A-23. Drugs used for hypertension II. Ca2+-channel blockers and other vasodilators

Question 1

What are the dihydropyridine calcium channel blockers (10)

Answer 1

Nifedipine
Nitrendipine
Nimodipine
Nicardipine
Nisoldipine
Clevidipine
Felodipine
Amlodipine
Lacidipine
Isradipine

Question 2

What is the phenylalkylamines calcium channel blockers

Answer 2

Verapamil

Question 3

What are the Benzothiazepine calcium channel blockers?

Answer 3

Diltiazem

Question 4

Mode of action of calcium channel blockers?

Answer 4

Inhibition of L-type calcium channel

Question 5

Where do CCB have their effect?

Answer 5

They cause vasodilation and reduces BP in the smooth muscle, including bronchiolar, GI, and uterine SM
(Makes them good meds for COPD since they relax the bronchi SM)
And in some cases (Verapamil, Diltiazem) affect cardiac muscle as well

Question 6

Which CCB are coronary specific

Answer 6

Nicardipine and nisoldipine (50x more affinity)

Question 7

Which CCB is cerebral vessel specific

Answer 7

Nimodipine

Question 8

The CCB that act on cardiac muscle specifically causes?

Answer 8

act on L type calcium channel causing decreased pacemaker activity, AV conduction, and contractility

Question 9

Indications of CCB listed

Answer 9

1. ) Hypertension
2. ) Angina
3. ) Arrhythmias
4. ) Atherosclerosis
5. ) Raunaud’s phenomenon
6. ) Peripheral vasoconstriction
7. ) Migraine prophylaxis
8. ) GI spasms
9. ) Subarachnoid hemorrhage prevention

Question 10

Which CCB is used in pregnancy? In combination of what?

Answer 10

In the 1st and 2nd trimester nifedipine is used in combo with alpha-methyldopa

Question 11

What is used in hypertensive emergencies? Chronic?

Answer 11

Sublingual/mouth spray nifedipine (5 min onset) or IV nifedipine/clevidipine
For chronic treatment use longer release CCB

Question 12

How does CCB work for Angina and which drugs?
Used for Prinzmetal Angina?
Effort Angina?

Answer 12

1.)They increase peripheral vasodilation decreasing afterload
2.)Coronary vasodilation (such as Nifedipine and nicardipine)
3.)Cardio-depressant effects and tissue protective effects via decreased Ca levels causes decreased oxidation
Prinzmetal angina is treated with any CCB as first line treatment (usually nifedipine)
Effort angina treated with verapamil or diltiazem, decreased inotropy causes decreased load on heart and longer time in diastole phase (more oxygen)

Question 13

Unstable angina contraindications?

Answer 13

Nifedipine is contraindicated due to coronary steal syndrome and reflex tachycardia

Question 14

Drugs used in Supraventricular tachycardias like A Fib

Answer 14

Verapamil and Diltiazem

Question 15

CCBs used in atherosclerosis

Answer 15

Lacidipine and isradipine

Question 16

Lacidipine mechanism of action

Answer 16

high affinity for cholesterol rich tissues, so atherosclerotic plaque, and slowly diffuses out to receptor like depot

Question 17

Isradipine MOA

Answer 17

Improves lipid profile and increases HDL

Question 18

Nimodipine used for?

Answer 18

subarachnoid hemorrhage prevention in patients with berry aneurysms or prevent vasospasms following an SAH

Question 19

Which drug is used for Migraine

Answer 19

Verapamil

Question 20

Which drug is used for GI spasms

Answer 20

Pinacerine

Question 21

Kinetics of of CCBs

Answer 21

Good oral absorption, high pass effect, high plasma protein binding, and extensive metabolism

Question 22

Short acting (2-7 hours) CCBs

Answer 22

Verapamil, Diltiazem, Nicardipine, Nimodipine, and Nifedipine (the shortest acting one lasting 2 hours)

