Indomethacin

commonly used to reduce fever, pain, stiffness, and swelling. It works by inhibiting the production of prostaglandins, molecules known to cause these symptoms.

Indications

ankylosing spondylitis, rheumatoid arthritis, osteoarthritis, juvenile arthritis, psoriatic arthritis, Reiter's disease, Paget's disease of bone, Bartter's disease, pseudogout, dysmenorrhea (menstrual cramps), pericarditis, bursitis, tendonitis, fever, headaches, nephrogenic , diabetes insipidus (prostaglandin inhibits vasopressin's action in the kidney)

Indomethacin has also been used clinically to delay premature labor, reduce amniotic fluid in polyhydramnios, and to treat patent ductus arteriosus.

Mechanism of action

Indomethacin is a nonselective inhibitor of cyclooxygenase (COX) 1 and 2, enzymes that participate in prostaglandin synthesis from arachidonic acid. Prostaglandins are hormone-like molecules normally found in the body, where they have a wide variety of effects, some of which lead to pain, fever, and inflammation.

Prostaglandins also cause uterine contractions in pregnant women. Indomethacin is an effective tocolytic agent, able to delay premature labor by reducing uterine contractions through inhibition of PG synthesis in the uterus and possibly through  calcium channel blockade.

Indomethacin easily crosses the placenta, and can reduce fetal urine production to treat polyhydramnios. It does so by reducing renal blood flow and increasing renal vascular resistance, possibly by enhancing the effects of vasopressin on the fetal kidneys.

Adverse effects

Since indomethacin inhibits both COX-1 and COX-2, it inhibits the production of prostaglandins in the  stomach and intestines which maintain the mucous lining of the

gastrointestinal tract. Indomethacin, therefore, like other nonselective COX inhibitors, can cause ulcers.

Many NSAIDs, but particularly indomethacin, cause lithium retention by reducing its excretion by the kidneys.

Indomethacin also reduces plasma renin activity and aldosterone levels, and increases

sodium and potassium retention. It also enhances the effects of vasopressin. Together these may lead to:

edema (swelling due to fluid retention)

hyperkalemia (high potassium levels)

hypernatremia (high sodium levels)

hypertension (high blood pressure)

Sulindac:  Is a pro‐drug closely related to Indomethacin. 

Converted to the active form of the drug. 

Indications and toxicity similar to  Indomethacin

Classification

1. Natural Alkaloids of Opium

Phenanthrenes -> morphine, codeine, thebaine

Benzylisoquinolines -> papaverine, noscapine

2. Semi-synthetic Derivatives

diacetylmorphine (heroin) hydromorphone, oxymorphone hydrocodone, oxycodone

3. Synthetic Derivatives

phenylpiperidines pethidine, fentanyl, alfentanyl, sufentnyl

benzmorphans pentazocine, phenazocine, cyclazocine

propionanilides methadone

morphinans levorphanol

Meperidine (Demerol)

Meperidine is a phenylpiperidine and has a number of congeners. It is mostly effective in the CNS and bowel

• Produces analgesia, sedation, euphoria and respiratory depression.
• Less potent than morphine, 80-100 mg meperidine equals 10 mg morphine.
• Shorter duration of action than morphine (2-4 hrs).
• Meperidine has greater excitatory activity than does morphine and toxicity may lead to convulsions.
• Meperidine appears to have some atropine-like activity.
• Does not constrict the pupils to the same extent as morphine.
• Does not cause as much constipation as morphine.
• Spasmogenic effect on GI and biliary tract smooth muscle is less pronounced than that produced by morphine.
• Not an effective antitussive agent.
• In contrast to morphine, meperidine increases the force of oxytocin-induced contractions of the uterus.
• Often the drug of choice during delivery due to its lack of inhibitory effect on uterine contractions and its relatively short duration of action.
• It has serotonergic activity when combined with monoamine oxidase inhibitors, which can produce serotonin toxicity (clonus, hyperreflexia, hyperthermia, and agitation)

 Adverse reactions to Meperidine

• Generally resemble a combination of opiate and atropine-like effects.

- respiratory depression, - tremors, - delirium and possible convulsions, - dry mouth

• The presentation of mixed symptoms (stupor and convulsions) is quite common in addicts taking large doses of meperidine.

Methyl salicylate

also known as oil of wintergreen, betula oil, methyl ester) is a natural product of many species of plants Structurally, it is methylated salicylic acid It is used as an ingredient in deep heating rubs

Inhalational Anesthetics

The depth of general anesthesia is directly proportional to the partial pressure of the anesthetic agent in the brain. These agents enter the body through the lungs, dissolve in alveolar blood and are transported to the brain and other tissues.

A. Rate of induction and rate of recovery from anesthesia:

1. The more soluble the agent is in blood, the more drug it takes to saturate the blood and the more time it takes to raise the partial pressure and the depth of anesthesia.

2. The less soluble the agent is in blood, the less drug it takes to saturate the blood and the less time it takes to raise the partial pressure and depth of anesthesia.

B. MAC (minimum alveolar concentration)

The MAC is the concentration of the anesthetic agent that represents the ED₅₀ for these agents. It is the alveolar concentration in which 50% of the patients will respond to a surgical incision.

The lower the MAC the more potent the general anesthetic agent.

C. Inhalation Anesthetic Agents 

• Nitrous Oxide
• Ether
• Halothane
• Enflurane
• Isoflurane

Azithromycin

Azithromycin is the first macrolide antibiotic belonging to the azalide group. Azithromycin is derived from erythromycin by adding a nitrogen atom into the lactone ring of erythromycin A, thus making lactone ring 15-membered.

Azithromycin has similar antimicrobial spectrum as erythromycin, but is more effective against certain gram-negative bacteria, particularly Hemophilus influenzae.

azithromycin is acid-stable and can therefore be taken orally without being protected from gastric acids.

Main elimination route is through excretion in to the biliary fluid, and some can also be eliminated through urinary excretion