Pharmacology Exam 4

Acutely less effective than class I. Better tolerated long-term than class I " True or False.

TRUE

What is the function of HMG-CoA reductase?

a. Reversible and competitive inhabitation of HMG-CoA reductase, the rate-limiting enzyme of the pathway that produces cholesterol in the liver; is the rate-limiting step in cholesterol synthesis

What are the difference between unfractionated heparin and low-molecular weight heparins (LMWHs)

a. Unfractionated heparin i. Varying sized molecules ii. Need to be administered in units of activity iii. Larger molecular sized pieces may be sensitizing iv. Need routine anticoagulation tests b. LMWHs i. Uniform sizes ii. May be administered in milligrams iii. Less sensitizing iv. No need for routine anticoagulation tests

Class III (K+ blockers)

- Prolong APD (not via Na channels) - Has less of an effect on ___ischemic tissue___ compared to class I

Class IA examples

1). Quinidine 2). Procainamide 3). Disopyramide (increases SVR)

What is the mechanism of action of Aspirin? from the video?

Acetylates (irreversibly) inhibits COX Reduced thromboxane A2 production Platelets cannot produce new COX Effect is apparent until new platelets are made

Deactivated state (channel=closed)

Activation gate= closed; inactivation gate=open; phase 4 Resting state; depolarization

What does heparin inhibit?

a. Xa and thrombin

Smooth muscle cells

a. proliferation and migration: growth factors secretion, proliferation, extracellular matrix forms and migration

endothelial dysfunction

a. retention and oxidation of LDL, endothelial cell "activation", chemokines secretion, adhesion of blood monocytes, and impaired NO secretion

Adenosine:

acts on Adenosine receptors (GPCR); decrease in adenylyl cyclase, decrease in cAMP,

One of the most commonly used agents in general is

amiodarone

Which antiarrhythmic class has the most effect on (phase 0) of the cardiac action

Class IC

To which antiarrhythmic class does propranolol belong?

Class II

Magnesium sulfate MOA

Competes with calcium entry into cells --> tocolytic

1. What is the most common side effect of Bile Acid Binding Resins (Bile acid sequestrants) ?

Constipation

The toxicity of flecainide is linnked to what? A. Age of patient. B. Type of arrhythmia. C. Whether the patient is being treated at home or in hospital. D. Plasma concentration.

D. Plasma concentration.

Class IV examples

Diltiazem Verapamil

What does DMARDs stand for?

Disease modifying anti-rhuematic drugs

Proatherosclerotic function of platelets

endothelial dysfunction, interleukins and chemokines secretion, thrombus formation, impaired NO secretion

Acetaminophen has anti-inflammatory properties. True or False

false

Aspirin acetylates COX enzyme, reversibly inhibiting its function. True or False

false

What are the side effects of HMG-CoA reductase inhibitors from the video and the slides?

heptatotoxicity and myagias

Inactivated state (channel=closed)

i. Activation gate=open/closing; inactivation gate=closed; phase 1,2,3 ii. Sodium ions cannot get through until depolarized

Activated state (channel=open)

i. Activation=open; inactivation gate=open; phase 0 ii. Fast influx of sodium into the cell causes depolarization

Does PCSK9 normally stimulate the degradation of LDL-R ?

yes

Describe the detailed mechanism of Aspirin-induced asthma. Textbook and powerpoint slide. You need to include 5-Lox

• Blocking COX pushes arachidonic acid towards 5-LOX pathway

What is the mechanism of Fibrinolytics?

break down an existing clot by activating plasminogen to plasmin

Class IV

calcium channel blockers

Under which class of anti-arrhythmic agents is Flecainide catagorised? A. Class I B. Class II C. Class III D. Class IV

A. Class I

What does the treatent of flecainide toxicity involve? (Choose 3) A. Increasing the Na concentration at the active site B. Regular exercise C. Surgery D. Increase in dose E. Prescription of physostigmine F. Decrease/removal of dose

A. Increasing the Na concentration at the active site E. Prescription of physostigmine F. Decrease/removal of dose

Flecainide has its greatest effect on cardaic function via ________ ______ & the __________ ___ ____. A. Purking fibres, bundle of his B. Purking fibres, medial temporal bundle C. Oxidative stress, bundle of his D. Parking fibres , bundle of her

A. Purking fibres, bundle of his

Flecainide has no effect on re-polarization. True or false? A. True B. False

A. True

ON your ER rotation you are called to help with a "code blue." As the team quickly assembles and begins ACLS, your attending physician asks you to run it. You are very nervous, but know that the attending and the team are motivated teachers and are there to help you. After a few minutes of drug that is usually listed as a class III antiarrhythmic, but has properties of all the four classes. Which is this?

