LEMSLIM

Indications

• Reversal of hypotension from spinal or epidural anesthesia
• Reversible airways obstruction (e.g., asthma, bronchospasm)
• Nasal congestion

Dosage

Children: For children aged 1 month to 11 years, the dose is 1 mg/kg/hour by intravenous infusion, adjusted according to plasma-theophylline concentration. For children aged 12 to 17 years, administer 500–700 micrograms/kg/hour by intravenous infusion, also adjusted according to plasma-theophylline concentration.

Adults: For reversal of hypotension, administer 3–7.5 mg by slow intravenous injection every 3–4 minutes, adjusting according to response, with a maximum of 9 mg per dose. For airways obstruction, 30–60 mg may be given orally three times a day.

Mechanism of action

Ephedrine acts by stimulating adrenergic receptors, leading to bronchodilation and vasoconstriction. It increases the release of norepinephrine from sympathetic nerve endings, enhancing its action on alpha and beta-adrenergic receptors, which results in increased peripheral resistance and cardiac output.

Pharmacodynamics

Ephedrine exhibits both alpha- and beta-adrenergic activity. Its alpha-adrenergic effects lead to vasoconstriction, while beta-adrenergic stimulation results in bronchodilation. The drug also has a mild central nervous system stimulant effect, which can contribute to side effects such as anxiety and insomnia.

Pharmacokinetics

Ephedrine is well-absorbed from the gastrointestinal tract and is distributed widely throughout the body. It has a relatively long half-life due to its resistance to metabolism. The drug is primarily excreted unchanged in the urine. Its pharmacokinetic profile can be influenced by factors such as renal function and the presence of other medications that may affect its clearance.

Contra-indications

• Hypersensitivity to ephedrine or any of its components
• Severe hypertension
• Tachyarrhythmias
• Severe coronary artery disease
• Hyperthyroidism
• Prostatic hypertrophy

Adverse effects

• Anxiety
• Headache
• Insomnia
• Nausea
• Tremor
• Dry mouth
• Dizziness
• Cardiac arrhythmias
• Hypertension
• Urinary retention
• Myocardial infarction
• Psychotic disorders
• Pulmonary edema

Interactions

• Other sympathomimetics
• Xanthines (e.g., theophylline)
• Monoamine oxidase inhibitors
• Antihypertensive agents
• Antidepressants
• Corticosteroids

Precautions

• Use with caution in patients with diabetes mellitus
• Caution in elderly patients
• Hypertension
• Ischaemic heart disease
• Glaucoma (risk of angle-closure)
• Chronic obstructive pulmonary disease

Pregnancy

Manufacturer advises avoidance due to potential risks, including increased fetal heart rate.

Breast-feeding

Present in breast milk; manufacturer advises avoidance due to reported irritability and disturbed sleep in infants.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Formulations

• Oral suspension
• Oral solution
• Tablets (15 mg, 30 mg)
• Solution for injection (30 mg per 10 ml)

Indications

• Management of apnea of prematurity
• Enhancement of alertness and cognitive performance
• Relief of headaches, particularly when combined with analgesics
• Enhancement of physical performance in sports

Dosage

Children: For infants, particularly for apnea of prematurity

Adults: The usual adult dose for alertness enhancement is 100 to 200 mg, taken as needed. For the management of apnea of prematurity, doses may vary and should be determined by a healthcare professional.

Mechanism of action

Caffeine acts primarily as an antagonist of adenosine receptors, inhibiting the action of adenosine, which normally promotes sleep and relaxation. This antagonism leads to increased neuronal firing and the release of neurotransmitters such as dopamine and norepinephrine. Caffeine also inhibits phosphodiesterase enzymes, enhancing levels of cyclic AMP and cyclic GMP, which are important for various cellular functions. Additionally, in the context of respiratory function, caffeine stimulates the respiratory centers in the central nervous system, enhancing ventilation.

Pharmacodynamics

Caffeine stimulates the central nervous system, increasing alertness and reducing fatigue. It relaxes smooth muscles, increases cardiac muscle contraction, and can enhance physical performance. Caffeine also promotes gastric acid secretion and gastrointestinal motility, and it exhibits mild diuretic properties. Its effects can lead to restlessness and agitation in some individuals, particularly at higher doses.

Pharmacokinetics

Caffeine is rapidly absorbed from the gastrointestinal tract, with peak plasma concentrations occurring within 30 to 120 minutes after ingestion. It is distributed widely throughout body tissues, readily crossing the blood-brain barrier. Caffeine is metabolized primarily in the liver by cytochrome P450 1A2, producing three primary metabolites: paraxanthine, theobromine, and theophylline. The elimination half-life varies significantly among individuals, influenced by factors such as age, liver function, pregnancy, and the use of certain medications. It is primarily excreted in urine.

