Pharm Exam 2: Derm and Cardio

-systemic corticosteroids (to decrease inflammation)

-antipileptics (used for seizures)

-tuberculostatics (used for TB)

-lithium (use for bipolar disorder)

drugs that induce acne

hydrocortisone

which corticosteroid does not cause acne?

benzoyl peroxide

what medication to treat acne penetrates stratum corneum and is turned into benzoic acid

Cutibacterium acnes

benzoic acid has activity against what microbe?

inhibits the conversion of testosterone to DHT

Azelaic acid is another medication used to treat acne

what is Its MOA?

Retinoic acid (tretinoin)

FIRST LINE ACNE TREATMENT

topical retinoid

acid form of vitamin A

-corrects abnormal follicular keratinization

-reduces C. acne

-reduces inflammation

aldosterone and androgen

spironolactone works by:

Blocking _____receptors and _____ receptors

intralesional steroids

adrenal suppression

what acne medication is used for injecting individual inflammatory nodule?

can have systemic absorption and cause ______

-local tissue atrophy (shrinking in cells)

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***EXAMPLE QUESTION THAT COULD BE ON EXAM***

a patient with acne has been on this ____ med, it kind of has been working but not getting them to goal, what do you want to add on?

or they failed this therapy what is next?

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CARDIO MEDS for lowering LDL cholesterol (lipids)

1st powerpoint

contributes to atherosclerosis leading to heart failure

why do we want to lower our lipid levels in the body

chylomicrons

triglycerides and cholesterol get broken down by bile salts and are turned into ____ because these are too big to be absorbed into blood stream.

fats (LIPIDS) are too big to be absorbed on own so need to be broken down

LPL (lipoprotein lipase)

When you eat fat (triglycerides + cholesterol), your intestinal cells package it into chylomicrons.

it carries dietary triglycerides (TG) and cholesterol through the blood and lymph.

As the chylomicron moves through capillaries (especially in adipose tissue, heart, and muscle), an enzyme called ____ breaks down the triglycerides inside the chylomicron.

produces free fatty acid, glycerol and CM remnants

liver, LRP (LDL like receptor protein)

After most of the triglycerides are removed, what’s left is called a chylomicron remnant (CM)

These remnants are smaller, richer in cholesterol, and still have some triglycerides.

The ____removes chylomicron remnants (CM) from circulation using a receptor called ____

VLDL

When you eat extra carbohydrates or fats acids, the liver can convert them into triglycerides (TG).

These TGs need to be shipped out of the liver (otherwise fat would just pile up there)

The liver packages the triglycerides together with cholesterol and proteins, forming ____ and released into the blood to deliver triglycerides to tissues.

IDL (intermediate density lipoprotein)

After TG removal, VLDL becomes ____ in the plasma

LDL

After VLDL loses some triglycerides via LPL, it becomes IDL.

IDL can then be hydrolized further (triglyceride breakdown) by hepatic lipase (HL) → turning IDL into ____

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LDL is now cholesterol-rich (not much TG left). CONTRIBUTES TO ATHEROCLEROSIS and in the blood

ApoB-100 mediated uptake by LDL receptor

how do we get LDL out of the blood?

______

liver has LDL receptor so it takes cholesterol out of the blood

if the liver has too much cholesterol in it, there will be decreased amount of receptors = can not get LDL out of blood

there are some medications that can starve the liver of cholesterol to have up-regulations of LDL receptors

ApoB-100 (Apolipoproteins)

what protein do we need to bind to the receptor to get cholesterol into the liver

atherosclerosis

if there is decrease LDL receptor activity= LDL accumulation in blood which leads to ___

atorvastatin

rosuvastatin

simvaststin

Antihyperlipidemics (lipid lowering agents)

HMG Co-A reductase inhibitors

THE STATINS

lovastatin

simvaststin

fluvastatin

pravastatin

atorvastatin

rosuvastatin

pitavastatin

what are the most common statins that we will use?

rosuvastatin

most potent statin (lipid lowering agent)

HMG-CoA Reductase inhibitor

statins MOA

inhibits this and decreases cholesterol synthesis

the liver is starved of cholesterol so we make more LDL receptors

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Reduce hepatic

cholesterol synthesis,

lowering intracellular

cholesterol, which

stimulates

upregulation of LDL

receptor and increases

the uptake of non-HDL

particles from the

systemic circulation.

decreased trigylcerides (VLDL)

decreased LDL

with the statins (HMG-CoA Reductase inhibitor)

what will we see in our systemic circulation (blood)

maybe increased HDL*

pleiotropic effects

reduces morbidity and mortality

what effect do we have when using the statins

patient will live longer, this is why we use the statins for often for Atherosclerotic Cardiovascular Disease (ASCVD)

Atorvastastin

rosuvastatin

simvastatin

some statins are metabolized by the CYP3A4 enzyme system

what are those drugs

so if patient taking statin with with CYP3A4 inhibitor (grapefruit juice) will increase the half life (overall increasing the amount of statin in body)

grapefruit juice

if someone is taking CYP450 drug, what should they not drink?