Amiodarone

Class III examples

Amiodarone Sotalol bretylium dreonedarone Ibutilide

Proarrthmias are most common in which 2 classes of anti-arrhythmic agents? A. Class II & Class IV B. Class I & Class III C. Class III & Class V D. Class I & Class V

B. Class I & Class III

Flecainide_________________________. A. Increases conduction velocity. B. Decreases conduction velocity C. Has no affect on conduction velocity. D. Can increase/decrease conduction velocity depending on concentration

B. Decreases conduction velocity

What is the most common side effect of anti-arrhythmic therapy? A. Pseudo arrhythmia B. Proarrhythmia C. Bradycardia. D. Tachycardia

B. Proarrhythmia

Calcium Channel Blockers MOA

Block L-type calcium channels which decrease the conduction through the AV nodes and also increase the effective refractory period

What is proarrhthmia? A. A worsening of existing arrhythmias B. A development of new arrhythmias C. A development of new arrhythmias and/or a worsening of existing arrhythmias D. The development of new myocytes

C. A development of new arrhythmias and/or a worsening of existing arrhythmias

What is an arrhythmia? A. Accelerated heart beat. B. Slow heart beat. C. Irregular heart beat. D. A type of heart cancer

C. Irregular heart beat.

How do anti-arrhythmic agents work? A. They change electrical conduction of the heart by targeting the defective myocytes. B. They change electrical conduction of the heart by targeting the pacemaker. C. They change electrical conduction of the heart by targeting the ion channels D. They change electrical conduction of the vasculature by targeting the ion channels

C. They change electrical conduction of the heart by targeting the ion channels

1. Antibodies against PCSK9 increase the degradation of LDL-R. True or False

FALSE

1. The binding of collagen and platelets due to a damaged vascular endothelium causes platelet degranulation that lead to ADP release and thromboxane A2 (TxA2) release. True or False

False

Class IC examples

Flecainide Propafenone moricizine

List the mediators of chronic inflammation in rheumatoid arthritis. worksheet.

IL-1, IL-2, IL-3, TNF alpha, interferons

What are some mediators for pyrogens (immunologically)? Worksheet

IL-1, IL-6, PGE2, IL-1beta, TNF-alpha

What is the mechanism of action of Hydroxychloroquine? Detailed description from the video.

Inhibits the processing effects of peptide antigens and their assembly into major histocompatibility complexes by antigen presenting cells

Is its activation reversible or irreversible?

Irreversible

Class IB examples

Lidocaine Mexiletine Phenytoin

Class I

Na channel blockers

What are the examples of Non-selective COX inhibitors?

Naproxen, Ibuprofen Piroxicam, Diflunisal

Class IC - _____ of APD

No change

What is the unique properties of Cavedilol compared to other beta blockers?

Non selective beta blocker, it also blocks alpha 1 receptor

What is the cause of gout? What is the mechanism of chronic gout treatment? Textbook, ppt slides

Overproduction or under-excretion of uric acid Reduce uric acid production or increase excretion Xanthine oxidase inhibitors are typically used Probenecid may be used

List mediators for inflammation/pain. Video and worksheet

Pain: Histamine, 5-HT, PGE2, bradykinins Inflammation: Eicosanoids (arachidonic acid metabolites) such as prostaglandins, thromboxanes, and leukotrienes

Class III

Potassium channel blockers

Class II examples

Propranolol Esmolol timolol metoprolol atenolol bisoprolol carvedilol

Describe everything about Non-selective COX inhibitors

Renal prostaglandins specifically PGE2 and PGI2 types cause dilation of the renal afferent arteriole which is important for maintaining glomerular filtration rate. Under normal conditions these prostaglandins have only minimal effect on renal perfusion. However, when kidney function becomes compromised the production of prostaglandins becomes a significant factor in preservation of the renal blood flow

What are the uses of Hydroxychloroquine?

