Drugs adv pharm test #2 Flashcards
Oxymetazoline (Afrin)
MoA: Adrenergic decongestants stimulate alpha1 receptors –> constriction of dilated arterioles in nose, reducing nasal blood flow, thus decreasing congestion
Indications: nasal stuffiness
Common adverse effects:
↑ BP, tachycardia, palpitations
Serious SE: arrythmia and may precipitate angina
* If prolonged use for >5 days = rebound congestion called rhinitis medicamentosa
Clonidine (Catapres)
MoA: acts centrally on alpha 2 adrenergic as an agonist
Indications:
HTN; pediatric use for HTN is off-label
Treatment of (ADHD) in children,
Management of tics commonly found with Tourette syndrome
Adjunct therapy for severing cancer-related pain
As an adjunct in neonatal opioid withdrawal syndrome
Common adverse effects:
Bradycardia, palpitations
Guanfacine (Intuniv)
MoA: Stimulates alpha-2 adrenergic receptors. Centrally acting antihypertensive.
Indications:
Adult: HTN, opioid withdrawal (off-label), Tourette syndrome (off-label)
Peds: ADHD (helps with impulse control and attention)
Common adverse effects:
Dizziness, drowsiness, headache, hypotension, blurred vision, confusion
Severe Adverse effects: Chest pain, dyspnea
Dobutamine
MoA: Beta1-selective vasoactive adrenergic drug structurally similar to naturally occurring catecholamine dopamine
Stimulates beta1 receptors on heart muscle (myocardium); increases cardiac output by increasing contractility (positive inotropy), which increases the stroke volume, especially in patients with HF
Indications: Heart failure
Intravenous drug; given by continuous infusion
Off label for chemical stress test (esp in people with asthma or COPD)
Epinephrine
MOA: Endogenous vasoactive catecholamine = adrenaline
Acts directly on both the alpha- and beta-adrenergic receptors of tissues innervated by the SNS
Prototypical nonselective adrenergic agonist
Indications: Administered in emergency situations:
Anaphylaxis – works by vasoconstriction (halts dropping BP), relax airway to help breathing
Severe asthma exacerbation
One of the primary vasoactive drugs used in many advanced cardiac life support protocols (asystole, VF, pulseless VT)
Midodrine (ProAmantine)
MoA: Prodrug that is converted in liver to its active form: desglymidodrine.
Alpha1-adrenergic receptor stimulator: Constricts arterioles and veins resulting in peripheral vasoconstrictions
Indications: Pressor: Used for symptomatic orthostatic hypotension
Adverse Reactions:
HTN
Thing to know:
Oral dosing
Should not be given within 4 hours of bedtime
Albuterol (ProAir, Ventolin, Proventil)
MoA: stimulate beta2-adrenergic receptors of bronchial smooth muscles cause relaxation of the muscles, resulting in bronchodilation
SABA
Indications: asthma
Common adverse effects:
Tachycardia, tremors, palpitations, sweating
Severe Adverse effects:
Dysrhythmias
Formoterol
Combo forms with steroids: budesonide/formoterol (Symbicort), mometasone/formoterol (Dulera)
MoA: Long acting B2 agonist (LABA). Stimulate beta2-adrenergic receptors of bronchial smooth muscles cause relaxation of the muscles, resulting in bronchodilation
Indications: asthma & COPD. Controller med.
Common adverse effects:
Dizziness, diarrhea, nausea, insomnia
Severe Adverse effects:
Paradoxical bronchospasm, arrythmia, HTN
Formoterol has a relatively rapid onset of action compared to other LABAs and is effective within 2-3minutes.
