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

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.

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.

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

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.

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.

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

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).

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.

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.

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.

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.

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

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

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.

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.

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.

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.

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)

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

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).

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

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.

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

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.

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 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.

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.

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.