First Generation Cephalosporins

Prototype Drugs are CEFAZOLIN (for IV use) and CEPHALEXIN (oral use).

1. Staph. aureus - excellent activity against b-lactamase-producing strains
Not effective against methicillin-resistant Staph. aureus & epidermidis

2. Streptococci - excellent activity versus Streptococcus sp.
Not effective against penicillin-resistant Strep. pneumoniae

3. Other Gm + bacteria - excellent activity except for Enterococcus sp.

4. Moderate activity against gram negative bacteria.

Caution: resistance may occur in all cases.
Susceptible organisms include:

E. coli
Proteus mirabilis
Indole + Proteus sp. (many strains resistant)
Haemophilus influenzae (some strains resistant)
Neisseria sp. (some gonococci resistant)

Uses
1. Upper respiratory tract infections due to Staph. and Strep.
2. Lower respiratory tract infections due to susceptible bacteria e.g. Strep.pneumoniae in penicillin-allergic patient (previous rash)
3. Uncomplicated urinary tract infections (Cephalexin)
4. Surgical prophylaxis for orthopedic and cardiovascular operations (cefazolin preferred because of longer half-life)
5. Staphylococcal infections of skin and skin structure

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.
 

Biguanides

metformin

Mechanism

↓ gluconeogenesis

appears to inhibit complex 1 of respiratory chain

↑ insulin sensitivity
↑ glycolysis
↓ serum glucose levels
↓ postprandial glucose levels

Clinical use

first-line therapy in type II DM

Toxicity

no hypoglycemia
no weight gain
lactic acidosis is most serious side effect 
contraindicated in renal failure 

Enflurane (Ethrane) MAC 1.68, Blood/gas solubility ratio 1.9
- Extremely stable chemically.
- Less potent and less soluble in blood than is halothane.
- Respiratory depression is similar to that seen with halothane.
- Cardiac output is not depressed as much as with halothane, and the heart is not sensitized to catecholamines to the same degree.
- Enflurane produces better muscle relaxation than does halothane.
- Metabolism of this agent is very low. Inorganic fluoride is a product of metabolism, but is not sufficient to cause renal problems.
- Enflurane differs from halothane and the other inhalational anesthetic agents by causing seizures at doses slightly higher than those that induce anesthesia. 
- Nausea appears to occur somewhat more often following Enflurane than it does following halothane.

Stages of anesthesia

Stage I

Analgesia

Still conscious but drowsy

Stage II

Excitement stage

Loss of consciousness, however, irregular ventilation may be present which affects absorption of inhalation agents.

Reflexes may be exaggerated.

This is a very dangerous stage

Stage III

Surgical anesthesia

Loss of spontaneous movement

Regular, shallow respiration

Relaxation of muscles

Stage IV

Medullary paralysis

Death

Hydromorphone

• About 8-10 times more potent than morphine when given intravenously.
• Slightly shorter duration of action.
• More soluble than morphine, thus higher concentrations may be injected if necessary.
• Better oral/parenteral absorption ratio than morphine, but not as good as codeine or oxycodone.

• It is used for the treatment of moderate to severe pain