Phenylephrine (Neo-Synephrine)
MoA:
Works almost exclusively on the alpha-adrenergic receptors
Indications:
Used primarily for short-term treatment to raise blood pressure in patients in shock
Control of supraventricular tachycardias
Vasoconstriction in regional anesthesia
Topical forms for ophthalmic uses and as a nasal decongestant
Intravenous route
Alpha Blockers
suffix - “osin”
Terazosin (Hytrin)
MoA: Antagonizes peripheral alpha-1 adrenergic receptors – relaxes vascular smooth muscle and bladder neck and prostate capsule making it easier to urinate
Indications: HTN & Benign Prostatic Hyperplasia (BPH)
Common adverse effects:
Orthostatic hypotension, dizziness, impotence, headache, abnormal ejaculation, rhinitis
Severe adverse effects: Syncope, A-fib, priapism
Remember – the “osins” don’t fix the problem with BPH; they help manage symptoms
tamsulosin (Flomax)
MoA: Blocking the alpha1 receptors of the prostate gland and bladder decreases resistance to urinary outflow thus reducing urinary obstruction and relieving the effects of BPH
Indications: Benign Prostatic Hyperplasia (BPH)
Common adverse effects:
Orthostatic hypotension, impotence, headache, abnormal ejaculation, rhinitis
beta blockers
suffix “olol”
Metoprolol (Lopressor)
Most commonly used beta1 blocker
Oral and injectable
Monitoring required when giving IV
Two oral forms—clarify orders if the order is for “metoprolol”
Metoprolol succinate: extended release, usually ordered once daily
Metoprolol tartrate: immediate release, usually ordered twice daily
Bethanechol (Urecholine)
MOA: Direct-acting cholinergic agonist
Indications: acute postoperative and postpartum nonobstructive urinary retention and for the management of urinary retention associated with neurogenic atony of the bladder
Contraindications: known drug allergy, hyperthyroidism, peptic ulcer, active bronchial asthma, cardiac disease or coronary artery disease, epilepsy, and parkinsonism
Adverse effects: syncope, hypotension with reflex tachycardia, headache, seizure, GI upset, and asthma attacks
Interactions: acetylcholinesterase inhibitors (i.e., indirect-acting cholinergics)
Pyridostigmine (Mestinon)
MoA: Indirect-acting cholinergic drugs that work to increase ACh by inhibiting acetylcholinesterase
Cause skeletal muscle contractions
Indication: myasthenia gravis
Adverse Effects: N/V, diarrhea, abd cramps, diaphoresis, urinary frequency
Edrophonium (Tensilon): indirect-acting cholinergic drug that is used to diagnose myasthenia gravis. It can also be used to differentiate between myasthenia gravis and cholinergic crisis.
pilocarpine (Salagen)
MoA: Stimulates muscarinic cholinergic receptors
Indications: Xerostomia (dry mouth)
Adverse Effects; Nausea, diaphoresis, flushing
Severe Adverse Effects: Impaired vision, bradycardia, tachycardia, syncope
Donezapil (Aricept)
MoA: Reversibly binds to and inactivates acetylcholinesterase
Indications: Alzheimers (first line)
Adverse Effects: N/V, diarrhea, muscle cramps, fatigue, dizziness
Treatment should be started when the diagnosis of mild AD is made although has been shown to be beneficial at all stages.
Start low and titrate gradually. Should not be stopped abruptly 2/2 rebound worsening of cognition
Atropine (Atropen)
MoA: Antagonizes Acetylcholine receptors. Blocks the parasympathetic/cholinergic effects on pacemaker cells of the SA and AV node.
Indications: ACLS (bradycardia) IV
Adverse Effects: HA, tachycardia, constipation, urinary difficulty/retention, restlessness
Used as antidote for cholinergic crisis
Tolterodine (Detrol)
MoA: Urinary antispasmodic. Antagonizes acetylcholine at muscarinic receptors, relaxes bladder smooth muscle, inhibits detrusor muscle contractions (anticholinergic)
Indications: OAB
Adverse Effects: xerostomia, HA, constipation, dry eyes
Dicyclomine (Bentyl)
MoA: Antagonizes acetylcholine at muscarinic receptors, relaxes smooth muscle, inhibits bradykinin and histamine induced spams. Antispasmodic by decreasing GI motility
Indications: IBS
Adverse Effects: xerostomia, nausea, nervousness, palpitations, mydriasis
heparin (unfractionated)
MOA: Indirect thrombin inhibition, heparin binds antithrombin III and this inhibits thrombin, thus no fibrin forms.
Heparin is the anticoagulant of choice during pregnancy.
