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 midgut gives rise to the appendix.
At week 6, the caecal diverticulum appears and is the precursor for the cecum and vermiform appendix. The cecum and appendix undergo rotation and descend into the right lower abdomen. The appendix can take up various positions:
1. Retrocecal appendix: behind the cecum
2. Retrocolic appendix: behind the ascending colon
3. Pelvic appendix: appendix descends into the pelvis

The appendix grows in length so that at birth, it is long and worm-shaped, or vermiform. After birth, the caecal wall grows unequally, and the appendix comes to lie on its medial side.

The midgut develops into the distal duodenum, jejunum, ileum, cecum, appendix, ascending colon, and proximal 2/3 of the transverse colon.

Randomisation allows for performance of experimental trials in a random order. Using this method gives us control over the confounding variables that are not supposed to be held constant.

For an instance, by employing randomisation we get to control biological differences among individual human beings during experimental trials.

Severity of a reduction in restrictive defect (%FVC) or obstructive defect (V1/FVC) predicted are classified as follows:

Mild 70-80%
Moderate 60-69%
Moderately severe 50-59%
Severe 35-49%
Very severe <35%

This patient has a %FVC predicted of 60.4% and this corresponds to a moderate restrictive deficit. V1/FVC ratio is 93.5%.

FEV1/FVC ratio 80% < predicted and VC < 80% = mixed picture.

FEV1/FVC ratio 80% < predicted and VC > 80% = obstructive picture.

FEV1/FVC ratio 80% > predicted and VC > 80% = normal picture.

FEV1/FVC ratio 80% > predicted and VC < 80% predicted= restrictive picture.

The integrity of the alveolar-capillary barrier is measured by carbon monoxide transfer factor (TLCO) and carbon monoxide transfer coefficient (KCO). These values are seen to be reduced in emphysema, interstitial lung diseases and in pulmonary vascular pathology. However, the KCO (as % predicted) is high in extrapulmonary restriction (pleural, chest wall and respiratory neuromuscular disease), and in loss of lung units provided the structure of the lung remaining is normal. The KCO distinguishes extrapulmonary (high KCO) causes of 'restriction' from intrapulmonary causes (low KCO).

Insulin is the primary anabolic hormone that dominates regulation of metabolism during digestive phase. It promotes glucose uptake in skeletal myocytes and adipocytes, and other insulin-target cells. It promotes glycogenesis and inhibits gluconeogenesis.

Glucagon is the primary counterregulatory hormone that increases blood glucose levels, primarily through its effects on liver glucose output.

Similar to glucagon, growth hormone, catecholamines and corticosteroids are also counterregulatory factors released in response to decreased glucose concentrations. Growth hormone promotes glycogenolysis and inhibits gluconeogenesis; catecholamines stimulate glycogenolysis and gluconeogenesis; while corticosteroids stimulate glycogenesis and gluconeogenesis.

The portal vein arises from the splenic and mesenteric veins, and is the biggest vessel in the portal venous system, accounting for about 75% of the hepatic blood flow.

It is responsible for draining blood from parts of the gastrointestinal system, the spleen, the pancreas and the gallbladder into the liver.

Cardiac conduction

Phase 0 – Rapid depolarization. Opening of fast sodium channels with large influx of sodium

Phase 1 – Rapid partial depolarization. Opening of potassium channels and efflux of potassium ions. Sodium channels close and influx of sodium ions stop

Phase 2 – Plateau phase with large influx of calcium ions. Offsets action of potassium channels. The absolute refractory period

Phase 3 – Repolarization due to potassium efflux after calcium channels close. Relative refractory period

Phase 4 – Repolarization continues as sodium/potassium pump restores the ionic gradient by pumping out 3 sodium ions in exchange for 2 potassium ions coming into the cell. Relative refractory period

The deep inguinal ring lies approximately 1.5-2cm above the midpoint of the inguinal ligament, the halfway point between the anterior superior iliac spine and the pubic tubercle, next to the epigastric vessels.

It is an important point in determining the nature of an inguinal hernia (direct or indirect). The patient is asked to cough after the hernia is reduced, with pressure applied to the deep inguinal ring. The hernia reappearing indicates it is direct, moving through the posterior wall of the inguinal canal.

