Amiodarone has a chemical structure that is similar to that of thyroxine and can bind to the nuclear thyroid receptor. It can cause both hypothyroidism and hyperthyroidism, though hypothyroidism is far more common, with 5-10% of patients suffering from it.

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).

Overdosing on calcium-channel blockers should always be taken seriously and regarded as potentially fatal. Verapamil and diltiazem are the two most lethal calcium-channel blockers in overdose. These work by binding the alpha-1 subunit of L-type calcium channels, preventing calcium from entering the cell. In cardiac myocytes, vascular smooth muscle cells, and islet beta-cells, these channels play an important role.

The following summarises the toxicity of calcium-channel blockers:
Cardiac effects
Vascular smooth muscle tone affects
Metabolic effects
Excessive negative inotropy: myocardial depression
Negative chronotropy: sinus bradycardia
Negative dromotropy: atrioventricular node blockade
Decreased afterload
Systemic hypotension
Coronary vasodilation
Hypoinsulinaemia
Calcium channel blocker-induced insulin resistance

The beta-adrenoceptors in the heart, peripheral vasculature, bronchi, pancreas, and liver are blocked by beta-adrenoceptor blocking drugs (beta blockers).

Beta blockers come in a wide range of strengths, with the choice largely determined by the disease being treated and the patient’s unique circumstances. The intrinsic sympathomimetic activity, lipid solubility, duration of action, and cardioselectivity of beta blockers all differ.

Some beta blockers are lipid (lipophilic) soluble, while others are water soluble (hydrophilic). Drugs that are more lipid-soluble are absorbed faster from the gut, undergo more first-pass metabolism, and are eliminated faster. They’re also more likely to get into the brain and cause central effects like insomnia and nightmares. Propranolol, pindolol, labetalol, and metoprolol are examples of lipid-soluble beta blockers. Beta blockers that are water-soluble are less likely to enter the brain and are more resistant to first-pass metabolism. They are excreted by the kidneys, and in renal impairment, dosage reduction is frequently required. Atenolol, nadolol, celiprolol, and sotalol are examples of water-soluble beta blockers.

Abciximab (ReoPro) is a glycoprotein IIb/IIIa receptor antagonist that is a chimeric monoclonal antibody. It is primarily used during and after coronary artery procedures such as angioplasty to inhibit platelet aggregation.

Bumetanide is a loop diuretic that is used to treat congestive heart failure. It is frequently used in patients who have failed to respond to high doses of furosemide.

It has a potency of about 40 times that of furosemide, with a 1 mg dose being roughly equivalent to a 40 mg dose of furosemide.
Seizures are not known to be triggered by bumetanide. In fact, it lowers the concentration of neuronal chloride, making GABA’s action more depolarizing, and it’s currently being tested as an antiepileptic in the neonatal period.

It takes effect after 1 hour of oral administration, and diuresis takes 6 hours to complete.

Bumetanide absorbs much better in the intestine than furosemide. Because it has a higher bioavailability than furosemide, it is commonly used in patients with gut oedema.

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.

A study published in the Cochrane Database of Systematic Reviews in 2010 found that a single 1000-mg dose of aspirin is effective in treating acute migraine. It was discovered that 24 percent of aspirin users were pain-free after two hours, compared to 11 percent of placebo users. Because the BNF recommends a maximum dose of 900 mg for analgesia and most non-proprietary aspirin comes in a dose of 300 mg, a dose of 900 mg is frequently prescribed in the UK.

Because aspirin is not recommended for children under the age of 16 due to the risk of Reye’s syndrome, it would be inappropriate to give it to the 12-year-old with the viral URTI.

For uncomplicated dental pain, aspirin is an acceptable option, but not for patients who are taking warfarin. The combination of aspirin’s antiplatelet action and warfarin’s anticoagulation properties puts the patient at high risk of bleeding. Furthermore, aspirin can deplete the therapeutic levels of warfarin by displacing it from plasma proteins. It would be better to use another NSAID or analgesic.

In gout, aspirin should be avoided because it reduces urate clearance in the urine and interferes with the action of uricosuric agents. Naproxen, diclofenac, and indomethacin are better options.

Although aspirin is useful for inflammatory pains, the dose of aspirin required for an adequate analgesic effect in severe pain is associated with significant side effects. Naproxen would be a better first-line treatment option.

Antiarrhythmic drug amiodarone is used to treat both ventricular and atrial arrhythmias. It’s a class III antiarrhythmic that works by prolonging the repolarization phase of the cardiac action potential, where potassium permeability is normally high and calcium permeability is low.

Dronedarone is sometimes used instead of amiodarone in certain situations. Although amiodarone is more effective than dronedarone, dronedarone has fewer side effects.

Grapefruit juice inhibits the metabolism of amiodarone.

The plasma half-life of amiodarone is very long, ranging from 2 weeks to 5 months. The half-life is about 2 months on average.
Because amiodarone is excreted in breast milk, it should be avoided by breastfeeding mothers.

Angina pectoris is the most common symptom of ischemic heart disease and presents with chest pain relieved by rest and nitro-glycerine.

Nitrates are the first-line treatment to relieve chest pain caused by angina. The commonly used nitrates are:
1. Nitro-glycerine (NTG) – angina pectoris (treatment/prophylaxis), acute coronary syndrome, heart failure, hypertension
2. Isosorbide mononitrate (ISMN) – chronic angina pectoris (treatment)
3. Isosorbide dinitrate (ISDN) – angina pectoris (treatment/prophylaxis)

The nitrate drugs cause vasodilation via the action of nitric oxide.

The contraindications to the use of nitrate are the following:
1. Allergy to nitrates
2. Concomitant use of phosphodiesterases (PDE) inhibitors such as tadalafil and sildenafil
3. Right ventricular infarction
4. Hypertrophic cardiomyopathy
5. Cardiac tamponade
6. Constrictive pericarditis
7. Hypotensive conditions
8. Hypovolaemia
9. Marked anaemia
10. Mitral stenosis
11. Raised intracranial pressure due to cerebral haemorrhage or head trauma
12. Toxic pulmonary oedema

Loop diuretics are drugs used to manage and treat fluid overload associated with CHF, liver cirrhosis, and renal disease. The drugs commonly used are:
Furosemide
Bumetanide
Torsemide
Ethacrynic Acid

Loop diuretics act on the apical membrane of the thick ascending loop of Henle and inhibit the Na-K-Cl cotransporter. This blocks the reabsorption of sodium and chloride and results in salt-water excretion. This relieves congestion and reduces oedema.

Other diuretics act on the following part of the nephron:
1. Thiazide diuretics – Na/Cl co-transporter in the distal convoluted tubule
2. Osmotic diuretics – PCT and the loop of Henle
3. Aldosterone antagonists – distal convoluted tubule
4. Carbonic anhydrase inhibitors – inhibit the carbonic anhydrase and act on proximal tubular cells

Digoxin is excreted through the kidneys, and impaired renal function can lead to elevated digoxin levels and toxicity.
The patient’s digoxin dose should be reduced in this case, and their digoxin level and electrolytes should be closely monitored.

