Effects and Toxic Actions on Organ Systems

1. Local anesthetics (dose dependent) interfere with transmission in any excitable tissue (e.g. CNS and CVS).

2. CNS effects

 a. Central neurons very sensitive.

 b. Excitatory-dizziness, visual and auditory disturbances, apprehension, disorientation and muscle twitching more common with ester type agents.

 c. Depression manifested as slurred speech, drowsiness and unconsciousness more common with amide type agents (e.g. lidocaine).

 d. Higher concentrations of local anesthetic may eventually produce tonic-clonic[grand mal]  convulsions.

 e. Very large doses may produce respiratory depression which can be fatal. Artificial respiration may be life-saving.

 3.CVS effects

 a. Local anesthetics have direct action on the myocardium and peripheral vasculature by closing the sodium channel, thereby limiting the inward flux of sodium ions.

 b. Myocardium usually depressed both in rate and force of contraction. Depression of ectopic pacemakers useful in treating cardiac arrhythmias.

 c. Concentrations employed clinically usually cause vasodilation in area of injection.

 d. Vasoconstrictors such as epinephrine may counteract these effects on myocardium and vasculature.

4.  Local Tissue Responses

 a. Occasionally focal necrosis in skeletal muscle at injection site, decreased cell motility and delayed wound healing.

 b. Tissue hypoxia may be produced by action of excessive amounts of vasoconstrictors.

Etomidate  -Intravenous Anesthetics

- A nonbarbiturate anesthetic used primarily to induce surgical anesthesia.
- It does not produce analgesia.
- Etomidate has minimal effect on the cardiovascular system and respiration during induction of anesthesia.
- Like the barbiturates, etomidate decreases cerebral blood flow, cerebral metabolic rate and intracranial pressure.
- No changes in hepatic, renal or hematologic function have been reported.
- Myoclonic muscle movements are relatively common.
- Postoperative nausea and vomiting are more common with etomidate than with barbiturates.

Erythromycin

used for people who have an allergy to penicillins. For respiratory tract infections, it has better coverage of atypical organisms, including  mycoplasma. It is also used to treat outbreaks of chlamydia, syphilis, and gonorrhea.

Erythromycin is produced from a strain of the actinomyces Saccaropolyspora erythraea, formerly known as Streptomyces erythraeus.

Mechanism of action Erythromycin prevents bacteria from growing, by interfering with their protein synthesis. Erythromycin binds to the subunit 50S of the bacterial ribosome, and thus inhibits the translocation of peptides.

Erythromycin is easily inactivated by gastric acids, therefore all orally administered formulations are given as either enteric coated or as more stable salts or  esters. Erythromycin is very rapidly absorbed, and diffused into most tissues and  phagocytes. Due to the high concentration in phagocytes, erythromycin is actively transported to the site of infection, where during active phagocytosis, large concentrations of erythromycin are released.

Most of erythromycin is metabolised by demethylation in the liver. Its main route elimination route is in the bile, and a small portion in the urine.

Erythromycin's half-life is 1.5 hours.

Side-effects. More serious side-effects, such as reversible deafness are rare. Cholestatic jaundice, Stevens-Johnson syndrome and toxic epidermal necrosis are some other rare side effects that may occur.

Contraindications Earlier case reports on sudden death prompted a study on a large cohort that confirmed a link between erythromycin, ventricular tachycardia and sudden cardiac death in patients also taking drugs that prolong the metabolism of erythromycin (like verapamil or diltiazem)

erythromycin should not be administered in patients using these drugs, or drugs that also prolong the QT time.

Ibuprofen

used to relieve the symptoms of arthritis, primary dysmenorrhoea, fever; and as an analgesic, especially where there is an inflammatory component.

Indications

rheumatoid arthritis, osteoarthritis, juvenile rheumatoid arthritis, primary dysmenorrhoea

fever, relief of acute and/or chronic pain states in which there is an inflammatory component

MOA

inhibition of  cyclooxygenase (COX); thus inhibiting prostaglandin synthesis.

Loperamide

• Similar chemically and pharmacologically to Diphenoxylate.
• Slows gastrointestinal motility by effects on the circular and longitudinal muscles of the intestine.
• Not well absorbed following oral administration.
• Useful in the treatment of diarrhea.

Pharmacodynamics

Pharmacodynamics is the study of what drugs do to the body and how they do it.

Dose-Response Relationships

- Basic Features of the Dose-Response Relationship:  The dose-response relationship is graded instead of all-or-nothing (as dose increases, response becomes progressively larger).

- Maximal Efficacy and Relative Potency

- Maximal Efficacy: the largest effects that a drug can produce

- Relative Potency:  Potency refers to the amount of drug that must be given to elicit an effect.

- Potency is rarely an important characteristic of a drug.

- Potency of a drug implies nothing about its maximal efficacy.