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.

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.

Valproic acid: broad spectrum (for most seizure types)

Mechanism: blocks Ca T currents in thalamic neurons (prevents reverberating activity in absence seizures), ↓ reactivation of Na channels (in tonic/clonic seizures; prolongs refractory periods of neurons, prevents high frequency cell firing)

Side effects: very low toxicity; common = anorexia, N/V; at high doses inhibits platelet function (bruising and gingival bleeding); rarely see idiosyncratic hepatotoxicity

Drug interactions: induces hepatic microsomal enzymes (↓ effectiveness of other drugs), binds tightly to plasma proteins so displaces other drugs

Classification Based on

a. Chemical structure

I. Sulphonamidcs.and others - c.g.. sulphadiazine. etc.

2. Beta-lactum ring - e.g.. penicillin

3. Tetracycline - e.g.. Oxytetracycline,.doxycycline.etc.

b. Mechanism of action

1. Inhibits cell-wall synthesis - penicillin. cephalosporin..cycloserine. etc.

2. Cause leakage from cell-membrane – polypeptides (polymyxin,  Bacitracin), polyenes (Nystatin)

3. Inhibit protein synthesis - tetracyclines. chloramphenicols. erythromycin.

4. Cause mis-reading of mRNA code - aminoglycosides

5. Interfere with DNA function - refampicin.. metronidazole

6. Interfere with intermediary metabolism - sulphonamides. ethambutole

c. Type of organism against which it is primarily activate

I. Antibacterial - penicillin.

2. Antifungal - nystatin.

d. Spectrum of activity

1. Broad spectrum - tetracylines .

2. Narrow spectrum - penicillin G (penG). streptomycin.erythromycin

e. Type of action

I. Bacteriostatic - sulphonamides, erythromycin.tertracyclines

2. Bacteriocidal - penicillin. aminoglycoside

f. Source

I. Fungi - penicillin. cephalosporins

2. Bacteria - Polymyxin B

Second Generation Cephalosporins

Prototype drug is CEFUROXIME (IV) and CEFUROXIME AXETIL (oral). CEFOXITIN has good activity vs. anaerobes.

1. Expanded activity against gram negative bacilli. Still have excellent activity against gram positive (Staph. and Strep.) bacteria.

Activity for Gram negative bacteria

Neisseria sp. (some gonococci resistant)
H. influenzae (including some ampicillin-resistant strains)
Moraxella catarrhalis (some resistance esp. to cefaclor)
E. coli
Proteus mirabilis
Indole + Proteus (some strains resistant)
Morganella morganii (some strains resistant)
Klebsiella pneumoniae
Serratia sp. (many strains resistant)

2. Anaerobic infections - CEFOXITIN & CEFOTETAN only

Moderate activity against Bacteroides fragilis group.

Good activity for other Bacteroides sp., Peptostreptococcus, Fusobacterium, Clostridium sp

Uses
1. Community-acquired pneumonia - Cefuroxime is widely used for empiric therapy. Has activity vs. many ampicillin-resistant H. influenzae strains.
2. Skin and soft tissue infection
3. Urinary tract infections
4. Upper respiratory tract infections (otitis media, sinusitis). Some resistance to H.influenzae to cefaclor (20-30%).
5. Mixed aerobic & anaerobic infections - Cefoxitin & Cefotetan. Resistance to B.fragilis is increasing.
6. Surgical prophylaxis - Cefoxitin or cefotetan are widely used in cases where mixed aerobic & anaerobic infections may occur, esp. intra-abdominal, colorectal, and gynecologic operations. For cardiovascular and orthopedic procedures, cefuroxime and others may be used, but cefazolin is cheaper and appears to work well.

Metabolism

Hepatic Drug-Metabolizing Enzymes:  most drug metabolism in the liverperformed by the hepatic microsomal enzyme system.

Therapeutic Consequences of Drug Metabolism
- Accelerated Renal Drug Excretion:  The most important consequence of drug metabolism is the promotion of renal drug excretion.  Metabolism makes it possible for the kidney to excrete many drugs that it otherwise could not.

- Drug Inactivation
- Increased Therapeutic Action: Metabolism may increase the effectiveness of some drugs.
- Activation of Prodrugs:  A prodrug is a compound that is inactive when administered and made active by conversion in the body.

- Increased or Decreased Toxicity

Factors that influence rate of metabolism:  

- Age:  Hepatic maturation doesn't occur until about a year old.

- Induction of Drug-Metabolizing Enzymes:  Some drugs can cause the rate of metabolism to increase, leading to the need for an increased dosage.  May also influence the rate of metabolism for other drugs taken at the same time, leading to a need for increased dosages of those drugs as well.

- First-Pass Effect:  Hepatic inactivation of certain oral drugs.  Avoided by parentaral administration of drugs that undergo rapid hepatic metabolism.

- Nutritional Status

- Competition between Drugs