Laboratory evaluation: aPTT, platelet count (For UFH)
Side effects: bleeding, and Heparin-induced thrombocytopenia (HIT): has 2 types
Type1 HIT: non-immune, transient low platelet count 2 days after starting heparin
Type2 HIT (HITT): immune-mediated, occurs 4-10 days after starting heparin. Presents with low platelets together with venous thromboembolism (DVT& PE)
Heparin (fractionated, LMWH)
Mechanism of action: Indirect inhibition of factor Xa. When LMWH binds to antithrombin III this accelerates the inactivation of factor Xa
Example: Enoxaparin (Lovenox®)
Indications: DVT prophylaxis – hip, knee, abdominal sx, restricted mobility, DVT, unstable angina, STEMI
Advantage over heparin: does not need to be routinely monitored by aPTT, and can be given at home
Preferred over Heparin
Side effects: bleeding, thrombocytopenia
warfarin
MOA: inhibits vit. K reductase, this interferes w/ hepatic synthesis vit K-dependent coag factors (II, VII, IX, X), end result of inhibit conversion of prothrombin to thrombin.
Indications: DVT/PE prophylaxis and tx, stroke prevention (non-valvular and valvular afib)
Adverse effect: bleeding (narrow therapeutic index, highly bound to proteins but with a relatively low affinity leading to a lot of drug interactions that potentiates the effect of warfarin)
Dose: adjusted according to the target INR, thus needs frequent lab monitoring with INR evaluation. Target usually 2-3.
Commonly bridged with heparin initially or interrupted
For upcoming surgeries, hold tx on day 5 and resume within 24 hrs post-op
Dabigatran (Pradaxa)
directly inhibiting thrombin.
Indication: stroke prevention in patients with non-valvular AF, DVT/PE (prevention & tx).
Compared to Warfarin: Dabigatran has much faster onset (on day one), more predictable response, limited drug interactions, wider therapeutic window, no dosage adjustment, no lab monitoring, no CYP implications, no antidote*.
Adverse effects: bleeding. *The newly introduce antidote for Dabigatran, Idarucizumab rapidly reverses the effects of dabigatran in bleeding patients.
Rivaroxaban (Xarelto®), Apixaban (Eliquis®), Betrixaban (Bevyxxa®), Endoxaban (Lixiana®):
All are orally active direct factor Xa inhibitors, which work on day one, NO monitoring required.
Indications: stroke prevention in non-valvular AF, DVT/PE (prevention and tx)
Adverse effects: internal bleeding. The FDA recently (May 2018) approved Andexanet alfa (AndexXa®) as the first and only antidote for the oral direct factor Xa inhibitors when reversal of anticoagulation is needed.
Clopidogrel (Plavix)
irreversible inhibitor of P2Y12 receptors. It is a prodrug: that needs to be activated by CYP2C19, the activity of which is genetically controlled & variable among populations. Omeprazole: is a strong inhibitor of CYP2C19, pantoprazole is NOT!
Ticagrelor (Brilinta)
A newer reversible ADP inhibitor. Not a prodrug. Indicated for acute coronary syndromes. Causes dyspnea, and more bleeding than Plavix.
Aspirin
irreversibly inhibits cyclooxygenase enzyme (COX) ;resultant inhibition of platelet aggregation (for 7-10 days, needs lower doses) 2. PGI2 production by endothelial cells, with resultant more platelet aggregation (for few hour turnover, needs higher doses)
Indications:
ACS, secondary prevention of ACSs (2 antiplatelets)
Stroke & TIA (1 antiplatelet)
Peripheral arterial disease (Aspirin and Cilostazole or Dipyridamole)
Inflammatory arthritis (RA, gout)
Antipyretic
Kawasaki Disease: aspirin reduces the incidence of coronary aneurysms
Essential thrombocythemia: Usually platelet count >1 million. For clotting use aspirin, for bleeding use Hydroxyurea and Anagrelide.
