Patients who have sustained thermal injuries are at high risk of becoming hypercatabolic with larger cardiac outputs and oxygen consumptions.

The hypermetabolic states increase with an increase in the burn severity and surface area of the skin affected. A patient with thermal injuries affecting 60% of the total surface area of the body will have twice the normal metabolic rate.

The optimal temperature for nursing patients with burn injuries is 30°C to conserve the energy usage. The areas affected by the burn injuries should be covered to reduce loss of fluid via evaporation. Resetting hypothalamic thermoregulation will cause a 1-2°C increase in core temperature.

Burn injuries will have an immediate effect on the intestine, destroying the barrier function and allowing for the movement of bacteria and endotoxins within hours.

Enteral nutrition allows for the delivery of nutrients directly to the stomach or intestine. It has correlation with a dampened hypermetabolic response to a thermal and injury, especially when initiated early as it helps to protect the integrity of the mucosal lining and prevents the movement of bacteria into circulation.

Diet changes have been linked to reduced mortality due to burn injuries. Diets high in protein especially (calorie: nitrogen ratio of 100: 1), have the highest correlation with improved survival rates.

Parenteral feeds may be required alongside enteral nutrition, even with the increased risks of infection.

The right coronary artery supplies the right ventricle, the right atrium, the sinoatrial (SA) node and the atrioventricular (AV) node.

The circumflex artery originates from the left coronary artery and is supplied by it.

The most common cause of hypoparathyroidism is injury or removing the parathyroid glands. They can be injured accidentally during surgery to remove the thyroid as they are located posterior to the thyroid gland.

A result of both low parathyroid hormone and low calcium is likely to mean that the parathyroid glands are not responding to hypocalcaemia. The hypocalcaemia can cause confusion, and the stay in the hospital is likely to refer to her surgery.

While a parathyroid adenoma is fairly common and can cause hypoparathyroidism, it much more likely causes hyperparathyroidism.

Chronic kidney disease is likely to cause hypocalcaemia, which would increase parathyroid hormone production in an attempt to increase calcium levels, causing hyperparathyroidism. Vitamin D is activated by the kidneys and then binds to calcium to be absorbed in the terminal ileum so that a deficiency would cause hyperparathyroidism.

Warfarin prevents reductive metabolism of the inactive vitamin K epoxide back to its active hydroquinone form. Thus, warfarin inhibits the synthesis of vitamin K dependent clotting factors: X, IX, VII, II (prothrombin), and of the anticoagulants protein C and protein S. The therapeutic range for oral anticoagulant therapy is defined in terms of an international normalized ratio (INR). The INR is the prothrombin time ratio (patient prothrombin time/mean of normal prothrombin time for lab)ISI, where the ISI exponent refers to the International Sensitivity Index and is dependent on the specific reagents and instruments used for the determination. A prolonged INR is widely used as an indication of integrity of the coagulation system in liver disease and other disorders, it has been validated only in patients in steady state on chronic warfarin therapy.

Prothrombin complex concentrate (PCC) is used to replace congenital or acquired vitamin-K deficiency warfarin-induced anticoagulant effect, particularly in the emergent setting.

Intravenous vitamin K has a slower onset of action compared to PCC, but is useful for long term therapy.

Fresh frozen plasma (FFP) prepared from freshly donated blood is the usual source of the vitamin K-dependent factors and is the only source of factor V. The factors needed, however, are found in small quantities compared to PCC.

Cryoprecipitate is indicated for hypofibrinogenemia/dysfibrinogenemia, von Willebrand disease, haemophilia A, factor XIII deficiency, and management of bleeding related to thrombolytic therapy.

Cardiopulmonary exercise testing (CPX, CPEX, CPET) is a non-invasive testing method used to determine the performance of the heart, lungs and skeletal muscle. It measures the exercise tolerance of the patient.

