Propoxyphene

• A methadone analog.Used orally to relieve mild to moderate pain.
• A typical opiate, it does not possess anti-inflammatory or antipyretic actions, but has little or no antitussive activity.
• Cannot be used parenterally because of irritant properties.
• Has a low addiction potential primarily due to its lack of potency as an opiate.
• The most common adverse side effects are:• dizziness, drowsiness, and nausea and vomiting. • these effects are more prominent in ambulatory patients.
• Withdrawal symptoms have occurred in both adults and in neonates following use of the drug by the mother during pregnancy.
• CNS depression is additive with other CNS depressants.

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

Antiemetics

 Antiemetic drugs are generally more effective in prophylaxis than treatment. Most antiemetic agents relieve nausea and vomiting by acting on the vomiting centre, dopamine receptors, chemoreceptors trigger zone (CTZ), cerebral cortex, vestibular apparatus, or a combination of these.
 
 Drugs used in the treatment of nausea and vomiting belong to several different groups. These include:
 
1. Phenothiazines, such as chlorpromazine, act on CTZ and vomiting centre, block dopamine receptors, are effective in preventing or treating nausea and vomiting induced by drugs, radiation therapy, surgery and most other stimuli (e.g. pregnancy).
They are generally ineffective in motion sickness.
Droperidol had been used most often for sedation in endoscopy and surgery, usually in combination with opioids or benzodiazepines

2. Antihistamines such as promethazine and Dimenhyrinate are especially effective in prevention and treatment of motion.

3. Metoclopramide has both central and peripheral antiemetic effects. Centrally, it antagonizes the action of dopamine. Peripherally metoclopramide stimulates the release of acetylcholine, which in turn, increases the rate of gastric. It has similar indications to those of chlorpromazine.

4. Scopolamine, an anticholinergic drug, is very effective in reliving nausea & vomiting associated with motion sickness.

5. Ondansetron, a serotonin antagonist, is effective in controlling chemical-induced vomiting and nausea such those induced by anticancer drugs. 

6. Benzodiazepines: The antiemetic potency of lorazepam and alprazolam is low. Their beneficial effects may be due to their sedative, anxiolytic, and amnesic properties

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.

TRIMETHOPRIM

It is a diaminopyrimidine. It inhibits bacterial dihydrofolate reductase( DHFRase).

In combination with sulphamethoxzole it is called Co-trimoxazole.

Spectrum of action

 S. Typhi. Serratia. Klebsiela and many sulphonamide resistant strains of Staph.aureus. Strep pyogens

Adverse effects

Megaloblastic anemia. i.e.. due to folate defeciency.

Contraindicated in pregnancy.

Diuretics if given with co-trimoxazole cause thrombocytopenia.

Uses

I. UTI. 2. RTI. 3. Typhoid. 5. Septicemias. 5. Whooping cough

GLP-1 analogs

Exenatide

Mechanism

GLP-1 is an incretin released from the small intestine that aids glucose-dependent insulin secretion
basis for drug mechanism is the observation that more insulin secreted with oral glucose load compared to IV 

Exenatide is a GLP-1 agonist

↑ insulin
↓ glucagon release
the class of dipeptidyl peptidase inhibitors ↓ degradation of endogenous GLP-1
e.g.) sitagliptin, -gliptins 
 

Clinical use
type II DM
 

Toxicity
nausea, vomiting
pancreatitis
hypoglycemia
if given with sulfonylureas