Cardiovascular Pharmacology Flashcards
How can hypertension be treated
Lifestyle changes (most effective), medications
Lifestyle modifications for hypertension
Weight reduction and exercise Diet changes Relaxation techniques Smoking cessation Medications Encourage self monitoring
What are antihypertensive medications
Diuretics, beta blocks, angiotensin receptor blockers, calcium channel blockers, ACE inhibitors
Diuretics
Lower bp by reducing circulating fluid volume.
What are the types of diuretics
Thiazides (hydrochlorothiazide) Loop diuretics (furosemide, ethracrynic acid) and potassium sparing diuretics (spironolactone)
Beta blockers
Block sympathetic nerve impulses in the heart leading to a reduction in heart rate…decreasing cardiac output
Examples of beta blockers
Atenolol
Propranolol
Metoprolol
Angiotensin receptor blockers (ARB)
Specifically blocks angiotensin II from binding to vessel receptors, preventing vasoconstriction
Examples of ARB
Losartan
Olmesartan
Calcium channel blockers
Cause systemic vasodilation resulting in a reduced peripheral vascular resistance
Examples of calcium channel blockers
Diltiazem
Verapamil
Nifedipine
ACE inhibitors
Decreases the amount of angiotensin II and aldosterone in the system resulting in vasodilation and lowering circulating fluid volume. Slow progression of renal damage in patients with diabetes
Examples of ACE inhibitors
Captopril
Lisinopril
Enalapril
Nitroprusside
Nitrate drug with potent venodilator and vasodilator properties. It is administered via IV and is broken down in the blood into NO, which in turn increases cGMP, leading to smooth muscle relaxation . Translating into vasodilation and venodilation which is helpful in rapidly reducing the blood pressure, as this drug is rapid acting and has a short half life
Why is nitroprusside given during malignant hypertension
Properties
What is malignant hypertension
Severe increase in bp causing impairment of one or more organ systems
Side effect nitroprusside
Cyanide toxicity
Nitroprusside administration can lead to iatrogenic cyanide toxicity if overused.
Sodium nitroprusside has 5CN ligand in its molecule, and breaks down into thiocyanate. This is usually detoxified in the blood, but can reach toxic levels in the blood
The half life of thiocyante is not as __ as nitroprusside, but is several days, and patients are at risk for toxicity and effects for longer
Short
Nitroprusside MOA
- direct release of NO(vasodilation and venodilation)
- Increased cGMP (NO activates guanyl cyclase in SM increasing cGMP)
- CGMP inactivated myosin light chains and causes SM relaxation or arteriosus action. This drug is a potent dilator of venues and arterioles
- the drug has a half life of 1-2 min and is rapidly acting
Indications nitroprusside
Malignant hypertension
How is nitroprusside administered
IV
Side effects nitroprusside
Cyanide toxicity
How does nitroprusside give canine toxicity
Sodium nitroprusside has 5 CN ligand in its molecules and breaks down into thiocyanate. This is usually detoxified in the blood but can reach toxic levels in the blood.
Symptoms of cyanide toxicity
Vertigo, confusion, difficulty breathing and headaches at low doses.
Minoxidil (loniten, rogaine)
Vasodilator that acts primarily on arterioles
Although minoxidil causes more severe adverse reactions than hydralazine it also does what
More intense arteriolar vasodilation
Indication for minoxidil
Severe hypertensiona nd baldness
Side effects minoxidil
Reflex tachycardia, blood volume expansion, and pericardial effusion, excessive hair growth or a rash
How minimize adverse effects of minoxidil
Give with beta blockers and diuretics and diuretics
MOA minoxidil
Vasodilator arterioles
By dilating the resistance vessels, the medication decreases afterload and subsequently cardiac workload. This action causes cardiac output and tissue perfusion to increase.
Does minoxidil have venous effects
No
Indications for minoxidil
Severe hypertension and baldness
Baldness and minoxidil
Topical
Side effects minoxidil
Reflex tachycardia, blood volume expansion, hypertrichosis, pericardial effusion, rash
Reflex tachycardia and minoxidil
As baroreceptors in the aortic arch and carotid sinus sense a decrease in bp, the vasomotor center of the medulla tries to restore normal blood pressure by increasing heart rate and myocardial contractility
Blood volume expansion and minoxidil
Chronic use of vasodilator causes prolonged reduction of bp, which triggers adrenal glands to secrete aldosterone to promote sodium and water retention. In addition, decreasing arterial pressure leads to decreased renal blood flow and reduced GFR. Decreasingthe filtrate volume increases the kidneys ability to reabsorbed sodium and water and leads to blood volume expansion
Minoxidil and hypertrichosis
Vasodilator effects cause proliferation of epithelial cells at the base of the hair follicle. Hair growth begins on the face and progresses to arms, legs, and back.