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the higher the level you start off with on the statins->> the better the reduction

increased liver enzymes and LFT (liver function test)

what is the biggest side effect when using statins (HMG-CoA Reductase inhibitor )?

if this happens we either reduce the dose of statin or discontinue use

yes

do we need to monitor the liver while taking statins?

increase

if patient was taking a statin and they drink it with grapefruit juice (strong CYP3A4 inhibitor) the level of the statin will____.

this could have enhanced effects on liver and cause liver failure

myalgia

myopathy

rhabdomyolysis (rare)

another side effect of taking statins can be

CPK

patients with Rhabdomyolysis will have very sore muscles and darkened urine STOP USING if this happens

what test would we use to monitoring myopathy?

hepatic disease

or pregnancy

when should we not use statins

statins

absolutely do not use ______ with pregnant people!!!!!!!

verapamil

amiodarone

niacin

grapfuite juice

what are CYP3A4 inhibitors that interact with statins

statins

WHAT IS OUR FIRST LINE TREATMENT FOR TREAT ATHEROSCLEROTIC CARDIO

VASCUALR DISEASE?

(LDL LOWERING DRUGS)

rosuvestatin

which statin has no CYP interactions

CLEAN

Ezetimibe (Zetia)

cholesterol absorption inhibitor

inhibits intestinal delivery of cholesterol to liver

Ezetimibe (Zetia) MOA

since there is decreased amount of cholesterol in liver we have increased up-regulation of LDL receptors

getting LDL out of blood

glucuronide metabolite

Ezetimibe and its active______circulate enterohepatically and are eliminated through biliary tract

so this is limited systemic exposure

LDL lowering effect

ezetamide is not as effective as a statin so it would would want to pair the two to have a ______

we wont see ezetimibe by itself

yes because we added statin

do we need to monitor hepatic (liver function) with ezetimibe + statin?

Fibric Acid Derivatives (Fibrates)

what medication would we want to avoid adding with ezetimibe?

it can lead to cholelithiasis (flow from bile to liver is blocker) and myopathies

Bile Acid Sequestrants

and antacids

what other medications will decrease the concentration of ezetimibe

ate

what are the fibric acid derivatives (fibrates) ORAL DRUGS

fenofibrate

bezafibrate

Gemfibrozil

all end in ____ except gemfibrozil

activates PPAR alpha

fibrates MOA

that increases fatty acid oxidation-> decrease VLDL (triglycerides)

THIS INCREASES HDL

increasing HDL and decreasing triglycerides

fibrates (fenofibrate

bezafibrate

Gemfibrozil )

are best at

fenofibrate

bezafibrate

Gemfibrozil

what medication would we want to give with a patient with hypertryglyceridemia

Ezetamibe

what medication do we want to avoid with fibrates because it can cause cholelithiasis?

statin

what medication do we want to avoid using with fibrates because it can cause myopathy

pregnant

dont use fibrates if patient is ______

or if liver/renal dysfunction or gal bladder disease

warfarin

avoid using fibrates with ___ because it can increase anticoagulant effects

fibrate (fenofibrate, benzofibrate, gemfibrozil)

if a patient has triglyceride levels greater than 1000 (high ) or has low HDL what would be our first line treatment

Cholestyramine, colestipol, colesevelam

what are our bile sequestrant drugs

bind to bile acid in the GI to prevent recirculation of cholesterol and excreted through feces

bile acids sequestrants "resins" MOA

liver produces mire bile acids and LDL receptors -> reduction in LDL

drug is never absorbed

pregnant patients and children

since bile acid sequestrants (resins) are never absorbed in the GI tract there is limited side effects

so we can use this drug in ____ and ____

comes in powder that you have to mix in with water, poor texture

why would see low compliance with bile acid sequestrants

1 hour

we have to take Cholestyramine, colestipol, colesevelam (bile acid sequestrants) within ____ hour of meal times

SEPARATE WITH OTHER MEDICATIONS BECAUSE THEY WILL BIND TO IT

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Cholestyramine, colestipol, colesevelam (bile acid sequestrants) can have severe GI effects :

-nausea

constipation

flatulence

fullness

bloating

poorly tolerated

triglycdrides (VLDL hypertriglyeridemia)

we would not want to give Cholestyramine, colestipol, colesevelam to patients with increased levels of ____

bile acid sequestrants will increase levels

decreases mobilization of free fatty acid in liver, decreasing synthesis of triglycerides

niacin is a vitamin B complex vitamin

what is its MOA

decrease triglycerides

increase HDL

niacin is used to

cutaneous flushing

immediate release of niacin can cause _______ because of prostaglandin mediated effect

*tells a story about this*

can also cause increase in LFT, glucose and uric acid

Aspirin

what can a patient take before using niacin (lowers TG and increase LDL)

PREMEDICATION

chronic liver disease

absolutely do not use niacin with patients who have

relative:

-gout

-peptid ulcer

-diabetes

niacin & fibrates

what meds are the best at ↑ HDL?

niacin & fibrates

which meds are the best at ↓ TG?