The purine nucleoside adenosine is used to diagnose and treat paroxysmal supraventricular tachycardia. Adenosine works by stimulating A1-adenosine receptors and opening potassium channels that are sensitive to acetylcholine. This causes the atrioventricular (AV) node’s cell membrane to become hyperpolarized, slowing conduction by inhibiting calcium channels.
Patients who have had a heart transplant are extremely sensitive to the effects of adenosine and should start with a lower dose of 3 mg, then 6 mg, and finally 12 mg.

Dipyridamole potentiates the effects of adenosine, so it should be used with caution in patients who are taking it.

The use of adenosine is contraindicated in the following situations:
Asthma
COPD (chronic obstructive pulmonary disease)
Decompensated heart failure 
Long QT syndrome
AV block in the second or third degree
Sinusitis is a condition in which the sinuses become (unless pacemaker fitted)
Hypotension that is severe

Overdosing on calcium-channel blockers should always be taken seriously and regarded as potentially fatal. Verapamil and diltiazem are the two most lethal calcium channel blockers in overdose. These work by binding the alpha-1 subunit of L-type calcium channels, preventing calcium from entering the cell. In cardiac myocytes, vascular smooth muscle cells, and islet beta-cells, these channels play an important role.

>10 tablets of verapamil (160 mg or 240 mg immediate or sustained-release capsules) or diltiazem can cause serious toxicity (180 mg, 240 mg or 360 mg immediate or sustained-release capsules)

In children, 1-2 tablets of verapamil or diltiazem (immediate or sustained-release)

Symptoms usually appear within 1-2 hours of ingestion with standard preparations. However, with slow-release preparations, significant toxicity may take 12-16 hours to manifest, with peak effects occurring after 24 hours.

The following are the main clinical features of calcium-channel blocker overdose:
Nausea and vomiting
Hypotension
Bradycardia and first-degree heart block
Myocardial ischaemia and stroke
Renal failure
Pulmonary oedema
Hyperglycaemia

The following are some of the most important bedside investigations to conduct:
Blood glucose
ECG
Arterial blood gas
Other investigations that can be helpful include
Urea & electrolytes
Chest X-ray (pulmonary oedema)
Echocardiography

Nitrates are used in the treatment of angina pectoris and the prevention of myocardial ischaemia. Commonly used examples of nitrates are glyceryl trinitrate and isosorbide dinitrate. Unwanted effects, however, are common and can limit therapy, particularly when angina is severe or when patients are unusually sensitive to the effects of nitrates.
The following are common or very common side effects of nitrates
Arrhythmias
Asthenia
Cerebral ischaemia
Dizziness
Drowsiness
Flushing
Headache
Hypotension
Nausea and vomiting
Diarrhoea, syncope and cyanosis can occur, but these are rare side effects. Dry eyes, bradycardia and metabolic acidosis have not been reported.

An ambulatory blood pressure reading of >150/95 is classified as stage 2 hypertension, according to the NICE care pathway for hypertension, and the patient should be treated with an antihypertensive drug.

A calcium-channel blocker, such as amlodipine, would be the most appropriate medication for a 48-year-old Afro-Caribbean man.

An ACE inhibitor, such as ramipril, or a low-cost angiotensin-II receptor blocker (ARB), such as losartan, would be the most appropriate medication for a 48-year-old Caucasian man.

Mannitol is the most widely used osmotic diuretic that is most commonly used to reduce cerebral oedema and intracranial pressure.
Mannitol has four FDA approved uses clinically:
1. Reduction of intracranial pressure and brain mass
2. reduce intraocular pressure if this is not achievable by other means
3. promote diuresis for acute renal failure to prevent or treat the oliguric phase before irreversible damage
4. promote diuresis to promote the excretion of toxic substances, materials, and metabolites

It can be used in rhabdomyolysis-induced renal failure, especially in crush injuries. Mannitol reduces osmotic swelling and oedema in the injured muscle cells and helps restore skeletal muscle function.

It is a low molecular weight compound and can be freely filtered at the glomerulus and not reabsorbed. This way increases the osmolality of the glomerular filtrate and tubular fluid, increasing urinary volume by an osmotic effect. It also does not cross the blood-brain barrier (BBB).

Mannitol causes an expansion of the extracellular fluid space, which may worsen congestive cardiac failure. Contraindications to the use of mannitol include:

1. Anuria due to renal disease
2. Acute intracranial bleeding (except during craniotomy)
3. Severe cardiac failure
4. Severe dehydration
5. Severe pulmonary oedema or congestion
6. Known hypersensitivity to mannitol

Mannitol is an osmotic diuretic that stops the absorption of water throughout the tubule, thus increasing the osmolality of both glomerular and tubular fluid. It is used to:
1. decrease intraocular pressure in glaucoma
2. decrease intracerebral pressure
3. oliguria.

Furosemide is a loop diuretic that inhibits the Na/K/2Cl transported in the ascending limb of the Loop of Henle.

Bendroflumethiazide is a thiazide diuretic which inhibits the Na/Cl transporter.

Spironolactone is a potassium-sparing diuretic that acts as an aldosterone receptor antagonist.

Acetazolamide is a carbonic anhydrase inhibitor.

An ambulatory blood pressure reading of >150/95 is classified as stage 2 hypertension, according to the NICE care pathway for hypertension, and the patient should be treated with an antihypertensive drug.

A calcium-channel blocker, such as amlodipine, would be the most appropriate medication for a 59-year-old Caucasian man.

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.

Angina pectoris is the most common symptom of ischemic heart disease and presents with chest pain relieved by rest and nitro-glycerine.

Nitrates are the first-line treatment to relieve chest pain caused by angina. The commonly used nitrates are:
1. Glyceryl trinitrate
2. Isosorbide dinitrate

The nitrate drugs are metabolized in the following steps:
1. Release Nitrite ions (NO2-), which are then converted to nitric oxide (NO) within cells.
2. NO activates guanylyl cyclase, which causes an increase in the intracellular concentration of cyclic guanosine-monophosphate (cGMP) in vascular smooth muscle cells.
3. Relaxation of vascular smooth muscle.

Although nitrates are potent coronary vasodilators, their principal benefit in the management of angina results from a predominant mechanism of venous dilation:
– Bigger veins hold more blood
– Takes blood away from the left ventricle
– Lowers LVEDV (preload), LA pressure
– Less pulmonary oedema → improved dyspnoea

Bumetanide is primarily used in patients with heart failure who have failed to respond to high doses of furosemide. Bumetanide and furosemide differ primarily in terms of bioavailability and pharmacodynamic potency. In the intestine, furosemide is only partially absorbed, with a bioavailability of 40-50 percent. Bumetanide, on the other hand, is almost completely absorbed in the intestine and has a bioavailability of about 80%. As a result, when it has a better bioavailability than furosemide, it is commonly used in patients with gut oedema.

