NEET MDS Lessons
Pharmacology
Sedative-Hypnotic Drugs
Sedative drug is the drug that reduce anxiety (anxiolytic) and produce sedation and referred to as minor tranquillisers.
Hypnotic drug is the drug that induce sleep
Effects: make you sleepy; general CNS depressants
Uses: sedative-hypnotic (insomnia ), anxiolytic (anxiety, panic, obsessive compulsive, phobias), muscle relaxant (spasticity, dystonias), anticonvulsant (absence, status epilepticus, generalized seizures—rapid tolerance develops), others (pre-operative medication and endoscopic procedures, withdrawal from chronic use of ethanol or other CNS depressants)
1- For panic disorder alprazolam is effective.
2- muscle disorder: (reduction of muscle tone and coordination) diazepam is useful in treatment of skeletal muscle spasm e.g. muscle strain and spasticity of degenerative muscle diseases.
3-epilepsy: by increasing seizure threshold.
Clonazepam is useful in chronic treatment of epilepsy while diazepam is drug of choice in status epilepticus.
4-sleep disorder: Three BDZs are effective hypnotic agents; long acting flurazepam, intermediate acting temazepam and short
acting triazolam. They decrease the time taken to get to sleep They increase the total duration of sleep
5-control of alcohol withdrawals symptoms include diazepam, chlordiazepoxide, clorazepate and oxazepam.
6-in anesthesia: as preanesthetic amnesic agent (also in cardioversion) and as a component of balanced anesthesia
Flurazepam significantly reduce both sleep induction time and numbers of awakenings and increase duration of sleep and little rebound insomnia. It may cause daytime sedation.
Temazepam useful in patients who experience frequent awakening, peak sedative effect occur 2-3 hr. after an oral dose.
Triazolam used to induce sleep in recurring insomnia and in individuals have difficulty in going to sleep, tolerance develop within few days and withdrawals result in rebound insomnia therefore the drug used intermittently.
Drugs and their actions
1. Benzodiazepines: enhance the effect of gamma aminobutyric acid (GABA) at GABA receptors on chloride channels. This increases chloride channel conductance in the brain (GABA A A receptors are ion channel receptors).
2. Barbiturates: enhance the effect of GABA on the chloride channel but also increase chloride channel conductance independently of GABA, especially at high doses
3. Zolpidem and zaleplon: work in a similar manner to benzodiazepines but do so only at the benzodiazepine (BZ1) receptor type. (Both BZ1and BZ2 are located on chloride channels.)
4. Chloral hydrate: probably similar action to barbiturates.
5. Buspirone: partial agonist at a specific serotonin receptor (5-HT1A).
6. Other sedatives (e.g., mephenesin, meprobamate, methocarbamol, carisoprodol, cyclobenzaprine):
mechanisms not well-described. Several mechanisms may be involved.
7. Baclofen: stimulates GABA linked to the G protein, Gi , resulting in an increase in K + conductance and a decrease in Ca2+ conductance. (Other drugs mentioned above do not bind to the GABA B receptor.)
8. Antihistamines (e.g., diphenhydramine): block H1 histamine receptors. Doing so in the CNS leads to sedation.
9. Ethyl alcohol: its several actions include a likely effect on the chloride channel.
Loop (High Ceiling) Diuretics
Loop diuretics are diuretics that act at the ascending limb of the loop of Henle in the kidney. They are primarily used in medicine to treat hypertension and edema often due to congestive heart failure or renal insufficiency. While thiazide diuretics are more effective in patients with normal kidney function, loop diuretics are more effective in patients with impaired kidney function.
Agent: Furosemide
Mechanism(s) of Action
1. Diuretic effect is produced by inhibit of active 1 Na+, 1 K+, 2 Cl- co-transport (ascending limb - Loop of Henle).
o This produces potent diuresis as this is a relatively important Na re-absorption site.
2. Potassium wasting effect
a. Blood volume reduction leads to increased production of aldosterone
b. Increased distal Na load secondary to diuretic effect
c. a + b = increase Na (to blood) for K (to urine) exchange which produces indirect K wasting (same as thiazides but more likely)
3. Increased calcium clearance/decreased plasma calcium
o secondary to passive decreases in loop Ca++ reabsorption.
o This is linked to inhibition of Cl- reabsorption.
o This is an important clinical effect in patients with ABNORMAL High Ca++
Midazolam -Intravenous Anesthetics
Midazolam is a benzodiazepine used for preoperative sedation, induction of anesthesia, or maintenance of anesthesia in short procedures.
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
Class III Potassium Channel Blockers
Prolong effective refractory period by prolonging Action Potential
Treatment: ventricular tachycardia and fibrillation, conversion of atrial fibrillation or flutter to sinus rhythm, maintenance of sinus rhythm
– Amiodarone (Cordarone) – maintenance of sinus rhythm
– Bretylium (Bretylol)
– Ibutilide (Corvert)
– Dofetilide (Tykosyn)
– Sotalol (Betapace)
Amiodarone
- Has characteristics of sodium channel blockers, beta blockers, and calcium channel blockers
- Has vasodilating effects and decreases systemic vascular resistance
- Prolongs conduction in all cardiac tissue
- Decreases heart rate
- Decreases contractility of the left ventricles
Class III - Adverse Effects
- GI- Nausea vomiting and GI distress
- CNS- Weakness and dizziness
- CV-Hypotension, CHF, and arrhythmias are common.
- Amiodarone associated with potentially fatal Hepatic toxicity, ocular abnormalities and serious cardiac arrhythmias.
Drug – Drug Interactions
These drugs can cause serious toxic effects if combined with digoxin or quinidine.
Factors affecting onset and duration of action of local anesthetics
pH of tissue
pKa of drug
Time of diffusion from needle tip to nerve
Time of diffusion away from nerve
Nerve morphology
Concentration of drug
Lipid solubility of drug
Miconazole
Miconazole is an imidazole antifungal agent commonly used in topical sprays, creams and ointments applied to the skin to cure fungal infections such as Athlete's foot and Jock itch. It may also be used internally to treat vaginal yeast infection.
When used by a person taking the anticoagulant medication warfarin, Miconazole may cause an adverse reaction which can lead to excessive bleeding or bruising.