Glitazones (thiazolidinediones)

Thiazolidinediones, also known as the "-glitazones"

pioglitazone
rosiglitazone

Mechanism

bind to nuclear receptors involved in transcription of genes mediating insulin sensitivity
peroxisome proliferator-activating receptors (PPARs)

↑ insulin sensitivity in peripheral tissue
↓ gluconeogenesis
↑ insulin receptor numbers
↓ triglycerides

Clinical use

type II DM
as monotherapy or in combination with other agents
contraindicated in CHF
associated with increased risk of MI (in particular rosiglitazone)

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.

Clavulanic acid is often combined with amoxicillin to treat certain infections caused by bacteria, including infections of the ears, lungs, sinus, skin, and urinary tract. It works by preventing bacterium that release beta-lactamases from destroying amoxicillin.

Ciprofloxacin : Ciprofloxacin is bactericidal and its mode of action depends on blocking of bacterial DNA replication by binding itself to an enzyme called DNA gyrase

Ciprofloxacin is a broad-spectrum antibiotic that is active against both Gram-positive and  Gram-negative bacteria.

Enterobacteriaceae, Vibrio,  Hemophilus influenzae, Neisseria gonorrhoeae

 Neisseria menigitidis,  Moraxella catarrhalis,  Brucella, Campylobacter,

 Mycobacterium intracellulare, Legionella sp., Pseudomonas aeruginosa,

Bacillus anthracis - that causes anthrax

Weak activity against: Streptococcus pneumoniae,

No activity against:  Bacteroides,  Enterococcus faecium, Ureaplasma urealyticum  and others

It is contraindicated in children, pregnancy, and epilepsy.

Ciprofloxacin can cause photosensitivity reactions and can elevate plasma

theophylline levels to toxic values. It can also cause  constipation and sensitivity to caffeine.

Dosage in respiratory infections is 500-1500 mg a day in 2 doses.

Agonist, Antagonist, and Partial Agonists

Agonists:  molecules that activate receptors.  A drug that mimics the body's own regulatory processes.
Antagonists:  produce their effects by preventing receptors activation by endogenous regulatory molecules and drugs.  Block activation of receptors by agonists.
Noncompetive Antagonist:  Bind irreversibly to receptors, and reduce the maximal response that an agonist can elicit.
Competitive Antagonist:  Bind reversibly to receptors, competing with agonists for binding sites.
Partial Agonists:  Have moderate intrinsic activity, the maximal effect that a partial agonist can produce is lower than that of a full agonist.  Act as antagonists as well as agonists.
 

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⁺⁺