When taken alone, Bendroflumethiazide is a moderately potent diuretic that is unlikely to control her oedema.

Mannitol is a type of osmotic diuretic used to treat cerebral oedema and high intracranial pressure.

Acetazolamide is a weak diuretic that inhibits carbonic anhydrase. It’s a rare occurrence.

End-organ damage (e.g. encephalopathy, intracranial haemorrhage, acute myocardial infarction or ischaemia, dissection, pulmonary oedema, nephropathy, eclampsia, papilledema, and/or angiopathic haemolytic anaemia) characterises a hypertensive emergency (also known as ‘accelerated hypertension’ or malignant hypertension’ It’s a life-threatening condition that necessitates rapid blood pressure reduction to avoid end-organ damage and a negative outcome.

In the setting of a stroke syndrome (i.e., in the presence of focal neurological deficits), hypertensive emergencies usually necessitate a slower and more controlled blood pressure reduction than in other situations. Rapid reduction of MAP in the presence of an ischaemic stroke can compromise blood flow, leading to further ischaemia and worsening of the neurological deficit. In this situation, intravenous labetalol is the drug of choice for lowering blood pressure.

Significantly elevated blood pressure (>185/110 mmHg) is a contraindication to thrombolysis, but there is some evidence for controlling blood pressure before thrombolysis in exceptional circumstances, when it is only slightly above this threshold.

Calcium-channel blockers, also known as calcium antagonists, stop calcium from entering cells through the L-type calcium channel. This causes vascular smooth muscle in vessel walls to relax, resulting in a decrease in peripheral vascular resistance.
They can be used for a variety of things, including:
Hypertension
Angina
Atrial fibrillation
Migraine

Calcium-channel blockers can be divided into two categories: dihydropyridines and non-dihydropyridines. The basic chemical structure of these two classes differs, as does their relative selectivity for cardiac versus vascular L-type calcium channels.

Dihydropyridines have a high vascular selectivity and lower systemic vascular resistance and blood pressure. As a result, they’re frequently used to treat hypertension. Modified release formulations are also used to treat angina, but their powerful systemic vasodilator and pressure-lowering effects can cause reflex cardiac stimulation, resulting in increased inotropy and tachycardia, which can counteract the beneficial effects of reduced afterload on myocardial oxygen demand.

The suffix -dpine distinguishes dihydropyridines from other pyridines. Examples of dihydropyridines that are commonly prescribed include:
Amlodipine
Felodipine
Nifedipine
Nimodipine

The phenylalkylamine class and the benzothiazepine class are two subgroups of non-dihydropyridines.

Phenylalkylamines are less effective as systemic vasodilators because they are relatively selective for the myocardium. This group of drugs lowers myocardial oxygen demand and reverses coronary vasospasm, making them useful in the treatment of angina. They are also occasionally used to treat arrhythmias. A phenylalkylamine calcium-channel blocker like verapamil is an example.

In terms of selectivity for vascular calcium channels, benzothiazepines fall somewhere between dihydropyridines and phenylalkylamines. They can lower arterial pressure without producing the same level of reflex cardiac stimulation as dihydropyridines because they have both cardiac depressant and vasodilator effects. Diltiazem is the only benzothiazepine currently in clinical use.

The clinical effects of Warfarin occur after a dose of greater than 0.5 mg/kg, and they will be observable 8-10 hours after consumption of the drug. The antidote used for Warfarin is Vitamin K.

1. In low-risk cases with no apparent bleeding:
an oral dose of 10 mg vitamin K

2. If there is clinically significant bleeding
an intravenous dose of 250-300 mcg/kg

Activated charcoal:
in cases of warfarin ingestion
binds to it and reduces the absorption of warfarin
the ingestion must have occurred within the last hour
There is, however, rarely a need for the use of activated charcoal because vitamin K is such as safe and effective antidote.

Clotting studies, including an INR, can be performed, but small children who have ingested warfarin do not require INRs or follow up if they have been treated with 10 mg vitamin K. This dose of vitamin will completely reverse the anticoagulative effects of warfarin.

Perform INR if any of the following are present:
1. Delayed presentation (>6 hours)
2. Patients with symptoms or signs of anticoagulation
3. Possible massive ingestion

Adrenaline (epinephrine) is a sympathomimetic amine that binds to alpha- and beta-adrenergic receptors and acts as an agonist. It is active at both alpha and beta receptors in roughly equal amounts.

When taken orally, it becomes inactive. Subcutaneous absorption is slower than intramuscular absorption. In cardiac arrest, it is well absorbed from the tracheal mucosa and can be given through an endotracheal tube.

At the adrenergic synapse, catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO) metabolise it primarily. The inactive products are then passed through the kidneys and excreted in the urine.

In adult cardiac arrest, the IV dose is 1 mg, which is equal to 10 ml of 1:10000 or 1 ml of 1:1000. In anaphylaxis, the IM dose is 0.5 ml of 1:1000. (500 mcg).

In open-angle glaucoma, adrenaline causes mydriasis and lowers pressure.

Adrenaline is used in cardiopulmonary resuscitation, the treatment of severe croup, and the emergency management of acute allergic and anaphylactic reactions (as a nebuliser solution).

Amiodarone has a lot of potential toxic side effects, so it’s important to get a full clinical evaluation before starting treatment with it.

The following are some of the most common amiodarone side effects:

Arrhythmias
Corneal microdeposits
Hepatic disorders
Hyperthyroidism
Hypothyroidism
Hepatic disorders and jaundice
Nausea
Peripheral neuropathy
Respiratory disorders (including lung fibrosis)
Sleep disturbance
Skin reactions
QT prolongation

Amiodarone can cause optic neuritis, which is a very rare side effect. If this happens, the amiodarone should be stopped right away because it poses a risk of blindness.

Most people who take amiodarone develop corneal microdeposits, which go away once the medication is stopped and rarely cause vision problems.

Amiodarone has a chemical structure that is similar to that of thyroxine and can bind to the nuclear thyroid receptor. It can cause both hypothyroidism and hyperthyroidism, though hypothyroidism is far more common, with 5-10% of patients suffering from it.

Abciximab (ReoPro) is a glycoprotein IIb/IIIa receptor antagonist that is a chimeric monoclonal antibody. It is primarily used during and after coronary artery procedures such as angioplasty to inhibit platelet aggregation.

It’s approved for use as a supplement to heparin and aspirin in high-risk patients undergoing percutaneous transluminal coronary intervention to prevent ischaemic complications. Only one dose of abciximab should be given (to avoid additional risk of thrombocytopenia).

Before using, it is recommended that baseline prothrombin time, activated clotting time, activated partial thromboplastin time, platelet count, haemoglobin, and haematocrit be measured. 12 and 24 hours after starting treatment, haemoglobin and haematocrit should be measured again, as should platelet count 2-4 hours and 24 hours after starting treatment.
When used for high-risk patients undergoing angioplasty, the EPIC trial(link is external)found that abciximab reduced the risk of death, myocardial infarction, repeat angioplasty, bypass surgery, and balloon pump insertion.

