GNLD STAGE 6

Indications

• Constipation
• Palliative care for bowel cleansing

Dosage

Children: Child 1 month–3 years: 3.75–15 mg once daily, adjusted according to response. Child 4–17 years: 3.75–30 mg once daily, adjusted according to response.

Adults: 7.5–15 mg once daily (max. per dose 30 mg daily), typically taken at bedtime. The initial dose should be low and increased gradually as needed, with higher doses prescribed under medical supervision.

Mechanism of action

Senna contains sennosides, which are metabolized in the colon to form active compounds that stimulate the peristaltic movement of the intestines. This promotes bowel evacuation by increasing the contraction of intestinal muscles and enhancing fluid secretion into the bowel, leading to softer stools.

Pharmacodynamics

The pharmacodynamic effect of senna includes increased intestinal motility and secretion of electrolytes and water into the intestines, resulting in softened stools and facilitation of bowel movements. Side effects may include abdominal cramps and gastrointestinal disturbances, as well as potential skin reactions.

Pharmacokinetics

Senna is not absorbed significantly in the gastrointestinal tract; its active metabolites exert their effects locally in the intestines. The onset of action is typically within 6 to 12 hours when taken orally. Metabolism occurs in the gut, and excretion is primarily via feces, with minimal systemic absorption.

Contra-indications

• Acute abdominal conditions
• Acute inflammatory bowel disease
• Intestinal obstruction
• Severe dehydration

Adverse effects

• Abdominal cramps
• Asthenia
• Gastrointestinal disorders
• Skin reactions
• Urine discolouration

Precautions

• Excessive use of stimulant laxatives can cause diarrhea and related effects such as hypokalaemia
• Local irritation - avoid prolonged contact with skin (incontinent patients or infants wearing nappies, risk of irritation and excoriation)
• Rodent studies indicate potential carcinogenic risk

Pregnancy

Manufacturers advise to avoid - limited information available.

Breast-feeding

Manufacturers advise to avoid - no information available.

Storage

Store at room temperature, away from moisture and heat.

Formulations

• Oral suspension
• Tablets
• Syrup
• Suppositories

Indications

• Topical anesthesia of oral mucosa
• Topical anesthesia of laryngeal mucosa
• Topical anesthesia of nasal mucosa

Dosage

Children: Refer to BNF for Children for specific paediatric dosing recommendations, as they are determined by age and weight.

Adults: Refer to BNF for specific adult dosing guidelines as it varies based on the clinical situation.

Mechanism of action

Cocaine produces anesthesia by inhibiting excitation of nerve endings or blocking conduction in peripheral nerves through reversible binding to sodium channels. It prevents sodium influx, essential for depolarization and impulse propagation. Cocaine also has vasoconstrictive properties due to its blockade of norepinephrine reuptake in the autonomic nervous system, and it inhibits the reuptake of dopamine, serotonin, and norepinephrine into presynaptic neurons, which is primarily responsible for its addictive potential.

Pharmacodynamics

Cocaine acts as a local anesthetic, indicated for the introduction of local anesthesia in accessible mucous membranes of the oral, laryngeal, and nasal cavities. Its ability to block sodium channels and inhibit neurotransmitter reuptake enhances its anesthetic effects while also inducing vasoconstriction, which may reduce bleeding during surgical procedures.

Pharmacokinetics

Cocaine is absorbed rapidly when applied topically to mucous membranes. It undergoes extensive metabolism in the liver, primarily through hydrolysis by plasma cholinesterases. The drug's half-life is variable, influenced by factors such as route of administration and individual patient metabolism. Cocaine is primarily excreted as metabolites in urine, with a minor percentage excreted unchanged.

Contra-indications

• Hypersensitivity to cocaine or any component of the formulation
• Severe cardiovascular disorders
• History of substance abuse
• Concurrent use of monoamine oxidase inhibitors

Adverse effects

• Anxiety
• Insomnia
• Restlessness
• Cardiovascular effects (e.g., hypertension, tachycardia)
• CNS effects (e.g., seizures, headache)
• Nausea and vomiting
• Local irritation at the site of application

Interactions

• Increased risk of cardiovascular effects when used with sympathomimetics
• May enhance the effects of other central nervous system stimulants
• Use with caution in patients taking anticoagulants due to potential for increased bleeding

Precautions

• Use with caution in patients with a history of seizures
• Monitor for signs of systemic absorption, especially in infants and elderly patients
• Avoid in patients with significant liver impairment
• Caution in patients with a history of cardiovascular disease

Pregnancy

Cocaine is classified as a Category C drug. Its use during pregnancy is not recommended due to potential risks to the fetus.

Breast-feeding

Cocaine is excreted in breast milk. Mothers should not breastfeed during and after treatment until the drug is cleared from their system.

Storage

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

Formulations

• Topical solution
• Ointment

Indications

• Cough and respiratory tract disorders
• Peptic ulcer disease
• Gastroesophageal reflux disease (GERD)
• Adrenal insufficiency
• Inflammatory conditions

Dosage

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

Adults: Refer to reputable clinical guidelines or pharmacopoeias for appropriate dosing.

Mechanism of action

Glycyrrhizin inhibits the enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), which typically converts active cortisol to its inactive form, cortisone. This inhibition leads to increased cortisol levels, resulting in mineralocorticoid-like effects such as sodium retention and potassium excretion, which can influence blood pressure and fluid balance. Additionally, liquorice exhibits antioxidant properties and may modulate immune responses.

