transmembrane, pore forming

10

intracellular

4

2

Transmembrane

3

extracellular

transmembrane

• Verapamil
• Diltiazem
• Nifedipine

Blocked by:

• Mibefradil
• Succinimide (Ethosuximide, Methsuximide)
• Sulfonimides (Zonisamide)
• Valproylamides (Valproate)
• Hydantoins (Phenytoin)

• Gabapentin
• Pregabalin
• alpha-2-delta ligand at PQRS-Ca channel
• decrease transmitter release

Selectivity of Ca Channel Blockers

Myocardial vs. Vascular

• Verapamil 1:1
• Diltiazem 1:5
• Nifedipine 1:15
• Felodipine 1:>100
• Nimodipine 1:>100

• 1:1 myocardial:vascular
• Decreases HR & O2 demand
• contraindicated in AV conduction abnormal
• Constipation
• edema
• digoxin levels
• ONLY WORKS FOR ATRIAL ARRYHTHMIA
• CLass IB works for ventricular arryhthmia

• arteriolar (>>vein) vasodilator
• 1:>100 myocardial:vascular
• oral (half life 3-4 hrs= frequent dosing)
• decrease afterload
• decrease BP
• increases HR

• 1:5 myocardial:vascular
• decreased HR & O2 demand (but less of an effect than Verapamil)
• relieves coronary artery vasospasm (variant angina)

• anti-epileptic
• (T-type are all anti-seizure)
• Ethosuximide
• Methsuximide

• mixed mode of action
• one MOA is interacts with T-type blocker
• Zonisamide

• mixed MOA
• T-type blocker
• Valproate
• naturally found in valerian

• Na/Ca channel blocker
• zero order kinetics (saturable)
• gum hyperplasia

• Phenytoin
• Triamterene
• Dapsone
• Trimethoprim
• Methotrexate

• St. John's wort
• efavirenz, nevirapine
• glucocorticoids
• rifampin
• carbamazepine
• barbituates
• phenytoin

• in striate muscle, ryanodine receptor controls intracellular Ca release

• Ryanodine Receptor Blocker
• used in ER (via IV) to take away muscle contraction in cases of muscle hyperactivity causing hyperthermia