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.

Immunosuppressive drugs are essential in managing various medical conditions, particularly in preventing organ transplant rejection and treating autoimmune diseases. They can be classified into five main groups:

1. Glucocorticoids: These are steroid hormones that reduce inflammation and suppress the immune response. They work by inhibiting the production of inflammatory cytokines and reducing the proliferation of immune cells. Common glucocorticoids include prednisone and dexamethasone. Their effects include:

   • Mechanism of Action: Glucocorticoids inhibit the expression of genes coding for pro-inflammatory cytokines (e.g., IL-1, IL-2, TNF-α).

   • Clinical Uses: They are used in conditions like rheumatoid arthritis, lupus, and to prevent transplant rejection.

   • Side Effects: Long-term use can lead to osteoporosis, weight gain, diabetes, and increased risk of infections.

2. Cytostatic Drugs: These agents inhibit cell division and are often used in cancer treatment as well as in autoimmune diseases. They include:

   • Examples: Cyclophosphamide, azathioprine, and methotrexate.

   • Mechanism of Action: They interfere with DNA synthesis and cell proliferation, particularly affecting rapidly dividing cells.

   • Clinical Uses: Effective in treating cancers, systemic lupus erythematosus, and other autoimmune disorders.

   • Side Effects: Can cause bone marrow suppression, leading to increased risk of infections and anemia.

3. Antibodies: This group includes monoclonal and polyclonal antibodies that target specific components of the immune system.

   • Types:

     • Monoclonal Antibodies: Such as basiliximab and daclizumab, which target the IL-2 receptor to prevent T-cell activation.
     • Polyclonal Antibodies: These are derived from multiple B-cell clones and can broadly suppress immune responses.

   • Clinical Uses: Used in organ transplantation and to treat autoimmune diseases.

   • Side Effects: Risk of infections and allergic reactions due to immune suppression.

4. Drugs Acting on Immunophilins: These drugs modulate immune responses by binding to immunophilins, which are proteins that assist in the folding of other proteins.

   • Examples: Cyclosporine and tacrolimus.

   • Mechanism of Action: They inhibit calcineurin, a phosphatase involved in T-cell activation, thereby reducing the production of IL-2.

   • Clinical Uses: Primarily used in organ transplantation to prevent rejection.

   • Side Effects: Nephrotoxicity, hypertension, and increased risk of infections.

5. Other Drugs: This category includes various agents that do not fit neatly into the other classifications but still have immunosuppressive effects.

   • Examples: Mycophenolate mofetil and sirolimus.

   • Mechanism of Action: Mycophenolate inhibits lymphocyte proliferation by blocking purine synthesis, while sirolimus inhibits mTOR, affecting T-cell activation and proliferation.

   • Clinical Uses: Used in transplant patients and in some autoimmune diseases.

   • Side Effects: Gastrointestinal disturbances, increased risk of infections, and potential for malignancies.

Halothane (Fluothane) MAC 0.76%, Blood/gas solubility ratio 2.3
- Nonflammable.
- Any depth of anesthesia can be obtained in the absence of hypoxia.
- Halothane produces a marked hypotensive effect 
- accompanies hypotension.
- Halothane “sensitizes” the ventricular conduction system in the heart to the action of catecholamines. However, ventricular arrhythmias are rare if
- respiratory acidosis, hypoxia and other causes of sympathetic stimulation are avoided.
- Respiration is depressed by all anesthetic concentrations.
- Halothane is metabolized to a significant extent and some of its metabolic produces have been shown to be hepatotoxic.
- Can produce a malignant hyperpyrexia due to an uncontrolled hypermetabolic reaction in skeletal muscle. 

Halothane is generally used with nitrous oxide, an opiate and a neuromuscular blocking drug.

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 

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.

Seizure classification:

based on degree of CNS involvement, involves simple ( Jacksonian; sensory or motor cortex) or complex symptoms (involves temporal lobe)

1.    Generalized (whole brain involved): 

a.    Tonic-clonic:

Grand Mal; ~30% incidence; unconsiousness, tonic contractions (sustained contraction of muscle groups) followed by clonic contractions (alternating contraction/relaxation); happens for ~ 2-3 minutes and people don’t breathe during this time

Drugs: phenytoin, carbamazepine, Phenobarbital, lamotrigine, valproic acid

Status epilepticus: continuous seizures; use diazepam (short duration) or diazepam + phenytoin

b.    Absence:

Petit Mal; common in children; frequent, brief lapses of consciousness with or without clonic motor activity; see spike and wave EEg at 3 Hz (probably relates to thalamocorticoreverburating circuit)

Drugs: ethosuximide, lamotrigine, valproic acid

c.    Myoclonic: uncommon; isolated clinic jerks associated with bursts of EEG spikes; 

Drugs: lamotrigine, valproic acid

d.    Atonic/akinetic: drop seizures; uncommon; sudden, brief loss of postural muscle tone
Drugs: valproic acid and lamotrigine

2.    Partial:  focal

a.    Simple:  Jacksonian; remain conscious; involves motor or sensory seizures (hot, cold, tingling common)

Drugs: carbamazepine, phenytoin, Phenobarbital, lamotrigine, valproic acid, gabapentin

b.    Complex: temporal lobe or psychomotor; produced by abnormal electrical activity in temporal lobe (involves emotional functions)

Symptoms: abnormal psychic, cognitive, and behavioral function; seizures consist of confused/altered behavior with impaired consciousness (may be confused with psychoses like schizophrenia or dementia)

Drugs: carbamazepine, phenytoin, laotrigine, valproic acid, gabapentin

Generalizations: most seizures can’t be cured but can be controlled by regular administration of anticonvulsants (many types require treatment for years to decades); drug treatment can effectively control seizures in ~ 80% of patients