Macrolide

The macrolides are a group of  drugs (typically antibiotics) whose activity stems from the presence of a macrolide ring, a large  lactone ring to which one or more deoxy sugars, usually cladinose and desosamine, are attached. The lactone ring can be either 14, 15 or 16-membered. Macrolides belong to the polyketide class of natural products.

The most commonly-prescribed macrolide antibiotics are:  

Erythromycin,  Clarithromycin, Azithromycin, roxithromycin,

Others are: spiramycin (used for treating  toxoplasmosis), ansamycin, oleandomycin, carbomycin and tylocine.

There is also a new class of antibiotics called ketolides that is structurally related to the macrolides. Ketolides such as telithromycin are used to fight respiratory tract infections caused by macrolide-resistant bacteria.

Non-antibiotic macrolides :The drug Tacrolimus, which is used as an

immunosuppressant, is also a macrolide. It has similar activity to  cyclosporine.

Uses : respiratory tract infections and soft tissue infections.

Beta-hemolytic  streptococci,  pneumococci, staphylococci and enterococci are usually susceptible to macrolides. Unlike penicillin, macrolides have shown effective against mycoplasma, mycobacteria, some rickettsia and chlamydia.

Mechanism of action: Inhibition of bacterial protein synthesis by binding reversibly to the subunit 50S of the bacterial ribosome, thereby inhibiting translocation of peptidyl-tRNA. This action is mainly bacteriostatic, but can also be bactericidal in high concentrations

Resistance : Bacterial resistance to macrolides occurs by alteration of the structure of the bacterial ribosome.

Metabolism

Hepatic Drug-Metabolizing Enzymes:  most drug metabolism in the liverperformed by the hepatic microsomal enzyme system.

Therapeutic Consequences of Drug Metabolism
- Accelerated Renal Drug Excretion:  The most important consequence of drug metabolism is the promotion of renal drug excretion.  Metabolism makes it possible for the kidney to excrete many drugs that it otherwise could not.

- Drug Inactivation
- Increased Therapeutic Action: Metabolism may increase the effectiveness of some drugs.
- Activation of Prodrugs:  A prodrug is a compound that is inactive when administered and made active by conversion in the body.

- Increased or Decreased Toxicity

Factors that influence rate of metabolism:  

- Age:  Hepatic maturation doesn't occur until about a year old.

- Induction of Drug-Metabolizing Enzymes:  Some drugs can cause the rate of metabolism to increase, leading to the need for an increased dosage.  May also influence the rate of metabolism for other drugs taken at the same time, leading to a need for increased dosages of those drugs as well.

- First-Pass Effect:  Hepatic inactivation of certain oral drugs.  Avoided by parentaral administration of drugs that undergo rapid hepatic metabolism.

- Nutritional Status

- Competition between Drugs

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.

CNS acting drugs are of major therapeutic and clinical importance. 

They can produce diverse physiologicaland psychologicaleffects such as:

•Induction of Anesthesia 
•Relief of Pain 
•Prevention of Epileptic seizures 
•Reduction of Anxiety 
•Treatment of Parkinsonism 
•Treatment of Alzheimer's disease 
•Treatment of Depression 
•Centrally acting drugs also include drugs that are administered without medical intervention like tea, coffee, nicotine, and opiates.
 

Kinins
Peptide that are mediated in the inflammation.
Action of kinin:
On CVS: vasodilatation in the kidneys, heart, intestine, skin, and liver. It is 10 times active than histamine as vasodilator.

On exocrine and endocrine glands: kinin modulate the tone of pancreas and salivery glands and help regulate GIT motility, also affect the transport of water and electrolytes, glucose and amino acids through epithelial cell transport.

Carbonic anhydrase inhibitors

Acetazolamide, Dichlorphenamide, Methazolamide, Ethoxzolamide

Mechanism of Action

1.    Carbonic anhydrase (CA) facilitates excretion of H+ and recovery of bicarbonate by the proximal renal tubule and ciliary epithelium of the eye. Sodium is recovered in exchange for H+. 
2.    Inhibitors block CA block sodium recovery. A very mild diuresis is produced (this is really a side effect of their use in glaucoma) because relatively unimportant mechanism for Na recovery and because proximal tubule site means that other sodium recovery mechansims continue to process their normal fraction of the sodium load.