Minoxidil and pericardial effusion
Fluid retention lead to fluid accumulation underneath the pericardium and develop pericardial effusion. May compress the heart and lead to cardiac tamponade
Why give minoxidil with beta blocker and diuretic
Minimize reflex tachycardia, so premeditate with beta blocker to prevent sympathetic stimulation of the heart. Since blood volume increase negates the effect of vasodilation, diuretics also given to prevent fluid retention and volume expansion (if diuretic therapy inadequate will need dialysis)
Hydralazine
Vasodilator that helps to relax smooth muscle and decrease peripheral resistance helping to lower blood pressure and reduce afterload
MOA hydralazine
Increases cGMP , leading to SM relaxation, and arteriodilation with a slight amount of venodilation. So it directly relaxes arteriolar muscle
Indications for hydralazine
Severe hypertension and CHF
What is hydralazine often combined with
Methyldopa to treat hypertension in pregnancy
Side effects hydralazine
Drug induced lupus
With anti histone antibodies
Reflex tachycardia due to the drugs sudden pressor actions and is often co-administered with a B blocker to prevent this
Indications for hydralazine
Reduce afterload, severe hypertension , CHF
How does hydralazine reduce afterload
Relaxes SM and preferentially vasodilator arterioles,creating an afterload reduction. It is indicated in diseases where there is a cardiac failure or excess systemic resistance
Severe hypertension and hydralazine
Not for essential hypertension
First line of hypertension during pregnancy
Hydralazine is indicated for pregnancy hypertension along with ___
Methyldopa
MOA hydralazine
Increase cGMP which inhibits contraction in SM and leads to bv relaxation
(Grater vasodilation of arterioles than veins)
Side effects hydralazine
Drug induced lupus(have antihistone antibodies) Reflex tachycardia (compensatory response to sudden decreased bp to maintain cardiac output.)
How prevent reflex tachycardia with hydralazine
Give with beta blocker
Who is hydralazine contraindicated in
Angina, CAD
It can also cause angina
Calcium channel blockers (verapamil and diltiazem)
Verapamil belongs to the phenylalkylamines class and diltiazem belongs to a class called the benzothiazepines
How are verapamil and diltiazem different from other calcium channel blockers
Have direct action on cardiac tissue at therapeutic levels
Verapamil and diltiazem are also classified as type IV antiarrhythmics and
Work to slow AV conduction
Indications calcium channel blockers (verapamil and diltiazem)
Angina pectoris, essential hypertension and arrhythmias
MOA calcium channel blockers
Block coltage dependent calcium channels. Since these channels are concentrated in SA and AV this drug class helps by decreasing conduction through the AV node.
Calcium channel blockers are contraindicated in
Heart block, espicially 2nd degree block and complete heart block
Indications for calcium channel blockers
Angina pectoris
Essential hypertension
Arrhythmias
Angina pectoris and calcium channel blockers
Calcium channels in SM or vasculature and blocking them allows blood vessels to dilate.
Essential hypertension and calcium channel blockers
Decrease blood pressure by dilation of the arterioles.
What calcium channel blocker is first line for treating chronic hypertension
Verapamil
Arrhythmias and calcium channel blockers
Espicially atrial tachyarrhythmias as they slow impulse conduction through the AV node
Side effects calcium channel blocker
Bradycardia Hypotension Constipation Peripheral edema Gingival hyperplasia
Calcium channel blockers bradycardia
Slow impulse conduction through the AV node to the ventricles
Hypotension and calcium channel blockers
Relaxing SM in vasculature, these medications can lead to the side effect of hypotension
Constipation and calcium channel blockers
Leads to decreased smooth muscle motility and can manifest as constipation (more so with verapamil)
Peripheral edema and calcium channel blockers
Arteriolar dilation leading to capillary hypertension which causes fluid extravasation into tissues
Gingival hyperplasia calcium channel blockers (verapamil)
Enlargement of the gums
Class I antiarrhythmics (Na channel blockers)
Treat tachyarrhythmias by blocking fast Na channels and there are several subcategories of drug based not heir specific effect on cardiac action potentials
class I antiarrhythmatics do what
Restore normal pacemaker and conduction activity and are selective for depolarized tissue, which is known as state dependent
MOA class I antiarrhythmics
Block Na channels to reduce rate of phase I depolarizationand prolong effective refractory period. This increases the threshold for firing within abnormal pacemaker cells.
