Term
|
Definition
Cerebral vascular accident (CVA)
Congestive heart failure (CHF)
Myocardial infarction (MI)
Kidney damage |
|
|
Term
|
Definition
normal less than 120/80
Pre HTN 121-139/80-89
Stage 1 140-159/90-99
Stage two over 160/100 |
|
|
Term
| 2 mechanisms controlling BP |
|
Definition
Baroreflexes (Sympathetic nervous system
Renin-Angiotensin-Alodosterone system |
|
|
Term
|
Definition
| Renin converts angiotensinogen to antiotensin 1 and ACE enzymes converts angiotensin 1 to angiotensin 2 |
|
|
Term
|
Definition
| Vasoconstriction, Aldosterone release which causes Na and water retention which leads to increased blood volume which increases BP also causes NE release |
|
|
Term
|
Definition
Lifestyle changes,
diuretics- Thiazide and loop
Beta blockers- non and cardio selective
renin-Angiotensin inhibitors- Ace
inhibitors, ARB, renin inhibitors
CCBs dihydropyridine and non dihydro
Alpha blockers
Others |
|
|
Term
| African american response to HTN treatment |
|
Definition
| respond better to diuretics, don't respond as well to BBs or ACEIs |
|
|
Term
|
Definition
respond to CCBs or ACEis and diuretics
more adverse affects from BB and a blockers |
|
|
Term
| 1st line of defense for HTN |
|
Definition
| Diuretics they are safe, effective, and inexpensive |
|
|
Term
|
Definition
Act mainly in distal tubule to ↓ reabsorption of Na (by inhibition of a Na/Cl cotransporter on luminal membrane of DCT)
Initially causes an increase in Na & water excretion (resulting in a decrease in blood volume)
Creates hyperosmolar urine- monitor K⁺ and Mg⁺⁺ (esp. elederly)
Inhibit urinary Ca⁺⁺ excretion
Long-term treatment results in normal plasma volume, but a decrease in peripheral vascular resistance (caused by relaxation of arteriolar smooth muscle) |
|
|
Term
|
Definition
Act mainly in distal tubule to ↓ reabsorption of Na (by inhibition of a Na/Cl cotransporter on luminal membrane of DCT)
Initially causes an increase in Na & water excretion (resulting in a decrease in blood volume)
Creates hyperosmolar urine- monitor K⁺ and Mg⁺⁺ (esp. elederly)
Inhibit urinary Ca⁺⁺ excretion
Long-term treatment results in normal plasma volume, but a decrease in peripheral vascular resistance (caused by relaxation of arteriolar smooth muscle) |
|
|
Term
|
Definition
Reduction of BP
Monotherapy or Combination with other antihypertensives
NOT effective in patients with inadequate kidney function (CrCl < 50 mL/min) |
|
|
Term
|
Definition
Electrolyte abnormalities
Hypokalemia
Follow K levels closely in patients prone to arrhythmias
Also monitor K levels closely if taking digoxin
Hyperuricemia-increase serum uric acid by ↓ amount of acid excreted byorganic acid secretory system (may ppt gouty attack)
Hypomagnesemia
Hyperglycemia- due to impaired release of insulin and tissue uptake of glucose
Hyperlipidemia- can cause ↑ in cholesterol and LDL levels bus usually return to normal w/long-term therapy |
|
|
Term
|
Definition
Pharmacokinetics
Orally active
Absorption & elimination rates are variable
1 to 3 weeks to produce a stable reduction in blood pressure
Utilizes acid secretory function of the nephron (compete with uric acid for elimination) |
|
|
Term
|
Definition
Inhibit cotransport of N/K/2Cl in luminal membrane in ascending limb of loop of Henle
Reabsorption of these ions is ↓
Most efficacious of diuretic drugs – ascending limb accounts for reabsorption of 25 to 30% of filtered NaCl and downstream sites are not able to compensate for ↑ Na load
Act promptly (even in pts w/poor renal fxn or have not responded to other diuretics)
Cause ↓ renal vascular resistance and ↑
Increase prostaglandin synthesis-helps play a role in diuretic action |
|
|
Term
|
Definition
Drug of choice for reducing acute pulmonary edema of heart failure