Adverse effects:
Bleeding due to platelet inactivation
Inhibition of PGE2 causes peptic ulcers and renal insufficiency
Asthma may result from altering leukotriene synthesis. (Samter’s Triad: is a combination of aspirin intolerance, asthma, and nasal polyps)
Tinnitus: in chronic aspirin intoxication
In toxic amounts aspirin leads to: hyperventilation, metabolic acidosis (with increased anion gap), encephalopathy and renal insufficiency.
Vorapaxar (Zontivity®)
Mechanism of action:
Vorapaxar is a new anti-platelet drug that is part of the PAR-1antagonist (Protease-activated receptor) family, a new class of anti-platelet drug.
It functions by inhibiting thrombin-related platelet aggregation. This mechanism works by a different pathway than other anti-platelet medications such as aspirin and P2Y12 inhibitors.
Unlike many other medication, vorapaxar does not affect ADP-mediated platelet aggregation, coagulation parameters, or bleeding time
Medical uses: Vorapaxar is used for persons with a history ofmyocardial infarction or persons withperipheral arterial disease
Contraindications: Vorapaxar is contraindicated for people with a history of stroke, transient ischemic attack, or intracerebral hemorrhage
Dipyridamole (Persantin®)
Mechanism of action: It inhibits phosphodiesterase enzyme (PDE), thus increasing cAMP in platelets which prevents their activation. Inhibiting PDE also causes increased cGMP, which leads to vasodilation.
Therapeutic indications: It is a weak drug that is never the first line of therapy, it can be combined with aspirin for stroke or PAD. Aggrenox® is a combination of aspirin/extended-release dipyridamole was approved by FDA for stroke secondary prevention.
Side effects: GI bleed (not too much risk). Dizziness and headache because of the vasodilation.
Cilostazol (Pletal®)
Mechanism of action:
Cilostazol decreases platelet aggregation.
It works by inhibiting a platelet enzyme known as phosphodiestarse III.
As a result, there is a reversible inhibition of platelet aggregation, vasodilation and inhibition of vascular smooth muscle cell proliferation.
Medical uses: Symptomatic management of peripheral vascular disease, primarily intermittent claudication (in addition to aspirin or clopidogrel).
Side effects: Because of vasodilation it results in headache (most common adverse effect) as well as dizziness and vertigo. The most serious adverse effect is worsening CHF.
Eptifibatide (Integrilin®), tirofiban (Aggrastat®)
Mechanism of action: Inhibit platelet aggregation by blocking the glycoprotein receptors (GP IIb/IIIa)
Indications: Acute coronary syndromes, ONLY iv
Adverse effects: Bradycardia, hypotension, edema dizziness bleeding, thrombocytopenia
Tissue Plasminogen Activator (tPA)
- Activated protein C/S complex inactivates an inhibitor of tPA - tPA converts plasminogen to plasmin - The circulating plasminogen is trapped in the fibrin clot - After approximately 24 hours, tPA becomes dis-inhibited , leading to plasmin formation - Plasmin dissolves the clot
alteplase (Activase®), reteplase (Retavase®), tenecteplase (TNKase®)
Mechanism of action: Thrombolytics activate the conversion of plasminogen to plasmin which breaks down (lyses) the thrombus.
Indications: MI, DVT, PE, and acute ischemic stroke
Adverse effects: Bleeding (internal, superficial, and intracranial).
Thrombolytics can also induce cardiac dysrhythmias
Simvastatin(Zocor®), atorvastation(Lipitor®), rosuvastatin(Crestor®)
Mechanism of action: HMG CoA reductase inhibitors
Usually given in the evening the ones with short t1/2; cholesterol synthesis is a nocturnal event
Side effects: The most common side effect is elevated liver enzymes, also myositis, myalgia do occur, and rhabdomyolysis (rare/high doses).
Contraindications: active liver disease, pregnancy (Category-X), & lactation
Drug interactions: CYP inhibitors affect the more CYP3A4 dependent statins (simvastatin, atorvastatin, lovastatin). The statins that are less CYP dependent are pravastatin, rosuvastatin
Monitoring: LFTs should be evaluated at the start of treatment, and monitored periodically (6-12 weeks), and the drug should be discontinued if the LFT increase to > 3 times normal.
