Singapore Drugs Database

Indication

For the treatment of rhinitis, urticaria, allergy, common cold, asthma and hay fever.

Mechanism of Action

Chlorpheniramine binds to the histamine H1 receptor. This blocks the action of endogenous histamine, which subsequently leads to temporary relief of the negative symptoms brought on by histamine.

Pharmacokinetics

Absorption

Well absorbed in the gastrointestinal tract.

Distribution

Metabolism

Primarily hepatic via Cytochrome P450 (CYP450) enzymes.

Elimination

Toxicity

Oral LD50 (rat): 306 mg/kg; Oral LD50 (mice): 130 mg/kg; Oral LD50 (guinea pig): 198 mg/kg [Registry of Toxic Effects of Chemical Substances. Ed. D. Sweet, US Dept. of Health & Human Services: Cincinatti, 2010.] Also a mild reproductive toxin to women of childbearing age.

Active Ingredient/Synonyms

1-(p-chlorophenyl)-1-(2-pyridyl)-3-dimethylaminopropane | 1-(p-chlorophenyl)-1-(2-pyridyl)-3-N,N-dimethylpropylamine | 2-[p-chloro-α-[2-(dimethylamino)ethyl]benzyl]pyridine | 3-(p-chlorophenyl)-3-(2-pyridyl)-N,N-dimethylpropylamine | Chlorophenylpyridamine | Chlorphenamin | Chlorphenaminum | Chlorpheniramine | Chlorpheniramine polistirex | Chlorpheniraminum | Clorfenamina | Clorfeniramina | γ-(4-chlorophenyl)-N,N-dimethyl-2-pyridinepropanamine | γ-(4-chlorophenyl)-γ-(2-pyridyl)propyldimethylamine | Chlorphenamine |

Indication

Phenylephrine is mainly used to treat nasal congestion, but may also be useful in treating hypotension and shock, hypotension during spinal anaesthesia, prolongation of spinal anaesthesia, paroxysmal supraventricular tachycardia, symptomatic relief of external or internal hemorrhoids, and to increase blood pressure as an aid in the diagnosis of heart murmurs.

Mechanism of Action

In general, α₁-adrenergic receptors mediate contraction and hypertrophic growth of smooth muscle cells. α₁-receptors are 7-transmembrane domain receptors coupled to G proteins, G_q/11. Three α₁-receptor subtypes, which share approximately 75% homology in their transmembrane domains, have been identified: α_1A (chromosome 8), α_1B (chromosome 5), and α_1D (chromosome 20). Phenylephrine appears to act similarly on all three receptor subtypes. All three receptor subtypes appear to be involved in maintaining vascular tone. The α_1A-receptor maintains basal vascular tone while the α_1B-receptor mediates the vasocontrictory effects of exogenous α₁-agonists. Activation of the α₁-receptor activates G_q-proteins, which results in intracellular stimulation of phospholipases C, A₂, and D. This results in mobilization of Ca²⁺ from intracellular stores, activation of mitogen-activated kinase and PI₃ kinase pathways and subsequent vasoconstriction. Phenylephrine produces its local and systemic actions by acting on α₁-adrenergic receptors peripheral vascular smooth muscle. Stimulation of the α₁-adrenergic receptors results in contraction arteriolar smooth muscle in the periphery. Phenylephrine decreases nasal congestion by acting on α₁-adrenergic receptors in the arterioles of the nasal mucosa to produce constriction; this leads to decreased edema and increased drainage of the sinus cavities.

Pharmacokinetics

Absorption

Completely absorbed after oral administration. It has a reduced bioavailability (compared to pseudoephedrine) following oral administration due to significant first-pass metabolism in the intestinal wall. Compared to IV administration, bioavailability is approximately 38%. Peak serum concentrations are achieved approximately 0.75-2 hours following oral administration. Phenylephrine should be administered parenterally to achieve cardiovascular effects. Occasionally, systemic effects are observed following oral inhalation.

Distribution

Metabolism

Undergoes extensive first-pass metabolism in the intestinal wall and extensive metabolism in the liver. Sulfate conjugation, primarily in the intestinal wall, and oxidative metabolism by monoamine oxidase (MAO) represent the principle routes of metabolism. Glucuronidation occurs to a lesser extent. Phenylephrine and its metabolites are mainly excreted in urine/ .

Elimination

Active Ingredient/Synonyms

(-)-m-Hydroxy-alpha-(methylaminomethyl)benzyl alcohol | (-)-m-Hydroxy-α-(methylaminomethyl)benzyl alcohol | Benzenemethanol, 3-hydroxy-.alpha.-[(methylamino)methyl]-, (R)- | Benzenemethanol, 3-hydroxy-alpha-((methylamino)methyl)-, (R)- | Benzyl alcohol, m-hydroxy-alpha-((methylamino)methyl)-, (-)- | Fenilefrina | l-(3-Hydroxyphenyl)-N-methylethanolamine | Phenylephrine | Phenylephrinum | R(-)-Phenylephrine | Phenylephrine |

Indication

Used as an anticoagulant during plasmophoresis as well as a neutralizing agent in the treatment of upset stomach and acidic urine [FDA Label] [L788] [L789].

Mechanism of Action

Citrate chelates free calcium ions preventing them from forming a complex with tissue factor and coagulation factor VIIa to promote the activation of coagulation factor X [A19410] [A19411]. This inhibits the extrinsic initiation of the coagulation cascade. Citrate may also exert an anticoagulant effect via a so far unknown mechanism as restoration of calcium concentration does not fully reverse the effect of citrate [A19410]. Citrate is a weak base and so reacts with hydrochloric acid in the stomach to raise the pH. It it further metabolized to bicarbonate which then acts as a systemic alkalizing agent, raising the pH of the blood and urine [L790]. It also acts as a diuretic and increases the urinary excretion of calcium.

Pharmacokinetics

Absorption

Tmax of 98-130min [A19414].

Distribution

19-39L [A19414].

Metabolism

Citrate is metabolized to bicarbonate in the liver and plays a role as an intermediate in the citric acid cycle [A19419] [L795].

Elimination

Clearance

Total clearance of 313-1107mL/min [A19414].

Toxicity

Overdose toxicity is mainly due to alkalosis as well as tetany or depressed heart function due to lack of free calcium [L790].

Active Ingredient/Synonyms

Sodium citrate anhydrous | Sodium citrate, anhydrous | trisodium citrate anhydrous | Trisodium citrate, anhydrous | Sodium Citrate |