Nimesulide

analgesic and  antipyretic properties

Nimesulide is a relatively COX-2 selective, non-steroidal anti-inflammatory drug (NSAID) with analgesic and antipyretic properties. Its approved indications are the treatment of acute pain, the symptomatic treatment of osteoarthritis and primary dysmenorrhoea in adolescents and adults above 12 years old.

Banned - not used

Amoxicillin

a moderate-spectrum

β-lactam antibiotic used to treat bacterial infections caused by susceptible

Mode of action Amoxicillin acts by inhibiting the synthesis of bacterial cell walls. It inhibits cross-linkage between the linear peptidoglycan polymer chains that make up a major component of the cell wall of Gram-positive bacteria. microorganisms. It is usually the drug of choice within the class because it is better absorbed, following oral administration, than other beta-lactam antibiotics. Amoxicillin is susceptible to degradation by  β-lactamase-producing bacteria, and so is often given clavulanic acid.

Microbiology Amoxicillin is a moderate-spectrum antibiotic active against a wide range of Gram-positive, and a limited range of Gram-negative organisms

Susceptible Gram-positive organisms : Streptococcus spp., Diplococcus pneumoniae, non β-lactamase-producing Staphylococcus spp., and Streptococcus faecalis.

Susceptible Gram-negative organisms  Haemophilus influenzae, Neisseria gonorrhoeae, Neisseria meningitidis, Escherichia coli, Proteus mirabilis and Salmonella spp.

Resistant organisms Penicillinase producing organisms, particularly penicillinase producing Staphylococcus spp. Penicillinase-producing N. gonorrhoeae and H. influenzae are also resistant

All strains of Pseudomonas spp., Klebsiella spp., Enterobacter spp., indole-positive

Proteus spp., Serratia marcescens, and Citrobacter spp. are resistant.

The incidence of β-lactamase-producing resistant organisms, including E. coli, appears to be increasing.

Amoxicillin and Clavulanic acid Amoxicillin is sometimes combined with clavulanic acid, a β-lactamase inhibitor, to increase the spectrum of action against

Gram-negative organisms, and to overcome bacterial antibiotic resistance mediated through β-lactamase production.

Morphine

Morphine is effective orally, but is much less effective than when given parenterally due to first-pass metabolism in the liver. Metabolism involves glucuronide formation, the product of which is excreted in the urine.

1. Central Nervous System Effects

• Morphine has mixed depressant and stimulatory actions on the CNS.

• Analgesia:

• Dysphoria – Euphoria

- morphine directly stimulates the chemoreceptor trigger zone, but later depresses the vomiting center in the brain stem. This center is outside the blood/brain barrier.

- opiates appear to relieve anxiety

• Morphine causes the release of histamine and abolishes hunger.

- causes the body to feel warm and the face and nose to itch.

• Pupils are constricted.- due to stimulation of the nuclei of the third cranial nerves.

- tolerance does not develop to this effect.

• Cough reflex is inhibited. - this is not a stereospecific effect.

- dextromethorphan will suppress cough but will not produce analgesia.

• Respiration is depressed

- due to a direct effect on the brain stem respiratory center.

- death from narcotic overdose is nearly always due to respiratory arrest.

- the mechanism of respiratory depression involves:

• a reduction in the responsiveness of the brain stem respiratory centers to an increase in pCO₂.

• depression of brain stem centers that regulate respiratory rhythm.

- hypoxic stimulation of respiration is less affected and O2 administration can produce apnea.

2. Cardiovascular Effects

• Postural orthostatic hypotension.- due primarily to peripheral vasodilation, which may be due in part to histamine release.

• Cerebral circulation is also indirectly influenced by increased pCO2, which leads to cerebral vasodilation and increased cerebrospinal fluid pressure.

• In congestive heart failure, morphine decreases the left ventricular workload and myocardial oxygen demand.

3. Endocrine Effects

• Increases prolactin secretion

• Increases vasopressin (ADH) secretion

• Decreases pituitary gonadotropin (LH & FSH) secretion.

• Decreases stress induced ACTH secretion.

4. Gastrointestinal Tract Effects

• Constipation (tolerance does not develop to this effect).

• Several of these agents can be used in the treatment of diarrhea.

There is an increase in smooth muscle tone and a decrease in propulsive  contractions.

Adverse Reactions

Generally direct extensions of their pharmacological actions.

1. respiratory depression, apnea

2. nausea and vomiting

3. dizziness, orthostatic hypotension, edema

4. mental clouding, drowsiness

5. constipation, ileus

6. biliary spasm (colic)

7. dry mouth

8. urine retention, urinary hesitancy

9. hypersensitivity reactions (contact dermatitis, urticaria)

Precautions

1. respiratory depression, particularly in the newborn

3. orthostatic hypotension

4. histamine release (asthma, shock)

5. drug interactions (other CNS depressants)

6. tolerance:

- analgesia, euphoria, nausea and vomiting, respiratory depression

7. physical dependence (psychological & physiological)

Example calculations of maximum local anesthetic doses for a 15-kg child

Articaine

5 mg/kg maximum dose × 15 kg = 75 mg

4% articaine = 40 mg/mL

75 mg/(40 mg/mL) = 1.88 mL

1 cartridge = 1.8 mL

Therefore, 1 cartridge is the maximum

Lidocaine

7 mg/kg × 15 kg = 105 mg

2% lidocaine = 20 mg/mL

105 mg/(20 mg/mL) = 5.25 mL

1 cartridge = 1.8 mL

Therefore, 2.9 cartridges is the maximum

Mepivacaine

6.6 mg/kg × 15 kg = 99 mg

3% mepivacaine = 30 mg/mL

99 mg/(30 mg/mL) = 3.3 mL

1 cartridge = 1.8 mL

Therefore, 1.8 cartridges is the maximum.

Prilocaine

8 mg/kg × 15 kg = 120 mg

4% prilocaine = 40 mg/mL

120 mg/(40 mg/mL) = 3 mL

1 cartridge = 1.8 mL

Therefore, 1.67 cartridges is the maximum

FUNDAMENTALS OF INJECTION TECHNIQUE

There are 6 basic techniques for achieving local anesthesia of the structures of the oral cavity:

 1. Nerve block

 2. Field block

 3. Infiltration/Supraperiosteal

 4. Topical

 5. Periodontal ligament (PDL)

 6. Intraosseous

 Nerve block- Nerve block anesthesia requires local anesthetic to be deposited in close proximity to a nerve trunk. This results in the blockade of nerve impulses distal to this point. It is also important to note that arteries and veins accompany these nerves and can be damaged. To be effective, the local anesthetic needs to pass only through the nerve membrane to block nerve conduction Field block/Infiltration/Supraperiosteal - Field block, infiltration and supraperiosteal injection techniques, rely on the ability of local anesthetics to diffuse through numerous structures to reach the nerve or nerves to be anesthetized:

  - Periosteum

 - Cortical bone

 - Cancellous bone

 - Nerve membrane

Topical - Topical anesthetic to be effective requires diffusion through mucous membranes and nerve membrane of the nerve endings near the tissue surface

PDL/Intraosseous - The PDL and intraosseous injection techniques require diffusion of local anesthetic solution through the cancellous bone (spongy) to reach the dental plexus of nerves innervating the tooth or teeth in the immediate area of the injection. The local anesthetic then diffuses through the nerve membrane

Buspirone

1. Short half-life (2–4 hours).
2. Relieves anxiety.
3. Does not act as an anticonvulsant.
4. Is not a good muscle relaxant.
5. Minimum abuse potential.