Properties of inhalation anesthetics

The lower the solubility, the faster the onset and the faster the recoverability.

All general anesthetics:

1. inhibit the brain from responding to sensory stimulation.

2. block the sensory impulses from being recorded in memory.

3. prevent the sensory impulses from evoking “affect”.

Most general anesthetic agents act in part by interacting with the neuronal membranes to affect ion channels and membrane excitability.

· If the concentration given is too low:

1. Movement may occur

2. Reflex activity present (laryngeal spasm)

3. Hypertension

4. Awareness

Premedication of analgesic drugs and muscle relaxants are designed to minimise these effects

· If the concentration given is too high:

1. Myocardial depression

2. Respiratory depression

3. Delayed recovery

Nitrous Oxide (N2O)

MAC 100%, blood/gas solubility ratio 0.47
- An inorganic gas., low solubility in blood, but greater solubility than N2
- Inflammable, but does support combustion.
- Excreted primarily unchanged through the lungs.
- It provides amnesia and analgesia when administered alone.
- Does not produce muscular relaxation.
- Less depressant to both the cardiovascular system and respiratory system than most of the other inhalational anesthetics.
- Lack of potency and tendency to produce anoxia are its primary limitations.
- The major benefit of nitrous oxide is its ability to reduce the amount of the secondary anesthetic agent that is necessary to reach a specified level of anesthesia.

Classification

I) Esters

 1. Formed from an aromatic acid and an amino alcohol.

 2. Examples of ester type local anesthetics:

 Procaine

Chloroprocaine

Tetracaine

Cocaine

Benzocaine- topical applications only

2) Amides

 1. Formed from an aromatic amine and an amino acid.

 2. Examples of amide type local anesthetics:

Articaine

Mepivacaine

Bupivacaine

Prilocaine

Etidocaine

Ropivacaine

Lidocaine

Ethosuximide (Zarontin): use in absence seizures (may exacerbate tonic-clonic seizures)

Mechanism: ↓ T-type Ca currents in thalamic neurons, inhibits bursts of APs, ↓ synchronous neuronal firing
i.    Thalamo-cortical reverberating circuits: during absence type seizures, have reverberating circuits between cerebral cortex and thalamus at 3 Hz maintained by T-type Ca channels (since blocking these channels blocks the reverberating circuit)

Side effects: quite non-toxic; common= N/V and anorexia; less common = headache, sedation, photophobia

Ether (diethylether)

Ether (diethylether) MAC 2.0%, Blood/gas solubility ratio 15
- Ether is generally mixed with 3% ethanol to retard oxidation. Peroxides form on exposure to air and can enhance the danger of an explosion.
- Slow rate of induction and recovery due to its high blood/gas solubility ratio.
- Produces profound muscular relaxation.
- Both the rate and the minute volume of ventilation tend to be elevated during the inhalation of ether.
- Ether maintains good circulatory stability and does not sensitize the heart to the arrhythmogenic action of catecholamines.
- More than 90% of the absorbed ether can be recovered unchanged in the expired air. Metabolism is not extensive and the metabolites are not hepatotoxic.
- Ether is a versatile anesthetic of unexcelled safety, but it is flammable and irritating to breathe. Secretions can be blocked with anticholinergics.

Insulin
Insulin is only given parenterally (subcutaneous or IV) Various preparations have different durations of action 
 

Mechanism

bind transmembrane insulin receptor
activate tyrosine kinase
phosphorylate specific substrates in each tissue type
liver
↑ glycogenesis
store glucose as glycogen
muscle
↑ glycogen and protein synthesis
↑ K+ uptake 
fat
increase triglyceride storage

Clinical use

type I DM
type II DM
life-threatening hyperkalemia
increases intracellular K+
stress-induced hyperglycemia
 

Toxicity
hypoglycemia
hypersensitivity reaction (very rare)

Insulin Synthesis
first generated as preproinsulin with an A chain and B chain connected by a C peptide. 
c-peptide is cleaved from proinsulin after packaging into vesicles leaving behind the A and B chains