Also used to treat hypercalcemia and hyperkalemia
IV or PO
Very rapid onset when given IV and useful in emergency situations |
|
|
Term
|
Definition
Ototoxicity- especially when used with aminoglycosides
Hyperuricemia-compete w/uric acid for renal & biliary secretory systems →gouty attacks
Acute hypovolemia-severe, rapid reduction in blood vol. can lead to hypotension, shock and cardiac arrhythmias
K⁺ depletion
↓Mg⁺⁺ |
|
|
Term
K sparing Diuretics (spironolactone)
MoA |
|
Definition
Aldosterone Antagonist:
Synthetic steroid that antagonizes aldosterone at intracellular cytoplasmic receptor sites- results in failure to produce proteins normally synthesized in response to aldosterone
Prevents Na⁺ reabsorption and K⁺ and H⁺ secretion
Blood levels of aldosterone are high in most edematous states
Often given w/thiazide or loop diuretics |
|
|
Term
|
Definition
Useful in secondary hyperaldosteronism
Helps prevent remodeling of heart that occurs w/progressive heart failure |
|
|
Term
|
Definition
GI upset and may cause peptic ulcers
May induce gynecomastia in males and menstrual irregularities in females (resembles sex steroids and may act at those receptors)
Hyperkalemia, N, lethargy and mental confusion can occur |
|
|
Term
|
Definition
Reduction of BP occurs primarily through reduction of cardiac output.
Some inhibition of renin release & possible reduction in sympathetic output from CNS
Selective b-1 receptor blockers are most commonly prescribed: (i.e. metoprolol, atenolol) |
|
|
Term
|
Definition
Population subsets
More effective in Caucasians & younger to middle-age patients
Hypertension with co-morbid disease
Previous MI, Chronic HF, Migraine HAs, Angina pectoris, SVT |
|
|
Term
|
Definition
Common
Cardiovascular: Bradycardia, hypotension
CNS: fatigue, insomnia
Other: sexual dysfunction
Less common
May adversely effect cholesterol |
|
|
Term
|
Definition
Orally active
May take several weeks of treatment to see the full effect
Propranolol (Inderal®): extensive 1st pass |
|
|
Term
|
Definition
Asthma/COPD: bronchoconstriction (esp. with non-selective BBs)
Blockade of B2 causes bronchoconstriction
Unstable HF (may cause further decompensation)
Heart is not functioning sufficiently & adding a B-Blocker may further cardiac function (worsening acute, unstable HF)
Peripheral vascular disease (potential for vasoconstriction)
Unopposed -stimulation due to -blockade
AV Block
Sympathetic drive may be the only factor allowing the heart to function properly if there is a atrial-ventricular block
Withdrawal: abrupt cessation of BBs may cause angina, MI, or sudden death (patients with ischemic heart disease) |
|
|
Term
|
Definition
Decrease BP by reduction of peripheral vascular resistance
Angiotensin I------>Angiotensin II
Angiotensin II: potent vasoconstriction & release of aldosterone
ACE is also responsible for the breakdown of bradykinin (bradykinin levels are increased with ACEI treatment)
Vasodilation occurs as result of lower vasoconstriction due to ↓ levels of angiotensin II and potent vasoldilating effect of ↑ bradykinin
↓ angiotensin II decreases secretion of aldosterone-- ↓ Na and water retention
Bradykinin may be involved in ACEI-associated cough
Slows progression of diabetic nephropathy
Decreases albuminuria
Prevention of cardiac remodeling after MI |
|
|
Term
|
Definition
HTN
Population subsets: most effective in young, Caucasian patients
Effective in African Americans when combined with a diuretic
Heart Failure (helps prevent remodeling)
Diabetic nephropathy (Esp. useful for patients with diabetes & hypertension) |
|
|
Term
|
Definition
HTN
Population subsets: most effective in young, Caucasian patients
Effective in African Americans when combined with a diuretic
