Cardiac Pharmacology Flashcards
Lifestyle changes recommendations
- Following a healthy diet
- Being physically active
- Maintaining a healthy weight
- Quitting smoking
- Moderating alcohol consumption
- Managing stress
Routes of administration
- Oral
- Intravenous (IV)
- Intramuscular (IM)
- Subcutaneous (SC)
- Sublingual
- Rectal
First pass metabolism
- Oral Medications, must traverse the intestinal epithelium, the portal venous system, and the liver prior to entering the systemic circulation
- While in the intestine, the drug may undergo metabolism, be transported into the portal vein, or undergo excretion back into the intestinal lumen.
- Both excretion into the intestinal lumen and metabolism decrease systemic bioavailability as well as.
- Drug uptake into the liver, can further limit bioavailability by metabolism or excretion into the bile.
- This elimination in intestine and liver, which reduces the amount of drug delivered to the systemic circulation, is termed presystemic elimination, presystemic extraction, or first-pass elimination.
Half life
- Most pharmacokinetic processes are first-order - The rate of the process depends on the amount of drug present.
- Half-life is the time required for 50% of a first-order process to be complete. - Thus, 50% of drug elimination is achieved after one drug-elimination half-life, 75% after two, 87.5% after three, etc
- The elimination half-life not only determines the time required for drug concentrations to fall to near-immeasurable levels after a single bolus, it is also the key determinant of the time required for steady-state plasma concentrations to be achieved after any change in drug dosing
Steady State
- Steady state describes the situation during chronic drug administration when the amount of drug administered per unit time equals drug eliminated per unit time.
- With a continuous intravenous infusion, plasma concentrations at steady state are stable,
- Chronic oral drug administration, plasma concentrations vary during the dosing interval but the time-concentration profile between dosing intervals is stable
Can nitroglycerin be used orally?
No, because it is completely extracted prior to reaching the systemic circulation
intravenous vs oral
- Some drugs with very extensive pre-systemic or first pass metabolism can still be administered by the oral route, but much higher doses are required than those for intravenous administration.
- Atypical intravenous dose of verapamil is 1–5 mg, compared to the single oral dose of 40–120 mg.
Temporal characteristics of drug effect
- A lag period is present before the plasma drug concentration (Cp) exceeds the minimum effective concentration (MEC) for the desired effect.
- Following onset of the response, the intensity of the effect increases as the drug continues to be absorbed and distributed.
- This reaches a peak, after which drug elimination results in a decline in Cp and in the effect’s intensity.
- Effect disappears when the drug concentration falls below the MEC
Physiology review facts
- Receptors are generally proteins
- Embedded into cell membranes or intracellular
- Generally extend on both sides
- Facilitate communication between 2 sides
- Always causes a secondary effect
- (Remember G proteins and secondary messengers)
Agonist
- binds specifically
- activates cell funciton
Antagonist
- binds specifically
- blocks agonist
- does not influence cell function
Antagonism
- A non-competitive antagonist binds to an allosteric (non-agonist) site on the receptor to prevent activation of the receptor - Doesn’t compete for same site, but still prevents activation
- A competitive antagonist binds to the same site as the agonist but does not activate it, thus blocks the agonist’s action. - Competes for same site, but still prevents activation
Hypertension
•Treat to BP <140/90 mmHg or BP <130/80 mmHg in patients with diabetes or chronic kidney disease.
- Majority of patients will require two medications to reach goal.
- Thiazide-type diuretics if initial medication for most. May consider ACEI, ARB, BB, CCB depending on patient comorbidities.
- Emerging evidence to suggest ACEI as initial drug therapy for HTN
- 2-drug combination for most (usually thiazide type diuretic and ACEI, or ARB, or BB, or CCB).