Also, recheck cholesterol in about 8 weeks once starting on a statin
HMG CoA reductase inhibitors
suffix - “statins”
Niacin (vit B3)
A vitamin B that has to be given in 100-300 times its dose as a vitamin to LDL, and TG, and HDL (Dose: >3g/day)
Unknown mechanism of action(VLDL synthesis, LPLase activity)
Drug of choice for young patients with no risk factors, yet with a polylipid disorders (Non-acute conditions)
Flushing: major side-effect ( by pretx. with ASA, and SR forms)
Other side-effects: vasodilation (may potentiate antihypertensives), diarrhea, drug-induced hepatitis.
Contraindications/cautions: niacin can exacerbate insulin resistance, can precipitate gout, liver disease or concomitant use with other drugs that may affect the liver(e.g. statins).
Bile Acid Sequestrants (Resins)
cholestyramine
(Questran®
Act to bind bile acids in the intestines, forming an insoluble complex that is excreted in the feces.
This decreases the return of cholesterol to the liver, the latter will respond by up-regulating the LDL receptors, which the plasma LDL uptake by the liver
Two examples are: cholestyramine(Questran®)(4-16g/d) & colesevelam (Welchol®)(3.75g/d) [should be taken before meals]
Adverse effects: flatulence, bloating& constipation. TG
Interactions: bind other medications and their absorption and bioavailability [oral anticoagulants, thyroid hormones, digoxin, penicillins, tetracyclins]. [take concomitant medications at least 1 hour before or 4 hours after the bile aid resins]
Important! Questan is powder and has a gritty/sandy consistency – adherence is a real problem. Welchol tablet is large and hard to swallow.
Fibric Acid Derivatives
Gemfibrozil (Lopid®), fenofibrate (TriCor®)
Mechanism of action: stimulation of lipoprotein lipase, promoting catabolism of VLDL & TG = use it to treat hypertriglyceridemia
Examples: Gemfibrozil (Lopid®), fenofibrate (TriCor®)
Side effects: gall stones, LFT abnormalities
Interactions: potentiate warfarin, insulin, sulfonylureas
Indication: severe hypertriglyceridemia >500 (and NOT for high cholesterol)
**Caution: Statin plus FAD can lead to severe myopathy and rhabdomyolysis. If choosing combo therapy, fenofibrate has been shown to be effective for mixed hyperlipidemia and is a safer option.
Omega 3 fatty acids (fish oil)
Lovaza, Vascepa
These help with hypertriglyceridemia
The direct mechanism of action is not accurately known, they lead to decreased triglyceride synthesis by the liver.
Cholesterol Absorption Inhibitors
ezetimibe (Zetia®)
Mechanism of action: inhibits cholesterol absorption from small intestine, thus the hepatic free cholesterol pool.
Reduced Tchol and LDL
Indications: HDL, mixed hyperlipidemia
Less preferred than statins.
Can be used with statins and FADs
Adverse Effects: Arthralgias, diarrhea, fatigue
Contraindications: moderate to severe hepatic insufficiency
Important! has no effect on overall mortality or cardiovascular mortality, although it significantly reduces the risk ofMI and stroke
PCSK9 inhibitor
Evolocumab (Repatha®), and Alirocumab (Praluent®)
PCSK9: Is an enzyme encoded by the PCSK9 gene in hypercholesterolemia pts.
When PCSK9 is blocked, more LDL receptors are recycled and are present on the surface of liver cells to remove LDL from the blood
Usually given with statins to further lower the LDL levels in patients with familial hypercholesterolemia or whenever maximally tolerated statin therapy is not sufficient to control LDL-C levels in “Very High Risk” ASCVD patients.
Administration: Every 2 weeks or once monthly as SC injection
Side effects: Injection site reaction, “flu” like symptoms, nausea, fatigue, diarrhea, might result in increased blood sugar levels.