Heart Failure (helps prevent remodeling)
Diabetic nephropathy (Esp. useful for patients with diabetes & hypertension) |
|
|
Term
|
Definition
Dry cough
Hypotension- esp. 1st dose
Hyperkalemia- do not use w/K⁺ sparing diuretics
Angioedema- rare- may also be due to ↑ bradykinin levels
Renal failure (patients with bilateral renal stenosis)
Other: fever, rash
TERATOGENIC
Enalapril, lisinopril |
|
|
Term
| Angiotensin Receptors blockers actions |
|
Definition
Block AT1 receptors (where angiotensin II binds)
Effects similar to ACE inhibitors
BP
Vasodilation
aldosterone secretion
Do not seem to increase bradykinin levels
Losartan, Valsartan |
|
|
Term
| Uses for Angiotensin Receptor Blockers |
|
Definition
Alternative to ACE inhibitors
HTN, HF, prevention of diabetic nephropathy |
|
|
Term
| Adverse Effects of Angiotensin Receptors blocked |
|
Definition
Similar to ACEI
Less risk of cough & angioedema
TERATOGENIC |
|
|
Term
| Renin Inhibitors actions and uses |
|
Definition
Direct inhibition of renin
HTN- works as well as ARBs, ACEI, and thiazides
Can be combined with other antihypertensive drugs |
|
|
Term
|
Definition
Hypotension
Diarrhea
Cough
Angioedema
TERATOGENIC
Hyperkalemia
Aliskiren (Tekturna®) |
|
|
Term
|
Definition
Block inward movement of calcium by binding to L-type Ca channels in the myocardium & smooth muscles of the peripheral vasculature
Causing vascular smooth muscle to relax
Also have intrinsic natriuretic effect and usually don’t require addition of diuretic |
|
|
Term
|
Definition
Uses-when 1st line is contraindicated or ineffective
HTN, angina
Population subsets
African Americans with HTN respond well to CCBs
Also a good choice for patients with peripheral vascular disease, angina, & asthma |
|
|
Term
| actions of Non-Dihydropyridines |
|
Definition
Act on Ca channels of vascular smooth muscle & myocardial smooth muscle
Additional actions-slow automaticity/AV nodal conduction
Verapamil-Pronounced negative inotropic effects
Diltiazem-similar to Verapamil, but less pronounced negative inotropic effects & more favorable SE profile |
|
|
Term
| Action is Dihydropyridines |
|
Definition
Cause vasodilation & decreased peripheral vascular resistance
Have greater affinity for vascular calcium channels than for Ca⁺⁺ channels in heart
Most useful for hypertension, but may cause reflex sympathetic stimulation (in response to vasodilation) & end up requiring treatment with a B-blocker |
|
|
Term
| Drugs for dihydropyridines |
|
Definition
Less drug interactions with other cardiac medications (including warfarin & digoxin)
Nifedipine (Adalat, Procardia®)
Amlodipine (Norvasc®)
Felodipine (Plendil®)
Isradipine (Dynacirc®)
Nicardipine (Cardene®)
Nisoldipine (Sular®) |
|
|
Term
|
Definition
Orally active
Short t ½ (3-8 hours)
Multiple daily dosing is required on many CCBs
Sustained Release (SR) products are available that permit longer dosing intervals
Amlodipine (Norvasc®) has a longer t 1/2 (once daily dosing) |
|
|
Term
|
Definition
Constipation
esp. with verapamil
Dizziness
HA
Fatigue
Verapamil
(-) inotropic, (-) dromotropic-velocity of conduction
Avoid in CHF or AV block |
|
|
Term
| Actions of alpha blockers |
|
Definition
Competitive blockade of α1-receptors
Relaxation of arterial & venous smooth muscle (peripheral vascular resistance & BP)
Cause minimal changes to cardiac output, renal blood flow and GFR
Reflex tachycardia may occur |
|
|
Term
|
Definition
|
|
Term
|
Definition
Postural hypotension
Tachycardia (reflex)
May require treatment with a B-blocker to prevent tachycardia
Edema
Syncope (esp. with 1st dose)
Tolerance to antihypertensive effects
Prazosin (Minipress), doxazosin (Cardura), terazosin (Hytrin) |
|
|
Term
