowing, epiglottis meets with corniculates to seal off airway

MUSCLES Abductors – open cords for inspiration � Posterior Cricoarytenoids are the sole abductors � “Pull Cords Apart”

Adductors – close cords for phonation, Partial closure for exhalation � Lateral Cricoarytenoids are the primary adductors � “Leave Cords Alone”

Aryepiglottic muscles closes laryngeal inlet Thyroepiglottic muscles opens laryngeal inlet Transverse arytenoids adducts vocal cords Oblique arytenoids controls sphincters to vestibule Thyroarytenoids relax cord tension Cricoarytenoids increases vocal cord tension

LIGAMENTS - VOCAL CORDS smallest area in the adult airway True vocal cords are pale white ligaments False cords are the aryepiglottic folds Two strong bands of elastic tissue attached to the angle of the thyroid cartilage and dorsally to the arytenoid cartilage

LIGAMENTOUS MEMBRANES Thyrohyoid membrane connects thyroid cartilage to hyoid bone Cricothyroid membrane connects thyroid cartilage and cricoid membrane Cricothyrotomy is performed through this membrane

TRACHEA air conduit to the lower airways
cricoid cartilage to the carina C 6 to T 4-5 17 to 18 horseshoe structures interconnected with fibroelastic tissue for expansion

MORE ABOUT THE TRACHEA Trachea is 10 – 12 cm long and 20 mm in diameter From lips to mid- trachea is 20 – 22 cm From lips to carina is 24 – 28 cm The larynx is @ C3 - C6 and the carina is @ T5 A properly placed ETT shows on x-ray with the distal tip at T2 (suprasternal notch)with distal tip above carina

TRACHEAL RECEPTORS Irritant receptors circumferential to trachea stimulation causes constriction Stretch receptors posterior wall regulates depth and rate of breathing stimulation causes dilation of airway to increase airflow

SENSORY NERVE SUPPLY Trigeminal Nerve (V) nerve supply to the nasopharynx, soft and hard palates and the anterior 2/3 of the tongue opthalmic division anteriorly maxillary division posteriorly (sphenopalatine nerves) mandibular division- lingual nerve - anterior 2/3 of tongue

Facial Nerve (VII) nerve supply to the soft and hard palates and the tongue Glossopharyngeal Nerve (IX) nerve supplies the posterior 1/3 of the tongue, the roof of the pharynx, tonsils and soft palate

Vagus Nerve (X) Recurrent laryngeal nerve � sensory to larynx below the cords and to the trachea Superior laryngeal nerve � divides into external (motor) and internal (sensory) laryngeal nerves that supplies the larynx above the cords (between epiglottis and cords)

Recurrent laryngeal nerve Major motor nerve all of the muscles of the larynx except the cricothyroid muscle External laryngeal nerve motor to cricothyroid muscle

LARYNGOSPASM Forceful involuntary spasm of laryngeal muscles d/t sensory stimulation of superior laryngeal nerve Pharyngeal secretions or passing of ETT through the larynx during extubation

LARYNGOSPASM
Treatment Gentle positive pressure Lido 1-1.5 mg/kg IV Sux 0.25-1mg/kg

LARYNGEAL NERVE DAMAGE

External branch of the Superior Laryngeal nerve weakness and huskiness of voice vocal cords can not be tensed cricothyroid muscle is paralyzed

LARYNGEAL NERVE DAMAGE
Recurrent laryngeal nerve - unilateral hoarseness paralyzed cord assumes an intermediate position Recurrent laryngeal nerve- bilateral aphonia both cords in intermediate position cords can flop together during inspiration obstruction emergency!!

AIRWAY ASSESSMENT Thyromental distance Distance from chin to thyroid Should be at least 6 cm (three fingerbreadths). If less anticipate difficulty visualizing trachea Mandibular shape Micrognathic, prognathic

Aortic slenosis is recognized by its characteristic systolic murmur, best heard in the second right intercostal space (over the aortic arch) with transmission into the neck. Aortic regurgitation is recognized by its dias- tolic murmur, best heard along the left sternal border.