Class I antiarrhythmic contraindicated
Hyperkalemia states, as excess potassium increases resisting membrane potential and can produce a sodium channel block so pronounced that asystole may result in patients taking class I
Arrhythmias
Refer to abnormal heart rate or regularity. They can be caused by either or regular impulse conduction or impulse generation
Indications class I
Arrhythmias and local anesthesia
MOA class I antiarrhythmics
- Block slow conduction (block fast sodium channels. Halting conduction espicially in depolarized cells
- block na channels to reduce rate of phase I depolarization and prolongs effective refractory period
- raise threshold. Bc of Na channel block they increase the threshold for firing within abnormal pacemaker cells
- State dependent -selectively depress tissue that is frequently depolarized, versus normally polarized tissue. This can include ischemic tissue
Contraindications for class I antiarrhythmics
Hyperkalemia
Toxicity bc k increases resting membrane potential and can produce a sodium channel blockade so pronounced that asystole may result
Class IA antiarrhythmics (na channel blocker)
Treat arrhythmias through blockage of na channels, prolonging action potentials and are effective for both atrial and ventricular arrhythmias
Indication for classI antiarrhythmias
Arrhythmias-atrial and ventricular,
Recent rant and ectopic suprventricular and ventricular tachycardia, wolff parkinson white syndrome
MOA class IA
Increase PA, effective refractory period, and QT interval
Commonly used class IA antiarrhythmia drugs
Disopyramide, procainamide
Quinidine
Shared side effects of class IA
Thrombocytopenia and torsades de pointes
Side effect procainamide
Drug induced lupus
Side effects quinidine
Cinchoism
Indications for class IA
Arrhythmias (vent ansupra vent)
Recent rant and ectopic supraventricular arrhythmias, such as Wolff parkinson white syndrome
MOA class IA
Increase AP, ERP, and QT interval
Disopyramide
Similar in action to quinidine, and has the longest half life of drugs in this class. It is indicated for ventricular arrhythmias, but has pronounced anticholinergic side effects, and can possibly worsen heart block and cause severe heart failure
Procainamide
Similar in action to quinidine, but has less GI side effects and is safer to use intravenously
Side effect procainamide
Drug induced lupus , which can be catalyze by medication. Patients with drug induced lupus typically show antihistone antibodies
Quinidine
Indicated for supraventricular and ventricular arrhythmias and also may be used for prevention.it is a state dependent block, meaning at higher heart rates, the block increases while at lower heart rates, the block decreases
Side effect quinidine
Cinchonism which resents as dizziness, ringing in the ears and diarrhea
Shared side effects of class iA
Thrombocytopenia
Torsades de points
Why may quinidine cause thrombocytopenia
Destruction of platelets by antibodies developed in response to protein quinine complexes in the circulation
Torsades de pointes
Quickly transform into ventricular fibrillation which may lead to sudden death. Torsades is a ventricular tachycardia which presented with shifting sinusoid waveformed on ECG. It may occur due to the increase in QT interval associated with this drug class
Class IB antiarrhythmics (Na channel blockers)
Class of antiarrhythmic drugs for treating ventricular arrhythmias by weakly blocking sodium channels and decreasing action potential duration. They also shorten the duration of refractory period
Indications for class IB
Arrhythmias (acute ventricular and digitalis-induced arrhythmias)
After MI arrhythmias
Class IB preferentially affect _ or _ purkinje and ventricular tissues, and act to decrease action potential duration by blocking sodium currents
Ischemic
Depolarized
Commonly used IB antiarrhythmias
Mexiletine
Lidocaine
Tocainide
Phenytoin
Mexiletine side effect
GI upset
Lidocaine side effect
CNS depresssion
Phenytoin
Anti-epileptic drug which also has class IB antiarrhythmic properties.
