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
Dissociation constants
|
Local anesthetic |
pKa |
% of base(RN) at pH 7.4 |
onset of action(min) |
|
Lidocaine |
7.8 |
29 |
2-4 |
|
Bupivacaine |
8.1 |
17 |
5-8 |
|
Mepivacaine |
7.7 |
33 |
2-4 |
|
Prilocaine |
7.9 |
25 |
2-4 |
|
Articaine |
7.8 |
29 |
2-4 |
|
Procaine |
9.1 |
2 |
14-18 |
|
Benzocaine |
3.5 |
100 |
- |
Pramlintide -Amylin mimetics
Mechanism
synthetic analogue of human amylin that acts in conjunction with insulin
↓ release of glucagon
delays gastric emptying
Clinical use
type I and II DM
Benzodiazepines (BZ):
newer; depress CNS, selective anxiolytic effect (no sedative effect); are not general anesthetics (but does produce sedation, stupor) or analgesics
BZ effects:
1. Central: BZs bind GABAA receptors in limbic system (amygdala, septum, hippocampus; involved in emotions) and enhance inhibition of neurons in limbic system (this may produce anxiolytic effects of BZs)
a. GABA receptor: pentameric (α, β, δ, γ subunits)
i. Binding sites: GABA (↑ conductance (G) of Cl-, hyperpolarization, inhibition), barbiturate (↑ GABA effect), benzodiazepine (↑ GABA effect), picrotoxin (block Cl channel)
b. GABA agonists: GABA (binds GABA → Cl influx; have ↑ frequency of Cl channel opening; BZs alone- without GABA don’t affect Cl channel function)
c. Antagonists: bicuculline (competitively blocks GABA binding; ↓ inhibition,→ convulsions; no clinical use), picrotoxin (non-competitively blocks GABA actions, Cl channel → ↓ inhibition → convulsions)
2. Other agents at BZ receptor:
a. Agonists: zolpidem (acts at BZ receptor to produce pharmacological actions)
b. Inverse agonists: β-carbolines (produce opposite effects at BZ binding site-- ↓ Cl conductance; no therapeutic uses since → anxiety, irritability, agitation, delirium, convulsions)
3. Antagonists: flumazenil (block agonists and inverse agonists, have no biological effects themselves; can precipitate withdrawal in dependent people)
Metabolism: many BZs have very long action (since metabolism is slow); drugs have active metabolites
2 major reactions: demethylation and hydroxylation (both very slow reactions)
Fast reaction: glucuronidation and urinary excretion
Plasma half life: long (for treating anxiety, withdrawal, muscle relaxants), intermediate (insomnia, anxiety), short (insomnia), ultra-short (<2hrs; pre-anesthetic medication)
Acute toxicity: very high therapeutic index and OD usually not life threatening (rarely see coma or death)
Treatment: support respiration, BP, gastric lavage, give antagonist (e.g., glumazenil; quickly reverses BD-induced respiratory depression)
Tolerance: types include pharmacodynamic (down-regulation of CNS response due to presence of drug; this is probably the mechanism by which tolerance develops), cross-tolerance (with other BZ and CNS depressants like EtOH and BARBS), acquisition of tolerance (tolerance develops fastest in anticonvulsant > sedation >> muscle relaxant > antianxiety; means people can take BZs for long time for antianxiety without → tolerance)
Physical dependence: low abuse potential (no buz) but physical/psychological dependence may occur; physical dependence present when withdrawal symptoms occur (mild = anxiety, insomnia, irritability, bad dreams, tremors, anorexia; severe = agitation, depression, panic, paranoia, muscle twitches, convulsions)
Drug interactions: minimally induce liver enzymes so few interactions; see additive CNS depressant effects (can be severe and → coma and death if BZs taken with other CNS depressants like ethanol)
Patient positioning
The most common medical emergency encountered in the dental office setting is syncope. So patients in the supine or semi-supine position to improve venous return and cerebral blood flow provided that the position is tolerated by the patient and is appropriate for their medical condition.
Antiemetics
Antiemetic drugs are generally more effective in prophylaxis than treatment. Most antiemetic agents relieve nausea and vomiting by acting on the vomiting centre, dopamine receptors, chemoreceptors trigger zone (CTZ), cerebral cortex, vestibular apparatus, or a combination of these.
Drugs used in the treatment of nausea and vomiting belong to several different groups. These include:
1. Phenothiazines, such as chlorpromazine, act on CTZ and vomiting centre, block dopamine receptors, are effective in preventing or treating nausea and vomiting induced by drugs, radiation therapy, surgery and most other stimuli (e.g. pregnancy).
They are generally ineffective in motion sickness.
Droperidol had been used most often for sedation in endoscopy and surgery, usually in combination with opioids or benzodiazepines
2. Antihistamines such as promethazine and Dimenhyrinate are especially effective in prevention and treatment of motion.
3. Metoclopramide has both central and peripheral antiemetic effects. Centrally, it antagonizes the action of dopamine. Peripherally metoclopramide stimulates the release of acetylcholine, which in turn, increases the rate of gastric. It has similar indications to those of chlorpromazine.
4. Scopolamine, an anticholinergic drug, is very effective in reliving nausea & vomiting associated with motion sickness.
5. Ondansetron, a serotonin antagonist, is effective in controlling chemical-induced vomiting and nausea such those induced by anticancer drugs.
6. Benzodiazepines: The antiemetic potency of lorazepam and alprazolam is low. Their beneficial effects may be due to their sedative, anxiolytic, and amnesic properties
Neurotransmitters can be classified into:
1. Biogenic amines:
ACh, NA, DA, 5-HT, Histamine
2. Amino acids:
Excitatory (glutamate & asparate)
Inhibitory (GABA& glycine)
3. Others:
Adenosine, melatonin