Erythromycin

used for people who have an allergy to penicillins. For respiratory tract infections, it has better coverage of atypical organisms, including  mycoplasma. It is also used to treat outbreaks of chlamydia, syphilis, and gonorrhea.

Erythromycin is produced from a strain of the actinomyces Saccaropolyspora erythraea, formerly known as Streptomyces erythraeus.

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

Mucosal protective agents. 

 These are locally active agents that help heal gastric and duodenal ulcers by forming a protective barrier between the ulcers and gastric acid, pepsin, and bile salts. They do not alter the secretion of gastric acid. These drugs include sucralfate and colloid bismuth compounds. (e.g. tripotassium, dicitratobismuthate). Colloidal bismuth compounds additionally exert bactericidal action against H.pylori. Also, Prostaglandins have both antisecretory and mucosal protective effects. 
 
 Example: Misoprostol- used for prevention of NSAID – induced ulcer. 

- Drugs that exert antimicrobial action against H.pylori such as amoxicillin, metronidazole, clarithromycin and tetracycline are included in the anti-ulcer treatment regimens. 

Barbiturates (BARBS): 

were used for antianxiety, sedation but now replaced by BZs; for IV sedation & oral surgery

Advantages: effective and relatively inexpensive (common in third world countries), extensively studied so have lots of information about side effects/toxicity

Peripheral effects: respiratory depression (with ↑ dose), CV effects (↓ BP and HR at sedative-hypnotic doses), liver effects (bind CYP450 → induction of drug metabolism and other enzymes → ↑ metabolism of steroids, vitamins K/D, cholesterol, and bile salts)

General mechanisms: potently depress neuron activity in the reticular formation (pons, medulla) and cortex 
o    Bind barbiturate site on GABAA receptor → enhanced inhibitory effect and ↑ Cl influx; → ↓ frequency of Cl channel opening but ↑ open time of Cl channels (in presense of GABA) so more Cl enters channel (at high [ ] they directly ↑ Cl conductance in absence of GABA- act as GABA mimetics)

Metabolism: liver microsomal drug metabolizing enzymes; most are dealkylated, conjugated by glucoronidation; renal excretion

Uses: anticonvulsant, preoperative sedation, anesthesia

Side effects: sedation, confusion, weight gain, N/V, skin rash

Contraindications: pain (can ↑ sensitivity to painful situations → restlessness, excitement, and delirium) and pulmonary insufficiency (since BARBS → respiratory depression)

Drug interactions: have additive depressant affects when taken with other CNS depressants, enhance depressive effects (of antipsychotics, antihistamines, antiHTNs, ethanol, and TCAs), and accelerates metabolism (of β blockers, Ca-channel blockers, corticosteroids, estrogens, phenothiazines, valproic acid, and theophylline; occurs with chronic BARB ingestion)

Acute toxicity: lower therapeutic index; can be fatal if OD; BARB poisoning a major problem (serious toxicity at only 10x hypnotic dose; → respiratory depression, circulatory collapse, renal failure, pulmonary complications which can be life-threatening)

Symptoms: severe respiratory depression, coma, severe hypotension, hypothermia

Treatment: support respiration and BP, gastric lavage (if recent ingestion)

Tolerance: metabolic (induce hepatic metabolic enzymes, occurs within a few days), pharmacodynamic (↓ CNS response with chronic exposure occurs over several weeks; unknown mechanism), and cross tolerance (tolerance to other general CNS depressants)

Physical dependence: develops with continued use; manifest by withdrawal symptoms (mild = anxiety, insomnia, dizziness, nausea; severe = vomiting, hyperthermia, tremors, delirium, convulsions, death)

Other similar agents: meprobamate (Equanil; pharmacological properties like BZs and barbiturates but mechanism unknown) and chloral hydrate (common sedative in pediatric dentistry for diagnostic imaging; few adverse effects but low therapeutic index)

Other drugs for antianxiety: β-adrenoceptor blockers (e.g., propranolol; block autonomic effects- palpitations, sweating, shaking; used for disabling situational anxiety like stage fright), buspirone (partial agonist at serotonin 1A receptor, produces only anxiolytic effects so no CNS depression, dependence, or additive depression with ethanol but onset of action is 1-3 weeks), lodipem (not a BZ but does act at BZ receptors)

SYMPATHOMIMETICS 

β2 -agonists are invariably used in the symptomatic treatment of asthma. 

Epinephrine and ephedrine are structurally related to the catecholamine norepinephrine, a neurotransmitter of the adrenergic nervous system 

Some of the important β 2 agonists like salmeterol, terbutaline and salbutamol are invariably used as bronchodilators both oral as well as
aerosol inhalants 

SALBUTAMOL
It is highly selective β2 -adrenergic stimulant h-aving a prominent bronchodilator action.
It has poor cardiac action compared to isoprenaline.

TERBUTALINE
It is highly selective β2  agonist similar to salbutamol, useful by oral as well as inhalational route.

SALMETEROL

Salmeterol is long-acting analogue of salbutamol 

BAMBUTEROL

It is a latest selective adrenergic β2 agonist with long plasma half life and given once daily in a dose of 10-20 mg orally.

METHYLXANTHINES (THEOPHYLLINE AND ITS DERIVATIVES)

THEOPHYLLINE
Theophylline has two distinct action:
smooth muscle relaxation (i.e. bronchodilatation) and suppression of the response of the airways to stimuli (i.e. non-bronchodilator prophylactic effects). 

ANTICHOLINERGICS

Anticholinergics, like atropine and its derivative ipratropium bromide block cholinergic pathways that cause airway constriction.

MAST CELL STABILIZERS

SODIUM CROMOGLYCATE

It inhibits degranulation of mast cells by trigger stimuli. 
It also inhibits the release of various asthma provoking mediators e.g. histamine, leukotrienes, platelet activating factor (PAF) and interleukins (IL’s) from mast cell 

KETOTIFEN
It is a cromolyn analogue. It is an antihistaminic (H1  antagonist) and probably inhibits airway inflammation induced by platelet activating factor (PAF) in primate. 
It is not a bronchodilator. It is used in asthma and symptomatic relief in atopic dermatitis, rhinitis, conjunctivitis and urticaria.

LEUKOTRIENE PATHWAY INHIBITORS

MONTELUKAST

It is a cysteinyl leukotriene receptor antagonist indicated for the management of persistent asthma. 

Nalidixic acid:

Nalidixic acid is the basis for quinolone antibiotics. It acts bacteriostatically (that is, it inhibits growth and reproduction) or bactericidally (it kills them) on both Gram positive and Gram negative bacteria, depending on the concentration. It is especially used in treating urinary tract infections, caused for example by Escherichia coli, Proteus, Enterobacter and Klebsiella.