Long term use of phenytoin
Associated with hirsuitism, but can yield many other side effects as well
Indications class IB
Acute ventricular and digitalis induced arrhythmias
Treat arrhythmias which arise from imporoper impulse conduction or impulse conduction or impulse generation
After MI as they preferentially affect ischemic tissue
MOA IB
Highly selective for ischemic or depolarized purkinje and ventricular tissue
Decrease AP duration bc of their block of sodium currents. They have fast onset/offset kinetics and have little effect on slower heart rates, but a greater effect on faster heart rates
Mexiletine
May cause GI upset
Lidocaine
IV
Treats damaged tissues and acts only on the sodium channel. It is the second line treatment for ventricular arrhythmias and has a low level of cardiotoxicity
Lidocaine side effect
CNS depression ==seizures in severe overdose
Tocainide
Orally active drug, similar to lidocaine
Phenytoin
Anti seizure drug that is occasionally used as an antiarrhythmic, specifically in digitalis overdose to reverse atrioventricular block. It is known to have many side effects, including drug induced lupus, gingival hyperplasia, teratogenic effects and hirsutism
Class IC antiarrhythmics
Treat severe ventricular tachyarrhythmias by blocking na channels and slowing conductance
Class IC have no effect on _ duration and are used as a last resort in ___ ___, which may become intractable or progress to ventricular fibrillation
AP
Refractory tachyarrhythmias
Examples of class IC
Flecainide
Propafenone
Propafenone
Acts as a b adrenergic antagonist and has the side effects of bradycardia ad CHF
Class IC contraindicated
In patients immediately after MI and in patients with structural abnormalities due to their propensity to increase mortality in these groups
Indications class IC
Last resort in refractory tachyarrhythmias
V tach which may progress to ventricular fibrillation
MOA class IC
No AP duration as opposed to other class I antiarrhymics
Examples of class CI
Propafenone
Flecainide
Propafenone
Treats rapid heart beat arrhythmias such as supraventricular arrhythmias,. Similar to quinidine, and possesses b adrenergic antagonist activity. It may also represent life threatening ventricular arrhythmias,
Side effects propafenone
CHF, bradycardia and new arrhythmias
Flecainide
Class IC antiarrhythmias drug indicated for ventricular tachyarrhythmias and for maintaining sinus rhythms in cases of paroxysmal a fib or a flutter
Contraindications of class IC
Post MI . Has proarrhythmic activity and are contraindicated post MI and after structural heart disease due to increased mortality incidence with these diseases
Class III antiarrhythmics (k channel blockers)
Used when other types of antiarrhythmics fail. Work to prevent arrhythmias and re-entrant arrhythmias by increasing myocyte action potential duration, effective refractory period and Qt interval
Commonly used class III antiarrhythmics
Aminodarone
Ibutilide
Dofetilide
Sotalol
Aminodarone
Dirty drug due to its multisystemic toxicities and prescribers should heck pulmonary, liver, and thyroid function tests in patients taking this drug (causes pulmonary fibrosis, hepatotoxicity, and hypo/hyperthyroidism)
Ibutilide and dofetilide
Helpful in restoring a fib and flutter to normal sinus rhythm
Sotalol
Nonselective b blocker which has class II antiarrhythmic properties, and use of this medication can cause excessive b block in patients
Indications for class III
Arrhythmias
MOA class III
Increased AP, ERP, and QT interval
DO NOT SLOW conduction veolcity, but rather, they prolong depolarization in atrio-ventricular myocytes
Amiodarone
Increases refractoriness and has a long half life. It is indicated for refractory life threatening ventricular arrhythmias, and is the first line treatment for patients not responding to CPR.
Why is amiodarone unique
Has class I, II, III, IV antiarrhythmic effects bc it alters the lipid membrane
Why do liver pulmonary and thyroid function tests when taking amiodarone
Toxicities of the drug. Can cause pulmonary fibrosis, hepatotoxicity, and hypo/jyperthyroidism
Why is amiodarone called a dirty drug
Can bind to several different targets or receptors and thus have a wide range of effects
Side effects amiodarone
CV effects (CHF, heart block, bradycardia), pulmonary fibrosis, hepatotoxicity, thyroid issues, corneal deposits, skin discolorations, neurological effects, and constipation
Ibutilide
Indicated for quick conversion of a flutter or a fib to a normal sinus rhythm.
How does ibutilide work
Give through IV infusion and works by prolonging action potential duration. A side effect is torsades de pointes
Side effect ibutilide
Torsades de pointes
Dofetilide
Indicated for converting and maintaining normal sinus rhythm in the care ofatrial flutter and atrial fibrillation
Sotalol
Non selective competitive b adrenergic receptor blocker , it has significant side effects, including dyspnea, dizziness, and torsades de pointes
Class IV antiarrhythmics (ca channel blocker)
Can be cardioselective or vasoselective, giving them a wide array of use
Cardioselevtive class IV
Verapamil
Diltiazem
Inhibit transport of Ca across the cell membrane during cardiac depolarization by blocking Ca channels, decreasing SA node discharge…decreasing conduction through AV leading to an increased PR interval and ERP
Indication for cardioselevtive class IV
Recent rant supraventricular tachycardia, also protects the ventricles from arrhythmias in atrial fluttter and fibrillation. Angina, hypertension, mostly due to SM relaxation
Vasoselective class VI
Nimodipine
MOA vasoselective class VI
Block Ca channels in SM and decrease vasoconstriction and spasm
Indication nimodipine
Treat subarachnoid hemorrhage due to its vasoselective properties
Side effects class iv
Cardiovascular (sinus node depression, AV block and CHF)
Impaired Ca transport leads to decrease gastric signaling and decreased gut motility, causing constipation in patients
Indications class IV
SVT (due to AV nodal reentry), atrial fib or flutter, subarachnoid hemorrhage (nimodipine has higher effects on vascular SM than on cardiac condution)
MOA class VI
Ca channels in SA and AV node blocked to decrease impulse conduction and velocity through AV
Also on SM and can treat hypertension
Decrease conduction through AV leading to an increases in PR and ERP
Verapamil
Cardioselective Ca channel blocker, and has higher activity on slowing AV conduction than it does on vasodilation. It is indicated for use in arrhythmia prevention, hypertension, angina, and cluster headaches
Diltiasem
Cardioselective Ca channel blocker which has actions similar to verapamil. It is used for SVT, angina, atrial flutter, and firillation, as well as hypertension
Nimodipine
Vasoselective Ca channel blocker and is used to treat subarachnoid hemorrhage
Side effects class IV
There are numerous cardiovascular side efffects implicated with Ca channel blocker use (AV block, sinus node depression)
Constipation (esp verapamil as Ca is a 2nd messenger for gastric, which is important for gastric motility—-motility impaired)
Adenosine (adenocard)
A naturally occurring nucleotide in body that works by blocking cAMP induced Ca influx in cardiac myocytes.
