Pharmacology- Lecture Flashcards
Categories of drugs to treat acute coronary syndrome (ACS)
- Beta blockers
- Anti-platelet medications
- Statins
- Thrombolytics (not always used)
We use beta blockers to reduce cardiac demand in the setting of ACS because of their _ and _ effects
We use beta blockers to reduce cardiac demand in the setting of ACS because of their chronotropic and ionotropic effects
Statins have three roles:
Statins have three roles:
1. Decrease LDL
2. Inhibit thrombosis
3. Inhibit inflammation
Statins are prescribed in the setting of ACS due to their anti-thrombosis and anti-inflammatory effects on the heart
Two drugs that stimulate B1 are _ and _
Two drugs that stimulate B1 are dobutamine and isoproterenol
Two drugs that inhibit B1 are _ and _
Two drugs that inhibit B1 are metoprolol and carvedilol
Name three indications for giving a beta blocker
Name three indications for giving a beta blocker: hypertension, angina, ACS
* Beta blockers are able to slow the heart rate, decrease contractility, and also decrease renin secretion which decreases blood pressure
If the drug ends in “-olol” it means that the drug is _
If the drug ends in “-olol” it means that the drug is selective for B1 or B1/B2
* If the drug starts with A-N: it is cardioselective (B1 only)
* If the drug starts with N-Z: it is nonselective (B1/B2)
If the drug ends in “-ilol” , “-alol” it means that the drug is _
If the drug ends in “-ilol” , “-alol” it means that the drug is combined alpha and beta blocker
* Affects a1, B1, B2
B2 is responsible for _ , so drugs that non-selectively block B1 and B2 can cause _ off-target toxicity
B2 is responsible for vascular smooth muscle relaxation (lungs) , so drugs that non-selectively block B1 and B2 can cause bronchospasm off-target toxicity
Beta-blocker use for HTN may cause _ mechanism-based toxicity
Beta-blocker use for HTN may cause bradycardia mechanism-based toxicity
Aspirin and ibuprofen have _ mechanism in the setting of ACS
Aspirin and ibuprofen block platelet activation
* COX inhibitor
* Blocks TXA2
Clopidogrel, prasugrel, ticagrelor, cangrelor all work by _
Clopidogrel, prasugrel, ticagrelor, cangrelor all work by P2Y12 inhibition
* Block ADP binding
* Block activation
Why do we not use warfarin in the setting of ACS?
ACS takes 7 days to work as an anticoagulant
* In the beginning, it causes a transient hypercoagulative state –> dangerous in ACS
Recall that heparins work by activating anti-thrombin ; Unfractionated heparin stimulates AT to work on factors _
Fondaparinux and Enoxaparin stimulates AT to work on factors _
Recall that heparins work by activating anti-thrombin ; Unfractionated heparin stimulates AT to work on factors thrombin & Xa
Fondaparinux and Enoxaparin stimulates AT to work on factor Xa only
The first generation thrombolytic drugs include _ and _ ; these drugs are _
The first generation thrombolytic drugs include streptokinase and urokinase ; these drugs are not-fibrin specific
2nd generation thrombolytic drugs include _ ; which is _
2nd generation thrombolytic drugs include alteplase ; which is fibrin-specific
3rd generation thrombolytic drugs include _ and _ ; these are _
3rd generation thrombolytic drugs include tenecteplase and reteplase ; these are even more fibrin-specific
All thrombolytic, “clot-busters” are _
All thrombolytic, “clot-busters” are plasminogen activators
* They are all enzymes
Atorvastatin and simvastatin work via _ mechanism
Atorvastatin and simvastatin work via inhibiting HMG-CoA reductase
* Simvastatin- short acting
* Atorvastatin- long acting
What are the effects of statins on LDL, HDL, TGs?
Statins- atorvastatin, simvastatin
* LDL: majorly decreased
* HDL: increased
* TGs: decreased
Drugs that begin with “Cole” like colestipol, cholestyramine, and colesevelam work via _
Drugs that begin with “Cole-“ like colestipol, cholestyramine, and colesevelam work via bile acid sequestration
The “cole” drugs, aka bile acid sequestrants have what effect on LDL, HDL, TGs?
Bile acid sequestrants:
* LDL: well decreased
* HDL: increased slightly
* TGs: increased slightly
The main side effect of bile acid sequestrant drugs is _
The main side effect of bile acid sequestrant drugs is GI upset
The two main side effects of HMG-CoA reductase inhibitors are _
The two main side effects of HMG-CoA reductase inhibitors are myopathy and liver damage
Niacin is an anti-lipid drug that acts as a _
Niacin is an anti-lipid drug that acts as a lipase inhibitor
The main side effect of niacin is _
The main side effect of niacin is flushing
What are the effects of niacin on LDL, HDL, and TGs?