The use of abciximab is contraindicated in the following situations:
Internal bleeding is present.
Within the last two months, you’ve had major surgery, intracranial surgery, or trauma.
Stroke in the previous two years
Intracranial tumour
Aneurysm or arteriovenous malformation
Haemorrhagic diathesis is a type of haemorrhagic diathesis.
Vasculitis
Retinopathy caused by hypertension

The following are some of the most common abciximab side effects:
Manifestations of bleeding
Bradycardia
Back ache
Pain in the chest
Vomiting and nausea
Pain at the puncture site
Thrombocytopenia

The use of a beta-blocker at the same time increases the risk of myocardial depression, but it is not a contraindication.
The use of adenosine is contraindicated in the following situations:
Asthma
COPD (chronic obstructive pulmonary disease)
Decompensated heart failure 
Long QT syndrome
AV block in the second or third degree
Sinusitis is a condition in which the sinuses become (unless pacemaker fitted)
Hypotension that is severe

In atrial flutter, ventricular rate control is usually used as a stopgap measure until sinus rhythm can be restored. A beta-blocker (such as bisoprolol), diltiazem, or verapamil can be used to lower the heart rate.

Electrical cardioversion, pharmacological cardioversion, or catheter ablation can all be used to restore sinus 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 has lasted for more than 48 hours. Emergency electrical cardioversion is the treatment of choice when there is an acute presentation with haemodynamic compromise. For the treatment of recurrent atrial flutter, catheter ablation is preferred.

Angina pectoris is the most common symptom of ischemic heart disease and presents with chest pain relieved by rest and nitro-glycerine.

Nitrates are the first-line treatment to relieve chest pain caused by angina. The commonly used nitrates are:
1. Glyceryl trinitrate
2. Isosorbide dinitrate

Side effects to nitrate therapy are common especially
The most common side effects are:
1. Headaches
2. Feeling dizzy, weak, or tired
3. Nausea
4. Flushing

The serious but less likely to occur side effects are:
1. Methemoglobinemia (rare)
2. Syncope
3. Prolonged bleeding time
4. Exfoliative dermatitis
5. Unstable angina
6. Rebound hypertension
7. Thrombocytopenia

Dry eyes, bradycardia, and metabolic acidosis have not been reported.

End-organ damage (e.g. encephalopathy, intracranial haemorrhage, acute myocardial infarction or ischaemia, dissection, pulmonary oedema, nephropathy, eclampsia, papilledema, and/or angiopathic haemolytic anaemia) characterises a hypertensive emergency (also known as ‘accelerated hypertension’ or malignant hypertension’ It’s a life-threatening condition that necessitates rapid blood pressure reduction to avoid end-organ damage and a negative outcome.

Hypertensive encephalopathy is a syndrome that includes headaches, seizures, visual changes, and other neurologic symptoms in people who have high blood pressure. It is reversible if treated quickly, but it can progress to coma and death if not treated properly.

Any patient with suspected hypertensive encephalopathy should have an urgent CT scan to rule out an intracranial haemorrhage, as rapid blood pressure reduction could be dangerous in these circumstances.

The drug of choice is labetalol, which reduces blood pressure steadily and consistently without compromising cerebral blood flow.
An initial reduction of approximately 25% in mean arterial pressure (MAP) over an hour should be aimed for, followed by a further controlled MAP reduction over the next 24 hours. In patients who are unable to take beta-blockers, nicardipine can be used as a substitute.

If amiodarone is unavailable in VF/pVT arrests, lidocaine at a dose of 1 mg/kg can be used instead, according to the latest ALS guidelines. If amiodarone has already been given, no lidocaine should be given.

Amlodipine is a calcium-channel blocker that is frequently used to treat hypertension. Ankle swelling is a very common side effect of calcium-channel blockers, and it occurs quite frequently.

Bumetanide is 40 times more powerful than furosemide, and one milligram is roughly equivalent to 40 milligrams of furosemide. This patient is currently taking 80 mg of furosemide and should be switched to a 2 mg bumetanide once daily.

Angiotensin-converting enzyme (ACE) inhibitors are the most common cause of drug-induced angioedema in the United Kingdom and the United States, owing to their widespread use.

Angioedema is caused by ACE inhibitors in 0.1 to 0.7 percent of patients, with data indicating a persistent and relatively constant risk year after year. People of African descent have a five-fold higher chance of contracting the disease.

Swelling of the lips, tongue, or face is the most common symptom, but another symptom is episodic abdominal pain due to intestinal angioedema. Itching and urticaria are noticeably absent.

The mechanism appears to be activated complement or other pro-inflammatory cytokines like prostaglandins and histamine, which cause rapid vasodilation and oedema.

Other medications that are less frequently linked to angioedema include:
Angiotensin-receptor blockers (ARBs)
Nonsteroidal anti-inflammatory drugs (NSAIDs)
Bupropion (e.g. Zyban and Wellbutrin)
Beta-lactam antibiotics
Statins
Proton pump inhibitors

The majority of these reactions are minor and can be treated by stopping the drug and prescribing antihistamines.

Amiodarone is a class III potassium channel blocker used to treat multiple types of arrhythmias.

Side effects include:
1. pulmonary fibrosis
2. blue discolouration of the skin
3. phototoxicity
4. corneal deposits
5. hepatic necrosis
6. thyroid dysfunction
7. sleep disturbances
8. peripheral neuropathy.

Xanthopsia is a condition where the patient complains of seeing yellow lines and is seen in digoxin overdose.

Aspirin works by inhibiting cyclo-oxygenase in an irreversible manner, resulting in a decrease in prostaglandin and thromboxane production. As a result, platelet activation and aggregation are reduced.

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

In a shockable (Vf/pVT) paediatric cardiac arrest, amiodarone should be administered after the third and fifth shocks. The dose is 5 mg/kg (maximum 300 mg) and should be administered over a three-minute period. If at all possible, administration via a central line is recommended.

Abciximab is glycoprotein IIb/IIIa receptor antagonist that decreases aggregation of platelets by prevent their cross-linking. In Glanzmann’s thrombasthenia there are low levels of these same receptors leading to decreased bridging of platelets as fibrinogen cannot attach. There is increased bleeding time both in this disease and when there is use of abciximab.

Warfarin is teratogenic and can cause a host of abnormalities in the growing foetus. These include hypoplasia of the nasal bridge, stippling of the epiphyses, multiple ophthalmic complications, growth retardation, pectus carinatum, atrial septal defect, ventriculomegaly and a patent ductus arteriosus.

Nitrates are used in the treatment of angina pectoris and the prevention of myocardial ischaemia. Commonly used examples of nitrates are glyceryl trinitrate and isosorbide dinitrate. Unwanted effects, however, are common and can limit therapy, particularly when angina is severe or when patients are unusually sensitive to the effects of nitrates.
The following are common or very common side effects of nitrates
Arrhythmias
Asthenia
Cerebral ischaemia
Dizziness
Drowsiness
Flushing
Headache
Hypotension
Nausea and vomiting
Diarrhoea, syncope and cyanosis can occur, but these are rare side effects. Dry eyes, bradycardia and metabolic acidosis have not been reported.