Question 23

Medium acting (8-11 hours) CCBs

Answer 23

Isradipine, Nisoldipine, and Nitrendipine

Question 24

Long acting (11-50 hours) CCBs

Answer 24

Amlodipine, Lacidipine

Question 25

Adverse effects of CCBs

Answer 25

1. ) Cardiac depression - Verapamil and diltiazem causes bradycardia, AV block, and cardiac arrest 2. ) Reflex Tachycardia (usually fast acting drugs) - immediate-acting nifedipine increases MI risk in HF patients via increased HR 3. )Gingival Hyperplasia (with verapamil) 4. )Vasodilatory side effects-flushing, dizziness, headache, peripheral edema 5. ) GI effects- nausea, constipation (via GI SM relaxation; >25% with verapamil)

Question 26

Contraindications/Interaction of CCBs

Answer 26

Heart block Heart failure in advanced or acute HF Beta blockers- coadministration of BB and non-DHPs can excessively depress nodal/ventricular function however BBs can be helpful with DHPs to decreased reflex tachycardia

Question 27

Specific Drugs contraindications

Answer 27

Verapamil- greatest cardio-depressant effects Diltiazem- intermediate cardio-depressive and vasodilatory effects Nifedipine- higher risk of sfx: flushing, headache and edema; increased mortality risk in post-MI patient due to reflex tachycardia

Question 28

Nitrate mode of action?

Answer 28

Metabolism in the vascular SM by CYP450 and glutathione S-thransferase causes the release of NO. NO activates guanylate cylcase increasing cGMP leading to decrease IC Ca2+ and MLC kinase activity causing relaxation of SM and vasodilation

Question 29

Where do Nitrates have their effect in low doses? | High doses?

Answer 29

Dilates coronaries and vein to decrease preload. In higher doses dilates arteries/arterioles decreasing afterload

Question 30

What causes tolerance of Nitrates?

Answer 30

metabolism requires -SH group; eventual sulfhydryl depletion

Question 31

Drugs that reduce the tolerance of nitrates? How do they reduce tolerance

Answer 31

NAS, captopril, antioxidants, or periodic withdrawal will decrease tolerance Contain sulfhydryl group so can replace metabolized store and remove free radicals

Question 32

What are the relevant cardiomyocyte function done by nitrates

Answer 32

ATP-dependent K+ channels stimulation reducing intracellular Ca2+ which is high in IHD

Question 33

Which form of nitrates forms tolerance quicker?

Answer 33

Pills and transdermal pathces

Question 34

Name of nitrate drugs

Answer 34

1. )Nitroglycerin 2. )Isosorbide mononitrate 3. )Isosorbide dinitrate 4. )Amylium nitricum

Question 35

Nitroglycerin sublingual and oral onset time? DOA?

Answer 35

1. ) Sublingual onset is 2-3 minutes with a DOA of 2-3 hours | 2. ) Oral onset is longer and DOA is 3-5 hours

Question 36

Isosorbide mononitrate onset and DOA?

Answer 36

Oral med that takes half an hour-2 hours onset with a 12-14 hour duration

Question 37

Isosorbide dinitrate absorption. Sublingual and oral onset and DOA?

Answer 37

transformed to mononitrate in liver. Sublingual 5-10 minute onset with a 1 duration of action Oral onset is 2-4 hour onset and 8 hour duration of action

Question 38

Amylium nitricum inhaled onset and duration of action

Answer 38

NOT used anymore as a drug in regular practice. | Fast onset with 5 min duration of action

Question 39

Indications of Nitrate drugs?

