A18. Drugs used for the treatment of peripheral vascular diseases. Therapy of migraine Flashcards
List the general drugs for Pheripheral vascular disease?
- CCBs: Diltiazem Nifedipine Felodipine Amlodipine flunarizine cinnarizine
- PDE inhibitors: Cilostazol Sildenafil Tadalafil
- α1 blockers: prazosin
- Prostaglansins: Alprostadil Iloprost Epoprostenol
- Others: Penthoxyphylline nicergoline Vinpocetin Niacin Naftidrofuryl
MOA?
o vasodilation o rheological effect: modifies red blood cells o inhibit platelet aggregation
Indications?
indicated in circulatory problems of the: o skin: ulcers, gangrene, Raynaud o skeletal muscles o cerebral vessels
Cinnarizine, flunarizine?
o inhibit calcium channels (including in smooth muscle), inhibit platelet aggregation, decrease red blood cell rigidity, inhibit histamine receptors o indications: peripheral circulatory problems, Meniere disease, brain circulatory problems, can be migraine prophylaxis o oral administration o side effects: depression, somnolence o CI: depression, lactation
What is the MOA of Vinpocetine?
It increases cerebral perfusion
Pentoxifylline?
a methylxanthine derivative (like theophylline) o improves red blood cell pathological formation, inhibits platelet aggregation, and decreases blood viscosity o indicated in atherosclerotic and diabetic circulatory problems, intermittent claudication, sickle cell anemia o oral administration o side effects: GI disturbances, tachycardia, angina, flushing, allergy
What is the MOA of Naftidrofuryl?
o increase peripheral circulation with complex MOA o indicated in Raynaud, other peripheral problems o side effects: arrhythmia, hypotension, angina. CI if have these problems already
Bencyclane?
o vasodilator, improves red blood cell flexibility, inhibits platelet aggregation, visceral spasmolytic (inhibits Ca2+ channels o oral or parenteral administration o indicated in Raynaud, brain circulatory problems, visceral spasmolytic disorders o side effects: GI, CNS (seizures), allergy, arrhythmia o interactions: contraindicated to use with calcium channel blockers, drugs which cause seizures, cardiac glycosides, sympathomimetic drugs, and drugs which cause hypokalemia o contraindications: AV block, MI, epilepsy, hypersensitivity
Types of headaches?
Headache syndromes • tension headache: headache returns very frequently. the most common kind. feel something compressing skull. not normally considered a disease, unless very frequent • cluster headache: also 1-sided headache, but not like migraine. constant, comes in periods like “clusters.” can cause lacrimation, salivation. more typical in men. “express pain” more than migraine patients - loud. • treatment of cluster headache: verapamil: high-dose (800-1000 mg). this would seem enough to cause them to collapse from hypotension, but doesn’t. doesn’t cause heart block either • migraine: usually 1-sided throbbing headache. Patients often have an “aura,” visual disturbances (e.g. narrowing visual field), and nausea/vomiting. must avoid strong light and noise to make H/A less intense. more common in women than men o causes: unclear. seems to be sterile inflammation with strange EEG pattern preceding the migraine attack. o there is an initial meningeal vasoconstriction that is mediated by serotonin receptors. serotonin is used up, and afterwards → vascular permeability increases. local edema appears via the local hormones that are released: NO, CGRP, substance-P, bradykinin. This increases pressure and causes severe pain.
Therapy for Migraine
Treatment of migraine: o ongoing attack: • serotonin 1B/1D, 1F agonists: acting on these causes vasoconstriction in vessels + ↓ nausea ▪ Sumatriptan: first drug, still used. ▪ Others: Naratriptan, Eletriptan ▪ orally given drugs, 1 dose is usually enough. ▪ Side effects: most important is sudden cardiac death. See below for others. ▪ no cross-resistance between these agents. if sumatriptan doesn’t work, can try the others. ▪ if none of these drugs act, then it’s a problem because we don’t have good agents against ongoing attack. Ergot alkaloids (e.g. ergotamine) may still be used in some countries but are not preferred due to their toxicity. • NSAIDs: high-dose diclofenac can be used, but not as effective. only mild migraines o prophylaxis: • beta blockers: propranolol, metoprolol. probably the mildest prophylaxis. • calcium channel blockers: verapamil, dihydropyridines • antiepileptics: valproate • TCAs: amitriptyline • SSRIs: may also help • [CGRP antagonist antibody: under investigation] o if someone has proven migraine, do NOT give nitrates because they can provoke attack. nitrates frequently cause an immediate headache, but in people who have migraines the nitrate will create a delayed effect with migraine ~ 4 hours later
Nicotinic acid aka Niacin?
o decreases triglyceride level, causes vasodilation o oral or parenteral administration o indicated in atherosclerotic circulatory problems, vasospasm o side effects: flushing, hypotension, tachycardia, GI disturbances
Sodium pentosan polysulfate?
o has rheological and anti-inflammatory effects, improves endothelial regeneration o indicated in arterial or venous thrombosis, thromboembolism, thrombophlebitis, diabetic and degenerative circulatory problems o oral or IM administration o side effects: allergy, diarrhea. CI: bleeding, surgery, precaution in pregnancy o interactions: CI to use with diuretics. precaution to administer with heparin, other anti-coagulants
What drugs are used for Raynaud disease?
- Dihydropyridine calcium channel blockers: (e.g. Amlodipine) can be used for Raynaud
- Tolazoline: Non-selective α1 + α2 blocker, also inhibits MAO and causes vasodilation, used for Raynaud (Remember the β blockers are contraindicated in Raynaud disease)
What are the indications for Vinpocetine?
It is indicated in brain circulatory problems and memory disturbances.
What is the MOA of Nicergoline?
Nicergoline is an ergoline derivative. It blocks α1 receptors, inhibits platelet aggregation, enhances dopamine turnover in brain.
