NEET MDS Lessons
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
Heroin (diacetyl morphine)
Heroin is synthetically derived from the natural opioid alkaloid morphine
Largely owing to its very rapid onset of action and very short half-life, heroin is a popular drug of abuse
It is most effective when used intravenously
Heroin is rapidly deacetylated to 6-monoacetyl morphine and morphine, both of which are active at the mu opioid receptor
More lipid soluble than morphine and about 2½ times more potent. It enters the CNS more readily.
Drugs used to induce vomiting
In case of poisoning with noncorrosive agents, and assuming incomplete absorption of the poison has taken place, induction of vomiting can be carried out. One of the drugs used for this purpose is emetine which causes irritation of the upper gut and, on absorption, it also acts on CTZ.
Chemotherapeutic agents (or their metabolites) can directly activate the medullary chemoreceptor trigger zone or vomiting center; several neuroreceptors, including dopamine receptor Type 2 and serotonin Type 3 (5-HT3) from cell damage(GIT and pharynx) play roles in vomiting.
Amphotericin B
Main use is in systemic fungal infections (e.g. in immunocompromised patients), and in visceral leishmaniasis. Aspergillosis, cryptococcus infections (e.g. meningitis) and candidiasis are treated with amphotericin B. It is also used empirically in febrile immunocompromised patients who do not respond to broad-spectrum antibiotics.
MOA:
As with other polyene antifungals, amphotericin B associates with ergosterol, a membrane chemical of fungi, forming a pore that leads to K+ leakage and fungal cell death
Side effects: nephrotoxicity (kidney damage) , headache, vomiting, convulsions and fever
The side-effects are much milder when amphotericin B is delivered in liposomes
Hydromorphone
- About 8-10 times more potent than morphine when given intravenously.
- Slightly shorter duration of action.
- More soluble than morphine, thus higher concentrations may be injected if necessary.
- Better oral/parenteral absorption ratio than morphine, but not as good as codeine or oxycodone.
- It is used for the treatment of moderate to severe pain
CARDIAC GLYCOSIDES
Cardiac glycosides (Digitalis)
Digoxin
Digitoxin
Sympathomimetics
Dobutamine
Dopamine
Vasodilators
α-blockers (prazosin)
Nitroprusside
ACE-inhibitors (captopril)
Pharmacology of Cardiac Glycosides
1. Positive inotropic effect (as a result of increase C.O., the symptoms of CHF subside).
2. Effects on other cardiac parameters
1) Excitability
2) Conduction Velocity; slightly increased in atria & ventricle/significantly
reduced in conducting tissue esp. A-V node and His-Purkinje System
3) Refractory Period; slightly ^ in atria & nodal tissue/slightly v in ventricles
4) Automaticity; can be greatly augmented - of particular concern in ventricle
3. Heart Rate
-Decrease due to 1) vagal stimulation and 2) in the situation of CHF, due to improved hemodynamics
4 Blood Pressure
-In CHF, not of much consequence. Changes are generally secondary to improved cardiac performance.
-In the absence of CHF, some evidence for a direct increase in PVR due to vasoconstriction.
5. Diuresis
-Due primarily to increase in renal blood flow as a consequence of positive inotropic effect (increase CO etc.) Possibly some slight direct diuretic effect.
Mechanism of Action of Cardiac Glycosides
Associated with an interaction with membrane-bound Na+-K+ ATPase (Na-K pump).
Clinical ramifications of an interaction of cardiac glycosides with the Na+ K pump.
I. Increase levels of Ca++, Increase therapeutic and toxic effects of cardiac glycosides
II. Decrease levels of K+ , Increase toxic effects of cardiac glycosides
Therapeutic Uses of Cardiac Glycosides
- CHF
- CHF accompanied by atrial fibrillation
- Supraventricular arrhythmias
Chloral hydrate
1. Short-acting sleep inducer—less risk of “hangover” effect the next day.
2. Little change on REM sleep.
3. Metabolized to trichloroethanol, an active metabolite; further metabolism inactivates the drug.
4. Used for conscious sedation in dentistry.
5. Can result in serious toxicity if the dose is not controlled.