Niacin (lipase inhibitor):
* LDL: well decreased
* HDL: well increased
* TGs: decreased
Fibrates like clofibrate, fenofibrate, and gemfibrozil work via _
Fibrates like clofibrate, fenofibrate, and gemfibrozil work via LPL activation
What effects do fibrates have on LDL, HDL, and TGs?
Fibrates (LPL activators):
* LDL: decreased
* HDL: increased
* TGs: significantly decreased
Ezetimibe is a drug that is a _
Ezetimibe is a drug that is a cholesterol absorption inhibitor
* It only decreased LDL consistently
* Side effect: diarrhea
Alirocumab and Evolocumab are _ type drugs
Alirocumab and Evolocumab are PCSK9 inhibitors
* These enzymes regulate the level of LDL receptors
* Blocking this enzyme puts more LDL receptors in the membrane
* Decreases LDL
What is the effect of the “-cumab” drugs on LDL, HDL, TGs?
The “-cumab” drugs (PCSK9 inhibitors)
* LDL: significantly decreased
* HDL: increased
* TGs: decreased
The side effect of the “-cumab” drugs is _
The side effect of the “-cumab” drugs is flu-like symptoms
The main side effect of fibrates is _
The main side effect of fibrates is dyspepsia (upset stomach)
The most effective anti-lipid drug class for decreasing TGs is _
The most effective anti-lipid drug class for decreasing TGs is fibrates
The two most effective drug classes for decreasing LDL are _ and _
The two most effective drug classes for decreasing LDL are statins and PCSK9 (mab) drugs
Statin drugs block the synthesis of _ during cholesterol synthesis
Statin drugs block the synthesis of mevalonate during cholesterol synthesis
Normally PCSK9 _ LDL receptors
Normally PCSK9 degrades LDL receptors
* We give PCSK9 inhibitors to stop this and increase number of LDL receptors on the liver
* Deprive the liver of cholesterol
* Causes the liver to pull LDL from the plasma
Examples of drugs that might increase statin toxicities include _
Examples of drugs that might increase statin toxicities include CYP3A4 inhibitors
* Azoles, amiodarone, grapefruit inhibit CYP
* Impairs metabolism of statins
Another anti-lipid drug called _ can also inhibit statin metabolism by blocking _
Another anti-lipid drug called Gemfibrozil (fibrate) can also inhibit statin metabolism by blocking glucuronidase
The antiarrythmic drugs that primarily affect the cardiac myocyte AP are _ and _
The antiarrythmic drugs that primarily affect the cardiac myocyte AP are class I and class III
* Class I blocks Na+ influx
* Class III blocks K+ efflux
The Class IA Na+ channel blockers also block _
The Class IA Na+ channel blockers also block K+ efflux
This means that both class I and class III antiarrythmics prolong the QT interval
The most potent Na+ channel blockers are class _ and they affect the ECG by _
The most potent Na+ channel blockers are class IC and they affect the ECG by prolongation of QRS
Drugs that block K+ channels have the following effects:
Drugs that block K+ channels…
1. Slow repolarization
2. Increase AP duration
3. Prolong QT interval
4. Increase the risk of torsades
Any drug that _ increases the risk for torsades
Any drug that prolongs QT interval increases the risk for torsades
Among the Class III drugs, _ has the lowest risk of torsades de point
Among the Class III drugs, amiodarone has the lowest risk of torsades de point
Class II antiarrythmics work by _
Class II antiarrythmics are beta blockers and they work by reducing phase 4 slope –> slowing AV node depolarization
Class IV antiarrythmics work by _
Class IV antiarrythmics work by blocking Ca2+ influx –> slow phase 0
Only _ type calcium channel blockers are anti-arrhythmics
Only non-dihydropyridine calcium channel blockers are anti-arrhythmics
* Since these are able to act on AV/SA node
* Ex: Verapamil, Diltiazem
What variables are we wanting to improve with the administration of heart failure medications?