•MAP approx= CO ×SVR
Diuretics
Goal is to reduce blood pressure by reducing blood volume
- 3 most comon types
- Loop
- Thiazide
- Aldosterone Receptor antagonists
Loop diuretics
block the Na+/K+/2Cl-resorption in the loop of Henle, high ceiling
- Most common: Furosemide (Lasix), drug of choice for HF and patients with CAD w/CKD
- Side effect: Hypokalemia, Hyponatremia, volume depletion, frequent voiding
Thiazide diuretics
block Na+ reabsorption in the distal tubule of nephron
- Most common: hydrochlorothiazide “HCTZ”, (Esidrix), 1st drug of choice for essential HTN
- Side effect: Hypokalemia, Hyponatremia, volume depletion, frequent voiding
Aldosterone receptor antagonists diuretics
Blocks Aldosterone and thus Interferes with Na-K+ exchange at distal tubule”aka Potassium Sparing Diuretic)
- Most common: Sprirolactone,(Aldactone)
- Side effect: Volume depletion, frequent voiding
Sympatholytics
- beta blockers
- alpha 1 blockers
- alpha 2 agonists
beta blockers
- olol
•Primarily target Beta-1 receptor cites, effects
•Reduces HR
•Reduces BP primarily by reducing contractility
•Reduces sympathetic tone
•Also has antiarrhythmic properties
•In low doses actually functions as an anti-anxiety medication
•Limits adverse ventricular remodeling (dilation) after MI
Beta blocker cautions
- Cautious use with patients with kidney or renal dysfunction
- Cautious with patients with pulmonary dysfunction or asthma
- Especially in non-selective beta blockers
- May block Beta-2 receptors and cause bronchoconstriction
- Suppresses sympathetic response to hypoglycemia in diabetics
- May not get tachycardia and shaky, may instead get sweaty and pale
Two categories of beta blockers
- Specific: Metoprolol (Lopressor), Atenolol
* Non-specific: Carvedilol, Propanolol
alpha 1-blockers
- Block Alpha-1 receptors on vascular smooth muscle, thus reduce TPR and BP
- Often prescribed along with other medications
- Has been shown to be effective in treating Benign Prostate Hypertrophy
- Most common: Doxazosin (Cardura), Prazosin (Minipress)
alpha 2-agonists
- Reduces vascular tone by central mediated methods by stimulating Alpha 2 receptors.
- Suppresses sympathetic outflow to vasomotor centers from the brainstem
- Not as commonly used
- Most common: Clonidine (Catapres)
ACE- Inhibitors
- Angiotensin Converting Enzyme Inhibitors “-pril”
- Blocks the conversion of Ang1 to Ang2
- Lowers BP
- Few adverse side effects other than orthostasis
- Decreases afterload and improves survival in patients with HF
- Increases survival and prevents L ventricle dilatation post MI
- Most Common
- Lisinopril (Zestril), Captopril (Capoten) and Enalapril(Vasotec)
ARBs
- Angiotensin 2 Receptor Blockers (ARBs) “-sartan”
- Similar effects as ACEI
- Used when patients don’t tolerate ACEI side effects “coughing”
- Most common
- Losartan (Cozar), Valsartan (Diovan)
- Also used to treat patients with Obstructive Sleep Apnea
Calcium channel blockers
•Selectively block Ca2+ entry into vascular smooth muscle cells.
•Management of hypertension
•Management of angina
•Management of vasospasm
•Reduce cardiac contractile force
•Used to treat supraventricular arrthymmias
•Most common “-dipine)
•Amlodipine (Norvasc), Diltiazem (Cardizem), Verapamil
(Calan)
Hydralazine
- Adirect-acting smooth muscle relaxant used to treat hypertension by acting as a vasodilator primarily in arteries and arterioles.
- Reduces BP by reducing TPR
- Side effects: May increase Na+ retention and thus fluid retention, often used in conjunction with a diuretic
Hypertensive medicine
- Hydralazine
- calcium channel blockers
- ARB’s
- ACE inhibitors
HTN medication considerations
- Alpha blockers, calcium channel blockers or vasodilating drugs may lead to sudden excessive hypotension post exercise (also more common in elderly people)
- Avoid suddenly stopping exercise and undertake an extended cool down period of light activity
- Beta blockers and diuretics may impair thermoregulation
Hyperlipidemia
- HMG-CoA reductase inhibitors (Statin): Blocks LDL synthesis, Increases HDL, some anti-inflammatory properties “-statin”
- Side effects: Renal and liver damage, skeletal muscle myopathy
- Common: Lovastatin (Mevacor), Simvastatin (Zocor), Atorvastatin (Lipitor), Rosuvastatin (Crestor)
4 groups most likely to benefit from statin therapy
- Patients with any form of clinical ASCVD
- Patients with primary LDL-C levels of 190 mg per dLor greater
- Patients with diabetes mellitus, 40 to 75 years of age, with LDL-C levels of 70 to 189 mg per dL
- Patients without diabetes, 40 to 75 years of age, with an estimated 10-year ASCVD risk ≥ 7.5%
Myopathy and statins
- Rhabdomyolysis associated with statin treatment is very rare (<0.1%)
- Classic triad is muscle pain, weakness, and dark urine
- More prominent in proximal muscle groups, such as the thighs and shoulders
- Other less common symptoms: Limb swelling, cramps and stiffness
- Myagliga and weakness are more frequent adverse symptoms (7%)
- Myalgia contributes up to 25% of all adverse events associated with statin use.
