Clonidine Stats - Substance Search

Pharmacology

DrugBank

State Solid Clearance The clearance of clonidine is 1.9-4.3mL/min/kg.

Description

Clonidine is an imidazole derivate that acts as an agonist of alpha-2 adrenoceptors. This activity is useful for the treatment of hypertension, severe pain, and ADHD. Clonidine was granted FDA approval on 3 September 1974.

Mechanism of Action

Clonidine is primarily an alpha-2 adrenoceptor agonist which causes central hypotensive and anti-arrhythmogenic effects. The alpha-2 adrenoceptor is coupled to the G-proteins G_o and G_i. G_i inhibits adenylyl cyclase and activates opening of a potassium channel that causes hyperpolarization. Clonidine binding to the alpha-2 adrenoceptor causes structural changes in the alpha subunit of the G-protein, reducing its affinity for GDP. Magnesium catalyzes the replacement of GDP with GTP. The alpha subunit dissociates from the other subunits and associates with an effector. The stimulation of alpha-2 adrenoceptors in the locus coeruleus may be responsible for the hypnotic effects of clonidine as this region of the brain helps regulate wakefulness. Clonidine can also decrease transmission of pain signals at the spine. Finally clonidine can affect regulators of blood pressure in the ventromedial and rostral-ventrolateral areas of the medulla.

Pharmacodynamics

Clonidine functions through agonism of alpha-2 adrenoceptors which have effects such as lowering blood pressure, sedation, and hyperpolarization of nerves. It has a long duration of action as it is given twice daily and the therapeutic window is between 0.1mg and 2.4mg daily.

Metabolism

The metabolism of clonidine is poorly understood. The main reaction in clonidine metabolism is the 4-hydroxylation of clonidine by CYP2D6, CYP1A2, CYP3A4, CYP1A1, and CYP3A5. Clonidine is <50% metabolized in the liver to inactive metabolites.

Absorption

Clonidine reaches maximum concentration in 60-90 minutes after oral administration. Race and fasting status do not influence pharmacokinetics of clonidine. A 100µg oral clonidine tablet reaches a C_max of 400.72pg/mL with an AUC of 5606.78h\*pg/mL and a bioavailability of 55-87%.

Indication

Clonidine tablets and transdermal systems are indicated for the treatment of hypertension alone or in combination with other medications. A clonidine injection is indicated for use with opiates in the treatment of severe cancer pain where opiates alone are insufficient. An extended release tablet of clonidine is indicated for the treatment of ADHD either alone or in combination with other medications. Clonidine is also used for the diagnosis of pheochromocytoma, treatment of nicotine dependance, and opiate withdrawal.

Half-life

The elimination half life after epidural administration is 30 minutes but otherwise can range from 6-23h.

Protein Binding

Clonidine is 20-40% bound to plasma proteins, especially albumin.

Elimination

Approximately 50% of a clonidine dose is excreted in the urine as the unchanged drug and 20% is eliminated in the feces.

Volume of Distribution

The volume of distribution of clonidine has been reported as 1.7-2.5L/kg, 2.9L/kg, or 2.1±0.4L/kg depending on the source.

Toxicity

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At therapeutic doses (0.2-0.9 mg/d), clonidine is commonly associated with adverse effects such as dry mouth, sedation, dizziness, and constipation. While generally safe, at toxic doses clonidine can cause serious cardiopulmonary instability and central nervous system (CNS) depression in children and adults. Caution should be used when clonidine is taken with other depressants. It is strongly recommended that one use harm reduction practices when using this substance.

LD50

LD50: 150 mg/kg (oral, rat)
LD50: 30 mg/kg (oral, dog)

Carcinogenicity

No indication of carcinogenicity to humans (not listed by IARC).

Liver injury risk

Low concern (rare serious cases reported)

FDA LiverTox / DILIrank. Reflects published case reports of liver injury, not absolute risk.

Overdose

Symptoms of clonidine overdose include constriction of pupils of the eye, drowsiness, high blood pressure followed by a drop in pressure, irritability, low body temperature, slowed breathing, slowed heartbeat, slowed reflexes, and weakness. There are case reports that show naloxone may be a useful antidote in treating clonidine overdoses. However, this is not in widespread clinical use.

Tolerance & Pharmacokinetics

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Tolerance Decay

Full tolerance 3d Half tolerance 8d Baseline ~14d

Experience Report Analysis

Erowid

25 Reports

1993–2020 Date Range

6 With Age Data

9 Effects Detected

Demographics

Gender Distribution

Age Distribution

Reports Over Time

Effect Analysis

Erowid

Effects aggregated from 25 experience reports (25 Erowid)

25 Reports

9 Effects Detected

6 Positive

2 Adverse

1 Neutral

Effect Sentiment Distribution

Confidence Distribution

Positive Effects 6

Sedation 44.0% 70%

Stimulation 28.0% 70%

Anxiety Suppression 24.0% 70%

Euphoria 20.0% 70%

Focus Enhancement 12.0% 70%

Music Enhancement 12.0% 70%

Adverse Effects 2

Increased Heart Rate 16.0% 70%

Motor Impairment 12.0% 70%

Dosage Distribution

Dose distribution from experience reports

Median: 0.3 mg IQR: 0.2–0.9 mg n=10

Real-World Dose Distribution

62K Doses

From 31 individual dose entries

Oral (n=26)

Median: 0.23mg 25th: 0.1mg 75th: 0.52mg 90th: 1.2mg

mg/kg median: 0.003 mg/kg 75th: 0.006

Form / Preparation

Most common forms and preparations reported

Body-Weight Dosing

Dose relative to body weight from reports with weight data

Median: 0.005 mg/kg IQR: 0.002–0.012 mg/kg n=10

Redose Patterns

Redosing behavior across 20 reports

0.0% Redosed

1.0 Avg Doses

Clonidine Stats & Data