Fifth Generation:

These are extended spectrum antibiotics.

Ceftaroline, Ceftobiprole

Effects and Toxic Actions on Organ Systems

1. Local anesthetics (dose dependent) interfere with transmission in any excitable tissue (e.g. CNS and CVS).

2. CNS effects

 a. Central neurons very sensitive.

 b. Excitatory-dizziness, visual and auditory disturbances, apprehension, disorientation and muscle twitching more common with ester type agents.

 c. Depression manifested as slurred speech, drowsiness and unconsciousness more common with amide type agents (e.g. lidocaine).

 d. Higher concentrations of local anesthetic may eventually produce tonic-clonic[grand mal]  convulsions.

 e. Very large doses may produce respiratory depression which can be fatal. Artificial respiration may be life-saving.

 3.CVS effects

 a. Local anesthetics have direct action on the myocardium and peripheral vasculature by closing the sodium channel, thereby limiting the inward flux of sodium ions.

 b. Myocardium usually depressed both in rate and force of contraction. Depression of ectopic pacemakers useful in treating cardiac arrhythmias.

 c. Concentrations employed clinically usually cause vasodilation in area of injection.

 d. Vasoconstrictors such as epinephrine may counteract these effects on myocardium and vasculature.

4.  Local Tissue Responses

 a. Occasionally focal necrosis in skeletal muscle at injection site, decreased cell motility and delayed wound healing.

 b. Tissue hypoxia may be produced by action of excessive amounts of vasoconstrictors.

PHARYNGEAL DEMULCENTS 
Administered in the form of lozenges, cough drops and cough linctus. 
Produce soothing action on throat directly and by increasing the flow of saliva and provide symptomatic relief from dry cough.

EXPECTORANT

Expectorants are the drugs which increase the production of bronchial secretion and reduce its viscosity to facilitate its removal by coughing. 

ANTITUSSIVES

They are central cough suppressants and act centrally to raise the threshold of cough centre and inhibit the cough reflex by suppressing the coordinating cough centre in the medulla oblongata. 

Codeine - it depresses cough centre but is less constipating and abuse liability is low.

Pholcodeine is similar to codeine in efficacy and is longer acting. It has no analgesic or addicting property.

Noscapine is another opium alkaloid of benzylisoquinoline group. It is used as antitussive with no analgesic and drug abuse or drug dependence property. 

Dextromethorphan is a synthetic compound and its dextroisomer is used as antitussive and is as effective as codeine

Pipazethate is another synthetic compound of phenothiazine category used as antitussive with little analgesic and sedative properties.

ANTIHISTAMINICS
They do not act on cough centre but provide relief due to their sedative and anticholinergic action.

BRONCHODILATORS
Bronchodilators are helpful in individuals with cough and bronchoconstriction due to bronchial hyperreactivity. They help by improving the effectiveness of cough in clearing secretions.

Gastric acid secretion inhibitors (antisecretory drugs):

 HCl is secreted by parietal cells of the gastric mucosa which contain receptors for acetylcholine (muscarinic receptors: MR), histamine (H2R), prostaglandins (PGR) and gastrin (GR) that stimulate the production, except PGs which inhibit gastric acid production.
 
Therefore, antagonists of acetylcholine, histamine and gastrin inhibit gastric acid secretion (antisecretory). On the other hand, inhibitors of PGs biosynthesis such as NSAIDs with reduce cytoprotective mechanisms and thus promote gastric mucosal erosion. Also, the last step in gastric acid secretion from parietal cells involve a pump called H+ -K+-ATPase (proton pump). Drugs that block this pump will inhibit gastric acid secretion. Antisecretory drugs include:

1. Anticholinergic agents such as pirenzepine, dicyclomine, atropine.
2. H2-receptors blocking agents such as Cimetidine, Ranitidine, Famotidine, Nizatidine (the pharmacology of these agents has been discussed previously).
3. Gastrin-receptor blockers such as proglumide.
4. Proton pump inhibitors such as omeprazole, lansoprazole.

Major clinical indications of antisecretory drugs:

• Prevention & treatment of peptic ulcer disease.
• Zollinger Ellison syndrome.
• Reflux esophagitis. 

Uses of NSAIDs

NSAIDs are usually indicated for the treatment of acute or chronic conditions where pain and inflammation are present. Research continues into their potential for prevention of colorectal cancer, and treatment of other conditions, such as cancer and cardiovascular disease.

NSAIDs are generally indicated for the symptomatic relief of the following conditions.

rheumatoid arthritis, osteoarthritis, inflammatory arthropathies (e.g. ankylosing spondylitis, psoriatic arthritis, Reiter's syndrome), acute gout, dysmenorrhoea, metastatic bone pain ,headache and migraine, postoperative pain, mild-to-moderate pain due to inflammation and tissue injury, pyrexia, renal colic

Aspirin, the only NSAID able to irreversibly inhibit COX-1, is also indicated for inhibition of platelet aggregation; an indication useful in the management of arterial thrombosis and prevention of adverse cardiovascular events.

Rofecoxib

Inhibit prostacyclin(PGI2) in vascular  endothelium , letting TXA2 act freely and  promote platelet aggregation. 

used in the treatment of osteoarthritis, acute pain conditions, and dysmenorrhea

Higher incidence of cardiovascular thrombotic  events.

Not used due to increase risk of heart attack, stroke