calcium channel blockers

T/F: Ca+ leads to smooth muscle dilation resulting in vasodilation and increase in BP

• false

  • causes smooth muscle contraction → vasoconstriction

what are the different types of calcium channels throughout the biological system? 

• L

• N

• R

• S

which channel does calcium enter through in the cardiovascular system?

a) L 
b) N 
c) R 
d) S

a) L 

what are the 3 major CV Conditions that CCBs are used for? Specifically, what muscle/part is targeted?

1. HTN (Arteries)

2. arrhythmia (cardiac muscle) 

3. angina (BV in heart)

T/F: Ca+ Is ubiquitous

• true 

  • it is everywhere 

T/F: this action potential diagram represents the stepwise events of calcium entry into a single cell of the cardiac system

• true 

a diagram showing the action potential of a single cardiac cell is 

a) electrocardiogram 

b) action potential diagram 

b) action potential diagram 

SATA: what 2 ions contribute to the electrical system completion by calcium

a) potassium 

b) magnesium 

c) sodium

d) nitrates 

a) potassium

c) sodium

 

what is the resting membrane potential of a cardiac cell?

• -80 mV

during resting membrane potential, the outside is (positive/negative) because of the (K+/Na+/Ca+) inside while the inside is (positive/negative) because of the (K+/Na+/Ca+) outside 

• outside = positive

  • because of only K+ inside cell 

• inside = negative

  • because both Ca+ and Na+ are outside 

what happens during phase 0

• Na+ Influx 

  • Na+ enters cell (outside → inside) 

  • increases positive membrane potential 

  • caused by stimulation of membrane ( ex. NT)

T/F: K+ hates Na+ and Ca+

• true

what happens during phase I?

• K+ starts to leave in small amounts 

what happens during phase 2?

• slow Ca+ Influx by channels

the slow phase or the plateau phase refers to…

a) Phase 0 

b) Phase 1 

c) Phase 2 

d) Phase 3

c) Phase 2 

what happens during phase 3?

• Potassium starts to leave the cell

  • in response to more Ca+ Influx 

• Na+ Still inside 

sodium influx into the cell refers to

a) Phase 0 

b) Phase 1 

c) Phase 2 

d) Phase 3

a) Phase 0 

when potassium starts to exit the cell, that refers to

a) Phase 0 

b) Phase 1 

c) Phase 2 

d) Phase 3

b) Phase 1 

when Ca+ starts to slowly enter the cell, that refers to

a) Phase 0 

b) Phase 1 

c) Phase 2 

d) Phase 3

c) Phase 2 

when K+ starts to leave the cell very quickly, that refers to

a) Phase 0 

b) Phase 1 

c) Phase 2 

d) Phase 3

d) Phase 3

what does calcium do once inside the cardiac cells?

• reacts with 3 proteins (myosin, actin, troponin) 

  • Ca+ takes myosin OUT → 

  • troponin + actin snap together → 

  • causes conduction or contraction 

when the action potential is restored By Na/K ATPase, that refers to

a) Phase 0 

b) Phase 3

c) Phase 4

d) Phase 1

c) Phase 4

what happens during phase 4? 

• action potential is restored 

  • Na+ and Ca+ exit cell 

  • K+ influx 

  • caused by K/Na ATPase 

how does the calcium enter into blood vessel epithelium occur? 

• through L-type cells 

  • less dependence on Na+ & K+ 

  • diagram = more bell shaped 

what are the 3 chemical nuclei that have properties to block CC?

1. dihydropyridines

2. arylalkylamines

3. benzothiazepines

what are DHP used for?

a) angina only

b) HTN and arrhythmia 

c) HTN only 

d) angina and HTN 

d) angina and HTN 

T/F: DHP can cause an indirect negative chronotropic effect

• false 

  • indirect positive chronotropic effect from baroreceptor reflex

what are benzothiazepines an arylalkylamines useful for?

a) HTN

b) angina 

c) arrhythmia 

d) All of the above 

d) All of the above 

CCB are more selective to (veins/arteries), which causes (veinous/arterial) vasodilation and decrease (preload/afterload) In angina.

• arteries

• arterial

• decrease afterload

what is the parent nucleus of dihydropyridines? 

• pyridine nucleus with one of the 3 double bonds = hydrogenated

  • 1 double bond = saturated 

  • 2 hydrogens = positions 1 + 4

which of the following is a correct description of the dihydropyridines? 
a) pyridine nucleus with 2 double bonds are saturated/hydrogenated 

b) pyridine nucleus with 1 double bond saturated/hydrogenated 

c) aliphatic tertiary nitrogen surrounded by carbon chains 

d) 1,4-thiazepine with various functional groups 

• b) pyridine nucleus with 1 double bond saturated/hydrogenated 

what type of CCB class is nifedipine? 