Overdosing on calcium-channel blockers should always be taken seriously and regarded as potentially fatal. Verapamil and diltiazem are the two most lethal calcium channel blockers in overdose. These work by binding the alpha-1 subunit of L-type calcium channels, preventing calcium from entering the cell. In cardiac myocytes, vascular smooth muscle cells, and islet beta-cells, these channels play an important role.

The standard ABC approach should be used to resuscitate all patients as needed. If life-threatening toxicity is expected, intubation and ventilation should be considered early on. If hypotension and shock are developing, early invasive blood pressure monitoring is recommended.

The primary goal of specific treatments is to support the cardiovascular system. These are some of them:

1. Fluid resuscitation: Give up to 20 mL of crystalloid per kilogramme of body weight.

2. Calcium supplementation
This can be a good way to raise blood pressure and heart rate temporarily.
via central venous access: 10% calcium gluconate 60 mL IV (0.6-1.0 mL/kg in children) or 10% calcium chloride 20 mL IV (0.2 mL/kg in children)
Boluses can be given up to three times in a row.
To keep serum calcium >2.0 mEq/L, consider a calcium infusion.

3. Atropine: 0.6 mg every 2 minutes up to 1.8 mg is an option, but it is often ineffective.

4. HIET (high-dose insulin-euglycemic therapy):
The role of HIET in the step-by-step management of cardiovascular toxicity has changed.

5. Vasoactive infusions:
This was once thought to be a last-ditch measure, but it is now widely recommended that it be used sooner rather than later.
Insulin with a short half-life 50 mL of 50 percent glucose IV bolus plus 1 U/kg bolus (unless marked hyperglycaemia present)
Short-acting insulin/dextrose infusions should be continued.
Glucose should be checked every 20 minutes for the first hour, then hourly after that.
Regularly check potassium levels and replace if they fall below 2.5 mmol/L.
Titrate catecholamines to effect (inotropy and chronotropy); options include dopamine, adrenaline, and/or noradrenaline infusions.

6. Sodium bicarbonate: Use 50-100 mEq sodium bicarbonate (0.5-1.0 mEq/kg in children) in cases where a severe metabolic acidosis develops.

7. Cardiac pacing: It can be difficult to achieve electrical capture, and it may not improve overall perfusion.
Bypass AV blockade with ventricular pacing, which is usually done at a rate of less than 60 beats per minute.

8. Intralipid transport
Calcium channel blockers are lipid-soluble agents, so they should be used in refractory cases.

Acetazolamide is a non-competitive, reversible inhibitor of carbonic anhydrase found in the cytosol of cells and on the brush border of the proximal convoluted tubule. Bicarbonate and hydrogen ions are converted to carbonic acid by carbonic anhydrase, which then converts carbonic acid to carbon dioxide and water. As a result, acetazolamide reduces the availability of hydrogen ions, causing sodium and bicarbonate ions to accumulate in the renal tubule, resulting in diuresis.
The mechanism of action of the various types of diuretics is summarised below:

1) Loop diuretics, e.g. furosemide, bumetanide
Act on the Na.K.2Cl co-transporters in the ascending loop of Henlé to inhibit sodium, chloride and potassium reabsorption.

2) Thiazide diuretics, e.g. Bendroflumethiazide, hydrochlorothiazide
Act on the Na.Cl co-transporter in the distal convoluted tubule to inhibit sodium and chloride reabsorption.

3) Osmotic diuretics, e.g. mannitol
Increases the osmolality of the glomerular filtrate and tubular fluid, increasing urinary volume by an osmotic effect.

4) Aldosterone antagonists, e.g. spironolactone
Acts in the distal convoluted tubule as a competitive aldosterone antagonist resulting in inhibition of sodium reabsorption and increasing potassium reabsorption.

5) Carbonic anhydrase inhibitors, e.g. acetazolamide
Inhibit the enzyme carbonic anhydrase preventing the conversion of bicarbonate and hydrogen ions into carbonic acid.

Mannitol is a low molecular weight compound and is therefore freely filtered at the glomerulus and is not reabsorbed. It, therefore, increases the osmolality of the glomerular filtrate and tubular fluid, increasing urinary volume by an osmotic effect. It also does not cross the blood-brain barrier (BBB).
Mannitol is primarily used to reduce the pressure and volume of cerebrospinal fluid (CSF). It decreases the volume of CSF by:
Decreasing the rate of CSF formation,and;
Withdrawing extracellular fluid from the brain across the BBB
Other uses of mannitol include:
Short-term management of glaucoma
Treatment of rhabdomyolysis
Preserve renal function in peri-operative jaundiced patients
To initiate diuresis in transplanted kidneys
Bowel preparation prior to colorectal procedures
The recommended dose of mannitol for the reduction of CSF pressure/cerebral oedema is 0.25-2g/kg as an intravenous infusion over 30-60 minutes. This can be repeated 1-2 times after 4-8 hours if needed.
Circulatory overload and rebound increases in intracranial pressure may occur following the use of mannitol. It is irritant to tissues and veins and can cause inflammation and phlebitis.
Mannitol causes an expansion of the extracellular fluid space, which may worsen congestive cardiac failure. Contraindications to the use of mannitol include:
Anuria
Intracranial bleeding (except during craniotomy)
Severe cardiac failure
Severe dehydration
Severe pulmonary oedema

Enoxaparin is a low molecular weight heparin (LMWH) that works in the same way as heparin by binding to and activating the enzyme inhibitor antithrombin III. Antithrombin III inactivates thrombin by forming a 1:1 complex with it. Factor Xa and a few other clotting proteases are also inhibited by the heparin-antithrombin III complex.

The following drugs have been linked to impaired glucose tolerance:
Thiazide diuretics, e.g. Bendroflumethiazide
Loop diuretics, e.g. furosemide
Steroids, e.g. prednisolone
Beta-blockers, e.g. atenolol

A rapid IV bolus of adenosine is given, followed by a saline flush. The standard adult dose is 6 mg, followed by 12 mg if necessary, and then another 12 mg bolus every 1-2 minutes until an effect is seen.

Patients who have had a heart transplant, on the other hand, are extremely sensitive to the effects of adenosine and should start with a lower dose of 3 mg, then 6 mg, and finally 12 mg.

Like other non-steroidal anti-inflammatory drugs, Ibuprofen cannot be given with Warfarin as it would increase the bleeding risk of this patient.

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

Many medications, including warfarin, require cytochrome P450 enzymes for their metabolism. When co-prescribing cytochrome p450 enzyme inducers and inhibitors with warfarin, it’s critical to be cautious.