| uses and actions for alpha and beta blocking agents |
|
Definition
Mainly used in heart failure
Block both α1 and β receptors
Carvedilol (Coreg) and labetaolol |
|
|
Term
| Centrally acting Adrenergics drug and MoA |
|
Definition
Clonidine (Catapress®)
α2-agonist
central adrenergic outflow |
|
|
Term
|
Definition
Used 2nd line for HTN or for refractory hypertension
Does not ↓ renal blood flow or GFR—useful in HTN w/renal disease |
|
|
Term
|
Definition
| AE: dry mouth, sedation, rebound hypertension with abrupt withdrawal |
|
|
Term
|
Definition
| α2-agonist (also central adrenergic outflow)- ↓total peripheral resistance and ↓ BP (no change to cardiac output and blood flow to vital organs not diminished) |
|
|
Term
|
Definition
| Often used for hypertension in pregnancy and renal insufficiency |
|
|
Term
|
Definition
Direct-acting smooth muscle relaxants (↓ resistance →↓BP)
Reflex stimulation of the heart may cause tachycardia
Potential to plasma renin concentration
Often given with diuretic & B-blocker
B-blocker to help with reflex tachycardia
Diuretic to help with Na retention (from renin) |
|
|
Term
|
Definition
Arterial & venous dilation
Predominant arterial dilation
Uses: HTN, HTN in pregnancy
AE: HA, tachycardia, nausea, sweating, arrhythmia, lupus-like syndrome |
|
|
Term
|
Definition
Dilation of arterioles
Uses: severe/refractory HTN, topically to treat male-pattern baldness
AE: reflex tachycardia & fluid retention, hypertrichosis
AEs may require treatment with a BB or diuretic to offset reflex effects |
|
|
Term
|
Definition
DBP> 130mmHg constitutes a hypertensive emergency in patients with other cardiovascular risk factors
Cerebral hemorrhage, left ventricular failure, aortic stenosis |
|
|
Term
|
Definition
| Sodium Nitroprusside, Labetol, Nicardipine, fenoldopam |
|
|
Term
|
Definition
IV: causes prompt vasodilation (arterial & venous)
Rapid metabolism (requires continuous infusion to maintain actions)
AE (mostly associated with very high doses or prolonged administration)
Cyanide ion production
Hypotension |
|
|
Term
|
Definition
α & B blockade
Non-selective B-blockade
Given as IV bolus or IV infusion in hypertensive emergencies
Does not cause reflex tachycardia because of B-blockade |
|
|
Term
|
Definition
Calcium Channel Blocker
Can be given as IV infusion in hypertensive emergencies |
|
|
Term
|
Definition
Parenteral antihypertensive
Different MoA
Dopamine-1 receptor agonist
Lowers BP but maintains or increases renal perfusion
Beneficial in patients with renal insufficiency |
|
|
Term
|
Definition
volume of blood in the heart
amount of myocardial fiber stretch that is present before contraction
Based primarily on the amount of circulating volume; the more the volume, the greater the stretch |
|
|
Term
|
Definition
Afterload- impedence opposing ejection of blood from the ventricle
amount of resistance (pressure) the left ventricle needs to overcome to open the aortic valve and eject the stroke volume |
|
|
Term
|
Definition
Force of contraction is related to the concentration of free Ca
Inotropic Drugs:
↑ Ca concentration
↑ sensitivity to Ca
Sources of Ca
Outside the cell
opening of voltage sensitive Ca channels or exchange with Na
Release from sarcoplasmic reticulum & mitochondria
Removal of Ca is required for myocardial relaxation
Na/Ca exchange
Uptake of Ca by the sarcoplasmic reticulum & mitochondria |
|
|
Term
| Drug Classes for intervention in HF |
|
Definition
Inhibitors of the renin-angiotensin-aldosterone system
B-blockers
Diuretics
Inotropic agents
Direct vasodilators
Aldosterone antagonists |
|
|
Term
| Compensatory physiology of HF |
|
Definition
↑ Sympathetic Activity
Activation of the Renin-Angiotensin System
Myocardial Hypertrophy |
|
|
Term