• 1,4- dihydropyridines 

what type of CCB is this? 

• 1,4-dihydropyridine 

is the nitrogen in nifedipine basic? can it be a salt?

• not basic 

  • lone pair = conjugate with double bonds and ester carbonyl 

• can not be salt

  • nitrogen needs to be able to donate a proton 

is nifedipine hydrophilic or lipophilic? why?

• lipophilic 

  • phneyl ring + 2 esters

how is nifedipine administered? how is it absorbed?

• given only ORALLY (very lipophilic)

  • extensive FPM 

  • low bioavailability because of esterases in GIT, liver, plasma

how is nifedipine metabolized? 

• esterases in GIT, liver, plasma 

what is nifedipine used for?

• HTN + angina

T/F: DHP are very effective in the treatment for arrhythmias

• false

  • do NOT use DHPS for arrhythmias 

why does nifedipine have low bioavailability?
a) Extremely lipophilic nature 

b) esterase metabolism 

c) o-demethylation metabolism 

d) dependent on pt being slow/fast acetylators 

b) esterase metabolism 

• esters at positions 3 + 5

DHP
a) dilate peripheral veins 

b) dilate peripheral arteries 

c) dilate both peripheral veins and arteries 

b) dilate peripheral arteries 

SATA: which of the following DHP have basic nitrogen atoms in the side chain? 

a) nifedipine 

b) nicardipine 

c) amlodipine 

d) felodipine 

b) nicardipine 

c) amlodipine 

what type of CCB is this? 

• DHP (Nicardipine) 

what type of CCB is this?

• DHP (amlodipine)

where does nicardipine have a basic nitrogen?

• basic nitrogen on ester alkyl position 3

where does amlodipine have a basic nitrogen?

• basic nitrogen in the side chain at position 2

what type of salt is nicardipine given as? How is it administered? 

• given as a HCl salt by injection 

can nicardipine be used orally?

• no, only use by injection 

  • ester hydrolysis can occur orally → decreases bioavailability 

can amlodipine made into a salt? how is it administered?

• make salt with weak organic acid (Besylate) 

  • slowly released in oral dosage form (Long-acting, use once per day)

T/F: amlodipine is made into a salt with HCl

• false

  • uses besylate 

  • HCl = hygroscopic = absorbs moisture = bad 

what drug is the prime example of aryl-alkyl amines

• verapamil 

what is verapamil used for?

1. HTN 

2. angina 

3. arrhythmia 

how is verapamil administered?

• -orally and by injection as a hydrochloride salt

what type of CCB is this? 

• aryl-alkyl amine (verapamil)

how well is verapamil absorbed? how is it metabolized? 

• verapamil = very lipophilic = well absorbed 

  • no strong polar groups

• liver metabolizes drug very fast = low bioavailability 

  • high FPM 

  • O-demethylation or N-demethylation

what is the common structure of aryl-alkyl amine? 

• aliphatic tertiary nitrogen surrounded by carbon chains attached to aromatic rings

nifedipine dose vs verapamil dose

• nifedipine = lower doses (5,10,20 mg) 

  • most active class

• verapamil = higher doses (200, 400 mg) 

  • least active class

T/F: verapamil has a high bioavailability and low FPM

• false 

  • very low bioavailability because of high FPM (lipophilic, O-demethylation/N-demethylation 

SATA: which of the following CCBs work on both the blood vessels and cardiac muscle?

a) nicardipine 

b) verapamil 

c) amlodipine 

d) diltiazem 

b) verapamil 

d) diltiazem

(aryl-alkyl amines and benzothiazepines  )

what are some functional groups in verapamil?

• ethers (o-demethylation)

• tertiary amine (N-demethylation)

• cyano or nitrile

• isopropyl

what type of drug is diltiazem?

• benzothiazepine CCB

what type of CCB is this? 

• benzothiazepine (diltiazem) 

what is the common structure of benzothiazepines?

• 1,4-thiazepine fused with a benzene

how is diltiazem administered?

• orally or by injection (hydrochloride salt) 

rank the CCB (nifedipine, verapamil, diltiazem) by dose strengths 

• verapamil (highest, hundreds) > diltiazem (50) > nifedipine (5-20) 

what is diltiazem used for?

• HTN 

• angina 

• arrhythmia 

how is diltiazem absorbed?

• well-absorbed

  • diltiazem = very lipophilic

  • low bioavailability (FPM) because of esters

what are some functional groups in diltiazem? how might they affect metabolism? 

• ether (o-demethylation) 

• ester (esterases in GIT) 

• amide (amidases) 

• tertiary amine (N-demethylation) 

• benzene ring (possible aromatic hydroxylation) 

how are verapamil and diltiazem similar and different?

• both can be HCl salt or orally 

• both affect cardiac and vascular tissues 

• diltiazem does not have as low bioavailability as verapamil