Cardio drugs - easier Flashcards
Which antiarrhythmics prolong the QT interval?
Class IA and Class III
Which antiarrhythmics cause constipation?
quinidine (may cause constipation due to antimuscarinic effects or diarrhea due to alpha effects)
amiodarone
Ca2+ channel blockers (verapamil, diltiazem)
Which antiarrhythmics are contraindicated in COPD and asthma?
β-blockers (class II) (Adenosine may cause bronchospasm)
Which antiarrhythmics may mask signs of hypoglycemia?
β-blockers (class II)
Which antiarrhythmic drug may exacerbate vasospasm in Prinzmetal angina?
propranolol
Which antiarrhythmic is contraindicated in cocaine users?
β-blockers
For overdose of which antiarrhythmic would you give glucagon?
β-blockers
Which class is flecainide in?
IC
Which class is propafenone in?
IC
Which class is mexiletine in?
IB
Which class is procainamide in?
IA
Which class is ibutilide in?
III
Which class is sotalol in?
III
Which class is dofetilide in?
III
Which class is carvedilol in?
II
Which class are K+ channel blockers?
III
Describe the curve of IC drugs
slope of phase 0 is very decreased
Describe the curve of IB drugs
slope of phase 0 is slightly decreased and AP duration is decreased
Describe the curve of IA drugs
slope of phase 0 is moderately decreased and AP duration is prolonged
Describe the curve of class III drugs
normal phase 0, very prolonged AP
Which drugs work on nodal cells rather than nerve fiber conduction?
Class II, IV
Caffeine and theophylline block the effects of which antiarrhythmic drug?
Adenosine
Which drug is used for diagnosing/abolishing paroxysmal supraventricular tachycardia?
Adenosine
Which antiarrhythmic drug has a duration of action of 15 seconds? Which has a T1/2 of 80 days?
15 seconds: adenosine
80 days: amiodarone
Which antiarrhythmic drug hyperpolarizes cells by ↑ K+ outflow? Which blocks K+ inflow thus prolonging repolarization?
Adenosine
Class III drugs s.a. amiodarone
What is the treatment for torsades de pointe?
Magnesium sulfate
Which drugs cause conduction delay?
drugs which affect AV node conduction:
- Ca2+ channel inhibitors (class IV)
- Beta blockers (class II)
- Digoxin
What is the most commonly noted side effect of amlodipine?
peripheral edema (it is a vascular-selective Ca2+ channel blocker)
What is the problem with reflex tachycardia? In which patients should vasodilators that cause reflex tachy be avoided?
↑ myocardial O2 demand → ischemia in patients with acute coronary syndrome
What is the mechanism of action of digoxin?
- Na+/K+ ATPase inhibitor → indirect inhibition of Na+/Ca2+ exchanger → ↑ [Ca2+]i → positive inotropy
- stimulates vagus nerve → ↓ HR
What two conditions is digoxin used for?
- CHF (because ↑ contractility)
2. A fib (b/c SA node depression and ↓ AV node conduction, both via vagus)
Does digoxin cause constipation or diarrhea?
Diarrhea via cholinergic effects (think about how it stimulates the vagus to ↓ HR; other cholinergic effects: vomiting, nausea, blurry yellow vision)
What is the mechanism of hydralazine? As such, what should be co-administered?
(NO donor?) → ↑ cGMP → smooth mm. relaxation, selective for arterioles
Should give beta-blocker to prevent reflex tachycardia and diuretics for edema
Which hypertension drugs act via the NO → cGMP pathway?
Hydralaine and nitroprusside
Which drug can cause cyanide toxicity if given for more than 24 -36 hours?
Nitroprusside
Which receptor do ARBs block?
AT-1 in vascular smooth muscle
What does aliskrein block?
Renin (so inhibits formation of AT1 from angiotensinogen)
What are the direct effects of captopril?
Blocks ACE → ↓ ATII and ↓ bradykinin breakdown
What are the actions of AT II?
Main two actions:
- AT I receptor → vasoconstriction → ↑ BP [blocked by ARBs]
- Renal cortex → ↑ aldosterone
Other actions:
- Efferent arteriole → vasoconstriction → ↑ GFR
- Posterior pit → ↑ ADH
- Proximal tubule → ↑ Na+/H+ activity → Na, HCO3, and H20 reabsorption (prevent contraction alkalosis)
- Hypothalamus → thirst
What are the enzymes and their respective inhibitors in the path below:
Angiotensinogen → (enzyme 1) → AT I →(enzyme 2)→ AT II
- renin, blocked by aliskiren
2. ACE, blocked by ACE inhibitors
How do class IA drugs cause a prolonged QT interval?
They also inhibit the K+ channel → delay phase 3 repolarization
What class of drugs are used to treat hypertensive patients post-MI?
