NEET MDS Synopsis
The Henderson-Hasselbalch Equation
Biochemistry
By rearranging the above equation we arrive at the Henderson-Hasselbalch equation:
pH = pKa + log[A-]/[HA]
It should be obvious now that the pH of a solution of any acid (for which the equilibrium constant is known, and there are numerous tables with this information) can be calculated knowing the concentration of the acid, HA, and its conjugate base [A-].
At the point of the dissociation where the concentration of the conjugate base [A-] = to that of the acid [HA]:
pH = pKa + log[1]
The log of 1 = 0. Thus, at the mid-point of a titration of a weak acid:
pKa = pH
In other words, the term pKa is that pH at which an equivalent distribution of acid and conjugate base (or base and conjugate acid) exists in solution.
PHARMACOLOGY OF VASOCONSTRICTORS
Pharmacology
PHARMACOLOGY OF VASOCONSTRICTORS
All local anesthetics currently used in dentistry today produce some degree of vasodilatation. This
characteristic results in the increased vascularity of the injected site and results in a shorter duration of local
anesthetic action due enhanced uptake of the local anesthetic into the bloodstream.
- Using a “chemical tourniquet” to prolong the effect of local anesthetics
- The vasoconstrictive action of epinephrine reduces uptake of local anesthetic resulting in a significant increase in the duration of local anesthetic action.
- the addition of vasoconstrictors in local anesthetic solutions will:
1. Prolong the effect of the local anesthetic
2. Increase the depth of anesthesia
3. Reduces the plasma concentration of the local anesthetic
4. Reduces the incidence of systemic toxicity
5. Reduces bleeding at surgical site
Local anesthetics containing epinephrine produce:
1. Localized
VASOCONSTRICTION MEDIATED BY ALPHA RECEPTOR ACTIVATION
i. Hemostasis at surgical site
ii. Ischemia of localized tissue
2. Systemic
HEART
i. Increased heart rate (β1)
ii. Increased force and rate of contraction (β 1)
iii. Increased cardiac output
iv. Increases oxygen demand
v. Dilation of coronary arteries
vi. Decreases threshold for arrhythmias
LUNGS
i. Bronchodilation (β2 )
SKELETAL MUSCLE
i. Predominately vasodilation (fight or flight response) (β 2 )
CNS
i. Minimal direct effect due to difficulty in crossing the blood-brain barrier. Most effects on the CNS are manifestations of the vasoconstrictor on other organs such as the heart.
Concentrations of vasoconstrictors
1. Epinephrine The most commonly used epinephrine dilution in dentistry today is 1:100000. However it appears that a 1:200000 concentration is comparable in effect to the 1:100000 concentration.
2. Levonordefrin Levonordefrin is a synthetic compound very similar in structure to epinephrine. It is the only alternate choice of vasoconstrictor to epinephrine. It is prepared as a 1:20000 (0.05mg/ml)(50 mcg/ml) concentration with 2 % mepivacaine.
Cardiovascular considerations
The plasma concentration of epinephrine in a patient at rest is 39 pg/ml.1 The injection of 1 cartridge of lidocaine 1:100000 epinephrine intraorally results in a doubling of the plasma concentration of epinephrine.
The administration of 15 mcg of epinephrine increased heart rate an average of 25 beats/min with some individuals experiencing an increase of 70 beats/min.
Clinical considerations
It is well documented that reduced amounts of epinephrine should be administered to patients with:
HEART DISEASE (ANGINA HISTORYOF MI)
POORLY CONTROLLED HIGH BLOOD PRESSURE
It is generally accepted that the dose of epinephrine should be limited to 0.04 mg (40 mcg) for patients that have these medical diagnoses
Regulation of Blood Pressure by Hormones
Physiology
Regulation of Blood Pressure by Hormones
The Kidney
One of the functions of the kidney is to monitor blood pressure and take corrective action if it should drop. The kidney does this by secreting the proteolytic enzyme renin.
Renin acts on angiotensinogen, a plasma peptide, splitting off a fragment containing 10 amino acids called angiotensin I.
angiotensin I is cleaved by a peptidase secreted by blood vessels called angiotensin converting enzyme (ACE) — producing angiotensin II, which contains 8 amino acids.
angiotensin II
constricts the walls of arterioles closing down capillary beds;
stimulates the proximal tubules in the kidney to reabsorb sodium ions;
stimulates the adrenal cortex to release aldosterone. Aldosterone causes the kidneys to reclaim still more sodium and thus water.
increases the strength of the heartbeat;
stimulates the pituitary to release the antidiuretic hormone (ADH, also known as arginine vasopressin).
All of these actions, which are mediated by its binding to G-protein-coupled receptors on the target cells, lead to an increase in blood pressure.
Clinical Physiology CVS
Physiology
Clinical Physiology
Heart Failure : Heart failure is inability of the heart to pump the enough amount of blood needed to sustain the needs of organism .
It is usually called congestive heart failure ( CHF) .
To understand the pathophysiology of the heart failure , lets compare it with the physiology of the cardiac output :
Cardiac output =Heart rate X stroke volume
Stroke volume is determined by three determinants : Preload ( venous return ) , contractility , and afterload (peripheral resistance ) . Any disorder of these factors will reduce the ability of the heart to pump blood .
Preload : Any factor that decrease the venous return , either by decreasing the intravenous pressure or increasing the intraatrial pressure will lead to heart failure .
Contractility : Reducing the power of contraction such as in myocarditis , cardiomyopathy , preicardial tamponade ..etc , will lead to heart failure .