Indication adenosine
Tachyarrhythmias to delay the PR interval and slow a patients heart rate to a normal sinus rhythm
Supraventricular tachyarrhythmias after other efforts like vagal maneuvers to slow the heart rate have failed.
Onset of adenosine
Seconds and resolves in 10 seconds. Side effects resolve in a minute
MOA adenosine
Slows AV conduction from the SA node through AV, which abolished tachyarrhythmias. Basically is a short term calcium channel blocker in the AV node that is induced by cAMP….causes prolonged PR
Indications adenosine
Supraventricular tachycardia (paroxysmal)
Must originate above AV node
Why does adenosine not work for a fib, a flutter, and verntricular arrhythmias
Do not typically involve AV node as part of the re-entrant circuit
Side effects adenosine
Bradycardia, flushing, dyspnea
Flushing with adenosine
Causes brief small vessel vasodilation .. could get buried hypertension, dizziness, or palpitations
Dyspnea adenosine
Induce bronchoconstriction
Caffeine and theophylline decrease effectiveness of adenosine
Caffeine increase HR.
Methylxanthines bocks the receptors for adenosine on the heart
Dipyridamole may intensify effects of adenosine
It is an antiplatelet medication hat blocks the uptake and metabolism of adenosine and may intensify effects,,,may get more serious side effects
How is adenosine given
Rapid IV push followed by a saline fracture lush. Bc it’s Half life is only a few seconds
Lidocaine (xylocaine)
Sodium Channel blocker that inhibits neuronal impulses. It is indicated to treat ventricular dysrhythmias and induce local anesthesia.
Side effects lidocaine
Drowsiness, confusion, paresthesia, seizures, and respiratory arrest
Lidocaine is an __-type anesthetic and it metabolized by the liver
Amide
Administering lidocaine with a ___ prolongs the duration of local anesthetic effects
Vasoconstrictor
MOA lidocaine
Blocks na channels, preventing action potentials from creating pain perception (skin), suppresses neuronal excitability in ventricular dysrhythmias (heart) it is a class IB antiarrhythmis
Indications for lidocaine
Ventricular arrhythmias, anesthetic
Ventricular arrhythmias and lidocaine
Slows nerve conduction in heart. Slows depolarization and accelerates depolarization duration.
Unlike other antidysrhthmic meds, lidocaine does not cause ___ effects
Anticholinergic
Lidocaine anesthetic
Nonselective amide local anesthetic blocks conduction to both sensory and motor neurons.
In what order does lidocaine block impulses
Autonomic, somatic, sensory, somatic motor
Side effects lidocaine
Paresthesia
Seizure (CNS excitation(benzodiazepine may manage))
Respiratory depression (high IV doses suppress CNS)
Drowsiness 9CNS excitation is followed by depressive symptoms)
Giving lidocaine with a vasoconstrictor (epi)
Extends the duration of the local anesthetic. By decreasing blood flow and delaying systemic absorption of the anesthetic, epi prolongs anesthesia and decreases the risk of toxicity.
Magnesium sulfate
CNS depressant that inhibits release of acetylcholine at neuromuscular junctions which prevents skeletal and uterine muscle contraction.