Inhibitors of the cytochrome p450 enzyme potentiate the effects of warfarin, resulting in a higher INR. To remember the most commonly encountered cytochrome p450 enzyme inhibitors, use the mnemonic O DEVICES:

O– Omeprazole
D– Disulfiram
E– Erythromycin (And other macrolide antibiotics)
V– Valproate (sodium valproate)
I– Isoniazid
C– Ciprofloxacin
E– Ethanol (acute ingestion)
S- Sulphonamides

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.

It is infused intravenously after being diluted to a volume of at least 50 ml in a suitable crystalloid solution. The dose is titrated to response and ranges from 0.5 to 40 g/kg/min. Extravasation-induced skin necrosis is uncommon, and dobutamine can be administered through a peripheral line.

At doses below 10 g/kg/min, side effects are rare, but at higher doses, they can include:
Nausea and vomiting
Tachycardia
Dysrhythmias
Angina
Hypertension
Headache

Bumetanide is a loop diuretic that inhibits sodium, chloride, and potassium reabsorption by acting on the Na.K.2Cl co-transporter in the ascending loop of Henlé. This reduces the osmotic gradient that forces water out of the collecting duct system and prevents the formation of a hypertonic renal medulla. This has a strong diuretic effect on the body.

It’s primarily used in patients with heart failure who aren’t responding to high doses of furosemide. Bumetanide and furosemide differ primarily in terms of bioavailability and pharmacodynamic potency.

In the intestine, furosemide is only partially absorbed, with a bioavailability of 40-50 percent. Bumetanide, on the other hand, is almost completely absorbed in the intestine and has a bioavailability of about 80%. Bumetanide is 40 times more potent than furosemide, and one milligram is roughly equivalent to 40 milligrams of furosemide.

Bumetanide also lowers the concentration of neuronal chloride, making GABA’s action more depolarizing. In the neonatal period, it is being studied as an antiepileptic.

Loop diuretics are drugs used to manage and treat fluid overload associated with CHF, liver cirrhosis, and renal disease. The drugs commonly used are:
Furosemide
Bumetanide
Torsemide
Ethacrynic Acid

Loop diuretics inhibit the Na-K-Cl pump in the ascending loop of Henle, resulting in salt-water excretion. This relieves congestion and reduces oedema.

The contra-indications to the use of loop diuretics are:
1. Anuria
2. Comatose and precomatose states associated with liver cirrhosis
3. Renal failure due to nephrotoxic or hepatotoxic drugs
4. Severe hypokalaemia
5. Severe hyponatremia
6. History of hypersensitivity to furosemide, bumetanide, or torsemide (or sulphonamides)

The following conditions or states are not contraindications, but loop diuretics needs to be used cautiously in these conditions:
1. Diabetes (but hyperglycaemia less likely than with thiazides)
2. Gout
3. Hypotension (correct before initiation of treatment)
4. Hypovolaemia (Correct before initiation of treatment)

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

Paroxysmal supraventricular tachycardia is an intermittent tachycardia (HR > 100 bpm) and has the following characteristics:
1. Sudden onset/offset (Contrast with sinus tachycardia)
2. Electrical activity originates above the ventricle (Contrast with ventricular tachycardia)
3. Produces narrow QRS complex (<120ms) The most common cause of PSVT is Atrioventricular nodal re-entrant tachycardia (AVNRT), most common in young women with a mean age onset of 32 years old. There are recurrent episodes of palpitations, and most of the episodes spontaneously. Sometimes, some vagal manoeuvres are required:
1. Valsalva manoeuvre
2. immersing the face in ice-cold water
3. carotid sinus massage.

If PSVT keeps persisting or is causing severe symptoms, the treatment of choice is intravenous adenosine. The patient’s ECG should be continuously monitored throughout the treatment.

The recommended doses in adults are as follows:
– Initial dose of adenosine is 6 mg by rapid IV bolus
– If unsuccessful, give another dose of adenosine 12 mg by rapid IV bolus
– If unsuccessful, give a further dose of adenosine 12 mg by rapid IV bolus
The latest ALS guidelines advocate 18 mg for the third dose, whereas the BNF/NICE guidelines advocate 12 mg.

If adenosine fails or is contraindicated, intravenous verapamil can be used as an alternative, but it should be avoided in patients recently treated with beta-blockers.

Synchronized electrical cardioversion will be necessary with signs of hemodynamic instability or if drug treatment has failed to restore sinus rhythm.
Recurrent episodes of paroxysmal supraventricular tachycardia can be treated by catheter ablation or prevented with drugs such as flecainide, sotalol, diltiazem, or verapamil.

Corneal microdeposits are almost universally present (over 90%) in people who have been taking amiodarone for more than six months, especially at doses above 400 mg/day. Although these deposits usually cause no symptoms, about 10% of patients report seeing a ‘bluish halo.’ This goes away once the treatment is stopped, and it rarely causes vision problems.

Other effects of amiodarone on the eye are much rarer, occurring in only 1-2 percent of patients:
Optic neuropathy is a condition that affects the eyes.
Non-arteritic anterior ischaemic optic neuropathy (N-AION)
Swelling of the optic disc

Heparin is a polymer of glycosaminoglycan. It occurs naturally and is found in mast cells. Clinically, it is used in two forms:
1. Unfractionated: widely varying polymer chain lengths
2. Low molecular weight: Smaller polymers only

Heparin works by binding to and activating the enzyme inhibitor antithrombin III. Antithrombin III inactivates thrombin (factor IIa) by forming a 1:1 complex with thrombin. The heparin-antithrombin III complex also inhibits factor Xa and some other proteases involved with clotting. The heparin-ATIII complex can also inactivate IX, XI, XII, and plasmin.

Heparin is not thrombolytic or fibrinolytic. It prevents the progression of existing clots by inhibiting further clotting. The lysis of existing clots relies on endogenous thrombolytics.

Heparin is used for:
1. Prevention and treatment of venous thromboembolism
2. Treatment of disseminated intravascular coagulation
3. Treatment of fat embolism
4. Priming of haemodialysis and cardiopulmonary bypass machines

There is no evidence that heparin is superior to low-molecular-weight heparins in preventing mortality from thrombosis.

Vitamin K is used to reverse the effects of warfarin but not heparin. For heparin, protamine sulphate is used to counteract its effects.

The purine nucleoside adenosine is used to diagnose and treat paroxysmal supraventricular tachycardia. Adenosine works by stimulating A1-adenosine receptors and opening potassium channels that are sensitive to acetylcholine. This causes the atrioventricular (AV) node’s cell membrane to become hyperpolarized, slowing conduction by inhibiting calcium channels.

Patients who have had a heart transplant are extremely sensitive to the effects of adenosine and should start with a lower dose of 3 mg, then 6 mg, and finally 12 mg. Dipyridamole potentiates the effects of adenosine, so it should be used with caution in patients who are taking it.

