Phenytoin, Carbamazepine, and Valproate act by inhibiting the sodium channels when these are open. These drugs also prolong the inactivated stage of these channels (Sodium channels are refractory to stimulation till these reach the closed/ resting phase from inactivated phase)

Carbamazepine is the drug of choice for partial seizures and trigeminal neuralgia

It can have neurotoxic side effects. Major neurotoxic effects include dizziness, headache, ataxia, vertigo, and diplopia

The half-life of carbamazepine is about 13-17 years.

It is metabolized in liver into active metabolite, carbamazepine-10,11-epoxide.

Midazolam is the benzodiazepine in question. It’s the only benzodiazepine that undergoes tautomeric transformation (dynamic isomerism). The molecule is ionised and water soluble at pH 3.5, but when injected into the body at pH 7.4, it becomes unionised and lipid soluble, allowing it to easily pass through the blood brain barrier.

The half-life of midazolam is only 2-4 hours.

It is a GABAA receptor agonist because it is a benzodiazepine. GABAA receptors are found in abundance throughout the central nervous system, particularly in the cerebral cortex, hippocampus, thalamus, basal ganglia, and limbic system. GABAA receptors are ligand-gated ion channels, with the inhibitory neurotransmitter gamma-aminobutyric acid as the endogenous agonist. It is a pentameric protein (2, 2 and one subunit) that spans the cell membrane, and when the agonist interacts with the alpha subunit, a conformational change occurs, allowing chloride ions to enter the cell, resulting in neuronal hyperpolarization.

For status epilepticus, midazolam is not the drug of choice. Lorazepam is the benzodiazepine of choice for status epilepticus.

Adrenaline acts on α1, α2, β1, and β2 receptors and also on dopamine receptors (D1, D2) and have sympathomimetic effects.

Natural catecholamines are Adrenaline, Noradrenaline, and Dopamine

Adrenaline is a sympathomimetic amine with both alpha and beta-adrenergic stimulating properties.
Adrenaline is the drug of choice for anaphylactic shock
Adrenaline is also used in patients with cardiac arrest. The preferred route is i.v. followed by the intra-osseous and endotracheal route.

Adrenaline is released by the adrenal glands, acts on α 1 and 2, β 1 and 2 receptors, and is responsible for fight or flight response.

It acts on β 2 receptors in skeletal muscle vessels-causing vasodilation.

It acts on α adrenergic receptors to inhibit insulin secretion by the pancreas. It also stimulates glycogenolysis in the liver and muscle, stimulates glycolysis in muscle.

It acts on β adrenergic receptors to stimulate glucagon secretion in the pancreas. It also stimulates Adrenocorticotrophic Hormone (ACTH) and stimulates lipolysis by adipose tissue

Dystonia is characterised by repetitive twisting movements or abnormal postures. They are classified as either primary or secondary.

Primary dystonia is a genetic disorder that is inherited in an autosomal dominant pattern.
Secondary dystonia can be caused by focal brain lesions, Parkinson’s disease, or certain medications.

The following drugs cause the most common drug-induced dystonic reactions:
Antipsychotics, antiemetics (especially prochlorperazine and metoclopramide), and antidepressants.

Following the administration of the neuroleptic prochlorperazine, 16 percent of patients experience restlessness (akathisia) and 4% experience dystonia.

Several published reports have linked the anaesthetics thiopentone, fentanyl, and propofol to opisthotonos and other abnormal neurologic sequelae. Dystonias following a general anaesthetic are uncommon. Tramadol has been linked to serotonin syndrome, while remifentanil has been linked to muscle rigidity.

The following are some of the risk factors:

Positive family history
Male
Children
An episode of acute dystonia occurred previously.
Dopamine receptor (D2) antagonists at high doses and recent cocaine use

Dystonia is treated in a variety of ways, including:

Benztropine (as a first-line therapy):

1-2 mg intravenous injection for adults
Child: 0.02 mg/kg to 1 mg maximum

Benzodiazepines are a type of benzodiazepine (second line treatment).

Midazolam:

1-2 mg intravenously, or 5-10 mg IV/PO diazepam

Antihistamines with anticholinergic activity (H1receptor antagonists):

Promethazine 25-50 mg IV/IM, or diphenhydramine 50 mg IV/IM (1 mg/kg in children) are used when benztropine is not available.

Mivacurium is metabolised primarily by plasma cholinesterase at an In vitro rate of about 70% that of succinylcholine. Mivacurium is contraindicated in patients with genetic and acquired plasma cholinesterase deficiencies.

The clearance of atracurium is by Hoffman degradation and ester hydrolysis in the plasma and is independent of both hepatic and renal function.

Rocuronium is eliminated primarily by the liver after metabolises to a less active metabolite, 17-desacetyl-rocuronium. Its duration of action is not affected much by renal impairment.