β-blockers
Drug class used for hypertensive patients with BPH:
α-blockers
Drugs classes used for hypertensive patients with dyslipidemia:
α-blockers (also ↓ lipids), CCBs, ACEi/ARB
anything but β-blockers or thiazides b/c these ↑ blood lipids
How do labetolol and carvedilol prolong survival in CHF patients?
α-1/β-1 blockade → prevents concentric remodeling (↓HR → ↑ symp → ↑ α1 → vasoconstrict → ↑ afterload → ↑ work → concentric hypertrophy)
What drugs are used to ↓ eccentric remodeling in CHF patients, thus prolonging survival?
RAAS pathway blockers (to ↓ preload): ACEIs, ARBs, spironolactone; theoretically aliskiren but no data; β-blockers (prevent renin release)
When would inotropes be beneficial in CHF management? Which drug is used?
acute only to ↑ CO to perfuse body (chronic use would → remodeling); digoxin is the drug of choice for ↑ contractility → ↑ CO
What is the strategy in CHF treatment?
- prevent remodeling via ↓ preload (RAASi) and ↓ afterload (α-blockers)
- increase CO in acute cases via ↑ contractility (inotrope=digoxin)
- ↓ edema (loop diuretics, spironolactone [also good for #1])
What are the pharmacokinetics of digoxin?
- Long T1/2 → high loading dose → ↑ risk for arrhythmias (b/c digoxin depolarizes cells)
- High protein binding → ↑ Vd → ↑ opportunity for displacement by quinidine, verapamil, amiodarone
- Renally cleared (and kidneys often underperfused in CHF → ↑ T1/2)
Why can’t β-agonists be as inotropes in CHF patients? What are the alternatives?
β-receptors rapidly desensitize; alternatives: phosphodiesterase inhibitors (inamrinone, milirinone) and digoxin
How would you treat arrythmia caused by digoxin toxicity?
Class IB - blocks inactivated Na channels in cells depolarized by digoxin; examples: lidocaine and phenytoin
What are the direct activities of digoxin?
Na+/K+ ATPase inhibition → depolarizes nerve cell membranes → ↑ vagal activity → ↑ ACh release onto nodal cells → ↓ HR
Related side effect:
- depol → other NT’s released → disorientation (drunk appearance)
What are the indirect activities of digoxin?
Na+/K+ ATPase inhibition → ↑ [Na+]i → inhibition of Na+/Ca2+ exchanger → ↑ [Ca2+]i → positive inotropy
Which drugs should you be careful about administering with digoxin?
- Drugs that → hypokalemia: loop and thiazide diuretics (K+ competes with digoxin for site on Na+/K+ ATPase so too little K+ → exaggerated activity of digoxin)
- Drugs that compete for renal clearance and displace digoxin from its protein binding sites: verapamil, amiodarone, quinidine
What is the antidote for digoxin overdose?
- slowly normalize K+ (digoxin can → hyperkalemia)
- cardiac pacer
- anti-digoxin Fab fragments
- Mg2+
(5. class IB drugs for arrhythmia)
What is the treatment strategy for prinzmetal angina?
- ↑ O2 delivery to heart by ↓ vasospasm: nitrates, CCBs
- ↓ O2 demand by ↓ TPR (α-block + β-block to prevent reflex tachy), CO (β-blockers), or both (β-blockers, nitrates, CCBs)
Where is NO normally synthesized? from what? which enzyme?
Endothelial cells convert L-Arginine to NO using NO synthase (which is activated by Gq in many inflamm. pathways) → release NO into blood
How does NO work?
synth in endothelial cells → enters smooth mm. cells of large veins from blood → activates guanylyl cyclase to convert GTP to cGMP → relaxation
What AA is required in the breakdown of nitroglycerine to NO?
cysteine as GSH
Why is nitroglycerine primarily used acutely in response to angina episodes?
rapidly acting, and can → acute tolerance (tachyphylaxis) due to GSH depletion (req’d to → NO)
What drug do you want to make sure patients aren’t taking when you give nitroglycerine?
sildenafil (PDE5 inhibitor) b/c it also ↑ cGMP and can → massive vasodilation → ↓ BP → reflex tachy → ischemia
What is isosorbide?
an oral extended release nitrate
How does angioedema usually manifest clinically?
edema of the lips and larynx
What CHF drug can cause angioedema?
ACE-I
What is the suffix for ARBs?
-sartan (e.g. Losartan)
What are the 3 side effects of adenosine?
flushing, hypotension, chest pain
What is the diagnosis and treatment of a patient with palpitations come and go suddenly?
paroxysmal SVT (if pacemaker is atrial tissue or AV node) adenosine
What activates and deactivates MLCK in smooth muscle?
