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Pharmacology

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)

Aminoglycoside

Aminoglycosides are a group of antibiotics that are effective against certain types of bacteria. They include amikacin, gentamicin, kanamycin, neomycin, netilmicin, paromomycin, streptomycin, and tobramycin. Those which are derived from Streptomyces species

Aminoglycosides work by binding to the bacterial 30S ribosomal subunit, causing misreading of t-RNA, leaving the bacterium unable to synthesize proteins vital to its growth.

Aminoglycosides are useful primarily in infections involving aerobic, Gram-negative bacteria, such as Pseudomonas, Acinetobacter, and Enterobacter. In addition, some mycobacteria, including the bacteria that cause tuberculosis, are susceptible to aminoglycosides. Streptomycin was the first effective drug in the treatment of tuberculosis, though the role of aminoglycosides such as streptomycin and amikacin have been eclipsed (because of their toxicity and inconvenient route of administration) except for multiple drug resistant strains.

Infections caused by Gram-positive bacteria can also be treated with aminoglycosides, but other types of antibiotics are more potent and less damaging to the host. In the past the aminoglycosides have been used in conjunction with penicillin-related antibiotics in streptococcal infections for their synergistic effects, particularly in endocarditis.

Because of their potential for ototoxicity and renal toxicity, aminoglycosides are administered in doses based on body weight. Blood drug levels and creatinine are monitored during the course of therapy.

There is no oral form of these antibiotics: they are generally administered intravenously, though some are used in topical preparations used on wounds.

Aminoglycosides are mostly ineffective against anaerobic bacteria, fungi and viruses.

Amphotericin B

Main use is in systemic fungal infections (e.g. in immunocompromised patients), and in visceral leishmaniasis. Aspergillosis, cryptococcus infections (e.g. meningitis) and candidiasis are treated with amphotericin B. It is also used empirically in febrile immunocompromised patients who do not respond to broad-spectrum antibiotics.

MOA:

As with other polyene antifungals, amphotericin B associates with ergosterol, a membrane chemical of fungi, forming a pore that leads to K+ leakage and fungal cell death

Side effects: nephrotoxicity (kidney damage) , headache, vomiting, convulsions and fever

The side-effects are much milder when amphotericin B is delivered in liposomes

Ketamine 
- Causes a dissociative anesthesia.
- Is similar to but less potent than phencyclidine.
- Induces amnesia, analgesia, catalepsy and anesthesia, but does not induce convulsions.
- The principal disadvantage of ketamine is its adverse psychic effects during emergence from anesthesia. These include: hallucinations, changes in mood and body image.
- During anesthesia, many of the protective reflexes are maintained, such as laryngeal, pharyngeal, eyelid and corneal reflexes.
- Muscle relaxation is poor.
- It is not indicated for intracranial operations because it increases cerebrospinal fluid pressure.
- Respiration is well maintained.
- Arterial blood pressure, cardiac output, and heart rate are all elevated.

Pharmacology is the study of drugs and the way they interact with living systems.  Clinical pharmacology is the study of drugs in humans.

A drug is any chemical that can effect living processes.

Therapeutics: the medical use of drugs.

An ideal drug has several important properties.  Three of these properties are of utmost importance: effectiveness, safety and selectivity. 

Effectiveness: This is the most important quality that a drug can have.  Effectiveness refers to the drug's ability to do what it is supposed to do.

Safety:  Although no drug can be totally safe, proper usage can lessen the risks of adverse effects.

Selectivity:  A truly selective drug would have no side effects, and would effect only the body process' for which it is designed and given.  Therefore, there is no such thing as a selective drug.

Pharmacokinetics: The way the body deals with a drug.  Pharmacokinetics is concerned with the processes of absorption, distribution, metabolism and excretion.

Pharmacodynamics:  What a drug does to the body.

Pharmacokinetics and pharmacodynamics are two of the processes that determine how a person will respond to a drug.  Other factors include how a drug is administered (dose, route, and timing of administration), interactions with other drugs, and individual physiological variables (weight, age, function of body systems).

Mechanism of Action

When a local anesthetic is injected, it is the ionized [cation] form of the local anesthetic that actually binds to anionic channel receptors in the sodium channel, thus blocking the influx of sodium ions which are responsible for lowering the -70mv resting potential towards the firing threshold of -55mv which then results in depolarization of the nerve membrane. However, only the lipid soluble nonionized [base] form of the local anesthetic can penetrate the various barriers [e.g., nerve membrane, fibrous tissue] between the site of injection and the targeted destination which is the sodium channel.

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.
 

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