The pH at which the drug exists in 50 percent ionised and 50 percent unionised forms is known as the pKa.

To calculate the proportion of ionised to unionised form of an ACID, use the Henderson-Hasselbalch equation.

pH = pKa + log ([A-]/[HA])

or

pH = pKa + log [(salt)/(acid)]
pH = pKa + log ([ionised]/[unionised]).

Hence, if the pKa − pH = 0, then 50% of drug is ionised and 50% is unionised.

In this example:

7.4 = 4.3 + log ([ionised]/[unionised])
7.4 − 4.3 = log ([ionised]/[unionised])
log 3.1 = log ([ionised]/[unionised])

Simply put, the antilog is the inverse log calculation. In other words, if you know the logarithm of a number, you can use the antilog to find the value of the number. The antilogarithm’s definition is as follows:

y = antilog x = 10x

Antilog to the base 10 of 0 = 1, 1 = 10, 2 =100, 3 = 1000, and 4 = 10,000.

If you want to find the antilogarithm of 3.1, for a number between 3 and 4, the antilogarithm will return a value between 1000 and 10,000. The ratio is 1:1 if pKa = pH, that is, pH pKa = log 0. (50 percent ionised and unionised).

According to the above value, there is only one unionised molecule for every approximately 1000 (1259) ionised molecules of this drug in plasma, implying that this drug is largely ionised in plasma (99.99 percent ).

Carbon dioxide absorbs the most infrared (IR) light between the wavelengths of 4.2-4.4m (4.26m is ideal).

Nitrous oxide absorbs infrared light at wavelengths of 4.4-4.6m (very similar to CO2) and less so at 3.9m.

At a frequency of 4.7m, carbon monoxide absorbs the most IR light.

At 3.3 m and throughout the ranges 8-12 m, the volatile agents have strong absorption bands.

Although oxygen does not absorb infrared light, it collides with CO2 molecules, interfering with absorption. The absorption band is widened as a result of this (so called collision or pressure broadening). A drop of 0.5 percent in measured CO2 can be caused by 95% oxygen.

Nitrous oxide causes a greater inaccuracy of 0.1 percent per ten percent of nitrous oxide.

Water vapour absorbs infrared light as well, resulting in absorption band overlap, collision broadening, and partial pressure dilution. Water traps and water permeable tubing are used to reduce inaccuracies.

Collision broadening is compensated for in modern gas multi-gas analysers.

The usual method of calculating the dose of a drug to be given to patients of normal weight is to use total body weight (TBW). This is because the lean body weight (LBW) and ideal body weight (IBW) dosing scalars are similar in these patients.

Because the LBW and fat mass do not increase in proportion in patients with morbid obesity, this is not the case. Drugs that are lipid soluble, such as propofol or thiopentone, can cause a relative overdose. Lean body mass is a better scalar in these situations.

Suxamethonium has a small volume of distribution, so the dose is best calculated using the TBW to ensure optimal and deep intubating conditions. The higher dose was justified because these patients’ plasma cholinesterase activity was elevated.

Other scalars include:

The dose of highly lipid soluble drugs like benzodiazepines, thiopentone, and propofol can be calculated using lean body weight (LBW). The formula LBW = IBW + 20% can be used on occasion.

Fentanyl, rocuronium, atracurium, vecuronium, morphine, paracetamol, bupivacaine, and lidocaine are all administered with LBW.

Formulas can be used to calculate the ideal body weight (IBW). There are a number of drawbacks, including the fact that patients of the same height receive the same dose, and the formulae do not account for changes in body composition associated with obesity. Because IBW is typically lower than LBW, administering a drug based on IBW may result in underdosing. The body mass index (BMI) isn’t used to calculate drug dosage directly.

Calcium channel blocker (CCB) blocks L-type of voltage-gated calcium channels present in blood vessels and the heart. By inhibiting the calcium channels, these agents decrease the frequency of opening of calcium channels activity of the heart, decrease heart rate, AV conduction, and contractility.

Three groups of CCBs include
1) Phenylalkylamines: Verapamil, Norverapamil
2) Benzothiazepines : Diltiazem
3) Dihydropyridine : Nifedipine, Nicardipine, Nimodipine, Nislodipine, Nitrendipine, Isradipine, Lacidipine, Felodipine and Amlodipine.

Even though verapamil as good absorption from GIT, its oral bioavailability is low due to high first-pass metabolism.

Nimodipine is a Cerebro-selective CCB, used to reverse the compensatory vasoconstriction after sub-arachnoid haemorrhage and is more lipid soluble analogue of nifedipine

Calcium channel antagonist can potentiate the effect of non-depolarising muscle relaxants.

The neuroleptic malignant syndrome is a rare complication in response to neuroleptic or antipsychotic medication.