Inferior and lateral to the pubic tubercle is the normal anatomical position of the neck of a femoral hernia.

Superior and medial to the pubic tubercle is the site of the superficial inguinal ring, and the normal anatomical position of the neck of an inguinal hernia.

The mid-inguinal point is located halways between the pubic symphysis and the anterior superior iliac spine. It is the surface marking for taking the femoral pulse.

The electrons in the outer shell of an oxygen molecule are unpaired, thus it has paramagnetic properties and is attracted into a magnetic field.

It utilizes null deflection -True
Null deflection is a crucial principle in paramagnetic analysers (reflected beam of light on two photocells) which gives very accurate results (typically 0.1%).

It can be used to measure the concentration of diamagnetic gases – False
Since most other gases are weakly diamagnetic they are repelled by a magnetic field (nitric oxide is also paramagnetic).

Can measure gases dissolved in the blood – False
For accurate analysis the sample gas must be dried before passing into the analysis cell, for example, by passage through silica gel. Therefore, they are unsuitable to measure gases dissolved in blood.

Does not require calibration – False
As with most measurement instruments paramagnetic analysers must be calibrated before use.

E) The readings are unaffected by water vapour – False
Water vapour affects the readings hence for accurate analysis the sample gas must be dried before passing into the analysis cell, for example, by passage through silica gel. That is why they are unsuitable to measure dissolved blood gases.

The international system of units, or system international d’unites (SI) is a collection of measurements derived from expanding the metric system.

There are seven base units, which are:

Metre (m): a unit of length
Second (s): a unit of time
Kilogram (kg): a unit of mass
Ampere (A): a unit of electrical current
Kelvin (K): a unit of thermodynamic temperature
Candela (cd): a unit of luminous intensity
Mole (mol): a unit of substance.

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.

A stock dose of Intravenous paracetamol available in the market is 10mg/ml. There is a recommended dose of IV paracetamol according to the profile of the patient (age, co-morbidities, weight).

Weight Recommended Dose Maximum per day
‰¤10 kg 7.5 mg/kg 30 mg/kg
>10 kg to ‰¤33 kg 15 mg/kg 60 mg/kg (not exceeding 2 g)
>33 kg to ‰¤50 kg 15 mg/kg 60 mg/kg (not exceeding 3 g)
>50 kg with additional risk factors for hepatotoxicity 1g 3 g
>50 kg with no additional risk factors for hepatotoxicity 1g 4 g

Special precaution must be observed for patients with hepatocellular insufficiency. The maximum dose per day should not exceed 3g.

The most likely of the differential diagnosis in this case is a duodenal ulcer located on the posterior abdominal wall.

These can cause an erosion of the abdominal wall, eventually affecting the gastroduodenal artery and resulting in major bleeding and haematemesis.

Gastroduodenal artery supplies the pylorus, proximal part of the duodenum, and indirectly to the pancreatic head (via the anterior and posterior superior pancreaticoduodenal arteries).

Ciprofloxacin belongs to the quinolone group of antibiotics, and doxycycline and minocycline are tetracyclines. So, they are not affected by beta-lactamase.
However, amoxicillin is a beta-lactam antibiotic and beta-lactamase cleaves the beta-lactam ring present in amoxicillin. This results in the breakdown of the antibiotic and thus the area of erythema dramatically increased.
Co-amoxiclav contains amoxicillin and clavulanic acid which protects amoxicillin from beta-lactamase.

The duodenojejunal flexure is the point where the duodenum becomes the jejunum.

The ligament of Treitz, which arises from the right crus of diaphragm, provides suspension for support.

Between the ileum and the caecum is the ligament of Treves.

Agitation or restlessness, Rapid heart rate, high Blood Pressure, loss of muscle coordination, or twitching muscles is common symptoms of Serotonin Syndrome.

Tramadol should not be given to patients taking selective serotonin receptor inhibitor (SSRI) therapy because of the risk of serotonin syndrome

Tramadol is a centrally acting analgesic that is an atypical opioid that relieves pain by opioids as well as additional mechanisms. Its affinity for µ opioid receptor is low, while that for κ and δ is very low. Unlike other opioids, it inhibits the reuptake of Noradrenaline (NA) and 5- Hydroxytryptamine (5-HT), increases 5-HT release, and thus activates monoaminergic spinal inhibition of pain.