The parameters measured include:

ECG and ST-segment analysis and blood pressure
Oxygen consumption (VO2)
Carbon dioxide production (VCO2)
Gas flows and volumes
Respiratory exchange ratio (RER)
Respiratory rate
Anaerobic threshold (AT)

The anaerobic threshold (AT) is an estimate of exercise ability. Any measurement below 11 ml/kg/min is usually related with an increase in mortality, especially when there is a background of myocardial ischaemia occurring during the test.

Peak VO2 <20 mL/kg with a low AT have a correlation with postoperative complications and a 30 day mortality. The CPX test is used for risk-testing patients prior to surgery to determine the appropriate postoperative care facilities. The V slope measured in CPX testing represents VO2 versus VCO2 relationship. During AT, the ramp of V slope increases, but does not provide a picture of postoperative mortality.

Direct laryngoscopy are performed using laryngoscopes and they can be classed according to the shape of the blade as curved or straight.

Miller, Soper, Wisconsin and Seward are examples of straight blade laryngoscopes. Straight blades are commonly used for intubating neonates and infants but can be used in adults too.

The tip of the miller blade is advanced over the epiglottis to the tracheal entrance then lifted in order to view the vocal cords.

The RIGHT-SIDED Macintosh blade is used in adults while the left-sided blade may be used in conditions that make intubation with standard blade difficult e.g. facial deformities.

The McCoy laryngoscope is based on the STANDARD MACINTOSH blade not Robertshaw’s. It has a lever operated hinged tip, which improves the view during laryngoscopy.

Polio blade is mounted at an angle of 120-135 degrees to the handle. Originally designed for use during the polio epidemic ​in intubation patients within iron lung ventilators, it is now useful in patients with conditions like breast hypertrophy, barrel chest, and restricted neck mobility.

The correct answer is the clotting cascade, which occurs via a positive feedback mechanism. As clotting factors are attracted to a site, their presence attracts further clotting factors. This continues until a functioning clot is formed.

This patient has presented with symptoms of hypothyroidism and symptoms include weight gain, lethargy, cold intolerance, dry skin, coarse hair and constipation. It can be treated by replacing the missing thyroid hormone with levothyroxine which is a synthetic version of thyroxine (T4).

Serum carbon dioxide (CO2) is controlled via a negative feedback mechanism as well. Chemoreceptors can detect when the serum CO2 is high, and send an impulse to the respiratory centre of the brain to increase the respiratory rate. As a result, more CO2 is exhaled which lowers the serum concentration.

Cortisol is also released according to a negative feedback mechanism. Cortisol acts on both the hypothalamus and the anterior pituitary. Its action serve to decrease the formation of corticotrophin releasing hormone (CRH) and adrenocorticotropic hormone (ACTH), respectively. CRH acts on the anterior pituitary to release ACTH. This then acts on the adrenal gland to cause the release of cortisol. Thus, inhibition of CRH and ACTH formation results in high levels of cortisol which inhibit its further release.

Blood pressure (BP) is controlled via a negative feedback mechanism. Low BP results in renin-angiotensin-aldosterone system (RAAS) activation. This leads to vasoconstriction and retention of salt and water which increased BP.
Blood sugar is controlled via a negative feedback mechanism. A rise in blood sugar causes insulin to be released. Insulin acts to transport glucose into the cell which lowers blood sugar.

When drugs are bound to proteins, drugs cannot cross membranes and exert their effect. Only the free (unbound) drug can be absorbed, distributed, metabolized, excreted and exert pharmacologic effect. Thus, when amide local anaesthetics are bound to ?1-glycoproteins, their duration of action are reduced.

The potency of local anaesthetics are affected by lipid solubility. Solubility influences the concentration of the drug in the extracellular fluid surrounding blood vessels. The brain, which is high in lipid content, will dissolve high concentration of lipid soluble drugs. When drugs are non-ionized and non-polarized, they are more lipid-soluble and undergo more extensive distribution. Hence allowing these drugs to penetrate the membrane of the target cells and exert their effect.

Tissue pKa and pH will determine the degree of ionization.