| Management of physical activity, lifestyle and medications |
|
Definition
Management of chronic heart failure
Moderation of physical activity
Low Na diet (< 1.5 g/day)
Treatment of comorbid conditions
Medications to help with HF
Diuretics
Renin-Angiotensin Inhibitors
Inotropic Agents
Beta-Blockers |
|
|
Term
| drugs that worsen Heart Failure |
|
Definition
NSAIDs
Alcohol
Ca channel blockers
Some antiarrhythmics |
|
|
Term
|
Definition
Prevent formation of angiotensin II (vasoconstrictor)
Diminish rate of bradykinin inactivation
Combination of ↓ angiotensin II & more bradykinin causes vasodilation
↓ the secretion of aldosterone
Less Na & water retention (prevents the expansion of blood volume & resultant ↑ workload of heart)
Actions
↓ vascular resistance, venous tone, blood pressure
Blunt the angiotensin II-mediated effect of ↑ epinephrine & aldosterone |
|
|
Term
| Uses of Ace inhibitors for HF |
|
Definition
Indications
Monotherapy: patients with mild dyspnea on exertion & no apparent signs of volume overload
Asymptomatic patients with an ejection fraction of < 35% (left ventricular dysfunction)
Patients with recent MI (initiate immediately after MI)
All stages of left ventricular failure w/ or w/o symptoms
Therapeutic Effects
Improvement in clinical signs/symptoms
Especially in patients receiving combination therapy of ACEI & diuretics or digoxin
↓ morbidity & mortality associated with HF
Also reduces arrhythmic death, MI, and CVA |
|
|
Term
|
Definition
Hypotension & postural hypotension
Renal insufficiency
Hyperkalemia
Angioedema
Persistent dry cough
Avoid in pregnancy (teratogenic) |
|
|
Term
|
Definition
Benzapril (Lotensin®)
Captopril (Capoten®)
Enalapril (Vasotec®)
Fosinopril (Monpril®)
Lisinopril (Zestril, Prinivil®)
Moexipril (Univasc®)
Quinapril (Accupril®)
Ramipril (Altace®) |
|
|
Term
|
Definition
Competitive antagonists of angiotensin I (AT1) receptors
More complete blockade of angiotensin action
Less effect on bradykinin |
|
|
Term
|
Definition
Used as a substitute for ACE Inhibitors
Uses
Hypertension
Substitutes for ACE inhibitors (esp. when ACEI are associated with cough &/or angioedema) |
|
|
Term
|
Definition
Hypotension & postural hypotension
Renal insufficiency
Hyperkalemia
Avoid in pregnancy (teratogenic)
Angioedema |
|
|
Term
| BB used for Heart failure actions |
|
Definition
B1 blockade: ↓ HR
Also ↓ BP (often occurs in patient with HF)
Some inhibition of renin release
↓ hypertrophy, cell death, and deletrious effects of NE on cardiac muscle cells |
|
|
Term
|
Definition
Benefits in HF: improved systolic functioning and prevention of remodeling (due to activation of the sympathetic nervous system)
May even reverse some of the remodeling
Not all BBs are FDA approved for the treatment of heart failure |
|
|
Term
|
Definition
Carvedilol (Coreg®)
Non-selective B-blockade
Also α-blockade
Metoprolol (Lopressor®): long acting version (Toprol)
B1 selective (Cardioselective) |
|
|
Term
|
Definition
Reduction of symptoms of volume overload
Pulmonary congestion
Peripheral edema
Orthopnea
Paroxysmal noctural dyspnea |
|
|
Term
|
Definition
Thiazides
Loose efficacy in kidney dysfunction
Hydrochlorothiazide (HCTZ)
Loop
More potent diuresis
Do not loose efficacy in the kidney dysfunction
Furosemide (Lasix®)
K-sparing/aldosterone antagonist
HF patients have ↑ aldosterone
Weak diuretic effect, but direct aldosterone antagonism
Spironolactone (Aldactone®) |
|
|
Term
|
Definition
Venous Dilators
Dilation of veins
↓ cardiac preload
Venous & Arterial Dilators
Nitrates-Nitroglycerin
Isosorbide
Arterial Dilators
Dilation of arteries
↓ systemic arteriolar resistance
↓ cardiac afterload
Hydralazine |
|
|
Term
|
Definition
(+) inotropic drugs enhance cardiac muscle contractility
