Drugs Used For The Treatment Of Hypertension II: Ca++ Channel Blockers And Other Vasodilators Flashcards
Name the Class I calcium channel blockers
Verapamil
Gallopamil
Name the Class II calcium channel blockers
Diltiazem
Name the short acting Class III calcium channel blockers
Nifedipine
Nicardipine
Nimodipine
Name the intermediate acting class III calcium channel blockers
Nitrendipine
Nisoldipine
Felodipine
Isradipine
Name the long acting class III calcium channel blockers
Amlodipine
Lacidipine
Lercanidipine
Manidipine
What receptor do calcium channel blockers work on?
L type voltage-gated Ca2+ channels
What is the result of CCBs binding to the L-type voltage gated calcium channel?
Depression of the heart (contraction and automaticity) and vasodilation
What are the pharmacokinetic properties of CCBs?
High plasma protein binding
Inactivation by CYP3A4
Which enzyme is responsible for the inactivation of CCBs?
CYP3A4
What is a pharmacodynamic property of verapamil?
Verapamil enhances the plasma level of digoxin - therefore they should not be given together
What are the serious toxicities associated with CCBs?
AV block
Cardiac depression
Bradycardia
What are the minor toxicities associated with CCBs?
Hypotension Dizziness Headache Angioedema Nausea Constipation Gingival hyperplasia (Reflect tachycardia - DHP)
What are the contraindications of CCBs?
Pregnancy
Short acting DHP in IHD
What is the general name for the CCBs in Class I?
Are these drugs selective or non-selective?
Phenylalkilamines
Non-selective
What are the indications for Class I CCBs?
Angina (stable, unstable, Pritzmental)
Supraventricular arrhythmia
Hypertension
What is the general name of the CCBs in Class II?
Non-selective
Benzothiazepines
Non-selective
What are the clinical uses of Class II CCBs?
Angina (stable, unstable, Pritzmental)
Supraventricular arrhythmia
Hypertension
What is the general name for Class III CCBs?
Are they selective or non-selective
Dihydropyridines (DHP)
Vasoselective
How is Nifedipine administered?
IV
Tablet spray
Slow releasing tablets
What are the clinical uses of Nifedipine when administered via IV?
Pritzmental angina
Hypertonic crisis
What are the clinical indications of Nifedipine when administered via tablet spray?
Prevention of stroke
When is Nifedipine given in slow releasing tablets?
Long-term treatment
What is the clinical use of Nimodipine?
Subarachnoid bleeding
What is the clinical indication of Isradipine?
Arteriosclerosis
What is the half life of Amlodipine?
Long plasma half life.
What is the dose of Amlodipine?
1x 5-10 mg
What is the characteristic of lacidipine?
High lipid solubility accumulation in the lipid membrane so can be useful in the management of atherosclerosis.
Plasma T 1/2 short
What is the characteristic of Lercanidipine?
High lipid solubility accumulation in the lipid membrane so can be useful in the management of atherosclerosis.
Plasma T 1/2 short
What is the characteristic of Manidipine?
High lipid solubility accumulation in the lipid membrane so can be useful in the management of atherosclerosis.
Plasma T 1/2 short
Which DHP have high lipid solubility accumulation in the lipid membrane and Plasma T 1/2 short
Lacidipine
Lercanidipine
Manidipine
What are the clinical uses of DHPs?
Angina (stable and unstable)
Hypertension
Peripheral vascular disease (e.g., Raynaud disease)
Name the direct acting vasodilators that work through NO
Hydralazine
Nitroprusside sodium
Which direct acting vasodilator works on arteries?
Hydralazine
Which direct acting vasodilator has a direct affect on the arteries?
Hydralazine
What is the clinical indication of Hydralazine?
Preeclampsia and eclampsia in pregnancy
Which direct acting vasodilator acts on the arterial and the venous side?
Nitroprusside sodium
What is the clinical indication of Nitroprusside sodium?
Not used nowadays
Was used for hypertensive emergencies (administered IV)
What are the side effects of nitroprusside sodium?
Cyanide toxicity
How to differentiate between drug induced lupus and SLE?
Drug induced lupus will regress after removal of the drug
Anti-his tone antibodies are present only in drug induced lupus
What are the K+ channel stimulants?
Minoxidil
Diazoxide
What is the pathomechanism of K+ channel stimulants?
They open K+ channels causing hyperpolarazation of smooth muscle.
What is the result of K+ channel stimulants?
Arteriolar vasodilation
What are the clinical uses of Minoxidil?
Alopecia to promote hair growth
Severe hypertension
When is Minoxidil given orally?
Only in very severe cases of alopecia
How is Minoxidil administered in mild to moderate alopecia?
Topically to promote hair growth
What are the clinical indications of Diazoxide?
Hypertensive crisis
Insulinoma
Why is Diazoxide used as treatment for insulinomas?
Diazoxide binds to and opens K+ channels causing hyperpolarisation of the beta cell, decreased calcium influx which results in decreased insulin release.
How is Diazoxide administered in hypertensive crisis?
Oral or IV
What are the adverse effects of K+ channels stimulants?
Hypertrichosis (Minoxidil) Hyperglycemia (Diazoxide) Edema Reflex tachycardia Increased cardiac O2 demand
What is the action of Fendoldopam mesylate?
Dilation of renal, mesenteric and coronary arteries
What sort of drug is Fenoldopam mesylate?
D1 receptor agonist
How is Fenoldopam administered in the treatment of HTN?
IV infusion
Which subunit do CCBs bind to?
Alpha 1 subunit
Where does Diltiazem bind?
EC surface of the L type voltage gated Ca+ channel
Where does verapamil bind to?
The inner cytoplasmic part of the L type voltage gated Na+ channel
What are the clinical indications of verapamil?
Migraine - causes vasodilation of cerebral vessels
Where are the L type calcium channels found?
Cardiac, skeletal, smooth muscle, neurons, endocrine cells and bones
What can hydralazine be administered in combination with?
b blockers and diuretics
What are the side effects of Hydralazine?
It increases the O2 demand on the heart Tachycardia Increased renin release leading to water retention Headache Vomiting Allergic reaction Drug induced lupus Edema Reflex tachycardia
What are the side effects of diazoxide?
Reflex tachycardia
Can provoke angina and MI in IHD patients
It increases blood sugar and uric acid levels - so pre existing metabolic disorders are worsened.
How does nitroprusside sodium have vasodilation effects?
NSP binds to hemoglobin: releasing cyanide, methemoglobin and NO.
What is the mechanism of action of NO?
NO activates guanylate cyclase in vascular smooth muscle and increases intracellular production of cGMP. cGMP activates protein kinase G which activates phosphatases which inactivate myosin light chains. Myosin light chains are involved in muscle contraction. The end result is vascular smooth muscle relaxation, which allow vessels to dilate
What is methemaglobin?
Hemoglobin in which the iron in the heme group is in the ferric (Fe3+) state
How does nitroprusside cause cyanide poisoning?
It binds to Hb forming metHb, which binds CN- ions forming cyanomethemoglobin. Cyanomethemoglobin means that there is no CN- to inhibit complex IV of the ETC. This leads to histotoxic hypoxia as cells are unable to make ATP.
What is the mechanism of action of sodium thiosulfate?
it converts cyanomethemoglobin to methemoglobin and thiocyanate
What is the treatment of cyanoxide poisoning?
Sodium thiosulfate
What is the mechanism of action of methylene blue?
It is used in the treatment of methemoglobinemia - it converts MetHb to oxyHb