Indications for magnesium sulfate
Preterm labor contractions
Preeclampsia
Side effects magnesium sulfate
Warm feeling, hypotension, decreased DTR, decreased respiratory rate, decreased urine output, paralytic ileus
Antidote for magnesium sulfate
Gluconate
MOA magnesium sulfate
Muscle relaxant and depresses the CNS by stopping the release of ach resulting in decreased neuromuscular irritability and cardiac conduction. The action resolves preterm labor contractions by relaxing the uterus. In addition, by depressing the CNS, magnesium sulfate can decrease hyperreflexia and prevent the onset of seizures from eclampsia
Indications for magnesium sulfate
Preterm labor contractions and preeclampsia
Preterm labor contractions and magnesium sulfate
Relaxes the uterine muscle and resolves preterm labor contractions
Preeclampsia and magnesium sulfate
Muscle relaxant decreases presence of hyperreflexia and lowers risk of seizures
Side effects magnesium sulfate
Warm feeling, hypotension, decreased DTR, creased respiratoy rate, decreased urine output, paralytic ileus,
Antidote to magnesium sulfate overdose
Calcium gluconate
Digoxin
Cardiac glycoside extracted from the plant deigitalis
MOA digoxin
Direct inhibition of the Na/K ATPase pump in the membranes of myocytes. Leads to increased sodium ions int he myocytes which decreases the sodium concentration gradient. Inhibiting the Na/Ca exchanger, which depends on a constant inward sodium gradient to pump calcium out of myocytes
Overall effect of digoxin
Decreases sodium concentration gradient and indirectly decreases subsequent calcium outflow
Result of digoxin MOA
Increased calcium concentration in heart cells leading to increased contractility of the heart also called positive inotropy
Digoxin indication
CHF who remain symptomatic despite adequate diuretic and ACE inhibitor treatment. Also has vagal activity thereby decreasing heart rate by slowing depolarization of pacemaker cells in the AV node. Slowed conduction through AV node makes the drug commonly used in AFIB with rapid ventricular response
In a fib, rapid ventricular rate leads to insufficient diastolic filling time. By slowing the conduction in the AV node, digoxin can do what
Reduce ventricular rate therefore improving ventricular filling and the pumping function of the heart
MOA gigoxin
Direct inhibitor of Na/K ATPase
Indirect inhibition of Na Ca exchanger
Increase Ca in cell
Positive inotropy
Indications for digoxin
CHF
Stimulation vagus nerve
Decreased conduction at AV node
A fib
First line of CHF treatment
Not dogoxin
Digoxin and vagal nerve
Stimulate thereby decreasing heart rate by slowing depolarization of pacemaker cels in AV node
A fib digoxin
Slowed conduction through AV node makes this drug used for a fib with rapid ventricular response.
Digoxin can reduce ventricular rate therefore improving ventricular filling and the pumping function of the heart
Acute digoxin MOA
Inhibit na/k atpase pump. In heart this results in increased calcium concentration in myocytes, as well as increased vagal tone
Why get adverse drug reactions with dogoxin
Narrow therapeutic index
Side effects digoxin
Hyperkalemia
Cholinergic
Blurry yellow green vision with halo of light
Arrhythmia(bradycardia)
Hyperkalemia digoxin
Paralysis of Na/K ATPase pump
Cholinergic digoxin
Cholinergic symptoms like nausea, vomiting diarrhea and GI
Arrhythmia from digoxin
Increased intracellular calcium
Pathognomonic of dogoxin toxicity
Combo of increased atrial arrhythmias and inhibited AV conduction like paroxysmal atrial tachycardia with AV block
EKG changes with dogoxin
Prolonged PR interval
Decreased QT
Scooping of EKG
T wave inversion
Why decreased QT
Increased calcium and increasedionotropy
How treat digoxin toxicity
Activated charcoal and normalize k+
If that doesn’t work
Digibind (antitoxin Fab)
Rate control done with magnesium sulfate, lidocaine, and cardiac pacing
Digibind
First line treatment if have. A lot of digixin.
Beta 1 agonistdobutamine
Catecholamine that works as a beta 1 agonist, increasing inotropic activity of the heart.
MOA dubatamine
Cardiac stimulant used to treat heart failure, or in patients who have had cardiac surgery.
Side effects dobutamine
As a beta 1 sympathomimetic, it can lead to tachycardia and arrhythmias, thus, patients should be closely monitored when this medication is give.
What meds may increase potency of dobutamine
MAIOs and TCAs
MOA dobutamine
Beta 1 agonist
Inotropic
Indications for dobutamine
Heart failure
Cardiac surgery or cardiogenic shock
Side effects dobutamine
Tachycardia, arrhythmias
Condiersations dobuatmine
Closed monitor patients for adverse cardiac side effects
Other meds increase potency so be aware.
Norepinephrine
Ok
Statins
Class of medications used in clinical setting to lower patient cholesterol levels. These emdicatios work by inhibiting the HMG-CoA reductive, a rate limiting enzyme int he cholesterol synthesis pathway.
Effect of statins
Increase HDL and decrease LDL and triglycerides, which are proven to reduce the risk of cardiovascular events in high risk patients.
