Local Anesthetics

1. Procaine (Novocaine)

a) Classic Ester type agent, first synthetic injectable local anesthetic.

 b) Slow onset and short duration of action

 2. Tetracaine (Pontocaine)

a) Ester type agent--ten times as potent and toxic as procaine.

 b) Slow onset but long duration of action.

 c) Available in injectable and topical applications.

 3. Propoxycaine (Ravocaine)

a) Ester type agent–five times as potent and toxic as procaine.

 b) Often combined with procaine to increase duration of action.

 4. Lidocaine (Xylocaine)

a) Versatile widely used amide type agent.

 b) Two - three times as potent and toxic as procaine.

 c) Rapid onset and relatively long duration of action.

 d) Good agent for topical application.

 5. Mepivacaine (Carbocaine)

a) Amide type agent similar to lidocaine.

 b) Without vasoconstrictor has only short duration of action.

6. Prilocaine (Citanest)

a) Amide type agent — less potent than lidocaine.

 b) Without vasoconstrictor has only short duration of action.

 c) Metabolized to o-toluidine which can cause methemoglobinemia — significant only with large doses of prilocaine.

 d) Higher incidences of paresthesia reported with 4 % preparation

7. Bupivacaine (Marcaine)

a) Amide type agent of high potency and toxicity.

 b) Rapid onset and very long duration of action even without vasoconstrictor.

 8. Articaine (Septocaine)

a) Amide type agent

 b) Only amide-type local anesthetic that contains an ester group, therefore metabolized both in the liver and plasma.

 c) Approved by the FDA in 2000

 d) Evidence points to improved diffusion through hard and soft tissues as compared to other local anesthetics.

 e) Reports of a higher incidence of paresthesia, presumably due to the 4% concentration

 f) Not recommended for use in children under 4 years of age

Nimesulide

analgesic and  antipyretic properties

Nimesulide is a relatively COX-2 selective, non-steroidal anti-inflammatory drug (NSAID) with analgesic and antipyretic properties. Its approved indications are the treatment of acute pain, the symptomatic treatment of osteoarthritis and primary dysmenorrhoea in adolescents and adults above 12 years old.

Banned - not used

PSEUDOEPHEDRINE

Pseudoephedrine appears to have less pressor activity and weaker central nervous system effects than ephedrine. It has agonist activity at both β1  and β2 adrenoceptors, leading to increased cardiac output and relaxation of bronchial smooth muscle.

Pseudoephedrine is rapidly absorbed throughout the body. It is eliminated largely unchanged in urine by N-demethylation.

It is indicated in symptomatic relief from stuffed nose, respiratory tract congestion, bronchospasm associated with asthma, bronchitis and other similar disorders.

Factors affecting onset and duration of action of local anesthetics

pH of tissue

pKa of drug

Time of diffusion from needle tip to nerve

Time of diffusion away from nerve

Nerve morphology

Concentration of drug

Lipid solubility of drug

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.

Excretion
Routes of drug excretion
The most important route of drug elimination from the body is via the kidney

Renal Drug Excretion

- Glomerular Filtration

- Passive Tubular Reabsorption: drugs that are lipid soluble undergo passive reabsorption from the tubule back into the blood.

- Active Tubular Secretion

Factors that Modify Renal Drug Excretion

- pH Dependent Ionization:  manipulating urinary pH to promote the ionization of a drug can decrease passive reabsorption and hasten excretion.

- Competition for Active Tubular Transport

- Age:  Infants have a limited capscity to excrete drugs.

Nonrenal Routes of Drug Excretion
Breast Milk
Bile, Lungs, Sweat and Saliva

The kidney is the major organ of excretion. The lungs become very important for volatile substances or volatile metabolites.

Drugs which are eliminated by the kidney are eliminated by:

a) Filtration - no drug is reabsorbed or secreted.

b) Filtration and some of the drug is reabsorbed.

c) Filtration and some secretion.

d) Secretion

By use of the technique of clearance studies, one can determine the process by which the  kidney handles the drug.

Renal plasma clearance = U x V ml/min U  / Cp = conc. of drug in urine

Cp = conc. of drug in plasma

V = urine flow in ml/min

Renal clearance ratio = renal plasma clearance of drug (ml/min) / GFR (ml/min)

Total Body Clearance = renal + non-renal