Bempedoic Acid (Nexletol®) ACL Inhibitors
Mechanism of action: Inhibits ATP citrate lyase enzyme, which is involved in the liver’s biosynthesis of cholesterol (upstream of HMG-CoA reductase)
Examples: Bempedoic acid (Nexletol®), in combination with ezetimibe (Nexlizet®)
Side effects: Muscle spasms, gout, diarrhea
Indication: Treatment of hypercholesterolemia in adults with familial hypercholesterolemia or with established ASCVD who need additional lowering of LDL. Administered orally in combination with diet and the highest tolerated statin therapy.
Ace Inhibitors
ex) Lisinopril,enalapril
suffix “prils”
Mechanism of action: They inhibit ACE (in the lungs), thus block the conversion of angiotensin I to angiotensin II. This causes reduced afterload (vasodilation) and reduced preload (due to decreased aldosterone production). They slow down cardiac remodeling.
Examples: (-prils) Captopril, lisinopril, enalapril, ramipril, perindopril, trandolapril. (* All are prodrugs EXCEPT captopril & lisinopril)
Some of them can come combined with thiazide diuretics for treatment of hypertension.
Clinical Use: CHF with reduced EF, hypertension, diabetic nephropathy
Side effects (CATCHH): Cough (dry, irritating), Angioedema (Both are ￪bradykinin effect), Teratogen, ￪Creatinine, Hyperkalemia, and Hypotension.
Absolute contraindication: bilateral renal artery stenosis. (Relatively CI in pregnancy 2/2 teratogenic affect).
Angiotensin II Receptor Blockers (ARBs)
ex) losartan (cozaar)
suffix - “artan”
Mechanism of action: They selectively block binding of angiotensin II to AT1 receptor. They have same effects of ACE-Is, but ARBs do NOT increase bradykinin
ARBs do NOT cause the dry irritating cough or angioedema
Clinical Use: Same indications of ACE-Is but for patients who do not tolerate the dry cough of ACE-Is
Side effects: Hypotension, hyperkalemia, teratogen, ↓GFR NEVER COMBINE ACE-Is AND ARBs
Angiotensin Receptor/ Neprilysin Inhibitor (ARNI)
Sacubitril/Valsartan (Entresto®):
Mechanism of action: Sacubitril inhibits the enzyme neprilysin thus, increasing the levels of natriuretic peptides. This causes vasodilation, reduction of preload via increased sodium excretion, and reduction of the maladaptive cardiac remodeling. The efficacy of sacubitril was found to increase when combined with an ARB.
Clinical Use: - CHF (with reduced EF), now, preferred over ACE-Is & ARBs. It reduces mortality and hospital stay.
Side effects: - Hyperkalemia, hypotension, dry cough, and reduced kidney function. - Angioedema, a rare but serious side effect, can occur in some patients
Mineralocorticoid Receptor Antagonists (MRAs) (potassium sparing diuretics)
ex) Spironolactone (Aldactone)
Mechanism of action: Competitive aldosterone receptor antagonists in the cortical collecting renal tubules.
Examples (-ones): Spironolactone (Aldactone®), and eplerenone (Inspra®).
Clinical Use: - 1st choice drug for CHF with systolic dysfunction (w/ EF <40%), hyperaldosteronism. - Spironolactone is used for ascites of hepatic failure (best initial diuretic therapy). - Spironolactone has antiandrogenic properties and can be used for acne, hirsutism, amenorrhea & PCOS
Side effects: Hyperkalemia Spironolactone causes gynecomastia
Alpha Blockers
Mechanism of action & Examples: - Nonselective (ɑ1 & ɑ2 blockers): Phenoxybenzamine, and phentolamine (OLD) - ɑ1 selective (-osin): Prazosin (Minipress®), Terazosin (Hytrin®), Doxazosin (Cardura®) - ɑ1 uro-selective: Tamsulosin (Flomax®) [Does NOT result in orthostatic hypotension] - ɑ2 selective: Mirtazapine used for depression
Clinical Use: - Phenoxybenzamine: used for pheochromocytoma (preoperatively). - Phentolamine: for cocaine-induced hypertension & the hypertensive crisis with MAO-Is interaction with tyramine-containing food. - Tamsulosin: the preferred symptomatic treatment of BPH (Terazosin & doxazosin can lower BP). - Prazosin: Was originally introduced as antihypertensive medication (but causes significant OH, esp 1st dose, pts fell)
Side effects: Orthostatic hypotension (especially with the 1st dose), dizziness, headache. Tamsulosin works more selectively on the ɑ1 receptors in the prostate and the bladder, hence, it does NOT cause hypotension.