Vecuronium undergoes hepatic metabolism into 3-desacetyl-vecuronium which has 50-80% the activity of the parent drug. It undergoes biliary (40%) and renal excretion (30%). The aminoglycoside antibiotics possess additional neuromuscular blocking activity. The potency of gentamicin > streptomycin > amikacin. Calcium can be used to reverse the muscle weakness produced by gentamicin but not neostigmine. When vecuronium and gentamycin are given together the effect on neuromuscular blockade is synergistic.

Significant residual neuromuscular block 2 hours after the administration of these drugs is unlikely In this scenario.

Any recovery from neuromuscular blockade with suxamethonium in a patient with deficiency of plasma cholinesterase demonstrate four twitches on a train of four count.

The following are the pharmacokinetic properties of drugs with a low hepatic extraction ratio:

Changes in liver blood flow have no effect on drug clearance.
When given orally, drug clearance is extremely sensitive to changes in protein binding, intrinsic metabolism, and excretion, and there is no first-pass metabolism.

Warfarin and phenytoin are two drugs with low hepatic extraction ratios.

The following are the pharmacokinetic properties of drugs with a high hepatic extraction ratio:

When taken orally, undergo extensive first-pass metabolism; drug clearance is dependent on liver blood flow, and drug clearance is less sensitive to changes in protein binding and intrinsic metabolism.

Morphine, lidocaine, propranolol, and etomidate are examples of drugs with high hepatic extraction ratios.

Gentamicin is a broad-spectrum antibiotic whose mechanism of action involves inhibition of protein synthesis by binding to 30s ribosomes. Its major adverse effect is nephrotoxicity and ototoxicity

Aminoglycoside bind to 30s subunit of ribosome causing misreading of mRNA

Tetracyclines inhibit protein synthesis through reversible binding to bacterial 30s ribosomal subunits, which prevent binding of new incoming amino acids (aminoacyl-tRNA) and thus interfere with peptide growth.

Chloramphenicol binds to the 50s subunit and inhibits peptidyl transferase

Clindamycin binds to the 50s ribosomal subunit of bacteria and disrupts protein synthesis by interfering with the transpeptidation reaction, which thereby inhibits early chain elongation.

Propofol is a short-acting medication used for starting and maintenance of general anaesthesia, sedation for mechanically ventilated adults, and procedural sedation.
The dose of propofol is 1-2 mg/kg.

Dose of some other important drugs are listed below:
Thiopental dose: 3-7 mg/kg
Ketamine dose: 1-2 mg/kg
Etomidate dose: 0.3 mg/kg
Methohexitone dose: 1.0-1.5 mg/kg

Resistance pulmonary arteries constrict in response to alveolar and airway hypoxia, diverting blood to better-oxygenated alveoli.

In atelectasis, pneumonia, asthma, and adult respiratory distress syndrome, hypoxic pulmonary vasoconstriction optimises O2 uptake. Hypoxic pulmonary vasoconstriction helps maintain systemic oxygenation during single-lung anaesthesia.

A redox-based O2 sensor within pulmonary artery smooth muscle cells is involved in hypoxic pulmonary vasoconstriction. The production of reactive oxygen species by smooth muscle cells in the pulmonary artery varies in proportion to PaO2. Hypoxic removal of these redox second messengers inhibits voltage-gated potassium channels, depolarizing smooth muscle cells in the pulmonary artery.

L-type calcium channels are activated by depolarization, which raises cytosolic calcium and causes hypoxic pulmonary vasoconstriction. Some anaesthetics suppress this response, increasing the risk of further deterioration in ventilation perfusion mismatch.

Agents that inhibit HPV are ether, halothane, and desflurane (>1.6 MAC).
Agents with no effect on HPV include thiopentone, fentanyl, desflurane (1MAC), isoflurane (<1.5MAC), sevoflurane(1MAC), and propofol.

The neuromuscular blocking agent is likely to be filtered and not reabsorbed by the renal tubules due to an exclusion process.

Neuromuscular blocking agents that contain one or more quaternary nitrogen atoms are polar and ionised. As a result, the molecules have low lipid solubility, low membrane diffusion capacity, and low distribution volume.

It’s unlikely that a compound with three quaternary nitrogen atoms is an ester. Its high polarity would prevent molecules from moving quickly into tissues.

When drugs have a low hepatic extraction ratio (0.3), the venous and arterial drug concentrations are nearly identical. The liver is not the primary site of drug metabolism.

Therefore:

Changes in liver blood flow have no effect on clearance.
Protein binding, intrinsic metabolism, and excretion are all very sensitive to changes in clearance.
When taken orally, there is no first-pass metabolism.

There is no reason for the lungs to eliminate any neuromuscular blocking agent.