Afterload : Any factor that may increase the peripheral resistance such as hypertension , valvular diseases of the heart may cause heart failure.
Pathophysiology : When the heart needs to contract more to meet the increased demand , compensatory mechanisms start to develope to enhance the power of contractility . One of these mechanism is increasing heart rate , which will worsen the situation because this will increase the demands of the myocardial cells themselves . The other one is hypertrophy of the cardiac muscle which may compensate the failure temporarily but then the hypertrophy will be an additional load as the fibers became stiff .
The stroke volume will be reduced , the intraventricular pressure will increase and consequently the intraatrial pressure and then the venous pressure . This will lead to decrease reabsorption of water from the interstitium ( see microcirculation) and then leads to developing of edema ( Pulmonary edema if the failure is left , and systemic edema if the failure is right) .
Enzyme Kinetics
Biochemistry
Enzyme Kinetics
Enzymes are protein catalysts that, like all catalysts, speed up the rate of a chemical reaction without being used up in the process. They achieve their effect by temporarily binding to the substrate and, in doing so, lowering the activation energy needed to convert it to a product.
The rate at which an enzyme works is influenced by several factors, e.g.,
the concentration of substrate molecules (the more of them available, the quicker the enzyme molecules collide and bind with them). The concentration of substrate is designated [S] and is expressed in unit of molarity.
the temperature. As the temperature rises, molecular motion - and hence collisions between enzyme and substrate - speed up. But as enzymes are proteins, there is an upper limit beyond which the enzyme becomes denatured and ineffective.
the presence of inhibitors.
competitive inhibitors are molecules that bind to the same site as the substrate - preventing the substrate from binding as they do so - but are not changed by the enzyme.
noncompetitive inhibitors are molecules that bind to some other site on the enzyme reducing its catalytic power.
pH. The conformation of a protein is influenced by pH and as enzyme activity is crucially dependent on its conformation, its activity is likewise affected.
The study of the rate at which an enzyme works is called enzyme kinetics.
Enflurane
Pharmacology
Enflurane (Ethrane) MAC 1.68, Blood/gas solubility ratio 1.9
- Extremely stable chemically.
- Less potent and less soluble in blood than is halothane.
- Respiratory depression is similar to that seen with halothane.
- Cardiac output is not depressed as much as with halothane, and the heart is not sensitized to catecholamines to the same degree.
- Enflurane produces better muscle relaxation than does halothane.
- Metabolism of this agent is very low. Inorganic fluoride is a product of metabolism, but is not sufficient to cause renal problems.
- Enflurane differs from halothane and the other inhalational anesthetic agents by causing seizures at doses slightly higher than those that induce anesthesia.
- Nausea appears to occur somewhat more often following Enflurane than it does following halothane.
Folate: Folic Acid, Folacin Folate
Biochemistry
Folate: Folic Acid, Folacin Folate, also known as folic acid or folacin, aids in protein metabolism, promoting red blood cell formation, and lowering the risk for neural tube birth defects. Folate may also play a role in controlling homocysteine levels, thus reducing the risk for coronary heart disease.
RDA for folate is 400 mcg/day for adult males and females. Pregnancy will increase the RDA for folate to 600 mcg/day.
Folate Deficiency
Folate deficiency affects cell growth and protein production, which can lead to overall impaired growth. Deficiency symptoms also include anemia and diarrhea.
A folate deficiency in women who are pregnant or of child bearing age may result in the delivery of a baby with neural tube defects such as spina bifida.
INVESTING
Dental Materials
INVESTING
Mixing investment with distilled water is done according to the manufacturers ratio in a clean dry bowl without entrapment of the air into the mix.
Mixing methods:
a. Hand mixing and the use of the vibrator to remove air bubbles.
b. Vacuum mixing- This is the better method because it removes air bubbles as well as gases that are produced and thus produces a smoother mix.
Methods of investing:
a. Hand investing
b. Vacuum investing
Hand investing:
First the mixed investment is applied on all the surfaces of the pattern with a soft brush. Blow off any excess investment gently, thus leaving a thin film of investment over the pattern, then apply again.
Then the coated pattern can be invested by two methods;
1. Placing the pattern in the ring first and then filling the ring full with investment.
2. Filling the ring with the investment first and then force the pattern through into it.
Vacuum investing :
Vacuum investing unit: This consists of the chamber of small cubic capacity from which air can be evacuated quickly and in which casting ring can be placed.
Evacuation of air can be done by electrically or water driven vacuum pump.
Procedure:
The ring filled with investment is placed in the vacuum chamber. Air entry tube is closed. Then the vacuum is applied. The investment will rise with froth vigorously for about 10-15 sec and then settles back. This indicates that air has been extracted from the ring. The pressure is now restored to atmospheric by opening the air entry tap gradually at first and then more rapidly as the investment settles back around the pattern. Then the ring is removed from the chamber and the investment is allowed to set. Modern investing unit does both mixing and investing under vacuum and is considered better than hand mixing and pouring.
Then there are two alternatives to be followed depending upon what type of expansion is to be achieved in order to compensate for metal shrinkage. They are:
1. If hygroscopic expansion of the investment is to be achieved then immediately immerse the filled ring in water at the temperature of 37C.
Or “under controlled water adding technique”. A soft flexible rubber ring is used instead of usual lined metal ring. Pattern is invested as usual. Then specified amount of water is added on top of the investment in the rubber ring and the investment is allowed to set at room temperature. In this way only enough water is added to the investment to provide the desired expansion.
2. If thermal expansion of the investment is to be achieved, then investment is allowed to set by placing the ring on the bench for 1 hour or as recommended by the manufacturer.