↑ cardiac output
MoA
↑ Cytoplasmic Ca |
|
|
Term
| inotropid crugs used especially dobutamine |
|
Definition
Digitalis
Digoxin
Dobutamine (β-agonist)
Given IV
Usually used in hospitalized, acute HF patients
↑ intracellular cAMP– results in activation of protein kinase
Slow Ca channels-important site of phosphorylation by protein kinase causing increased entry into myocardial cell =↑ contraction |
|
|
Term
| MoA of Digitalis or (Digoxin) |
|
Definition
Regulation of cystosolic Ca concentration
Promotes Ca entry into the cell and causes retention of Ca in the cell
↑ cardiac contractility
↑ force of contraction
Leads to ↓ in end diastolic volume
Better ejection fraction & improved circulation |
|
|
Term
|
Definition
Indicated in severe left ventricular systolic dysfunction
After initiation of a ACE & diuretic |
|
|
Term
|
Definition
Very potent
Narrow therapeutic index
Long t ½ (36 hours)
Eliminated via kidney
Dosage adjustment required in impaired renal function
Large Vd (accumulates in muscle tissue)
Loading dose is used if rapid therapeutic effect is needed |
|
|
Term
|
Definition
Cardiac Effects
Arrhythmias
Slowing of AV conduction
GI Effects
Anorexia, N/V
CNS Effects
HA, fatigue, confusion, blurred vision, alteration of color perception & halos
Can kill someone with this |
|
|
Term
|
Definition
Electrolyte abnormalities
Toxicity is enhanced by hypokalemia
May precipitate a serious arrhythmia
Most common in patients taking diuretics
Toxicity may also be worsened with other electrolyte abnormalities (hypercalcemia & hypomagnesemia)
Toxicity is more frequent in patients with renal dysfunction
Renal impairment necessitates more frequent monitoring of digoxin levels
Dosage adjustment may be necessary
Severe toxicity may result in ventricular arrhythmias |
|
|
Term
| what drug causes blurred vision and halows as well as color perception |
|
Definition
|
|
Term
| What adds to Digoxin toxity, drugs and medical conditions? |
|
Definition
Antiarrhymics-Quinidine, Amiodarone
Verapamil
Corticosteriods
Hypothyroidism
Hypoxia
Renal failure
Myocarditis |
|
|
Term
| Phosphodiesterase inhibitors action and uses |
|
Definition
Amrinone and milrinone
↑ intracellular cAMP
Long-term therapy may be associated w/increased mortality
Short term IV milrinone for refractory HF --symptomatic improvement w/no increased mortality |
|
|
Term
|
Definition
Overt Heart Failure
Usually loop diuretics are initiated first to provide relief of volume overload symptoms
Angiotensin Converting Enzyme (ACE) Inhibitor
Or ARB as alternative
BB are initiated after the patient is stable on ACEI
Digoxin is added if needed
Patients who remain symptomatic despite optimal treatment regimen |
|
|
Term
| Treatment of Hyperlipidemias General mechanisms |
|
Definition
Block cholesterol absorption from the diet
Directly increase the amount of cholesterol eliminated from the body
Decrease the amount of cholesterol synthesized in the body |
|
|
Term
|
Definition
HMG-CoA Reductase Inhibitors (Statins)
Bile Acid Sequestrants
Nicotinic Acid
Fibrates
Cholesterol absorption inhibitors
Fish Oil |
|
|
Term
HMG-CoA reductase inhibitors (Statins)
MoA |
|
Definition
HMG-CoA Reductase inhibition
Inhibition of cholesterol synthesis
Lower LDL
↑ # of LDL receptors on liver cells (further decreasing the LDL in the blood)
Due to depletion of intracellular stores of cholesterol
May also ↑ HDL and ↓ TG in some pts |
|
|
Term
|
Definition
Hypercholesterolemia
Primary & secondary prevention of CV Events |
|
|
Term
|
Definition
Atorvastatin (Lipitor®)
Fluvastatin (Lescol®)
Lovastatin (Mevacor®)
Pravastatin (Pravachol®)
Rosuvastatin (Crestor®)
Simvastatin (Zocor®) |
|
|
Term
|
Definition
Mild/Transient-Headache, Rash, GI upset
Rare/Severe
