enzyme to sythesize cholesterol

inhibited by statins

produces only small increase in blood levels

inhibits endogenous cholesterol production

component of all cell membranes and membranes of intracellular organisms

required for synthesis of certain hormones (reproductive) and bile salts

deposited in stratum corneum of skin

recog. sites for cell-surface receptors

activate enzyme that metabolize lipoprotiens

increases structural stability of lipoprotiens

Diabetes

inc. age

HTN

smoking

dec. HDL, inc. LDL

Family Hx

Therapeutic lifestyle changes

TLC diet

weight control

excercise

smoking cessation

Drugs should be used only if these fail

Atorvastatin (Lipitor)

most effective

reduces LDL

elevates HDL

Reduces triglycerides

Non lipid action: promotes plaque stability, reduces risk for CV event, inc. bone formation

hypercholesterolemia

primary and secondary prevention of CV events

post MI therapy

diabetes?

dec. risk of stroke

Common: HA, Rash, Gi disturb.

Rare: myopathy(muscle pain, weakness, tenderness)/rhabdomyolysis(muscle dissolves)

hepatotoxicity(monitor LFT, baseline, then 6-12 Months)

peripheral neuropathy

maybe connection with parkinsons

most lipid lowering drugs (except bile acid sequesterants)

Drugs that inhibit CYP3A4 (macrolide antibx, antifungals,

once daily in evening

greatest impact when given in evening because endogenous cholesterol syn. goes up in the night

nicotinic acid (niacin)

Niaspan (long acting niacin)

Reduces LDL and TG levels (better at dec. TG)

inc. HDL more effectively than any other drug

dec. production of VLDL

lowering TG levels

mixed elevation of LDL's and TG's

used for low HDL's

skin (flushing, itching): initially intense preTx w/ ASA

Gastrointestinal: hepatotoxicity

hyperglycemia

gouty arthritis

raise blood level of homocysteine (inc. risk for CHD)

Colesevelam (Welchol)

previously first line drugs but now adjunt to statins

reduction in LDL

inc. in VLDL (in some Pts)

not absorbed in GI, Binds with bile acids

also lowers LDL by inc. LDL receptors on hepatocytes

Constipation

does not decrease uptake of fat-soluble vitamins (as other bile sequesterants do)

does not significantly reduce absorprtion of statins, warfarin, or digoxin

most effective drugs for lowering TG levels

can raise HDL

Little to no effect on LDL

can inc. risk for bleeding for Pts on warfarin(watch PT-INR)

can inc. risk for rhabdomyolysis in Pts taking statins

Dec. plasma TG content

Lowers VLDL

Can raise HDL

ppar alpha?

Displaces warfarin from plasma albumin

measure INR frequently

reduces high levels of plasma triglycerides and VLDLs

less effective than statins in reducing LDL

can raise HDL (not approved for this)

rashes

GI disturb.

gallstones

myopathy

liver injury (hepatotoxic)

Ezetimibe (Zetia)

inhibits cholesterol absorption in small intestine

reducing total cholesterol, LDL, and apolipoprotien B

approved for monotherapy and combonation with statins (slightly inc. risk for liver damage)

myopathy

rhabdomyolysis

hepatitis

pancreatitis

thrombocytopenia (watch platelets)

statins

fibrates

bile-acid sequesterants

cyclosporine

O2 supply to heart is insufficient to meet O2 demand

sudden pain beneath sternum, often radiating to left shoulder and arm

1. prevention of MI and death

2. prevention of myocaridial ishemia and anginal pain

1. organic nitrates (e.g. nitro, isosorbide (isordil))

2. CCB's (diltiazem, nifedipine)

3. BB's (propanolol, metoprolol)

HR

myocardial contractility

intramyocardial wall tension (preload/afterload)

myocardial blood flow

myocardial perfusion only in diastole

Chronic stable angina (exertional)

pathophysiology

emotional excitement

large meals

cold exposure

coronary heart disease

inc. cardiac O2 supply

dec. O2 demand

organic nitrates

beta blockers

ccb's

ranolazine

CCB's

Organic nitrates

symptoms of angina at rest

new-onset exertional angina

intensification of existing angina

maintain O2 supply

dec. O2 demand

Morphine

O2-4 liters (given first)

Nitro-contra hypotension

ASA

used for acute coronary syndrome

works directly on vasc. smooth muscle for Venodilation

dec. cardiac workload

dec. pre/afterload= dec. O2 demand

inc. O2 supply

stable, variant, and unstable angina

vasodilator

HA (vasodilation of cerebral BV's)

orthostatic hypotention

reflex tachycardia

can develop rapidly

cross tolerance to all other nitrates

use lowest effective dose to minimize

long acting (isosorbide) for prophylaxis

hypotensive drugs

phosphodiesterase type5 inhibitors

BB's, verapamil, diltiazem

acute anginal therapy

sustained anginal therapy

IV for perioperative control of blood pressure, and Tx of heart failure with MI, unstable angina, and uncontrolled exacerbations of chronic angina

diltiazem(cardizem) and nifedipine(procardia)

blocks calcium channels in VSM

reflex tachycardia (from hypotension)

dilation of peripheral arterioles

hypotension

bradycardia

heart failure

AV block

propanolol(inderol) and metoprolol(lopressor)

Dec. cardiac O2 demand

bradycardia and hypotension

dec. AV conduction

reduction of contractility

asthmatic effects

depression insomnia and bizzare dreams

sexual dysfuntion

CABG

Percutaneous transluminal coronary angioplasty (PTCA)

antiplatelet drugs

cholesterol lowering drugs

ACE inhibitors

antianginal agents

streptokinase(streptase): fibrinolytic, causes lysis of thrombus

Altepase (tPa)

major: Bleeding (minor oozing to life threatening amount)

likely sites: recent wounds, needle pricks, invasive procedure sights

acute coronary thrombosis (acute MI)

Large deep venous thrombosis

massive pulmonary emboli

bleeding- excessive fibrinolysis can be reversed with aminocaproic acid (amicar)

antibody production

hypotension

fever

intercranial hemorrhage