-cumab

PCSK9 inhibitor

these are injectable monoclonal antibodies

-alirocumab

-evolocumab

these meds end in _____

*very expensive* ONLY INJECTABLE

Hypersensitivity reactions, anaphylaxis

since we are introducing a foreign protein into the body with PCSK9 inhibitor -alirocumab

-evolocumab

this can cause ____

decrease LDL

PCSK9 inhibitor (cumab) MOA

block the enzyme and keeps LDL receptors active longer to ________

Cumab (PCSK9 inhibitor)

which drug has undetectable LDL

(LDL receptors are active longer reducing LDL)

Cholestyramine, colestipol, colesevelam (bile acid sequestrants)

a patient needs to be treated for hyperlipidemia

there TG levels are elevated which drug (OUT OF ALL THE HYPERLIPIDEMIA DRUGS) is contraindicated (DO NOT USE)

*said this in class

lipids

we want to measure ____ during follow ups to assess adherence to treatments, not to achieve a specific LDL target

(see if patient is compliant with taking meds to lower LDL so there is no atherosclerotic cardiovascular disease)

atherosclerotic cardiovascular

190

diabetes

7.5%

four major statin benefit groups (people who would benefit from statin use)

-those who have _______ disease

-people with LDL >___

-people with _____ (40-75 years old) with LDL 70-189

-people with out clinical atherosclerotic cardiovascular disease, or DM with LDL 70-189 and estimated 10 year ASCVD risk> ____

Atorvastatin and rosuvastatin

most potent statin that lowers LDL by 50%

rosuvastatin

if patient is on CYP3A4 inhibitor medication, which statin could we use ?

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anti-hypertensions cardio drugs

2nd power point

diuretics

_____are used to help decrease hypertension

by increasing urine flow and increase salt (NaCl) excretion from the renal tubules.

Na/K/2Cl pump

Loop diuretics (most potent)

Inhibit the Inhibit the ______ in the thick ascending limb.

this leads to increase urine output

thick ascending limb

where do loop diuretics work in the kidneys

flurosemide

bumetanide

torsemide

ethacrynic acid

what are our loop diuretic drugs

"IDES"

metabolic acidosis

since there is volume depletion (peeing out more urine-getting rid of fluids) with loop diuretics we can see _______, due to increased HCO3 reabsorption

low volume kicks off the renin angiotensin system.

hypokalemia

hypocalcemia

hyperglycemia

using flurosemide

bumetanide

torsemide

ethacrynic acid (loop diuretics)

we will see ______

to decrease hypertension

main reason to use loop diuretics

30

loop diuretics (flurosemide, bumetanide,, torsemide, ethancrynic acid) are still effective with creatine clearance rates below ______ ml/min (normal is 60-100)

gout

loop diuretics will increase uric acid levels->>> this can cause

ototoxicity

seizures (hyponatremia)

Increase BUN

adverse side effect of loop diuretics

Ethracrynic acid

what loop diuretic will not cause an allergic reaction and can be used in patients with sulfa allergies since the others are sulfamide drugs

----

when would we use loop diuretics?

volume overload conditions:

pulmonary edema

cirrhosis of liver

heart failure

hypertension

hypercalcemia

NSAIDS

what drug should we not use with loop diuretics because it can blunt the response

don't use it with aminoglycosides, warfarin, lithium, digitalis

distal convoluted tubules

where do thiazide diuretics work in the kidneys?

often use in combination with Loops to lower hypertension

chlorothiazide, Hydrochlorothiazide, chlorthalidone, metolazone, idapamide

what are the thiazide diuretic drugs

inhibit the the Na/Cl transporter in Distal convoluted tubule (DCT)

MOA of chlorothiazide, Hydrochlorothiazide, chlorthalidone, metolazone, idapamide (thiazide diuretics)

hypercalcemia (decreased renal calcium excretion)

has the same major actions as loop diuretics

hypokalemia (excrete more K+)

hypomagnesia

hyperglycemia

GOUT

BUT WHAT IS DIFFERENT (it can cause_____)

hypertension

when do we use thiazide, (similar to loops) _____

volume overload problems:

-Chronic heart failure

cirrhoisis

hypercalcemia and renal calcium stones

we could also use thiazide diuretics to prevent ______

SOUNDS CONTRADICTORY BUT TRUE in hypercalcemia, reducing calcium loss in urine prevents kidney stone formation and excessive calcium wasting.

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Thiazide diuretics work best in people that are:

1. Elderly

2. obsese

3. african american

4. sodium retentive

these patients have thicken blood vessel (due to salt and water deposited into the walls of vessel)

->>>>>>so the the amount of blood flow is reduced because the vessel is narrow

Thiazide diuretics helps with the "water logged" vessels.

it makes the wall thinner, diameter gets wider, so now there is no hypertension