Anti-coagulants
- unfractionated heprin
- low-molecular weight heparin
- coumadin (warfarin
Unfractionated heparin
- Blocks clotting factors in blood, traditionally IV med, time to effect 24Hrs
- Used to post operatively to prevent clots, DVT
Low-molecular weight heparin
•Similar effects as Heparin, faster effect time (3-5hrs),•Used in patients with better kidneys•Often given as SC injections Enoxoparin (Lovenox)
Coumadin
- Blocks effect of Vitamin K-epoxide reductase
* Used for long term anticoagulation (Afib, Afib, Chronic DVT)
Anti-platelets
- aspirin
- clopidogrel
aspirin
- COX1 and COX2 inhibitor, prevents platelet aggregation
* Often used in low doses, chronically •Given in larger doses during MI
Clopidogrel
(plavix)
- ADP inhibitor, prevents platelet aggregation
thrombolytic
- Tissue Plasminogen Activators (TPA)-clot busters “-kinase)
- Facilitate breakdown of clots that have already formed by converting plasminogen to plasmin
- Used in Acute MI, if used within 1hr of symptoms reduces mortality by 50%
- Most common: Streptokinase (Streptase), UroKinase (Abbokinase)
Anti-arrhythmic
Class 1-4
Adenosine used to treat SVT, Atropine used for Bradycardia
Class 1 Anti-arrhythmic
Na+ Channel Blockers: Lidocane, Flecanide
•Vtach, Vfib,
Class 2 anti-arrhythmic
-Beta Blockers: (Propanolol)
•Atrial arrhythmias (Afib) and SVT
Class 3 anti-arrhythmic
K+ Channel Blockers : Sotalol, Amiodarone
•Slows repolarization phase, used in acute coronary syndromes
•SVT, Vtach, Vfib
Class 4 anti-arrhythmic
Ca2+ Blockers (Verapamil, Diltiazem)
•SVT
Acute coronary syndrome
- Anti-anginals
- Sublingual Nitroglycerin (NTG)
- Rapid acting vasodilator, takes 2min (veins>arteries)
- Reduces preload and afterload, reduces angina
- Taken under tongue, every 5minutes, 3max, have patient sit when taking
.•Aspirin
•Prevent platelet aggregation and some pain relief
- Morphine (IV)
- Acts as a vasodilator, and helps reduces pain and anxiety
- Beta-Blockers (IV)
- Given to reduce mVO2 and to prevent deadly arrhythmias
- Supplemental 02: Improve coronary 02 sat, Prevent respiratory failure
- Anticoagulation: (Heparin/LMWH): given if patient is to get PCI
- ACE Inhibitors: post MI, prevents long term mortality and remodeling
- Statin Therapy: post MI, risk reduction
Heart failure meds
- Goals of treatment
- Decrease preload (Diuretic)-Lasix or Spironlactone
- Decrease afterload (Ace-Inhibitor)-Lisinopril
- Control sympathetic stimulation (Beta Blocker)-Carvedilolor Metoprolol
•Ca2+ blockers not used due to adverse effects in patients with HF
Decompensated HF
- Positive Inotropes: usually administered via IV
- Dobutamine (sympathomimetic, stimulates B1 receptors in heart)
- IV dopamine (B1 adrenergic; precursor of NorEpH)
- PDE Inhibitors (Milrinione) and Amrinone (inocor) IV or infusion
- Afterload reducers: usually administered via IV
- (Hydralazine)-Arterial: Afterload reduction, to improve LV output
- (Long acting nitrates)-Venous: –reduces filling pressures and preload
- (Isosorbide dinitrate) -Non-selective –treats both elevated filling pressures and low LV output
•Maintain MAP: IV Norepinephrine and Epinephrine
Cardiac Glycoside
- Digitals (Digoxin)
- Comes from the foxglove plant
- Effects
- Positive Inotrope w/o increasing mVO2
- Anti-arrhythmic (HF w/ Afib)
- Controls sympathetic tone
- However can also cause arrhythmias and prolong QT interval.
- Beginning to be phased out
