Toxicology - Exam 1 (CVD, Lipids, Anti-clotting drugs)

Hypertension

>130mmHg or >80mmHg

Antihypertensives lower BP via three ways

sympathetic NS signaling to head, vasculature, kidneys (sympatholytics)

RAAS or directly on kidney (diuretics, ACE inhibitors, ARBs)

smooth muscle of vasculature (calcium channel blockers)

Drugs for heart failure

sympatholytics

diuretics

ACE inhibitors

ARBs

vasodilators (NOT calcium channel blockers)

MC drug used for angina

antianginals - nitrates, calcium blockers, beta-blockers

Sympatholytics are used in

HTN, CHF, Angina

Diuretics are used in

HTN and CHF

ACE inhibitors are used in

HTN and CHF

Angiotension receptor antagonists (ARBs) are used in

HTN and CHF

Vasodilators are used in

HTN, CHF, Angina

Sympatholytics (adrenergic receptor antagonists)

Epi/NE blockers

MC prescribed block beta adrenergic receptors (beta-blockers)

Normal physiology - Beta-1 (heart and kidney)

stimulation produces cardiac stimulation (inc HR, contractility, conduction velocity)

increase renin secretion from juxtaglomerular cells

Normal physiology - Beta-2 (smooth muscle)

stimulation relaxes bronchial, uterine, peripheral vascular smooth muscle

mediates glycogenolysis in liver to increase blood glucose

Beta-1 antagonists

block renin secretion

leads to decrease in CO (HR and contractility), HR, BV = decrease BP

Beta blockers in CHF

decrease sympathetic stimulation

decrease energy demands on heart

decrease stimulation of RAAS

Beta blockers in Angina

decrease HR, BP, contractility

prevent coronary vasospasm (vasodilation to dec pressure)

Two types of beta-blockers

non-selective beta blockers

selective beta blockers

Non-selective beta blockers

block BOTH receptor types 1+2

more side effects

Adverse effects of non-selective beta blockers

bronchoconstriction in asthmatics and COPD

peripheral vasoconstriction in Raynaud’s

diabetics inhibit epi stimulated glycogenolysis in liver

Selective beta blockers

block ONLY Beta-1 receptors

cardio selective = preferred use in HTN, CHF, angina, arrhythmias

Adverse effects of all beta blockers

hypotension and bradycardia

fatigue and insomnia

erectile dysfunction

inc triglycerides and dec HDL cholesterol

TQ = T/F Do NOT abruptly discontinue tx with these drugs (lead to MI or sudden death in pt with ischemic heart disease)

True

Interactions of all beta blockers

NSAIDs - decrease effectiveness

herbs and supplements used for lowering BP or anti-diabetic

• elevated risk for hypoglycemia

Nutrient depletions of all beta blockers

CoQ10

melatonin

Beta blocker names

End in -olol (propranolol, atenolol, metaoprolol (MC), nebivolol, caredilol)

Diuretics

reduce blood volume which decreases CO and eventually peripheral vascular resistance

prevents reabsorption of sodium (water follows sodium excretion)

lowers BP by 10-15mmHg

Types of Diuretics

Thiazides (distal convoluted tubule)

Loop (loop of henle)

Potassium-sparing (collecting duct)

Thiazides clinical uses

HTN, CHF, osteoporosis

Thiazides names

End in -ide (hydrochlorthiazide, indapamide)

Adverse effects of thiazides and loop diuretics

hypokalemia, hyponatremia, hypomagnesemia

hyperuricemia and hyperglycemia

allergic reactions

Drug/herb interactions of thiazides and loop diuretics

NSAIDs - diminish effects of drugs

anthroquinone glycoside laxitives - electrolyte disturbances

glycyrrhiza glabra

taraxacum

Nutrient depletions of thiazides and loop diuretics

potassium, sodium, magnesium

zinc

vitamins C, B1, B6

Nutrient depletions via thiazides only

CoQ10

Loop diuretics clinical uses

intensive diuresis in CHF, acute hypercalcemia, tx resistant HTN

Loop diuretic names (Lasix)

End in -ide (furosemide, bumetanide)

Adverse effects of Loop diuretics

hypocalcemia and ototoxicity (reversible hearing loss)

Nutrient depletions caused by only loop diuretics

calcium

Potassium-sparing diuretics

function on sodium transporters that are affected by aldosterone

they block them causing sodium excretion and potassium retention

Potassium-sparing diuretics clinical uses

HTN and CHF and Conn’s syndrome (secondary hyperaldosteronism)