Pharmacodynamics

Liquorice displays a variety of pharmacological effects including anti-inflammatory, antiviral, and gastroprotective actions. Its anti-inflammatory effects are attributed to the inhibition of pro-inflammatory cytokines and the suppression of immune cell activation. The antiviral properties are primarily linked to its action against viruses such as herpes simplex and hepatitis C. Moreover, liquorice can enhance mucus secretion in the respiratory tract, facilitating the expulsion of phlegm.

Pharmacokinetics

Liquorice is absorbed from the gastrointestinal tract, with glycyrrhizin being the most bioactive compound. Its metabolites can be detected in the plasma, and the elimination half-life is variable, generally between 6 to 12 hours. The metabolism of glycyrrhizin occurs primarily in the liver, and it undergoes phase I and phase II metabolic processes. Excretion mainly occurs through urine, with both active and inactive metabolites present.

Contra-indications

• Hypersensitivity to liquorice or any of its components
• Severe hypertension
• Heart disease
• Kidney disease
• Cirrhosis of the liver

Adverse effects

• Hypertension
• Hypokalemia
• Edema
• Headache
• Fatigue
• Gastrointestinal disturbances
• Muscle weakness
• Arrhythmias

Interactions

• Corticosteroids - may enhance the effects of corticosteroids
• Digoxin - may increase the risk of digoxin toxicity due to hypokalemia
• Diuretics - may reduce effectiveness of potassium-sparing diuretics and increase potassium loss
• Antihypertensives - may counteract the effects of antihypertensive medications

Precautions

• Use with caution in patients with hypertension
• Monitor electrolytes, particularly potassium levels in long-term use
• Avoid excessive consumption, particularly in patients with underlying cardiovascular conditions

Pregnancy

Use during pregnancy is not well studied; consult a healthcare provider before use.

Breast-feeding

Limited information available; consult a healthcare provider before use.

Storage

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

Formulations

• Dried root
• Powder
• Extracts
• Syrups

Mechanism of action

Cocaine produces anesthesia by inhibiting excitation of nerve endings or by blocking conduction in peripheral nerves. This is achieved by reversibly binding to and inactivating sodium channels. Sodium influx through these channels is necessary for the depolarization of nerve cell membranes and subsequent propagation of impulses along the course of the nerve. Cocaine is the only local anesthetic with vasoconstrictive properties. This is a result of its blockade of norepinephrine reuptake in the autonomic nervous system. Cocaine binds differentially to the dopamine, serotonin, and norepinephrine transport proteins and directly prevents the re-uptake of dopamine, serotonin, and norepinephrine into pre-synaptic neurons. Its effect on dopamine levels is most responsible for the addictive property of cocaine. The presence and function of cannabinoid CB(2) receptors in the brain have been the subjects of much debate. /The investigators/ found that systemic, intranasal or intra-accumbens local administration of JWH133, a selective CB(2) receptor agonist, dose-dependently inhibited intravenous cocaine self-administration, cocaine-enhanced locomotion, and cocaine-enhanced accumbens extracellular dopamine in wild-type and CB(1) receptor knockout (CB(1)(-/-), also known as Cnr1(-/-)) mice, but not in CB(2)(-/-) (Cnr2(-/-)) mice. This inhibition was mimicked by GW405833, another CB(2) receptor agonist with a different chemical structure, and was blocked by AM630, a selective CB(2) receptor antagonist. Intra-accumbens administration of JWH133 alone dose-dependently decreased, whereas intra-accumbens administration of AM630 elevated, extracellular dopamine and locomotion in wild-type and CB(1)(-/-) mice, but not in CB(2)(-/-) mice. Intra-accumbens administration of AM630 also blocked the reduction in cocaine self-administration and extracellular dopamine produced by systemic administration of JWH133. These findings suggest that brain CB(2) receptors modulate cocaine's rewarding and locomotor-stimulating effects, likely by a dopamine-dependent mechanism. Cocaine hydrochloride is a local anesthetic which blocks initiation or conduction of nerve impulses following local application; when applied topically to mucous membranes, the drug also produces intense vasoconstriction. When applied topically to the mucous membranes of the nose or mouth, cocaine reduces the acuity of smell or taste, respectively. Cocaine exerts an indirect adrenergic effect by interfering with the uptake of norepinephrine by adrenergic nerve terminals, and therefore potentiates the effects of catecholamines. The indirect adrenergic effect is apparently the mechanism by which the drug produces vasoconstriction and mydriasis. Cocaine has CNS stimulating effects. The drug is also markedly pyrogenic, augmenting heat production by stimulating muscular activity and decreasing heat loss through vasoconstriction. Cocaine has multiple central and peripheral pharmacological actions. The action responsible for the rewarding property, and hence the abuse liability, of cocaine is an action in the dopaminergic synapse; in the rat the major set of critical dopaminergic synapses appears to be in the nucleus accumbens. Cocaine prolongs the activity of dopamine in the synapse by blocking the dopamine reuptake mechanism (which usually inactivates the transmitter by removing it from the proximity of its synaptic targets). This is an action shared with amphetamine; in addition to blocking the dopamine reuptake mechanism, amphetamine also augments dopaminergic function by augmenting dopamine release directly into the synapse. While amphetamine and cocaine have discriminable subjective effects, perhaps due to differences in rate of onset and metabolism or perhaps due to different side effects, cocaine shares its rewarding impact and abuse liability very closely with amphetamine. When drug access is unlimited, cocaine and amphetamine have the same ability to dominate behavior, reducing other beha

Pharmacodynamics

Cocaine is a local anesthetic indicated for the introduction of local (topical) anesthesia of accessible mucous membranes of the oral, laryngeal and nasal cavities.