Side effects statins
Rhabdomyolysis and hepatotoxicity
Satstins __ HMG-CoA reductase
Inhibit
What does HMG-CoA reductase do
Cholesterol synthesis rate limiting enzyme
Statins decrease LDL _ times as much as they lower triglycerides
3
Statins increase __
HDL
Actor a statin (lipitor)
MNG-CoA ereductase inhibitor
Suffix of meds that inhibit HMG-CoA reductase
Statin
Indication for statins like atorvastain
Hypercholesterolemia
Side effect atorvastatin
Rash, hepatotoxicity, myopathy, rhabdomyolysis
You should monitor _ enzymes on statin
Liver
Why avoid grapefruit juice on statins
Contains chemicals that inhibit CPY3A4, causing levels of the. Statin to increase
Why give statins at bed time
Liver makes majority of cholesterol at night time
Hepatotoxicity and statins
Liver makes cholesterol and may be harsh
Monitor for jaundice and liver function tests
How monitor rhabdomyolysis ons tatin
Serum CK levels
Why is too much CK bad for kidney
Plugs the glomeruli and prevents normal glom filtration
Vitamin B3
Niacin
Essential vitamin used in energy reactions as a component of NAD.
How is niacin created
From aa tryptophan and requires vitamin B6 in order to convert the aa to niacin
Pellet RA
Niacin defiency
4 Ds of pellegra defiency
Diarrhea
Dermatitis
Dementia
Death
Niacin deficient often results from depletion of tryptophan as is seen in ___ and ___
Hartnup disease
Serotonin syndrome
Niacin can also be used as a cholesterol medication
More significant side effects though
Niacin and NAD
Niacin is an essential component of NAD which is a coenzyme found in all living cels. It is commonly used in oxidation reduction reactions.
Hartnup diseases
B6 defiency
Inability ofkidney to reabsorbed aa including tryptophan. This can cause a niacin defiency bc there is no tryptophan for conversion
Carcinoid syndrome and niacin
From metastatic carcinoid tumor, which actively secretes serotonin.
How is serotonin created
Derived from tryptophan and can cause a niacin defiency due to depletion of tryptophan
Pellegra niacin defiency
Diarrhea
Dermatitis
Dementia
Death
Glossitis and niacin defiency
Tongue red? Idk
How can flushing from niacin therapy be treated
Aspirin
Niacin
B3
Use of B3
Decrease cholesterol
Effects of niacin therapy
Decrease LDL and triglycerides
Increase HDL
MOA niacin
Inhibition of lipolysis in adipose tissue, as well as reduction of hepatic VLDL secretion
Side effect of niacin
Red, flushed face
Why get flushing with niacin
Prostaglandin activation
How can we reduce flushing from niacin
Asprin by blocking the prostaglandin mediated pathway
Side effect niacin therapy
Hyperglycemia and hyperuricemia
MOA niacin B3
- Inhibits lipolysis in adipose tissue (cant make vldl and ldl)
- Reduces hepatic vldl secretion—->decrease in FFA also suppresses hepatic expression of apolipoprotein C3 and leads to a reduced VLDL
Indications for niacin
Want to decrease triglycerides, LDL and increase HDL
What is a triglyceride
Esters derived from glycerol and three fatty acids—->high levels can lead to atherosclerosis so use statins
Side effects niacin
Flushing-give asprin
Hyperglycemia
Hyperuricemia(may exacerbate gout)
Why may niacin exacerbate gout
May cause hyperuricemia
Fibrates
Carboxylic acid medications indicated for use in hyperlipidemia and other dyslipidemias
Action of fibrates
Decrease triglycerides, increase HDL (slight), decrease LDL (slight)
MOA fibrates
Upregulate LPL, allowing accessibility to triglyceride-rich lipoproteins for lipolysis
Increasing hepatic uptake of fatty acids and decreasing hepatic production of triglycerides, decreasing their overall levels
What causes a slight increase in HDL with fibrates
Increased amounts of apoporoteins A-1 and A-II which allow more efficient reverse cholesterol transport
Why get slight decrease of LDL with fibrates
Formation of LDL with a higher affinity for its receptor, allowing it to be catabolized quicker
Side effects of fibrates
Hepatotoxicity and increase LFT values as well as cholesterol gallstones, which is due to increased cholesterol content in bile. Also myagias, increased CPK and resulting acute kidney injury
Indications for fibrates
Hyperlipidemia
MOA fibrates
Upregulated LPL(metabolizes triglyceride)
Decrease triglycerides
Slight increase in HDL
Slight decrease in LDL
Side effect fibrates
Hepatotoxicity
Cholesterol gallstones
Why get cholesterol gallstones with fibrates
Increase the cholesterol content of bile
Ezetimibe
Lowers the plasma cholesterol in patients with hyperlipidemia by preventing cholesterol reabsorption at the small intestine brush border
With ezetimibe, what happens when cholesterol reabsorption at brush border is inhibited
LDL receptors are upregulated , causing increased LDL uptake into cells. Thus there is a lower LDL value in circulating blood
Side effect ezetimibe
Diarrhea-from large amounts of cholesterol being trapped in the gut lumen
Also increased LFT values
Indications for ezetimibe
Hyperlipidemia
MOA ezetimibe
Cholesterol absorption blockers at brush border Decreases LDL (but upregulation of LDL receptors so increased LDL uptake into cells and decreased levels in bloos)
What is ezetimibe often combined with
Statins
Why is upregulating LDL receptors good with ezetimibe
Increase uptake into shell
Side effects ezetimibe
Diarrhea and increased LFT values
Bile acid resins
Sequester bile acids and disrupt enterohepatic circulation of bile
Indication for bile acid resin
Hyperlipidemia
MOA bile acid resins
Bind to bile acids and represent their reabsorption in the GI system, leaving them to be excreted. Circulating cholesterol is then utilized to replace the lost bile, decreasing blood levels of cholesterol.