The main features are:
– Elevated creatinine kinase
– Hyperthermia and tachycardia
– Altered mental state
– Increased white cell count
– Insidious onset over 1-3 days
– Extrapyramidal dysfunction (muscle rigidity, tremor, dystonia)
– Autonomic dysfunction (Labile blood pressure, sweating, salivation, urinary incontinence)

Management is supportive ICU care, anticholinergic drugs, increasing dopaminergic activity with Amantadine, L-dopa, and dantrolene, and non- depolarising neuromuscular blockade drugs

Phase I and phase II metabolism are used by the liver to break down paracetamol.

1st Phase:

Prostaglandin synthetase and cytochrome P450 (CYP1A2, CYP2E2, CYP3A4 and CYP2D6) to N-acetyl-p-benzoquinoneimine (NAPQI) and N-acetylbenzo-semiquinoneimine. NAPQI is a toxic metabolite that binds to the sulfhydryl groups of cellular proteins in hepatocytes, making it toxic. This can result in centrilobular necrosis.

Glutathione and glutathione transferases prevent NAPQI from binding to hepatocytes at low paracetamol doses by preferentially binding to these toxic metabolites. The cysteine and mercapturic acid conjugates are then excreted in the urine. Depletion of glutathione occurs at higher doses of paracetamol, resulting in high levels of NAPQI and the risk of hepatocellular damage. Hepatotoxicity would not be an issue if the body’s glutathione stores were sufficient.

N-acetylcysteine is a precursor for glutathione synthesis and is the drug of choice for the treatment of paracetamol overdose.

Phase II:

Conjugation with glucuronic acid to paracetamol glucuronide is the most common method of metabolism and excretion, accounting for 60% of renally excreted metabolites. Paracetamol sulphate (35%), unchanged paracetamol (5%), and mercapturic acid are among the other renally excreted metabolites (3 percent ). The capacity of conjugation pathways is limited. The capacity of the sulphate conjugation pathway is lower than that of the glucuronidation pathway.

Because of the low pH in the stomach, paracetamol absorption is minimal (pKa value is 9.5). Paracetamol is absorbed quickly and completely in the alkaline environment of the small intestine. Oral bioavailability is extremely high, approaching 100%.

As a result, measuring paracetamol levels in plasma after an injury is important. Peak plasma concentrations are reached after 30-60 minutes, with a volume of distribution of 0.95 L/kg. It binds to plasma proteins at a rate of 10% to 25%.

When the loading dose of Digoxin is given, the primary thing to consider is the volume of distribution. The volume of distribution is the proportionality factor that relates the total amount of drug in the body to the concentration. LD is computed as:

LD = Volume of distribution X (desired plasma concentration/bioavailability)

Digoxin is an anti-arrhythmic drug with a large volume of distribution and high bioavailability, and only a small percentage of Digoxin is bound to plasma proteins (,20%).

In the case, since the arrhythmia is not life-threatening, there is no need for the medication to work rapidly.

Anticholinergic agents are a group of drugs that blocks the action of the neurotransmitter called acetylcholine at synapses in the central and peripheral nervous system.

Hyoscine, atropine, and glycopyrrolate are anticholinergic which acts at muscarinic receptors with little activity at the nicotinic receptors.

Hyoscine and atropine are naturally occurring esters. Since Glycopyrrolate is a synthetic quaternary amine, it does not cross the blood brain barrier. Noteworthy, hyoscine, butylbromide also does not cross the blood brain barrier significantly.

Therapy with gabapentin requires dose adjustment with renal diseases. However, plasma monitoring of the drug is not necessary.

Gabapentin is not a liver enzyme inducer unlike other anticonvulsants like phenytoin and phenobarbitone

Gabapentin has not been shown to be associated with visual disturbances.

Gabapentin is used for add-on therapy in partial or generalized seizures and used in the management of chronic pain conditions but is of no use in petit mal.

Accumulation of morphine-6-glucuronide is a risk factor for opioid toxicity during morphine treatment. Morphine is metabolized in the liver to morphine-6-glucuronide and morphine-3-glucuronide, both of which are excreted by the kidneys. In the setting of renal failure, these metabolites can accumulate, resulting in a lowering of the seizure threshold. However, it does not occur in all patients with renal insufficiency, which is the most common reason for accumulation of morphine-6-glucuronide; this suggests that other risk factors can contribute to morphine-6-glucuronide toxicity.

The active metabolites of codeine are morphine and the morphine metabolite morphine-6-glucuronide. The enzyme systems responsible for this metabolism are: CYP2D for codeine and UGT2B7 for morphine, codeine-6-gluronide, and morphine-6-glucuronide. Both of these systems are subject to genetic variation. Some patients are ultrarapid metabolizers of codeine and produce higher levels of morphine and active metabolites in a very short period of time after administration. These increased levels will produce increased side effects, especially drowsiness and central nervous system depression.