Adverse effects

• Restlessness
• Agitation
• Insomnia
• Increased heart rate
• Nausea
• Gastrointestinal discomfort
• Headaches

Interactions

• caffeinecitrate+adenosine: Unknown (decreases efficacy)
• caffeinecitrate+antiarrhythmics: Unknown (decreases efficacy)

Precautions

• Use cautiously in patients with a history of anxiety disorders, insomnia, or cardiac arrhythmias.
• Monitor caffeine intake in individuals with certain medical conditions, such as hypertension.

Pregnancy

Caffeine crosses the placenta; excessive intake during pregnancy may be associated with adverse outcomes. It is generally recommended to limit caffeine consumption.

Breast-feeding

Caffeine is excreted in breast milk; moderate consumption is considered safe, but excessive intake may affect the infant's sleep and behavior.

Storage

Store in a cool, dry place away from direct light. Keep out of reach of children.

Formulations

• Tablets
• Oral solutions
• Injectable preparations
• Caffeine citrate

Indications

• Bronchial asthma
• Hypotension
• Nasal congestion
• Cardiac arrest

Dosage

Children: Refer to the BNF for Children for appropriate paediatric dosing information.

Adults: Refer to the BNF for specific dosing guidelines based on the condition being treated.

Mechanism of action

Ephedrine acts by activating alpha-adrenergic and beta-adrenergic receptors. Directly, it stimulates these receptors, leading to vasoconstriction (alpha-1), increased cardiac chronotropy and inotropy (beta-1), and bronchodilation (beta-2). Indirectly, it inhibits norepinephrine reuptake and promotes the release of norepinephrine from nerve cells, resulting in prolonged sympathetic stimulation.

Pharmacodynamics

Ephedrine elevates blood pressure through increased heart rate and cardiac output, while also variably raising peripheral resistance. It induces bronchodilation through beta-adrenergic receptor activation in the lungs. Additionally, it enhances urine outflow resistance by stimulating alpha-adrenergic receptors in bladder smooth muscle. The therapeutic dose range is broad, with potential dosages from 5mg to 50mg, and caution is advised regarding the risk of hypertension and tachyphylaxis.

Pharmacokinetics

Ephedrine is rapidly absorbed and reaches peak plasma concentrations within 1 to 2 hours following oral administration. It is metabolized in the liver and excreted primarily via the kidneys. The duration of action is variable, but it generally lasts for 2 to 4 hours. Its pharmacokinetic profile can be influenced by individual patient characteristics, including renal function.

Adverse effects

• Tachycardia
• Hypertension
• Palpitations
• Nervousness
• Dizziness
• Nausea
• Vomiting

Interactions

• mianserin+ephedrine: Unknown (decreases effects)
• volatile halogenated anaesthetics+ephedrine: Unknown (additive effect)

Precautions

• Use with caution in patients with cardiovascular disorders
• Monitor blood pressure and heart rate during treatment
• Consider potential for tachyphylaxis with prolonged use

Pregnancy

Use only if clearly needed, as safety in pregnancy has not been established.

Breast-feeding

Caution is advised; ephedrine may pass into breast milk.

Storage

Store in a cool, dry place, away from direct sunlight.

Formulations

• Oral tablets
• Injectable solution

Mechanism of action

The mechanism of action of caffeine is complex, as it impacts several body systems, which are listed below. The effects as they relate to various body systems are described as follows: **General and cellular actions** Caffeine exerts several actions on cells, but the clinical relevance is poorly understood. One probable mechanism is the inhibition of nucleotide phosphodiesterase enzymes, adenosine receptors, regulation of calcium handling in cells, and participates in adenosine receptor antagonism. Phosphodiesterase enzymes regulate cell function via actions on second messengers cAMP and cGMP. This causes lipolysis through activation of hormone-sensitive lipases, releasing fatty acids and glycerol. **Respiratory** The exact mechanism of action of caffeine in treating apnea related to prematurity is unknown, however, there are several proposed mechanisms, including respiratory center stimulation in the central nervous system, a reduced threshold to hypercapnia with increased response, and increased consumption of oxygen, among others. The blocking of the adenosine receptors enhances respiratory drive via an increase in brain medullary response to carbon dioxide, stimulating ventilation and respiratory drive, while increasing contractility of the diaphragm. **Central nervous system** Caffeine demonstrates antagonism of all 4 adenosine receptor subtypes (A1, A2a, A2b, A3) in the central nervous system. Caffeine's effects on alertness and combatting drowsiness are specifically related to the antagonism of the A2a receptor. **Renal system** Caffeine has diuretic effects due to is stimulatory effects on renal blood flow, increase in glomerular filtration, and increase in sodium excretion. **Cardiovascular system** Adenosine receptor antagonism at the A1 receptor by caffeine stimulates inotropic effects in the heart. Blocking of adenosine receptors promotes catecholamine release, leading to stimulatory effects occurring in the heart and the rest of the body. In the blood vessels, caffeine exerts direct antagonism of adenosine receptors, causing vasodilation. It stimulates the endothelial cells in the blood vessel wall to release nitric oxide, potentiating blood vessel relaxation. Catecholamine release, however, antagonizes this and exerts inotropic and chronotropic effects on the heart, ultimately leading to vasoconstriction. Finally, caffeine is shown to raise systolic blood pressure measurements by 5 to 10 mmHg when it is not taken regularly, versus no effect in those who consume it regularly. The vasoconstricting effects of caffeine are beneficial in migraines and other types of headache, which are normally caused by vasodilation in the brain. Caffeine competitively inhibits phosphodiesterase, the enzyme that degrades cyclic 3',5'-adenosine monophosphate (AMP). Increased levels of intracellular cyclic AMP mediate most of caffeine's pharmacologic actions. Caffeine stimulates all levels of the CNS... Caffeine's cortical effects are milder and of shorter duration than those of amphetamines. In slightly larger doses, caffeine stimulates medullary, vagal, vasomotor, and respiratory centers, promoting bradycardia, vasoconstriction, and increased respiratory rate. Caffeine constricts cerebral vasculature. In contrast, the drug directly dilates peripheral blood vessels...