Bile acids: by promoting apoprotein A1 synthesis, HDL levels __ __
Slightly increase
Bile acids: by activating phosphatidic acid phosphatase, triglyceride synthesis is promoted slightly ____ ___
Raining triglycerides
These drugs lead to upregulation of __ receptors in hepatocytes
LDL. So it is taken intracellular lh, decreasing plasma LDL cholesterol levels
Common bile acids
Colestipol, cholestyramine, which can be used for diarrhea treatment and toxin absorption and colesevalam
Side bile acid resins
Complaint of bad taste and GI disturbances that accompany their use. These medications lead to decreased absorption of fat soluble vitamins and cholesterol gallstones aw well.
Indications for bile acid resins
Hyperlipidemia -
Familial hyperlipidemia type IIa
What is familial hyperlipidemia type IIa
An inherited disease where patients display xanthelasmas, arcus senilis, and tendon xanthomas
MOA bile acid resins
Bile acid reabsorption prevented (bind to bile acids in GI and makes insoluble so excreted in poop)
Slight increase HDL/Triglycerides
Activate phosphatidic acid phosphatase (which promotes hepatic TG synthesis and slightly raises their levels)
Decrease LDL…upregulation of hmg coa reductase and LD reductase restulting in increase uptake of LDL particles by hepatocytes and reduction in plasma LDL
Colestipol
Bile acid resin
Can bind to other medications and decrease their absorption/MOA such as digoxin, lasix and tetracycline
Cholestyramine
Bile acid resin
Used for crohns who had ileal resection to prevent diarrhea
Can also be used to absorb toxins during C diff infection
Colesevelam
Bile acid resin
Also used to improve glycemic control in TIID
Side effects bile acid resins
Cholesterol gallstones
Decreased absorption of fat soluble vitamins
Patients hate it(taste bad and lead to GI discomfort)
Nitroglycerin
I rate medication used to treat angina and pulmonary edema . Fast acting and a potent vasodilator
Low doses of nitroglycerin
Angina and pulmonary edema, as it vendor lates on a larger scale than it vasodilator, causing it to decrease cardiac preload
High doses nitroglycerin
Vasodilator more than venodilates and can be sued as an antihypertensive agent
Nitroglycerin is broken down in the blood stream into __ which does what
NO
Activates guanyl cyclase and a resulting increase in cGMP. This acts to relax SM, decreasing venous pressure
Side effects nitroglycerin
Directly related to vasodilator effects
-hypotension, reflex tachycardia, flushing and Monday disease(industrial workers mainly)
Contraindication nitroglycerin
In combination with viagra (sildenafil) as it can lead to unsafe , rapid decreases in blood pressure
Nitroglycerin indications
Pulmonary edema (quick potent vasodilator to reduce preload—>>decreases amount of blood flowing into heart and decreasing edematous in lungs) Angina
MOA nitroglycerin
Decreases preload->potent vasodilator and at low doses venodilates more than vasodilates. (High doses opposite and decreases afterload to be used as an antihypertensive agent)
Releases NO in blood-activated guanyl cyclase in smooth muscle, leading to an increase in cGMP, which acts to relax muscle contraction and leads to vasodilation
Side effects nitroglycerin
Hypotension, reflex tachycardia, flushing, Monday disease
Why get reflex tachycardia with nitroglycerin
Compensatory mechanism for maintaining cardiac output as bp drops
Why get flushing with nitroglycerin
Vasodilator effects-common face ad neck
Monday disease and nitroglycerin
Usually industrial workers exposed to nitroglycerin.
Cerebral vasodilation and terrible headaches. Workers develop tolerance to nitroglycerin and feel fine throughout week. After weekend when not exposed they return to work and feel the effects of nitroglycerin on Monday
Contraindications for nitroglycerin
Viagara
Both drugs potential cGMP and venodilates. This combination is unsafe due to huge drops in bp
