Entonox is a mixture of 50% Oxygen and 50% nitrous oxide and is given in an inhaled form as a quick form of analgesia. Entonox causes non-competitive inhibition of NMDA (N-methyl-D-aspartate) receptors, which are a subtype of the glutamate receptor.

It is stored in blue and white cylinders and administered via a pressure regulator and demand valve. The administration of this medicine reduces pain and anxiety in paediatric and dental procedures ands during labour.

Effects are apparent after 20 seconds, and peak action occurs after 3 to 5 minutes as it is a drug with a rapid onset and the patient will also recover rapidly from its effects. Entonox is widely used as it does not accumulate in the body and does not cause many side effects. However, a notable side effect is the inhibition of Vitamin B12 synthesis.

Angiotensin-converting enzyme (ACE) inhibitors prevent angiotensin I from being converted to angiotensin II. Angiotensin II has a variety of effects:
Sympathetic activity has increased.
Vasoconstriction in the arteries
Secretion of Vasopressin
Secretion of aldosterone

The increase in systemic blood pressure is caused by arteriolar vasoconstriction. Vasopressin stimulates water reabsorption in the kidneys as well as the thirst sensation. In the distal convoluted tubules and collecting ducts, aldosterone causes the reabsorption of sodium and water from the urine in exchange for potassium secretion. As a result, ACE inhibitors lower systemic blood pressure while also causing hyperkalaemia.

Angiotensin-converting enzyme inhibitors (ACE inhibitors) are used in a variety of clinical settings, including heart failure. According to a meta-analysis, ACE inhibitors reduce death, MI, and overall admission in patients with heart failure by 28%.
ACE inhibitors are also used in the following clinical settings:
Hypertension
Chronic kidney disease
Diabetic nephropathy 
Following a myocardial infarction

In the presence of renal artery stenosis, ACE inhibitors are contraindicated because they can cause or exacerbate renal failure.
The most common side effect of ACE inhibitors is a dry cough caused by increased bradykinin production. There is, however, no known link to fibrosis of the lungs.

In most cases of atrial flutter, ventricular rate control is used as a stopgap measure until sinus rhythm is restored. A beta-blocker (e.g. bisoprolol), diltiazem, or verapamil can be used to reduce the rate of contractions in the heart.
Electrical cardioversion, pharmacological cardioversion, and catheter ablation can all be used to return the heart to a normal rhythm. Cardioversion should not be attempted until the patient has been fully anticoagulated for at least three weeks if the duration of atrial flutter is unknown or it has lasted longer than 48 hours. Emergency electrical cardioversion is the treatment of choice when there is a sudden onset of symptoms and haemodynamic compromise. For recurrent atrial flutter, catheter ablation is preferred.

Verapamil is a calcium-channel blocker that is non-dihydropyridine phenylalkylamine and can be used to treat supraventricular arrhythmias. It’s a calcium channel blocker with a high negative inotropic effect that lowers cardiac output, slows the heart rate, and may impair atrioventricular conduction. At high doses, it can cause heart failure, exacerbate conduction disorders, and cause hypotension.

Adults should take 240-480 mg of verapamil in 2-3 divided doses. 5-10 mg IV over 30 seconds is the corresponding intravenous (IV) dose. After an IV injection, the peak effect lasts 3-5 minutes, and the action lasts 10-20 minutes.

Verapamil should not be taken with beta-blockers like atenolol or quinidine because the combination of their negatively inotropic and negatively chronotropic effects can result in severe hypotension, bradycardia, impaired atrioventricular conduction, heart failure (due to impaired cardiac contractility), and sinus arrest.
The use of verapamil is contraindicated in the following situations:
Acute porphyrias are a type of porphyria that occurs suddenly.
Accessory conducting pathways are linked to atrial flutter or fibrillation (e.g. Wolff-Parkinson-White-syndrome)
Bradycardia
Shock caused by the heart
Insufficiency of the heart (with reduced ejection fraction)
Left ventricular function has been significantly harmed in the past (even if controlled by therapy)
Hypotension (blood pressure less than 90 mmHg)
AV block in the second and third degrees
Sinusitis is a condition in which the sinuses become
Sino-atrial occlusion

Digoxin is a cardiac glycoside that is used to treat atrial fibrillation and flutter, as well as congestive heart failure. In cardiac myocytes, it works by inhibiting the membrane Na/K ATPase. Through Na/Ca exchange, this raises intracellular sodium concentration and indirectly increases intracellular calcium availability. Increased intracellular calcium levels have both a positive inotropic and negative chronotropic effect.

Digoxin therapeutic plasma levels are typically between 1.0 and 1.5 nmol/l, though higher concentrations may be required, and the value varies between laboratories. At concentrations greater than 2 nmol/l, the risk of toxicity increases dramatically.

In patients with normal renal function, digoxin has a long plasma half-life of 36 to 48 hours. This can take up to 5 days in patients with impaired renal function.

Hypokalaemia, rather than hyperkalaemia, has been shown to increase the risk of digoxin toxicity.

In the treatment of persistent and permanent atrial fibrillation, digoxin is no longer widely used. Beta-blockers, also known as rate-limiting calcium channel blockers, are now the first-line treatment for this condition.