Activation: Ca2+Calmodulin complex (M3/α1→Gq→↑Ca2+)
Deactivation (phosphorylation): PKA (β2 → Gs→adenylyl cyclase → ↑cAMP→ PKA)
Which smooth muscle receptors ↑ [Ca2+]i (i.e. → contraction)?
Bronchial, GI, eye: M3
Vessels: α-1
Both are coupled to Gq
Which receptors and what enzyme → ↑ NO?
Gq coupled M3, bradykinin, H1 receptors on endothelium → stimulate nitric oxide synthase (NOS) → NO production
What enzyme does NO activate?
guanylyl cyclase
What reaction does guanylyl cyclase catalyze?
GTP → cGMP
What does cGMP activate?
protein kinase G
What does protein kinase G activate? What does the activated enzyme do?
phosphatase - dephosphorylates myosin light chain so that it can’t interact with actin (relaxes smooth muscle)
How do the final targets of cAMP and cGMP differ?
cAMP → → phosphorylation of MLCK (becomes inactive)
cGMP → → dephosphorylation of MLC
Both lead to relaxation of smooth muscle
What are two examples of drugs that cause selective arteriolar dilation? When are they used?
hydralazine, minoxidil; severe HTN refractory to other tx b/c → reflex tachy & edema (use w/ sympatholytic and diuretic)
What doe HMG-CoA reductase produce?
mevalonic acid (mevalonate), a precursor to cholesterol
What are the two mechanisms of statins?
- block HMG-CoA reductase → ↓ mevalonic acid → ↓ cholesterol synthesis
- ↓ hepatic VLDL synthesis → ↓ triglycerides
What drug besides statins ↓ VLDL synthesis, therefore reducing plasma triglycerides?
niacin (B3)
Why are statins especially good for diabetics?
diabetics usually have high cholesterol and triglycerides, and statins work to ↓ both
Why do statins cause rhabdomyolysis?
inhibition of HMG-CoA reductase → ↓ Coenzyme Q, a product of the cholesterol pathway and component of ETC → ↓ ATP → ↓ Na+/K+ pump → ↑ Na+ intracell → cell swelling and rupture
Why do statins cause hepatotoxicity?
↓ VLDL synthesis → ↓ ability for liver to eliminate fat produced
What do we monitor with statins?
LFTS: ALT/AST
Rhabdo: muscle CK
Would chronic or acute EtOH users have a higher risk of toxicity with statin use?
acute → inhibits p450 → ↑ [statin]
Why can’t you combine statins with the other lipid lowering drugs niacin and fibrates?
↑ risk for rhabdomyolysis: fibrates ↓ elimination of drug at kidney through competition
What are two drugs that sequester bile acid in the gut?
cholestyramine and colestipol
What effect do cholesterol lowering drugs have on LDL? Why?
↓ LDL b/c ↓ cholesterol → ↑ LDL receptor production in liver → ↑ liver sequestration of LDL from blood stream
What lipid-lowering drugs ↑ risk of bleeding?
bile acid sequestrants b/c ↓ absorption of fat soluble vitamins (so will also have risk of osteomalacia, night blindness, etc..)
What interactions do bile acid resins s.a. cholestyramine have with other drugs?
Any orally administered drug will have ↓ absorption because the lipid soluble portion of drugs is what we absorb, which requires bile salts to absorb
Why do VLDL and TG ↑ with the use of bile acid resins?
compensatory mechanism for loss of LDL: liver has to make more VLDL → IDL → LDL; TGs are synthesized along with VLDL
What is the clinical use for bile acid resins?
only in pure hypercholesterolemia b/c it causes ↑/exacerbation of hypertriglyceridemia and ↑ VLDL
What is the primary side effect of niacin in it’s high-dose use as a lipid-lowering agent? How can we treat the side effect?
hypersensitivity → facial flushing; the fact that we can prevent it with an asprin a day indicates that the mechanism of the side effect is mediated by prostaglandins, NOT histamine
What side effect does niacin have on the liver?
fatty liver b/c blocked VLDL production → buildup of fat
What is the mechanism of fibrates (e.g. gemfibrozil)? What patients are they used for?
Induces lipoprotein lipases → causes TG to be taken up into cells (and stored as fat) → ↓↓↓ triglyceride levels; can only be used in patients with triglyceride imbalance (causes ↑ LDL in pts. w/ hypercholesterolemia)
Recap on antihyperlipidemics:
- drug used ONLY in ↑ cholesterol and NOT if pt has ↑ TG?
- drug used ONLY in ↑ TG and NOT in pt. w/ ↑ cholesterol?
- drug used if combined ↑ TG and ↑ cholesterol?
- Cholestyramine, cholestipol
- Gemfibrozil
- Statins (can synergize with ezetimibe) and niacin