Krebs’ cycle (tricarboxylic acid cycle or citric acid cycle) is a sequence of reactions to release stored energy through oxidation of acetyl coenzyme A (acetyl-CoA). Some of the products are carbon dioxide and hydrogen atoms.

The sequence of reactions, known collectively as oxidative phosphorylation, only occurs in the mitochondria (not cytoplasm).

The Krebs cycle can only take place when oxygen is present, though it does not require oxygen directly, because it relies on the by-products from the electron transport chain, which requires oxygen. It is therefore considered an aerobic process. It is the common pathway for the oxidation of carbohydrate, fat and some amino acids, required for the formation of adenosine triphosphate (ATP).

Pyruvate enters the mitochondria and is converted into acetyl-CoA. Acetyl-CoA is then condensed with oxaloacetate, to form citrate which is a six carbon molecule. Citrate is subsequently converted into isocitrate, alpha-ketoglutarate, succinyl-CoA, succinate, fumarate, malate and finally oxaloacetate.

The only five carbon molecule in the cycle is Alpha-ketoglutarate.

The surface marking for locating the femoral artery is the mid-inguinal point, which is the halfway point between the anterior superior iliac spine (ASIS) and the pubic symphysis.

The other mentioned options are not specific for any landmark.

However, it is important to note the difference between the mid inguinal point and the midpoint of the inguinal ligament, which is travels from the ASIS to the pubic tubercle.

Marsh (adult) model, when used with children caused over-estimation of plasma concentration. To address this issue Kataria et al developed a three-compartmental model for propofol in children. The pharmacokinetic models used by Target controlled infusion (TCI) systems are used to calculate the relative sizes of the central (vascular), vessel-rich peripheral, and vessel-poor peripheral compartments. The relative volumes of these compartments are different in young children when compared to adults.

Kataria, therefore, is the correct option as described above.

The Maitre model is a three-compartmental model for alfentanil TCI.

The Marsh model describes a propofol TCI model for adults

The Minto model applies to TCI remifentanil.

The Schnider model is also an adult model for propofol that incorporates age and lean body mass as covariates.

This patient is morbidly obese and has a high risk of developing hypoxia. This will be exacerbated by the patient’s supine position, as a result of:

Functional residual capacity has been reduced (FRC)
Increased closing capacity (CC)
Reduced tidal volume due to increased airway resistance, decreased thoracic cage compliance, and decreased respiratory muscle strength and endurance
Following induction of general anaesthesia, there is a tendency for atelectasis and increased O2 consumption due to the increased workload of respiratory muscles and the overall increase in metabolism.

Pre-oxygenation with 100 percent oxygen via a tight-fitting mask can be done using either tidal volume breaths for three to five minutes or four vital capacity breaths in normal circumstances. In the head-up position, this patient is much more likely to be adequately pre-oxygenated, maximising the FRC and minimising the CC. In spontaneously breathing patients, the Mapleson A and circle systems are both effective, but the Mapleson D requires 160-200 ml/kg/minute to prevent rebreathing.

Arrhythmias and/or hypotension are the most common causes of death from tricyclic antidepressant (TCA) overdose.

The quinidine-like actions of tricyclic antidepressants on cardiac tissues are primarily responsible for their toxicity. Conduction through the His-Purkinje system and the myocardium slows as phase 0 depolarisation of the action potential slows. QRS prolongation and atrioventricular block are caused by slowed impulse conduction, which also contributes to ventricular arrhythmias and hypotension.

Arrhythmias can also be caused by abnormal repolarization, impaired automaticity, cholinergic blockade, and inhibition of neuronal catecholamine uptake, among other things.

Acidaemia, hypotension, and hyperthermia can all exacerbate toxicity.

The anticholinergic effects of tricyclic antidepressants, as well as the blockade of neuronal catecholamine reuptake, cause sinus tachycardia. Sinus tachycardia is usually well tolerated and does not require treatment. It can be difficult to tell the difference between sinus tachycardia and ventricular tachycardia with QRS prolongation.