Amiodarone (Pacerone)
Mechanism of action: Amiodarone is a potent antiarrhythmic medication that is primarily K+ channel blocker, but also has beta-blocking effect as well as blocking inactivated Na+ and Ca2+ channels
Clinical Use: - Drug of choice for V-fib & V-tach in acute resuscitation when used with defibrillation. - It is the single best med. To maintain sinus rhythm with A-fib. - For chronic ventricular arrhythmias, it is used in conjunction with implantable defibrillator
Side effects: - Hyperthyroidism & hypothyroidism - - Pulmonary fibrosis - Non-sight-threatening corneal deposits (bluish halos) - - Blue skin
Ivabradine (Corlanor®)
Mechanism of action: Selective inhibition of funny sodium channels. Negative chronotropic effect (without affecting inotropy). Reduces cardiac O2 requirements.
Clinical Use: - Chronic stable angina in patients who cannot tolerate beta-blockers. - CHF with reduced ejection fraction in patients who cannot tolerate beta-blockers.
Ivabradine lowers mortality in this group of CHF.
Side effects: - Luminous phenomena/visual brightness - Bradycardia (not to be used in HR ＜70 bpm)
Class IA antiarrythmic
sodium channel blocker
Procainamide
Major or unique side effects– prolonged QT, drug induced lupus;
Common antiarrythmic indications: AVRT and preexisting a fib and a flutter
Class II antiarrythmic
beta blocker
Metoprolol, esmalol
slows rate of depolorization in slow AP cells; major side effects/toxicity: bronchospasm, depression, exercise intolerance, sexual dysfunction; indicated for rate control of afib/aflutter, suppression of PVCs, PACs, and VT
Class III Antiarrythmic
Amioderone
K+ channel blocker
side effects: pulmonary fibrosis, thyroid disease, hepatic dysfunction (increase LFTs); indications: cardio version of afib/aflutter, maintenance of SR in PAF, suppression pf VT
Class IV antiarrhythmic
Verapamil
Diltiazem
Calcium channel blockers
side effect- negative ionotropy,
indications: rate control of Afib/afluttter, prevention of AVNRT
Digoxin
increase vagal tone, inhibits Na/K pump; slows rate of depolarization in slow AP cells,
side effects: very pro arrhythmic
indications: rate control of afib (second line)
calcium channel blockers
Dihydropyridines (-dipines)
Amlodipine (Norvasc®), Nifedipine (Procardia®), Nicardipine (Cardene®),Clevidipine (Cleviprex®)
MOA:Block voltage-dependent L-type calcium channels of cardiac muscle and smooth muscles → ↓ muscle contractility
Site of action:Vascular smooth muscles > Heart
Indications: mainly HTN;Hypertension, angina (including Prinzmetal), Raynaud phenomenon, Pulmonary HTN
adverse effects:
Postural hypotension, constipation, peripheral edema, dizziness, flushing
Calcium channel blockers
Nondihydropyridines
Verapamil (Calan®),
Diltiazem (Cardizem®)
MOA: Block voltage-dependent L-type calcium channels of cardiac muscle and smooth muscles → ↓ muscle contractility
Site of action:Heart > Vascular smooth muscles
Indications: Mainly for cardiac arrhythmias & ischemia; Angina, Atrial fibrillation/flutter, hypertension
Adverse effects: AV-block, cardiac depression, ↑prolactin, constipation, gingival hyperplasia
Furosemide (Lasix)
Sulfonamide loop diuretic (cannot be used in pts with sulfa allergy)
Mechanism of action: Lasix inhibits Na+ reabsorption in the thick ascending limb of loop of Henle. It also has a PG-mediated vasodilatory effect on the afferent arteriole. Lasix increases Ca2+ excretion. Lasix does not need an adequate GFR to exert its diuretic effect.