Its analgesic action is only partially reversed by the opioid antagonist naloxone.

There are different types of temperature measurement. These include:

Thermistor – this is a type of semiconductor, meaning they have greater resistance than conducting materials, but lower resistance than insulating materials. There are small beads of semiconductor material (e.g. metal oxide) which are incorporated into a Wheatstone bridge circuit. As the temperature increases, the resistance of the bead decreases exponentially

Thermocouple – Two different metals make up a thermocouple. Generally, in the form of two wires twisted, welded, or crimped together. Temperature is sensed by measuring the voltage. A potential difference is created that is proportional to the temperature at the junction (Seebeck effect)

Platinum resistance thermometers (PTR) – uses platinum for determining the temperature. The principle used is that the resistance of platinum changes with the change of temperature. The thermometer measures the temperature over the range of 200°C to1200°C. Resistance in metals show a linear increase with temperature

Tympanic thermometers – uses infrared radiation which is emitted by all living beings. It analyses the intensity and wavelength and then transduces the heat energy into a measurable electrical output

Gauge/dial thermometers – Uses coils of different metals with different co-efficient of expansion. These either tighten or relax with changes in temperature, moving a lever on a calibrated dial.

Oxygen consumption (VO2) refers to the optimal amount of oxygen used by the body during exercise.

It is calculated mathematically by:

VO2 = 3.5 x 50 x 8 = 1400 mL/kg/minute

where,

1 MET = 3.5 mL O2/kg/minute is utilized by the body.

Note:

1 MET Eating
Dressing
Use toilet
Walking slowly on level ground at 2-3 mph
2 METs Playing a musical instrument
Walking indoors around house
Light housework
4 METs Climbing a flight of stairs
Walking up hill
Running a short distance
Heavy housework, scrubbing floors, moving heavy furniture
Walking on level ground at 4 mph
Recreational activity, e.g. golf, bowling, dancing, tennis
6 METs Leisurely swimming
Leisurely cycling along the flat (8-10 mph)
8 METs Cycling along the flat (10-14 mph)
Basketball game
10 METs Moderate to hard swimming
Competitive football
Fast cycling (14-16 mph).

The mitral valve is the valve between the left atrium and left ventricle. It opens when the heart is in diastole (relaxation) which allows blood to flow from the left atrium to the left ventricle. In systole (contraction), the mitral valve closes to prevent the backflow of blood from the left ventricle to the left atrium.

The mitral valve is located posterior to the sternum at the level of the 4th costal cartilage. It is best auscultated over the cardiac apex, where its closure marks the first heart sound.

The mitral valve anatomy is composed of five main structures:
1. Left atrial wall – the myocardium of the left atrial wall extends over the posterior leaflet of the mitral valve. (left atrial enlargement is one of the causes for mitral regurgitation)
2. Mitral annulus – a fibrous ring that connects with the anterior and posterior leaflets. It functions as a sphincter that contracts and reduces the surface area of the valve during systole (Annular dilatation can also lead to mitral regurgitation)
3. Mitral valve leaflets (cusps) – The mitral valve is the only valve in the heart with two cusps or leaflets. One anterior and one posterior.
i. The anterior leaflet is located posterior to the aortic root and is also anchored to the aortic root.
ii. The posterior leaflet is located posterior to the two commissural areas.
4. Chordae tendinae – The chordae tendinae connects both the cusps to the papillary muscles.
5. Papillary muscles – These muscles and their cords support the mitral valve, allowing the cusps to resist the pressure developed during contractions (pumping) of the left ventricle

The anterior and posterior cusps are attached to the chordae tendinae which itself is attached to the left ventricle via papillary muscle.

Elimination of phenytoin from the body follows first-order kinetics. This means that the rate of elimination is proportional to plasma concentration.

The rate of elimination can be described by the equation:

C = C0·e-kt

Where:

C = drug concentration
C0 = drug concentration at time zero (extrapolated)
k = Rate constant
t = Time

Enzyme systems become saturated when phenytoin concentrations exceed the normal range and elimination of the drug becomes zero-order. At this point, the drug is metabolised at a fixed rate and metabolism is independent of plasma concentration.

Aspirin and ethyl alcohol are other drugs that behave this way.