A QRS duration of more than 100 milliseconds indicates a higher risk of arrhythmia and should be treated with systemic sodium bicarbonate.

The tricyclic is dissociated from myocardial sodium channels by serum alkalinization, and the extracellular sodium load improves sodium channel function.

The upper five cervical segments of the spinal cord give rise to the XI cranial nerve. They connect with a few smaller branches before exiting the skull through the jugular foramen. The sternomastoid and trapezius muscles get their motor supply from the accessory root. Except for the palatoglossus, the hypoglossal nerve supplies motor supply to all tongue muscles.

The inability to shrug the shoulder on the affected side and rotate the head to the side against resistance is caused by damage to the spinal accessory nerve. This is due to the trapezius and sternomastoid muscles’ weakness.

The hypoglossal nerve is damaged, resulting in tongue wasting and inability to move from side to side.

The stylopharyngeus receives motor supply from the glossopharyngeal nerve. It also carries taste sensory fibres from the back third of the tongue, as well as the carotid sinus, carotid body, pharynx, and middle ear.

Motor supply to the larynx, pharynx, and palate; parasympathetic innervation to the heart, lung, and gut; and sensory fibres from the epiglottis and valleculae are all provided by the vagus nerve.

The descending thoracic aorta begins at the lower border of T4 near the midline as a continuation of the arch of the aorta. It descends and ends at the level of T12 at the aortic hiatus in the diaphragm, where it becomes the abdominal aorta.

The aorta gives off the following branches: (descending order)

1. Bronchial arteries
2. Mediastinal arteries
3. Oesophageal arteries
4. Pericardial arteries
5. Superior phrenic arteries

The posterior intercostal arteries are branches that originate throughout the length of the posterior aspect of the descending thoracic aorta.

The inferior thyroid artery is usually derived from the thyrocervical trunk, a branch of the subclavian artery.

Her symptoms are suggestive of trigeminal neuralgia which is a short, sudden, severe sharp unilateral pain in the facial region. The pain often follows the sensory distribution of the trigeminal nerve (CN V).

The trigeminal nerve gives rise to 3 sensory and 1 motor nuclei. Neuralgia can arise from any of the 3 sensory divisions.

The ophthalmic division gives rise to 3 further sensory branches, which are the frontal, lacrimal and nasociliary.

The frontal branch of the ophthalmic division of the trigeminal nerve is responsible for the innervation of the area in question.

The superior alveolar dental, zygomatic and sphenopalatine nerves are all branches arising from the maxillary division of the trigeminal nerve.

The mandibular division of the trigeminal nerve provides sensory and motor innervation. The sensory innervation is carried out by the auriculotemporal nerve which supplies the lower third of the face, while the motor fibres are responsible for controlling the muscles of mastication.

The somatic sensory branches of the vagus nerve are responsible for sensory innervation of the external acoustic meatus and tympanic membrane.

A major source of caloric expenditure and oxygen consumption in the body is work of breathing (WOB) and 70% of this is to overcome elastic forces. The remaining 30% is for flow-resistive work

In a normal patient breathing normally, the total area of hysteresis pressure volume curve represents the flow-resistive WOB.

The area of the expiratory resistive work increases during an asthma attack making the compliance curve larger in area. The larger the area the greater the work required to breathe.

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.

Venous cutdown is a surgical procedure when venous access is difficult, and other procedures like the Seldinger technique, ultrasound-guided venous access, and intraosseous vascular access have failed.

The vein of choice for venous cutdown is the long/great saphenous vein. It is part of the superficial venous collecting system of the lower extremity. It is the preferred vein as the long saphenous vein has anatomic consistency and is superficially located at the ankle anterior to the medial malleolus. It is also the most commonly used conduit for cardiovascular bypass operations.