Answer 39

1. ) Angina- chronic stable (effort) and Prinzmetal angina (w/ CCB + BB) 2. )Acute coronary syndromes 3. ) Hypertensive emergency 4. ) pulmonary edema- as an acute treatment 5. ) Ischemic Heart Disease

Question 40

Contraindication of Nitrate drugs

Answer 40

1. ) Right-sided MI due to decreased RV preload (instead IV fluids to increase preload) 2. ) PDE5 inhibitor treatment- sildenafil should not be taken within 24 hours of nitrates 3. ) HOCM- LV outlfow obstruction + resultant decrease in ejection fraction is worsened by decreased preload from nitrate

Question 41

Side effects of Nitrate drugs

Answer 41

Lose dose 1.) Headache- strong cerebral vasodilation; increase migraine attack risk 2.) Flushing and dizziness High dose 1.) Orthostatic hypotension- via venous pooling 2.) Reflex tachycardia- coadmin BB to counteract this 3.) Methemoglobinemia- Prolonged IV infusion; nitrite reacts with hemoglobin causing ferrous to ferric iron conversion in Hgb which lowers Hemoglobin affinity for O2

Question 42

Nirate-related drugs (2 drugs)

Answer 42

Nicorandil and Molsidomin

Question 43

MOA of Nicorandil

Answer 43

``` NO donor (less tolerance) and direct ATP-dependent K+ channel stimulator -decreases preload and dilates coronaries ```

Question 44

MOA of Molsidomin

Answer 44

SIN-1 (active metabolite) direct vasodilaters and a spontaneous NO donor (doesn't need -SH enzymes) -Decreases preload and dilates the coronaries

Question 45

Other Vasodilators (5 drugs)

Answer 45

1. ) Sodium Nitroprusside 2. ) Minoxidil 3. ) Diazoxide 4. ) Hydralazine 5. ) Dihydralazine

Question 46

Sodium Nitroprusside MOA

Answer 46

Releases NO causing systemic vasodilation (both arterial and venous) which decreases pre/afterload almost immediately

Question 47

Sodium Nitroprusside Indications

Answer 47

Hypertensive emergency and severe HF that is refractory (doesn't respond to any other drugs)

Question 48

Sodium Nitroprusside Side Effects

Answer 48

1. ) Lactic acidosis from CN- release causing altered mental status/seizures, monitor lactate continuously 2. ) Intoxication after 2 days use causes headache, nausea, vomiting, and disorientation 3. )Hypotension

Question 49

Sodium Nitroprusside Kinetics and byproduct

Answer 49

Onset is 30 seconds and 3 of DOA (given in slow infusion for long duration) -Sulphocyanide is formed from it in the liver leading to side effects; elimination takes 3 days to occur

Question 50

Minoxidil and Diazoxide MOA

Answer 50

Stimulates ATP-dependent K channels causing hyperpolarization leading to inhibit Ca influx=SM relaxation Mainly arterial vasodilation

Question 51

Minoxidil and Diazoxide side effects

Answer 51

1. ) Salt and water retention via indirect renin section increases 2. )Increased blood glucose (hyperglycemia)- stimulation of beta cells SUR K channels 3. ) Increased Uric acid (hyperuricemia) 4. ) Increased hair growth- minoxidil is used as a topical cream for hair loss

Question 52

Minoxidil and Diazoxide indication

Answer 52

Hypertensive emergencies- combine with BB to reduce tachycardia and diuretic to decrease Na/water retention

Question 53

Minoxidil and Diazoxide contraindications

Answer 53

Ischemic heart disease since they cause reflex tachycardia

Question 54

Hydralazine and Dihydralazine MOA

Answer 54

Direct arteriolar dilation (little effect on veins) causing decreased afterload

Question 55

Hydralazine and Dihydralazine kinetics

Answer 55

Parenteral administration

Question 56

Hydralazine and Dihyrdalazine Indications

Answer 56

Hypertension emergencies, safe in pregnancy so used in pre-eclampsia (In combo with nitrate venodilator, to treat symptoms and decrease in LV dysfunction HF)

Question 57

Hydralazine and Dihyrdalazine Side Effects

Answer 57

- Sudden hypotension- reflex tachycardia and Na/water retention (via SNS and RAAS activation) and may worsen angina (often co-admin with BB to counterat this) - Lupus-like syndrome athralgia, myalgia, percarditis, pleuritis, rash and fever