Clinical Use: - All Edema states: CHF, cirrhosis, nephrotic syndrome, pulmonary edema
- Hypertension, hypercalcemia
Side effects: Ototoxicity, Hypokalemia, Hypomagnesemia, Dehydration, Allery (sulfa), metabolic alkalosis, nephritis (interstitial).
Chlorthalidone (Hygroton®), Chlorothiazide (Diuril®), Hydrochlorothiazide (HydroDiuril®, Esidrix®)
Thiazide Diuretics:
Mechanism of action: Inhibit Na+ reabsorption in the early distal tubule. They also ↓ Ca2+excretion = retains Ca2+
in the body
Clinical Use: Hypertension, HF (with furosemide), idiopathic hypercalciuria, osteoporosis (as it inhibits Ca2+ excretion)
Side effects: Hypokalemic metabolic alkalosis, hyponatremia, hyperglycemia, hyperlipidemia, hyperuricemia, hypercalcemia, sulfa allergy, and erectile dysfunction.
To be used with caution in patients with gout.
Spironolactone (Aldactone®)
Potassium-sparing Diuretics [aka: Aldosterone Antagonists]
Mechanism of action: - - Spironolactone antagonizes aldosterone in the collecting tubule.
- Triamterene and amiloride block the Na+ channels in the collecting tube as well.
Clinical Use: HF, hepatic ascites (Spironolactone), nephrogenic DI (Amiloride), K+ depletion. The antiandrogenic activity of spironolactone helps with acne, hirsutism, amenorrhea, PCOS.
Side effects: Hyperkalemia
- Nitroglycerin (Nitro-Bid®): both rapid-acting (sublingual, spray) and long-acting (patch)
- Isosorbide dinitrate (Isordil®) (both rapid and long acting).
- Isosorbide mononitrate (Imdur®) (primarily long acting)
Nitrates
Mechanism of action: Vasodilate by ↑ NO in vascular smooth muscle → smooth muscle relaxation. Nitrates dilate veins much more than arteries leading to preload reduction.
Clinical Use: - Angina, acute coronary syndromes, pulmonary edema. - Nitrate tolerance: The patient should be allowed a 12-hour nitrate free period when using
the long-acting forms to replenish NO stores in the vascular endothelium
* Have patients sit down before taking nitrates to reduce the risk of falling 2/2 OH
Side effects: - Orthostatic hypotension, flushing, headache, reflex tachycardia.
Hydrazine (Apresoline)
Mechanism of action: Smooth muscle relaxation. Dilate arteries much more than veins → afterload reduction.
Clinical Use: - Hypertensive emergencies
- Hydralazine (Apresoline®), is safe to use during pregnancy. - The combination Hydralazine/Isosorbide dinitrate (BiDil®): is used for CHF (it was proved to achieve 43% mortality reduction in self-identified African-American patients.
Side effects: - Reflex tachycardia & angina (contraindicated in angina/CAD). - Fluid retention, headache. - SLE-like syndrome (Drug-induced lupus)
Ranolazine (Ranexa®)
when all other meds fail
Mechanism of action:
- Inhibits Na+ channels, and consequently
the Na+/Ca2+ exchanger which reduces the
wall tension and O2 consumption.
- Does not affect heart rate or contractility
(a plus!)
Clinical Use: - Chronic stable angina as an add-on
therapy when other medications fail
Side effects: - Dizziness, headache
- Nausea, constipation
- QT prolongation
Dapagliflozin (Farxiga®):
Empagliflozin (Jardiance®)
SGLT-2 inhibitors
not just for diabetes
Mechanism of action: Their protective effects in heart failure is attributed primarily to hemodynamic effects, where SGLT2 inhibitors potently reduce intravascular volume through osmotic diuresis and natriuresis. This consequently may lead to a reduction in preload and afterload, thereby alleviating cardiac workload and improving left ventricular function
Clinical Use: - HFrEF: They reduce mortality
- HFpEF: They reduce hospitalization
Side effects: - Dehydration & orthostatic hypotension (due to their osmotic diuretic effect)
- Rapid weight loss & tiredness (due to their heavy glycosuric effect)
- UTI (due to increased amounts of glucose in urine)
