Pharm - All drugs Flashcards
(42 cards)
Statins
inhibit HMG CoA reductase (RLS of cholesterol synthesis in hepatocytes), upregulate LDL receptors; fecal 60%/renal 20% elimination; AEs include mild GI & sleep disturbance, increased liver enzymes, myalgia/myositis, rhabdomyolysis, teratogenic (CatX)
Lovastatin
CYP3A4. lipid soluble. intermediate potency. 20-40mg.
Simvastatin
CYP3A4. lipid soluble. 10-40mg.
Pravastatin
water soluble. low potency. 10-80mg.
Atorvastatin
CYP3A4. active as given and long half life. high potency.
Rosuvastatin
CYP2C9 (minimal). active as given.
Fluvastatin
CYP 2C9.
Bile acid resins/sequestrants
these bind bile acids in GI lumen and prevent reuptake/reuse of the cholesterol in the bile acid; fecal elimination; AEs include GI disturbance (bloating, constipation, nausea, flatulence), also fecal impaction and paradoxical HTG; can prevent uptake of other drugs. Includes Colestipol, Cholestyramine, Colesevelam.
Cholesterol Absorption Inhibitor(s)
acts at the epithelial brush border in the small intestine to prevent uptake of cholesterol from the diet, also upregulates LDL receptor expression in hepatocytes. Only one in class is Ezetimibe.
Nicotinic acid
inhibits FFA mobilization from adipocytes and thereby reduces hepatic VLDL synthesis, enhances LPL and thereby promotes VLDL-->LDL conversion; AEs include cutaneous flushing, elevated transaminases, hepatitis, liver failure, GI disturbance (nausea, peptic ulcers), hyperurecemia/gout, conjunctivitis, cystoid macular edema, retinal detachment, myositis, dry skin, pruritis, insulin resistance, teratogenic (catC); available in immediate and extended release forms. Only one in class is Niacin.
Fibrates/Fibric acid derivatives
serves as ligand for nuclear receptor PPARalpha in hepatocytes; reduces synthesis of VLDL and raises synthesis of HLDL
Gemfibrozil
UGT1A1. safe in renal disease. don’t co-administer with statins (UGT enzyme interference).
Fenofibrate
hepatic metabolism. renal elimination. don’t administer in renal disease (can accumulate).
N-3 Fatty acids
ligand for PPARalpha nuclear receptor in hepatocytes; reduces TG synthesis by increased FA oxidation. Best source is fish oil.
Common mechanism of cholesterol lowering drugs:
increased expression of LDL receptors and increased LDL uptake
MOA of Beta-blockers
Blocks beta-1 (NE, heart and kidneys) and/or beta-2 (NE, lungs; Epi, skeletal muscle vessels) receptors.
When blocked:
Beta-1:
- inhibit stimulation of SA/AV node/ectopic pacemakers –> dec. HR
- inhibit myocytes –> dec. contractility
- inhibit juxtaglomerular cells –> don’t release renin
Beta-2:
- inhibit skeletal muscle vessels –> vasodilation
Altogether treats HTN.
MOA of alpha-2 antagonists
Block the alpha-2 receptor, which is a NE autoregulatory receptor. Stimulating alpha-2 inhibits NE release, blocking it promotes NE release. Central effects outweigh the local (vessel) effects.
When do you want to use CCBs?
DHPs - together with beta-blockers for vasodilation and reduced afterload in sinus bradycardia, SA/AV block, or valvular insufficiency
Non-DHPs - in asthma/bronchospastic COPD, severe PVD, and labile (variable glu levels) IDDM
MOA of Ranolazine.
Clinical uses and contraindications.
A novel metabolic modulator that is a partial FA oxidase inhibitor, which increases glucose oxidation and efficiency of O2 utilization in the heart. Also inhibits the late Na current. No effect on HR/BP or cardiac event prevention.
Used for chronic stable angina together with amlodapine, BB, or nitrates when refractory to these.
Contraindicated in concurrent CYP3A4 inhibitors (or hepatic impairment), tricyclic antidepressants, or existing long-QT.
Hierarchy of drug choice in agina
- Beta-blockers (unless vasospastic angina, then these are ineffective)
- CCBs (DHP+BB)
MOA of Nitrates
enter smooth muscle cell and undergoes denitration to release NO, which induces relaxation by activating GC and increasing cGMP. Dilation of coronaries increases flow to myocardium, and venodilation results in decreased preload which reduces wall stress: so the subendocardial blood vessels have less resistance (heart wall has less pressure on it) and there is less O2 demand. Beware of tolerance - don’t dose at night.
MOA of Ranolazine.
Clinical uses and contraindications.
A novel metabolic modulator that is a partial FA oxidase inhibitor, which increases glucose oxidation and efficiency of O2 utilization in the heart. Also inhibits the late Na current. No effect on HR/BP or cardiac event prevention.
Used for chronic stable angina together with amlodapine, BB, or nitrates when refractory to these.
Contraindicated in concurrent CYP3A4 inhibitors (or hepatic impairment), tricyclic antidepressants, or existing long-QT.
What meds are used to prevent MI and CHD death in patients with angina?
Preventing CHD death: Beta-blockers work best. CCBs do sometimes. Nitrates dondo not.
ASA reduces reinfarction, CHD death, and stroke.
ACEIs increase survival in pts post-MI with LV dysfunction; reduces MI in high-risk pts.
Thrombolysis reduces first year mortality following MI.
Statins reduce recurrent MI.; HDL raisers reduce recurrent MI/CHD death
MOA of Ca channel blockers
CCBs bind L-type Ca channels (specific to the CV system; not N- and P-type in neurons) and increase the time they are closed, thereby prevent Ca entry into the cell (cardiac myocytes and [more so arterial] vascular smooth muscle cells). Closing the channels prevents Ca entry and contraction (normally Ca will bind troponin and release inhibition of actin-myosin cross bridges, allowing contraction). Result is vasodilation, reduced afterload, reduced inotropy, slowed AV conduction. DHPs are selective vasodilators and non-DHPs are equipotent for cardiac tissue (myocytes, SA&AV nodes) and vasculature.