Pharmacodynamics

Caffeine stimulates the central nervous system (CNS), heightening alertness, and sometimes causing restlessness and agitation. It relaxes smooth muscle, stimulates the contraction of cardiac muscle, and enhances athletic performance. Caffeine promotes gastric acid secretion and increases gastrointestinal motility. It is often combined in products with analgesics and ergot alkaloids, relieving the symptoms of migraine and other types of headaches. Finally, caffeine acts as a mild diuretic.

Mechanism of action

Ephedrine is a direct and indirect sympathomimetic amine. As a direct effect, ephedrine activates alpha-adrenergic and beta-adrenergic receptors. As an indirect effect, it inhibits norepinephrine reuptake and increases the release of norepinephrine from vesicles in nerve cells. These actions combined lead to larger quantities of norepinephrine present in the synapse for more extended periods of time, increasing stimulation of the sympathetic nervous system. Ephedrine acts as an agonist of alpha-1, beta-1 and beta-2-adrenergic receptors. The stimulation of alpha-1-adrenergic receptors causes the constriction of veins and a rise in blood pressure, the stimulation of beta-1-adrenergic receptors increases cardiac chronotropy and inotropy, and the stimulation of beta-2-adrenergic receptors causes vasodilation and bronchodilation. Ephedrine alkaloids are members of a large family of sympathomimetic compounds that include dobutamine and amphetamine. Members of this family increase blood pressure and heart rate by binding to alpha- and beta-adrenergic receptors present in many parts of the body, including the heart and blood vessels. These compounds are called sympathomimetics because they mimic the effects of epinephrine and norepinephrine, which occur naturally in the human body. In addition to their direct pharmacological effects, many of these compounds also stimulate the release of norepinephrine from nerve endings. The release of norepinephrine further increases the sympathomimetic effects of these compounds, at least transiently. Ephedrine does not contain a catechol moiety, and it is effective after oral administration. The drug stimulates heart rate and cardiac output and variably increases peripheral resistance; as a result, ephedrine usually increases blood pressure. Stimulation of the alpha-adrenergic receptors of smooth muscle cells in the bladder base may increase the resistance to the outflow of urine. Activation of beta-adrenergic receptors in the lungs promotes bronchodilation. Ephedrine stimulates both alpha- and beta-adrenergic receptors. It is believed that beta-adrenergic effects result from stimulation of the production of cyclic adenosine 3',5'-monophosphate (AMP) by activation of the enzyme adenyl cyclase, whereas a-adrenergic effects result from inhibition of adenyl cyclase activity. In contrast to epinephrine, ephedrine also has an indirect effect by releasing norepinephrine from its storage sites. With prolonged use or if doses are given frequently, ephedrine may deplete norepinephrine stores in sympathetic nerve endings and tachyphylaxis may develop to the cardiac and pressor effects. Tachyphylaxis to the bronchial effects of the drug may also occur, but it is not the result of norepinephrine depletion.

Pharmacodynamics

Ephedrine increases blood pressure by stimulating heart rate and cardiac output and variably increasing peripheral resistance. It causes bronchodilation due to the activation of beta-adrenergic receptors in the lungs. By stimulating alpha-adrenergic receptors in bladder smooth muscle cells, ephedrine also increases the resistance to the outflow of urine. The therapeutic window of ephedrine is wide, as patients can be given doses of 5mg up to 50mg. Patients should be counselled regarding the pressor effects of sympathomimetic amines and the risk of tachyphylaxis. Also, the use of ephedrine for hypotension prophylaxis is associated with a higher risk of hypertension, compared to when ephedrine is used to treat hypotension.