Pharmacology of Non-Dihydropyridine CCBs

Study Notes

Non-dihydropyridine CCBs, such as diltiazem and verapamil, are more selective for cardiac tissues compared to vascular smooth muscle.
Verapamil significantly decreases heart rate; diltiazem has a lesser effect.
CCBs are primarily used for managing angina pectoris and hypertension, with non-dihydropyridines also treating cardiac arrhythmias.
Effective in treating angina linked to coronary vasospasm.
Nimodipine, related to nifedipine, specifically targets cerebral arteries for vascular spasms post-aneurysmal subarachnoid hemorrhage.
Verapamil is indicated for cluster headache and migraine prophylaxis; nifedipine treats Raynaud’s syndrome and chronic anal fissure.
Amlodipine and felodipine allow once-daily dosing due to their extended duration of action.
Common side effects include flushing, headache, and ankle swelling; verapamil is known for causing constipation.
Amlodipine and other CCBs should generally be avoided in patients with heart failure as they may worsen cardiac function.

Designed to modify blood lipid levels, helping manage dyslipidemias and reduce cardiovascular risks.
Main classes of lipid-regulating drugs include:
- Statins (e.g., atorvastatin, rosuvastatin)
- Fibrates (e.g., fenofibrate, gemfibrozil)
- Nicotinic acid (e.g., acipimox)
- Bile acid sequestrants (e.g., colesevelam)
- Absorption inhibitors (e.g., ezetimibe)
- Others (e.g., alirocumab, evolocumab)
Statins block HMG-CoA reductase, crucial in cholesterol synthesis, effectively lowering LDL but less effective than fibrates for triglycerides.
Statins are used for primary and secondary prevention in dyslipidemia with documented coronary artery disease.
Rosuvastatin and atorvastatin have the longest half-lives and are preferred due to lower hepatotoxicity risks.
Omega-3 fatty acids can reduce triglyceride levels significantly and are utilized as adjunct therapy in hypertriglyceridemia.
PCSK9 inhibitors (alirocumab, evolocumab) can reduce LDL-C by up to 60% in combination with statins, administered subcutaneously.
Lomitapide and mipomersen are for homozygous familial hypercholesterolemia and have black box warnings for hepatotoxicity.
Bempedoic acid lowers LDL-cholesterol and is indicated for inadequate responses to other therapies.

Nitrates are vasodilators used for angina pectoris, heart failure, myocardial infarction, and anal fissures.
Sublingual Glyceryl Trinitrate (GTN) offers rapid relief from angina; aerosol sprays are alternatives for ease of use.
Proper usage involves placement under the tongue without swallowing or inhaling.
Patient instructions for managing acute angina include rest, GTN administration, and seeking medical help if pain persists after three doses in 15 minutes.

Categories include direct thrombin inhibitors (e.g., dabigatran) and direct factor Xa inhibitors (e.g., rivaroxaban, apixaban).
DOACs provide rapid onset, predictable pharmacokinetics, and eliminate the need for routine monitoring compared to warfarin.
For treating or preventing recurrent VTE, edoxaban and dabigatran require initial treatment with parenteral anticoagulants for five days.
Lower risks of intracranial hemorrhage are associated with target-specific anticoagulants.
Idarucizumab reverses dabigatran effects, while andexanet alfa reverses apixaban and rivaroxaban effects.

Injectable direct thrombin inhibitors include lepirudin, bivalirudin, argatroban, and desirudin; they are preferred in patients with a history of heparin-induced thrombocytopenia (HIT).
Fondaparinux serves as an effective alternative to low molecular weight heparin (LMWH) for VTE treatment and prevention after surgery without routine coagulation testing requirements.

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