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