Origin- in the foot at the confluence of the dorsal vein of the first digit and the dorsal venous arch of the foot
Route- runs ANTERIOR to the medial malleolus and travels up in the medial leg and upper thigh.
Termination: in the femoral vein within the femoral triangle

Regarding the other options:
The short saphenous vein passes posterior to the lateral malleolus.
The dorsalis pedis vein accompanies the dorsalis pedis artery on the anterior foot.
The posterior tibial vein is part of the deep venous system accompanying the posterior tibial artery. There is no significant sural vein (there is a sural nerve), but the sural veins accompany the sural arteries and drain to the popliteal vein.

The Mapleson A (Magill) and coaxial version of the Mapleson A system (Lack circuit) are more efficient for spontaneous breathing than any of the other Mapleson circuits. The fresh gas flow (FGF) required to prevent rebreathing is slightly greater than the alveolar minute ventilation (4-5 litres/minute). This is delivered to the patient through the outer coaxial tube and exhaust gases are moved to the scavenging system through the inner tube. In the Lack circuit, the expiratory valve is located close to the common gas outlet away from the patient end. This is the main advantage of the Lack circuit over the Mapleson A circuit.

The Mapleson E circuit is a modification of the Ayres T piece and the FGF required to prevent rebreathing is 1.5-2 times the patient’s minute volume.

The Bain circuit is the coaxial version of the Mapleson D circuit.

The FGF for spontaneous respiration to avoid rebreathing is 160-200 ml/kg/minute.

The FGF for controlled ventilation to avoid rebreathing is 70-100 ml/kg/min.

After the carotid body, the thyroid gland is the second most richly vascular organ in the body.

The global blood flow to the thyroid gland can be measured using:
1. Colour ultrasound sonography
2. Quantitative perfusion maps using MRI of the thyroid gland using an arterial spin labelling (ASL) method.

This table shows the blood flow to various organs of the body at rest:
Organ Blood Flow(ml/minute/100g)
Hepatoportal 58
Kidney 420
Brain 54
Skin 13
Skeletal muscle 2.7
Heart 87
Carotid body 2000
Thyroid gland 560

The diaphragm has three opening through which different structures pass from the thoracic cavity to the abdominal cavity:

Inferior vena cava passes at the level of T8.

Oesophagus, oesophageal vessels and vagi at T10.

Aorta, thoracic duct and azygous vein through T12.

Sympathetic trunk and pulmonary branches of vagus nerve form a posterior pulmonary plexus at the root of the lung. Fibres continue posteriorly from superficial cardiac plexus to form Anterior pulmonary plexus. It contains vagi nerves and superficial cardiac plexus. These fibres then follow the blood vessel and bronchi into the lungs.

The lower border of the pleura is at the level of:

8th rib in the midclavicular line

10th rib in the lower level of midaxillary line

T12 at its termination.

Both lungs have oblique fissure while right lung has transverse fissure too.

The trachea expands from the lower edge of the cricoid cartilage (at the level of the 6th cervical vertebra) to the carina.

The nerve stimulators deliver a stimulus lasting for 1-2 milliseconds (not second) to perform nerve blockage.

There are just 2 leads (not 3); one for the skin and other for the needle.

Prior to the administration of the local anaesthesia, a current of 0.25 – 0.5 mA (not 1-2mA) at the frequency of 1-2 Hz is preferred.

If the needle tip is close to the nerve, muscular contraction could be possible at the lowest possible current.

Insulated needles have improved the block success rate, as the current is only conducting through needle tip.

Stimulus to the femoral nerve which is placed in the mid lingual line causes withdrawer of the quadriceps and knee extension, that’s the dancing patella ( not plantar flexion).

Oxytocin is secreted by the posterior pituitary along with Antidiuretic Hormone (ADH). It increases the contraction of the upper segment (fundus and body) of the uterus whereas the lower segment is relaxed facilitating the expulsion of the foetus.

Oxytocin acts through G protein-coupled receptor and phosphoinositide-calcium second messenger system to contract uterine smooth muscle.

It has 0.5 to 1 % ADH activity introducing possibilities of water intoxication when used in high doses.

The sensitivity of the uterus to oxytocin increases as the pregnancy progresses.