Dobutamine is a synthetic isoprenaline derivative that is used to provide inotropic support to patients with low cardiac output caused by septic shock, myocardial infarction, or other cardiac conditions.

Dobutamine is a sympathomimetic drug that stimulates beta-1 adrenergic receptors in the heart to produce its primary effect. As a result, it has inotropic properties that increase cardiac contractility and output. It also has a small amount of alpha1- and beta-2-adrenergic activity.

A summary of the mechanism and effects of different inotropic agents is shown below:
Inotrope
Mechanism
Effects
Adrenaline (epinephrine)
Beta-1 and -2 agonist at increasing doses;
Alpha-agonist at high doses
Increased cardiac output;
Vasoconstriction at higher doses
Noradrenaline (norepinephrine)
Mainly alpha-agonist;
Beta-1 and -2 agonist at increasing doses
Vasoconstriction;
Some increased cardiac output
Dopamine
Dopamine agonist at low doses;
Beta-1 and -2 agonist at increasing doses;
Alpha-agonist at high doses
Increased cardiac output;
Vasoconstriction at higher doses
Dobutamine
Mainly beta-1 agonist
Increased cardiac output

Lidocaine is a tertiary amide local anaesthetic and also a class IV antiarrhythmic.

Like other local anaesthetics, lidocaine works on the voltage-gated sodium ion channel on the nerve cell membranes. It works in the following steps:
1. diffuses through neural sheaths and the axonal membrane into the axoplasm
2. binds fast voltage-gated Na+ channels in the neuronal cell membrane and inactivates them
3. With sufficient blockage, the membrane of the postsynaptic neuron will not depolarise and will be unable to transmit an action potential, thereby preventing the transmission of pain signals

The same principle applies to Lidocaine’s actions in the heart as it blocks the sodium channels in the conduction system and the myocardium. This raises the threshold for depolarizing, making it less likely for the heart to initiate or conduct any action potential that can cause arrhythmia.

Hypoperfusion, renal failure, and the oligohydramnios sequence are all linked to ACE inhibitor use in the second and third trimesters.

The oligohydramnios sequence refers to a foetus’ or neonate’s atypical physical appearance as a result of oligohydramnios in the uterus. It’s also linked to aortic arch obstructive malformations and patent ductus arteriosus.

The inhibitory effects on the renin-angiotensin-aldosterone system appear to be the cause of these defects. To avoid these risks, ACE inhibitors should be stopped before the second trimester.

Clopidogrel, a thienopyridine derivative, prevents platelet aggregation and cross-linking by the protein fibrin by inhibiting the ADP receptor on platelet cell membranes (inhibits binding of ADP to its platelet receptor (P2Y12 ADP-receptor).

A patient suffering from acute ischemic stroke can commonly present with hypertensive emergencies. Thrombolytic therapy is contraindicated in a patient with:
1. Systolic blood pressure greater than 185 mmHg
2. Diastolic blood pressure greater than 110 mmHg

But delaying thrombolytic therapy is associated with increased morbidity in patients with acute ischemic stroke.

Managing high blood pressure in acute ischemic stroke requires a slower and more controlled reduction in BP. In the presence of an ischaemic stroke, rapid reduction of MAP can compromise blood flow, causing further ischemia and worsening of the neurological deficit.

Intravenous labetalol is the agent of choice. The dose is 10 mg IV over 1-2 minutes. This dose can be repeated, or an infusion can be set up that runs at 2-8 mg/minute. Thrombolysis can be performed once the blood pressure is brought down to less than 180/105 mmHg.

A nitrate infusion (for example, Isoket) can be used as an alternative in patients with contraindications to the use of beta-blockers (e.g., asthma, heart block, cardiac failure).

Dopamine is a catecholamine that occurs naturally and is used to treat low cardiac output, septic shock, and renal failure. It is both adrenaline and noradrenaline’s immediate precursor.

Dopamine acts on D1 and D2 dopamine receptors in the renal, mesenteric, and coronary beds at low doses (1-5 g/kg/min). Dopamine causes a significant decrease in renal vascular resistance and an increase in renal blood flow at these doses. Within this dose range, it is also involved in central modulation of behaviour and movement.

Dopamine stimulates beta- and alpha-adrenergic receptors directly and indirectly at higher doses. Beta-stimulation predominates at a rate of 5-10 g/kg/min, resulting in a positive inotropic effect that increases cardiac output and coronary blood flow. Alpha-stimulation predominates at infusion rates greater than 15 g/kg/min, resulting in peripheral vasoconstriction and an increase in venous return and systolic blood pressure.

Because clearance varies greatly in critically ill patients, plasma concentrations cannot be predicted reliably from infusion rates.
Dopamine is given as an intravenous infusion, and because extravasation can cause tissue necrosis and sloughing, a central line is usually used (especially at higher doses >240 g/min). In an emergency, however, dopamine can be administered through a large vein (cephalic or basilic) while a central line is being prepared. Alkaline intravenous solutions inactivate it, so sodium bicarbonate should not be infused with it.

The following are the most common dopamine side effects:
Nausea and vomiting
Tachycardia
Dysrhythmias
Angina
Hypertension