SLE

Which drug acts by competitive inhibition of vitamin K reductase?

Warfarin

Describe the relationship between COVID-19 and Hydroxychloroquine. You can read below journal article.

We propose that hydroxychloroquine (HCQ), which exhibits an antiviral effect highly similar to that of CQ could serve as a better therapeutic approach. HCQ is likely to attenuate the severe progression of COVID-19, inhibiting the cytokine storm by suppressing t cell activation

Class III are used for

Wolff Parkinson-white syndrome, ventricular tachycardias, atrial tachyarrhythmias

Abatacept blocks T-cell activation by blocking _____. Video on the website above and the ppt slide.

_CD80 and CD86

What is the mechanism of aspirin?

a. Acetylates (irreversibly) inactivates Cox-1 enzyme thus effectively disrupting clot formation

What are the side effects of heparins?

a. Bleeding, osteoporosis with long-term use, alopecia, allergy, and heparin-induced thrombocytopenia

What is the mechanism of action of Niacin?

a. Commonly used as vitamin supplement; increasd liver enzymes and plasma glucose and uric acid

Describe the roles of Oxidized low-density lipoprotein (OxLDL) in different types of cells.

a. Contributes to the atherosclerotic plaque formation and progression by several mechanisms

Describe the mechanism of action of fibrates

a. Decrease release to triglycerides into plasma and increase tissue utilization of triglycerides b. As a secondary mechanism, these drugs increase cholesterol transport destined for bile production

What are two groups of Novel Oral Anticoagulants (NOACs)?

a. Direct Thrombin Inhibitors: Dabigatran b. Factor Xa Inhibitors: Rivaroxaban, apixaban, and edoxaban

What is the mechanism of Action of Ezetimibe (Zetia) ?

a. Inhibiting the interaction between NPC1L1/cholesterol complex with clathrin/AP2, thereby preventing endocytosis of the NPC1L2/cholesterol complex into the enterocytes of the small intestine. Therefore, there is a reduction in the amount of Apo-B48 containing lipoproteins available to go into circulation

Describe the intrinsic and extrinsic pathway

a. Intrinsic pathway which is activated by damage directly to the blood vessel wall and extrinsic pathway which is activated by trauma to the vascular wall as well as surrounding tissue. Intrinsic pathway starts with clotting factor XII XIIa, XI Xia, IX IXa, X Xa. Extrinsic pathway starts with VII VIIa, X Xa

Why can't Heparin be administered orally?

a. Its size and polyanionic charge

Proteins C and S are dependent on which vitamin for synthesis?

a. K

What are the side effects of Niacin?

a. Prostaglandin-induced reaction b. NSAID reduces this effect

Class II

beta blockers

Digoxin

inhabitation of the Na+/K+ ATPase in the myocardium. Power the sodium potassium exchanger. Increase of intracellular of Ca++

Cell formation

monocyte differentiation, LOL oxidation, macrophage tapping, foam cell formation

NSAIDs can be divided into

non-selective inhibitors, cox-2 selective inhibitors, cox-1 selective inhibitors

Class V

other

Uses of Magnesium sulfate

pre-eclampsia/eclampsia and first line for torsades de pointes

What is the role of cox-1?

produces prostaglandins that activate platelets and protect the stomach and intestinal lining

Class IA - ___________ Action potential Duration (APD)

prolong

Class IB - ____________APD

shorten

Class II is best for

supraventricular tachyarrhythmias

1. Although Novel Oral anticoagulants (NOACs)/direct oral anticoagulants (DOACs) are not recommended in the course of advanced chronic kidney disease (CrCl<30mL/min) or during dialysis they are a reasonable choice for individuals with mild to moderate CKD True or False

true

1. Cox1 is involved in the constitutive production of prostanoids in particular in the stomach and platelets. True or False

true

1. PGHS2 (cox2) is inducible and typically produces proteinoids that mediate responses to physiological stresses such as infection and inflammation. True or False

true

TNF-a is a pro-inflammatory cytokine produced by macrophages. Trueor False

true