Preload, afterload, etc
We want to give drugs that can help:
1. Decrease preload
2. Decrease afterload
3. Increase contractility
4. Decrease cardiac remodeling
If we want to decrease preload, decrease afterload, and decrease cardiac remodeling we can administer _ drugs
If we want to decrease preload, decrease afterload, and decrease cardiac remodeling we can administer ACE inhibitor, ARBs, ARNi or b1 antagonist
* Benazepril is an ACE inhibitor
* Losartan is a ARB
* Sacubitril + valsartan is an ARNi
* Metoprolol is a b1 blocker
ACEi, ARBs, and ARNis have neurohormonal effects of _
ACEi, ARBs, and ARNis have neurohormonal effects of reverse remodeling –> lowers wall stress –> decreases myocardial oxygen demand
* Ventricle gets smaller, decreased fibrosis, decreased sodium and water retention, decreased sympathetic tone
ACEi, ARBs, and ARNis have hemodynamic effects of _
ACEi, ARBs, and ARNis have hemodynamic effects of reducing afterload –> decreases myocardial oxygen demand and increases stroke volume
_ drugs are twice as effective at decreasing mortality compared to their counterparts
Angiotensin neprilysin inhibitors (ARNi) drugs are twice as effective at decreasing mortality compared to their counterparts
Describe the beta blocker paradox; when should we use beta blockers and when should we avoid them?
SNS activation is good in acute heart failure –> we want SNS to compensate for poor perfusion to organs
Chronically, SNS activation is maladaptive so we use beta blockers in chronic settings
On target toxicities of beta blockers include _
On target toxicities of beta blockers include bradycardia, heart block, inhibition of reflex tachycardia (hiding hypoglycemia)
* Therefore they are contraindicated in situations of acute decompensated HF, severe bradycardia, heart block
Off target toxicities of beta blockers include _
Off target toxicities of beta blockers include bronchoconstriction via blockage of B2
Patient with heart failure was given dapagliflozin and empagliflozin to alleviate heart failure symptoms; what is the mechanism of action?
Patient with heart failure was given dapagliflozin and empagliflozin –> these block sodium glucose transporter in the nephrons –> decreasing reabsorption of glucose, sodium and water
_ is a drug that can be used to increase inotropy in heart failure patients by blocking Na/K ATPase
Digoxin is a drug that can be used to increase inotropy in heart failure patients by blocking Na/K ATPase
Digoxin side effects include:
Digoxin side effects include: arrhythmias, confusion, somnolence, seizure, visual disturbances, nausea/vomiting
* Digoxin is not commonly used anymore due to its narrow therapeutic window
Acute heart failure instances/ cardiogenic shock may be treated with _
Acute heart failure instances/ cardiogenic shock may be treated with
* Phenylephrine- alpha1 agonist
* Milrinone- PDE3 inhibitor
* Dobutamine- beta1 agonist
* Epi, NE, Dopamine
* Vasopressin
_ and _ are examples of drugs that inhibit alpha1 and prevent vasoconstriction (may be used in hypertension)
Doxazosin and Prazosin are examples of drugs that inhibit alpha1 and prevent vasoconstriction (may be used in hypertension)
* They are able to lower blood pressure without directly affecting cardiac output
Catecholamines like _ , _ , and _ are important int the context of acute HF or cardiogenic shock
Catecholamines like Epi , NE , and dopamine are important int the context of acute HF or cardiogenic shock
Of the catecholamines, _ is selective for beta2
Of the catecholamines, Epi is selective for beta2 –> makes since because we use Epi in anaphylaxis to bronchodilate
Dopamine is normally only selective for dopamine receptors unless _
Dopamine is normally only selective for dopamine receptors unless we increase concentration such that it becomes nonselective across all receptors
Vasopressin is a hormone that is produced in the _ and secreted by the _ to help increase arterial blood pressure
Vasopressin is a hormone that is produced in the hypothalamus and secreted by the posterior pituitary to help increase arterial blood pressure
Vasopressin is different from aldosterone.. how?
Vasopressin directly increases water reabsorption
Aldosterone indirectly increases water reabsorption via sodium reabsorption
Via its V1 receptor, vasopressin causes _
Via its V1 receptor, vasopressin causes blood vessel constriction
* This is a rapid way it increases BP
Via its V2 receptor, vasopressin causes _
Via its V2 receptor, vasopressin causes water reabsorption via aquaporin channels in kidney
* This is a slow way it increases BP
Dobutamine acts on _ to _
Dobutamine acts on beta1 to increase heart rate and contractility
Milrinone is a drug that is used for _ and works by _
Milrinone is a drug that is used for increasing contractility and works by inhibiting phosphodiesterase 3
* PDE3 inhibitor –> stops the degradation of cAMP –> leads to an increase in cAMP
