Drug/Small Molecule:

nifedipine

Overview

IUPAC Name:	dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
Trade Names:	Adalat; Adalat 10; Adalat 20; Adalat 5; Adalat CC; Adalat CR; Adalat Crono; Adalat Ft; Adalat Gits; Adalat Gits 30; Adalat LA; Adalat LP; Adalat Oros; Adalat PA; Adalat Retard; Adalate; Adapine; Adapress; Alat; Aldipin; Alfadal; Alonix; Alonix S; Alpha-Nifedipine Retard; Angipec; Anifed; Anpine; Apo-Nifed; Aprical; Bonacid; Calcibloc; Calcigard; Calcilat; Camont; Cardifen; Cardilat; Cardionorm; Chronadalate; Chronadalate Lp; Citilat; Coracten; Coral; Cordafen; Cordaflex; Cordalat; Cordicant; Cordilan; Cordipin; Corinfar; Corotrend; Corynphar; Depin; Dignokonstant; Dilafed; Dilcor; Dipinkor; Duranifin; Ecodipi; Ecodipin; Ecodipin E; Fedcor; Fedcor Retard; Fenamon; Fenamon Sr; Fenihidin; Fenihidine; Glopir; Hadipin; Hexadilat; Introcar; Kordafen; Macorel; Megalat; Myogard; N1fedilat; Nedipin; Nicardia; Nifangin; Nifar; Nifdemin; Nifebene; Nifecard; Nifecor; Nifedepat; Nifedicor; Nifedin; Nifedine; Nifedipine Retard; Nifedipres; Nifedirex LP; Nifelan; Nifelat; Nifelat Q; Nifelate; Nifensar XL; Nificard; Nifidine; Nifipen; Niphedipine; Orix; Oxcord; Pidilat; Procardia; Procardia XL; Sepamit; Tibricol; Zenusin
PharmGKB Accession Id:	PA450631

Description

A potent vasodilator agent with calcium antagonistic action. It is a useful anti-anginal agent that also lowers blood pressure. [PubChem]

Indication

For the management of vasospastic angina, chronic stable angina and hypertension.

ATC Therapeutic Category

• C08CA:Dihydropyridine derivatives

Pharmacology and Interactions

Mechanism Of Action

Nifedipine inhibits the influx of extracellular calcium through myocardial and vascular membrane pores by physically plugging the channel. The decrease in intracellular calcium inhibits the contractile processes of smooth muscle cells, causing dilation of the coronary and systemic arteries, increased oxygen delivery to the myocardial tissue, decreased total peripheral resistance, decreased systemic blood pressure, and decreased afterload.

Pharmacology

Nifedipine, the prototype of the dihydropyridine class of calcium-channel antagonists, is similar to other dihydropyridines including amlodipine, felodipine, isradipine, and nicardipine. Nifedipine is used to treat Prinzmetal's angina, hypertension, and other vascular disorders such as Raynaud's phenomenon. By blocking the calcium channels, Nifedipine inhibits the spasm of the coronary artery and dilates the systemic arteries, results in a increase of myocardial oxygen supply and a decrease in systemic blood pressure.

Food Interactions

Avoid alcohol. Avoid natural licorice. Avoid taking with grapefruit juice. Take with low fat meal.

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Hepatic.

Protein Binding

92-98%

Absorption

Rapidly and fully absorbed following oral administration.

Half Life

2 hours

Toxicity

Symptoms of overdose include dizziness, drowsiness, nausea, severe drop in blood pressure, slurred speech, and weakness. LD₅₀=494 mg/kg (orally in mice); LD₅₀=1022 mg/kg (orally in rats)

Chemical Properties

Chemical Formula:

C₁₇H₁₈N₂O₆

SMILES Code:

CC1=C(C(C(=C(N1)C)C(=O)OC)c2ccccc2N(=O)=O)C(=O)OC

(Format: OpenEye Isomeric)

Molecular Weight ( average / monoisotopic )

346.3346 / 346.1165

In-Depth Annotations ()

1. rs4987161 at chr7:99204017 in CYP3A, CYP3A4
   Defining variant for CYP3A4*17, defective in metabolizing the hypertensive drug nifedipine in vitro; exhibited lower turnover numbers than wild-type for testosterone and chlorpyrifos in vitro.

   Variant Name:

   CYP3A4:F189S; CYP3A4:670 T>C; CYP3A4:189 Phe>Ser; CYP3A4*17

   Related Drugs:

   nifedipine

   Evidence:

   http://www.pharmgkb.org/.../haplotype.jsp#ImportantHaplotypeInformationforCYP3A4-3
   

Curated Annotations ()

1. rs699 at chr1:228912417 in AGT
   The AGT:Met235Thr variant was not associated with response to antihypertensives in a study of 97 hypertensive British individuals.

   Variant Name:

   AGT M235T, AGT:Met235Thr

   Related Drugs:

   atenolol, lisinopril, nifedipine

   Related Diseases:

   Hypertension

   Evidence:

   PMID:8728305
   

2. rs1123617 at chr18:41506881 in SLC14A2
   In a Chinese population, this SNP was significantly associated with blood pressure response to nifedipine treatment.

   Variant Name:

   SLC14A2:Val227Ile

   Related Drugs:

   nifedipine

   Related Diseases:

   Hypertension

   Evidence:

   PMID:17344938
   

3. rs3745009 at chr18:41516357 in SLC14A2
   In a Chinese population, this SNP was significantly associated with blood pressure response to nifedipine treatment.

   Variant Name:

   SLC14A2:Ala357Thr

   Related Drugs:

   nifedipine

   Related Diseases:

   Hypertension

   Evidence:

   PMID:17344938
   

Curated Information

The following genes are in curated knowledge about this drug.

	Gene	Relationship	Evidence
	ABCB1	FA	Publications
	ACE	CO PD       GN	Publications
	ACE2	CO PD       GN	Publications
	AGT	PD       GN	Publications, Variants
	CACNA1C	PD	Publications
	CYP3A		Variants
	CYP3A4	PK FA GN	Publications, Variants
	CYP3A5	PK FA	Publications
	NOS3	PD       GN	Publications
	SLC14A2		Variants

Non-Curated Information

A list of non-curated publications that mention this drug along with other genes is available.

Metabolizing Enzymes

• CYP3A4
• CYP2D6
• CYP2E1

Drug Targets

• CACNA2D1

BioCarta Pathways†

• cadmium induces dna synthesis and proliferation in macrophages - (BioCarta via Pathway Interaction Database)

Non-Curated Information

A list of non-curated publications that mention this drug along with other drugs is available.

Drug Interactions

Curated Information

The following diseases are in curated knowledge about this drug.

	Disease	Relationship	Evidence
	Gestational hypertension	PD       GN	Publications
	Hypertension	CO PD       GN	Publications, Variants
	Pre-Eclampsia	PD       GN	Publications

Non-Curated Information

A list of non-curated publications that mention this drug along with other diseases is available.

Curated Phenotype Datasets

These datasets are sorted alphabetically by title.

1. In vivo and in vitro characterization of variants

   • 
   • 
   • 
   • 
   • PD
   • PK
   • FA

   Submitted by Mary Relling, PharmD involving CYP3A, CYP3A4, CYP3A5, NR1I2, , midazolam, nifedipine, rifampin and troleandomycin

Additional Datasets

These datasets are minimally curated and are sorted alphabetically by title.

1. Physicochemical determinants of human renal clearance
2. The Connectivity Map: using gene-expression signatures to connect small molecules, genes, and disease

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LinkOuts

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Non-Curated Publications

A list of non-curated publications that mention this drug is available.