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

Types of Neurons (Function)

•There are 3 general types of neurons (nerve cells): 

1-Sensory (Afferent ) neuron:A neuron that detects changes in the external or internal environment and sends information about these changes to the CNS. (e.g: rods and cones, touch receptors). They usually have long dendrites and relatively short axons. 

2-Motor (Efferent) neuron:A neuron located within the CNS that controls the contraction of    a muscle or the secretion of a gland. They usually have short dendrites and long axons. 

2-Interneuron or association neurons: A neuron located entirely within the CNS in which they form the connecting link between the afferent and efferent neurons. They have short dendrites and may have either a short or long axon.

Prostaglandines:

Every cell in the body is capable of synthesizing one or more types of PGS. The four major group of PGs are E, F, A, and B.

Pharmacological actions:

stimulation of cyclicAMP production and calcium use by various cells

CVS
PGE2 acts as vasodilator; it is more potent hypotensive than Ach and histamine

Uterous
PGE2 and PGF2α Contract human uterus

Bronchial muscle

PGF2α and thromboxan A2 cause bronchial muscle contraction.

PGE2 & PGI2 cause bronchial muscle dilatation

GIT: PGE2 and PGF2α cause colic and watery diarrhoea

Platelets

Thromboxan A2 is potent induce of platelets aggregation

Kidney

PGE2 and PGI2 increase water, Na ion and K ion excretion (act as diuresis) that cause renal vasodilatation and inhibit
tubular reabsorption

USE
PGI2: Epoprostenol (inhibits platelets aggregation)
PGE1: Alprostadil (used to maintain the potency of arterioles in neonates with congenital heart defects).
PGE2: Dinoproste (used as pessaries to induce labor)
Synthetic analogue of PGE1: Misoprostol (inhibit the secretion of HCl).

DOBUTAMINE

It is a derivative of dopamine and has relatively β1 -selective action and it also activates α1 receptors and do not have D1  receptor agonistic property. It increases the force of myocardial contraction and cardiac output without significant change in heart rate, blood pressure and peripheral resistance. It is used as inotropic agent and for short term management of CHF and also in patients who are unresponsive to digitalis.

Immunosuppressive antibodies can be classified mainly into monoclonal and polyclonal antibodies, targeting specific components of the immune system.

1. Monoclonal Antibodies:

   • Basiliximab: Targets the IL-2 receptor on T cells, inhibiting T-cell activation. It is FDA approved for use in renal transplantation to prevent acute rejection.

   • Alemtuzumab: Targets CD52, a protein found on the surface of mature lymphocytes. It is used for treating chronic lymphocytic leukemia and as an induction agent in kidney transplantation.

   • Rituximab: Targets CD20 on B cells, leading to B-cell depletion. It is used in various conditions, including non-Hodgkin lymphoma and rheumatoid arthritis.

   • Daclizumab: Targets the IL-2 receptor (CD25) and is used in renal transplantation to prevent acute rejection.

   • Eculizumab: Targets complement component C5, inhibiting the complement cascade. It is used in conditions like paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome.

2. Polyclonal Antibodies:

   • Rabbit Antithymocyte Globulin (rATG): A polyclonal antibody that targets multiple T-cell surface markers, leading to T-cell depletion. It is used as an induction agent in kidney transplantation and for treating acute rejection.

   • Equine Antithymocyte Globulin (eATG): Similar to rATG, it targets T cells and is used in transplantation settings.

3. Mechanisms of Action:

   • Depletion of Immune Cells: Many antibodies work by depleting specific immune cell populations (e.g., T cells or B cells) to reduce the immune response against transplanted organs or in autoimmune diseases.

   • Blocking Activation Signals: Some antibodies block key receptors involved in T-cell activation, preventing the immune response from being initiated.

   • Inhibition of Complement Activation: Antibodies like eculizumab inhibit the complement system, which can contribute to tissue damage in antibody-mediated rejection.

4. Clinical Applications:

   • Organ Transplantation: Antibodies are commonly used to prevent rejection in kidney, liver, and heart transplants.

   • Autoimmune Diseases: They are also used in treating conditions like rheumatoid arthritis, lupus, and multiple sclerosis.

5. Potential Side Effects:

   • Infections: Due to immune suppression, patients are at increased risk of infections.
   • Allergic Reactions: Some patients may experience allergic reactions to antibody therapies.
   • Infusion Reactions: These can occur during the administration of monoclonal antibodies, leading to symptoms like fever, chills, and hypotension.

Inhalational Anesthetics

The depth of general anesthesia is directly proportional to the partial pressure of the anesthetic agent in the brain. These agents enter the body through the lungs, dissolve in alveolar blood and are transported to the brain and other tissues.

A. Rate of induction and rate of recovery from anesthesia:

1. The more soluble the agent is in blood, the more drug it takes to saturate the blood and the more time it takes to raise the partial pressure and the depth of anesthesia.

2. The less soluble the agent is in blood, the less drug it takes to saturate the blood and the less time it takes to raise the partial pressure and depth of anesthesia.

B. MAC (minimum alveolar concentration)

The MAC is the concentration of the anesthetic agent that represents the ED₅₀ for these agents. It is the alveolar concentration in which 50% of the patients will respond to a surgical incision.

The lower the MAC the more potent the general anesthetic agent.

C. Inhalation Anesthetic Agents 

• Nitrous Oxide
• Ether
• Halothane
• Enflurane
• Isoflurane