Potassium-sparing diurteic names

Spironolactone, amiloride, triamterene

Spironolactone (potassium-sparing diuretic)

aldosterone analog and receptor antagonist

also used as androgen blocker for PCOS/PMOS

Adverse effects of potassium-sparing diuretics

hyperkalemia

androgen blocking effects

acute renal failure

trimeterene can cause kidney stones

Drug/herb interactions with potassium-sparing diuretics

potassium supplements and diet rich in potassium

triamterene w/indomethacin = acute renal failure

Nutrient depletions from potassium-sparing diuretics

amiloride = folic acid and calcium

triamterne = folic acid, calcium, zinc

ACE inhibitors

blocks formation of vasoconstrictor angiotensin II

blocks degradation of vasodilator bradykinin

ACE inhibitor names

End in -pril (lisinopril, captopril, enalapril)

Clinical uses for ACE inhibitors

HTN, CHF, post-MI, diabetics

Adverse effects of ACE inhibitors

cough (w/inc bradykinin levels)

taste change (drug binds to zinc)

pregnancy problems (fetal death in 2/3tri)

Drug/herb interactions of ACE inhibitors + ARBs

antacids

potassium-sparing diuretics

NSAIDs

Nutrient depletion from ACE inhibitors + ARBs

zinc

Angiotension Receptor Antagonists (ARBs)

block angiotension receptors in vascular smooth muscle and adrenal cortex

causes vasodilation and decreased aldosterone secretion

inhibits angiotension action MORE than ACE inhibitors and don’t inhibit bradykinin

• pts don’t cough

ARBs names

End in -sartan (losartan, valsartan, olmesartan, irbesartan)

Clinical uses for ARBs

HTN, CHF, post-MI

Adverse effects of ARBs

pregnancy problems (fetal death in 2/3tri)

Vasodilators (Calcium channel blockers)

relax smooth muscle of arterioles (decrease systemic resistance) = decrease BP

inhibit calcium flow into smooth and cardiac muscle cells = decrease contraction

Clinical uses of calcium channel blockers

HTN, angina, arrhythmias

Calcium channel blockers names

End in -pine (amlodipine, felodipine, nifedipine, verapamil, diltiazem)

Adverse effects of calcium channel blockers

suppress cardiac contractility (contraindicated in CHF pts)

hyptension/syncope

(MC) peripheral edema

Drug/herb interactions with calcium channel blockers

melatonin

increase statin levels (if taking with)

grapefruit juice

What is the ONLY drug class that NSAIDs don’t impact

vasodilators - calcium channel blockers

Positive inotropes (Digoxin)

used in CHF and arrhythmias

increase force of heart contraction (directly inhibit Na/ATPase in cardiac myocytes)

narrow therapeutic window + long half-live = easy to overdose

Potassium channel blockers are used in

CHF and arrhythmias

8 ways drugs are used to lower blood lipids

statins - decrease cholesterol production by liver

ezetimibe - prevent absorption of dietary cholesterol

PCSK9 inhibitors - increase LDL receptors in liver

lipoprotein a lowering drugs

bile acid binding proteins - prevent enterohepatic recycling of bile acids

fibrates - affect transcription of genes associated w/lipid metabolism

niacin - decrease release of FFAs from adipose tissue

EPA/DHA fatty acid esters (fish oil) - dec production of triglycerides

HMG-CoA Reductase Inhibitors (statins)

End in -statin (lovastatin/parent compound, atorvastatin (MC), simvastatin, rosuvastatin)

HMG-CoA Reductase inhibitors characteristics

competitive inhibitors or rate limiting step in cholesterol biosynthesis

HMG-CoA Reductase enzyme job

converts HMG-CoA → melavonate

HMG-CoA Reductase inhibitors reduce ____ causing

hepatic cholesterol synthesis and serum levels; increased expression of LDL receptors on liver (cholesterol is pulled from periphery)

What may be a risk factor when taking HMG-CoA Reductase inhibitors

insulin resistance

HMG-CoA Reductase inhibitors clinical use

hypercholesterolemia

mixed hyperlipidemia

slow progression of atherosclerosis

HMG-CoA Reductase inhibitors adverse effects

elevate serum hepatic enzymes → hepatitis

myalgia, rhabdomyolysis, acute renal failure

Individuals can take ____ to decrease the risk of muscle issues while using HMG-CoA Reductase inhibitors

CoQ10

Interactions with HMG-CoA Reductase inhibitors

fibrates + lots of niacin (inc myopathies)

drugs metabolized by CYP3A4 (inc serum levels)

grapefruit juice (inc serum levels)

red yeast rice (acts as a statin too)

Contraindications to taking HMG-CoA Reductase inhibitors

pregnancy (fetal abnormalities)

Nutrient depletions with HMG-CoA Reductase inhibitors

CoQ10 (at least 100mg/d)

L-Arginine relationship with HMG-CoA Reductase inhibitors

co-administration can enhance triglyceride-lowering effect

Vitamin D relationship with HMG-CoA Reductase inhibitors

deficiency can increase risk of myalgia

LDL targets for high