The use of adenosine is contraindicated in the following situations:
Asthma
COPD (chronic obstructive pulmonary disease)
Decompensated heart failure 
Long QT syndrome
AV block in the second or third degree
Sinusitis is a condition in which the sinuses become (unless pacemaker fitted)
Hypotension that is severe

It has a half-life of less than 10 seconds and acts quickly within that time frame. The actions last between 10 and 20 seconds.
Because of the short half-life of the drug, any side effects are usually only temporary. These are some of them:
a feeling of impending doom
Flushing of the face
Dyspnoea
Uncomfortable chest
Tastes metallic

An antidote for digoxin overdose is digoxin-specific antibody (Digifab). It’s a lyophilized preparation of digoxin-immune ovine Fab immunoglobulin fragments that’s sterile, purified, and lyophilized. These fragments were extracted from the blood of healthy sheep that had been immunised with a digoxin derivative called digoxin-dicarboxymethoxylamine (DDMA), a digoxin analogue that contains the functionally important cyclopentaperhydrophenanthrene:lactone ring moiety coupled to keyhole limpet hemocyanin (KLH).

Digifab has a higher affinity for digoxin than digoxin does for its sodium pump receptor, which is thought to be the site of its therapeutic and toxic effects. When given to a patient who is intoxicated, Digifab binds to digoxin molecules, lowering free digoxin levels and shifting the equilibrium away from binding to receptors, reducing cardio-toxic effects. The kidney and reticuloendothelial system then clear the Fab-digoxin complexes.

The following summarises the indications for Digifab in acute and chronic digoxin toxicity:
Acute digoxin toxicity
Chronic digoxin toxicity
Cardiac arrest
Life-threatening arrhythmia
Potassium level > 5 mmol/l
>10 mg digoxin ingested (adult)
>4 mg digoxin ingested (child)
Digoxin level > 12 ng/ml
Cardiac arrest
Life-threatening arrhythmia
Significant gastrointestinal symptoms
Symptoms of digoxin toxicity

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.

Below is a summary of the mechanisms and effects of various inotropic agents:
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.

End-organ damage (e.g. encephalopathy, intracranial haemorrhage, acute myocardial infarction or ischaemia, dissection, pulmonary oedema, nephropathy, eclampsia, papilledema, and/or angiopathic haemolytic anaemia) characterises a hypertensive emergency (also known as ‘accelerated hypertension’ or malignant hypertension’ It’s a life-threatening condition that necessitates rapid blood pressure reduction to avoid end-organ damage and a negative outcome.

In the presence of cardiac ischaemia, hypertensive emergencies require immediate treatment to prevent myocardial infarction.

Similarly, if myonecrosis occurs in the presence of an existing infarction, prompt treatment is required to prevent further myonecrosis. When thrombolysis is used as the primary reperfusion therapy for acute myocardial infarction, blood pressure control is especially important.

An intravenous nitrate is the drug of choice in this situation (e.g. GTN). These have a dual purpose in that they can help patients with ischaemic chest pain manage their symptoms. Because lowering blood pressure with nitrates isn’t always enough to achieve optimal results, intravenous beta-blockers are frequently used as a supplement. For this, intravenous atenolol and metoprolol are commonly used.

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).

Flecainide is an antiarrhythmic drug of class Ic that works by blocking the Nav1.5 sodium channel in the heart, prolonging the cardiac action potential and slowing cardiac impulse conduction. It has a significant impact on accessory pathway conduction, particularly retrograde conduction, and significantly reduces ventricular ectopic foci.

Many different arrhythmias can be treated with flecainide, including:
Pre-excitation syndromes (e.g. Wolff-Parkinson-White)
Acute atrial arrhythmias
Ventricular arrhythmias
Chronic neuropathic pain

The use of flecainide is contraindicated in the following situations:
Abnormal left ventricular function
Atrial conduction defects (unless pacing rescue available)
Bundle branch block (unless pacing rescue available)
Distal block (unless pacing rescue available)
Haemodynamically significant valvular heart disease
Heart failure
History of myocardial infarction
Long-standing atrial fibrillation where conversion to sinus rhythm not attempted
Second-degree or greater AV block (unless pacing rescue available)
Sinus node dysfunction (unless pacing rescue available)

Flecainide should only be used in people who don’t have a structural heart problem. The CAST trial found a significant increase in sudden cardiac death and all-cause mortality in patients with an ejection fraction of less than 40% after a myocardial infarction, where it tended to be pro-arrhythmic.

Anti-arrhythmic drugs have a limited and ineffective role in the treatment of atrial flutter. It’s important to keep in mind that flecainide shouldn’t be used by itself to treat atrial flutter. When used alone, there is a risk of inducing 1:1 atrioventricular conduction, which results in an increase in ventricular rate that is paradoxical. As a result, it should be used in conjunction with a beta-blocker or a calcium channel blocker with a rate-limiting effect.

Heparin works by binding to and activating the enzyme inhibitor antithrombin III.

Antithrombin III inactivates thrombin (factor IIa) by forming a 1:1 complex with thrombin. The heparin-antithrombin III complex also inhibits factor Xa and some other proteases involved with clotting. The heparin-ATIII complex can also inactivate IX, XI, XII, and plasmin.

Heparin is a polymer of glycosaminoglycan. It occurs naturally and is found in mast cells. Clinically, it is used in two forms:
1. Unfractionated: widely varying polymer chain lengths
2. Low molecular weight: Smaller polymers only

Heparin is not thrombolytic or fibrinolytic. It prevents the progression of existing clots by inhibiting further clotting. The lysis of existing clots relies on endogenous thrombolytics.

Heparin is used for:
1. Prevention and treatment of venous thromboembolism
2. Treatment of disseminated intravascular coagulation
3. Treatment of fat embolism
4. Priming of haemodialysis and cardiopulmonary bypass machines

Amiodarone is an anti-arrhythmic medication that can be used to treat both ventricular and atrial arrhythmias. It’s a class III anti-arrhythmic that works by blocking a variety of channels, including Na+ and K+ channels, as well as beta-adrenoreceptors. As a result, it slows conduction through the SA and AV nodes and prolongs phase 3 of the cardiac action potential (slowing repolarisation).

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.

Mannitol is the most widely used osmotic diuretic that is most commonly used to reduce cerebral oedema and intracranial pressure.
It is recommended to use mannitol for the reduction of CSF pressure/cerebral oedema in a dose of 0.25-2 g/kg as an intravenous infusion over 30-60 minutes. This can be repeated 1-2 times after 4-8 hours if needed.

Mannitol has several contraindications and some of them are listed below:
1. Anuria due to renal disease
2. Acute intracranial bleeding (except during craniotomy)
3. Severe cardiac failure
4. Severe dehydration
5. Severe pulmonary oedema or congestion
6. Known hypersensitivity to mannitol

Many medications, including warfarin, require cytochrome P450 enzymes for their metabolism. When co-prescribing cytochrome p450 enzyme inducers and inhibitors with warfarin, it’s critical to be cautious.