It is used for induction of labour in post maturity and uterine inertia.

Mapleson breathing system (or circuit) analysed five different arrangements of components of the breathing system:
Mapleson A – It is the most efficient for spontaneous respiration. The flow of fresh gas required is 70-85 ml/kg/min, i.e., approximately 5-6 lit./min fresh gas flow for an average adult.
Mapleson B and C – inefficient for both SV and PPV; requires gas flow of two to three times minute volume (100 ml/kg/min). Not commonly used but category C may be used for emergency resuscitation.
Mapleson D – efficient for PPV at gas flow equivalent to patient’s minute volume; the Bain’s circuit is a coaxial version of the Mapleson D
Mapleson E and F – for paediatric use; requires gas flow at two to three times the patient’s minute volume. The Mapleson F consists of an open-ended reservoir bag (Jackson-Rees modification).

Tachyphylaxis is the swiftly declining response to successive drug doses which vastly reduces its effectiveness in a short space of time, mostly as a result of an acute consumption of neurotransmitters.

Tolerance or desensitisation is the slow decline in a person’s reaction to a drug due to continued use. It requires a longer time span than tachyphylaxis, usually over days or weeks.

Down- regulation is a reduction in the amount of receptors available on target cells which decreases the affinity of the agent to the cells. For this to occur, the down-regulation of receptors must occur at a rate faster than receptor synthesis. This down-regulation often occurs with beta1 receptors due to:

1) The transportation or receptors from the cell surface to the interior of the cell

2) Degradation of receptors occurring over time.

In this case, dobutamine is prescribed to treat cardiogenic shock. It is able to function by binding to beta1-adrenergic receptors to increase the contraction of the heart, thereby improving cardiac output. It also binds to beta2- and alpha1-adrenergic receptors to balance out the effects produced by binding to beta1 receptors and reduce the risk of system vasculature responses.

Creatinine clearance is a test used to approximate the glomerular filtration rate (GFR) as an assessment of kidney function.

Creatinine is formed during the breakdown of dietary sources of meat and skeletal muscle. It is secreted at a consistent concentration and pace into the body’s circulation, and is easily filtered across the glomerulus without being reabsorbed or metabolized by the kidney.

It is represented mathematically as:
Creatinine clearance (CL) = U x V/P
where,
U: Urinary creatinine concentration (mg/mL)
V: Volume of urine (mL/min)
P: Plasma creatinine concentration (mg/mL)

Therefore, in this case:
CL: 1.25 x 1 = 125mL/min
0.1

Number needed to treat can be defined as the number of patients who need to be treated to prevent one additional bad outcome.

It can be found as:

NNT=1/Absolute Risk Reduction (rounded to the next integer since number of patients can be integer only).

where ARR= (Risk factor associated with the new drug group) — (Risk factor associated with the currently available drug)

So,

ARR= (165/1050)-(132/1044)

ARR= (0.157-0.126)

ARR= 0.031

NNT= 1/0.031

NNT=32.3

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.

When responsiveness diminishes rapidly after administration of a drug, the response is said to be subject to tachyphylaxis. This may be due to frequent or continuous exposure to agonists, which often results in short-term diminution of the receptor response.

Many mechanisms may be responsible, such as blocking access of G protein to activated receptor, or receptor molecules internalized by endocytosis to prevent exposure to extracellular molecules.

Tolerance occurs when larger doses are required to produce the same effect. This may be due to changes in receptor number or function due to exposure to the drug.

Desensitization refers to the common situation where the biological response to a drug diminishes when it is given continuously or repeatedly. It is a chronic loss of response, occurring over a longer period than tachyphylaxis. It may be possible to restore the response by increasing the dose (or concentration) of the drug but, in some cases, the tissues may become completely refractory to its effect.

Drug dependence is defined as a psychic and physical state of the person characterized by behavioural and other responses resulting in compulsions to take a drug, on a continuous or periodic basis in order to experience its psychic effect and at times to avoid the discomfort of its absence.