Inhibitors of the cytochrome p450 enzyme inhibit the effects of warfarin, resulting in a lower INR. To remember the most commonly encountered cytochrome p450 enzyme inducers, use the mnemonic PC BRASS:

P– Phenytoin
C– Carbamazepine
B– Barbiturates
R– Rifampicin
A– Alcohol (chronic ingestion)
S– Sulphonylureas
S– Smoking

Abciximab (ReoPro) is a glycoprotein IIb/IIIa receptor antagonist that is a chimeric monoclonal antibody. It is primarily used during and after coronary artery procedures such as angioplasty to inhibit platelet aggregation.

The use of abciximab is contraindicated in the following situations:
Internal bleeding is present.
Within the last two months, you’ve had major surgery, intracranial surgery, or trauma.
Stroke in the previous two years
Intracranial tumour
Aneurysm or arteriovenous malformation
Haemorrhagic diathesis is a type of haemorrhagic diathesis.
Vasculitis
Retinopathy caused by hypertension

At muscarinic receptors, atropine blocks the action of the parasympathetic neurotransmitter acetylcholine. As a result, it inhibits the vagus nerve’s effects on both the SA and AV nodes, increasing sinus automaticity and facilitating AV node conduction.

At muscarinic receptors, atropine blocks the action of the parasympathetic neurotransmitter acetylcholine. As a result, it inhibits the vagus nerve’s effects on both the SA and AV nodes, increasing sinus automaticity and facilitating AV node conduction.

The most common cause of asystole during cardiac arrest is primary myocardial pathology, not excessive vagal tone, and there is no evidence that atropine is helpful in the treatment of asystole or PEA. As a result, it is no longer included in the ALS algorithm’s non-shockable section. Atropine is most commonly used in the peri-arrest period. It is used to treat bradycardia (sinus, atrial, or nodal) or AV block when the patient’s haemodynamic condition is compromised by the bradycardia.

If any of the following adverse features are present, the ALS bradycardia algorithm recommends a dose of 500 mcg IV:
Shock
Syncope
Myocardial ischaemia
Heart failure

Atropine is also used for the following purposes:
Topically as a cycloplegic and mydriatic to the eyes
To cut down on secretions (e.g. in anaesthesia)
Organophosphate poisoning is treated with
Atropine’s side effects are dose-dependent and include:
Mouth is parched
Vomiting and nausea
Vision is hazy
Retention of urine
Tachyarrhythmias
It can also cause severe confusion and hallucinations in patients, especially the elderly.

In non-shockable (PEA/asystole) cardiac arrests, adrenaline should be given as soon as circulatory access is gained. The dose is 1 mg via IV or IO (10 mL of 1:10,000 or 1 mL of 1:1000).

Once chest compressions have been resumed after the third shock in a shockable (Vf/pVT) cardiac arrest, adrenaline should be administered. The dosage is one milligram (10 mL of 1:10,000 or 1 mL of 1:1000)

It should be given every 3-5 minutes after that (i.e. alternate loops) and without interrupting chest compressions.
Systemic vasoconstriction is caused by the alpha-adrenergic effects of adrenaline, which raises coronary and cerebral perfusion pressures.

Adrenaline’s beta-adrenergic effects are inotropic (increased myocardial contractility) and chronotropic (increased heart rate), and they can increase coronary and cerebral blood flow. However, concomitant increases in myocardial oxygen consumption and ectopic ventricular arrhythmias (especially in the absence of acidaemia), transient hypoxemia due to pulmonary arteriovenous shunting, impaired microcirculation, and increased post-cardiac arrest myocardial dysfunction may offset these benefits.

Although there is no evidence of long-term benefit from its use in cardiac arrest, the improved short-term survival reported in some studies justifies its use.

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.

Propranolol, like other non-selective beta-blockers, is contraindicated in patients with asthma. These drugs can cause acute bronchospasm, therefore worsening symptoms, especially in high doses. However, there has been some recent evidence that long-term use of selective beta-blockers in mild or moderate asthma patients can be safe.

Atropine is used to treat bradycardia (sinus, atrial, or nodal) or AV block when the patient’s haemodynamic condition is compromised by the bradycardia.

If any of the following adverse features are present, the ALS bradycardia algorithm recommends a dose of atropine 500 mcg IV:
Shock
Syncope
Myocardial ischemia
Insufficiency of the heart

If this does not work, give additional 500 mcg doses at 3-5 minute intervals until a maximum dose of 3 mg is reached. The heart rate can be slowed paradoxically if the dose is higher than 3 mg.

The ALS bradycardia algorithm also suggests the following interim measures:
Transcutaneous pacing
Isoprenaline infusion 5 mcg/min
Adrenaline infusion 2-10 mcg/minutes
Alternative drugs (aminophylline, dopamine, glucagon, glycopyrrolate)

End-organ damage (e.g. encephalopathy, intracranial haemorrhage, acute myocardial infarction or ischaemia, dissection, pulmonary oedema, nephropathy, eclampsia, papilledema, and/or angiopathic haemolytic anaemia) characterises a hypertensive emergency (also known as ‘accelerated hypertension’ or malignant hypertension’ It’s a life-threatening condition that necessitates rapid blood pressure reduction to avoid end-organ damage and a negative outcome.

Hypertensive encephalopathy is a syndrome that includes headaches, seizures, visual changes, and other neurologic symptoms in people who have high blood pressure. It is reversible if treated quickly, but it can progress to coma and death if not treated properly.

Any patient with suspected hypertensive encephalopathy should have an urgent CT scan to rule out an intracranial haemorrhage, as rapid blood pressure reduction could be dangerous in these circumstances.

The drug of choice is labetalol, which reduces blood pressure steadily and consistently without compromising cerebral blood flow.
An initial reduction of approximately 25% in mean arterial pressure (MAP) over an hour should be aimed for, followed by a further controlled MAP reduction over the next 24 hours. In patients who are unable to take beta-blockers, nicardipine can be used as a substitute.

Amiodarone is an anti-arrhythmic medication that can be used to treat both ventricular and atrial arrhythmias.

The use of amiodarone is contraindicated in the following situations:
Conduction disturbances that are severe (unless pacemaker fitted)
Sinus node disease is a condition that affects the lymph nodes in (unless pacemaker fitted)
Sensitivity to iodine
Blockage of the Sino-atrial heart valve (except in cardiac arrest)
Bradycardia in the sinuses (except in cardiac arrest)
Thyroid disorders

Mannitol is the most widely used osmotic diuretic that is most commonly used to reduce cerebral oedema and intracranial pressure.
It is recommended to use mannitol for the reduction of CSF pressure/cerebral oedema in a dose of 0.25-2 g/kg as an intravenous infusion over 30-60 minutes. This can be repeated 1-2 times after 4-8 hours if needed.

Mannitol has several contraindications and some of them are listed below:
1. Anuria due to renal disease
2. Acute intracranial bleeding (except during craniotomy)
3. Severe cardiac failure
4. Severe dehydration
5. Severe pulmonary oedema or congestion
6. Known hypersensitivity to mannitol