Hepatotoxicity
May progress to liver failure (rare)
LFTs done prior to treatment & every 6-12 months
Discontinue if LFTs change significantly
Myopathy/Rhabdomyolysis
Injured muscle tissue (manifesting as muscle aches/weakness)
May progress to myositis & rhabdomyolysis: muscle destruction with possible kidney failure
If patient has muscle pain/weakness, obtain labs
Discontinue if labs indicate muscle injury |
|
|
Term
|
Definition
Kinetics
Liver metabolism: CYP 450
Significant 1st pass effect
Excretion: bile, feces, urine |
|
|
Term
| contraindication of Statins |
|
Definition
| Teratogenic: Contraindicated in pregnancy |
|
|
Term
| Drug interactions of Statins |
|
Definition
Other cholesterol meds (Fibrates & Ezetimibe): ↑ risk of myopathy
Many drug interactions due to CYP 450 metabolism
CYP 450 inhibitors/inducers
Antibiotics: (mostly macrolides), antifungals (azoles)
Amiodarone
Calcium channel blockers: Diltizem, Verapamil
Digoxin
Warfarin
Grapefruit Juice
Cyclosporine
HIV medications |
|
|
Term
| Nicotinic Acid (Niacin) MoA |
|
Definition
Directly reduces the secretion of VLDL from the liver, inhibits the hepatic synthesis of cholesterol
Strongly inhibits lypolysis in adipose tissue, which is primary precursor of free fatty acids
Liver utilizes FFA as major precursor for triacylgycerol synthesis, which is required for VLDL
↓LDL (5-25%)
↓TG (20-50%)
↑ HDL (15-35%) (better than other medications) |
|
|
Term
|
Definition
Used to increase HDL
Familial hyperlipidemias
To decrease LDL & TG
Other Effects
Increases the secretion of tissue plasminogen activator & lowers plasma fibrinogen level (may prevent thrombotic action associated with hypercholesterolemia & atherosclerosis) |
|
|
Term
|
Definition
Flushing (esp. facial flushing) & itching
Diminishes over several weeks, may be attenuated by taking Aspirin 325 mg 30 minutes before medication
Less flushing with extended release dosage forms
Many patients find this SE intolerable
GI Upset
Hyperuricemia (gout): inhibits tubular secretion of uric acid
Increase in blood glucose
Hepatotoxicity
More likely to occur with certain fromulations of Niacin
Assess LFTs prior to treatment & periodically |
|
|
Term
Bile Acid Sequestrants/Bile Acid Resins
MoA |
|
Definition
Anion exchange resins that bind negatively charged bile acids & bile salts in the small intestine
Prevents the bile acids from returning to the liver
Lowering bile acid concentration causes cholesterol synthesis to be diverted to make more bile acids to replenish the bile acid supply
The lowering of cholesterol in the liver causes the liver to pull more cholesterol out of the blood (therefore lowering plasma LDL)
This causes an up-regulation of hepatic LDL receptors to help pull cholesterol out of the blood
Modest rise in HDL |
|
|
Term
| MoA of Bile Acid Sequestrants/Bile Acid Resins |
|
Definition
Anion exchange resins that bind negatively charged bile acids & bile salts in the small intestine
Prevents the bile acids from returning to the liver
Lowering bile acid concentration causes cholesterol synthesis to be diverted to make more bile acids to replenish the bile acid supply
The lowering of cholesterol in the liver causes the liver to pull more cholesterol out of the blood (therefore lowering plasma LDL)
This causes an up-regulation of hepatic LDL receptors to help pull cholesterol out of the blood
Modest rise in HDL |
|
|
Term
| Uses of Bile Acid Sequestrants/Bile Acid Resins |
|
Definition
Reduce LDL (15-30%)
Treat Type IIa and IIb familial hyperlipidemias |
|
|
Term
| Bile Acid Sequestrants Kinetics |
|
Definition
Insoluble in water and very large-not absorbed or metabolically altered in the intestine
typically excreted unchanged in the feces |
|
|
Term
| SE of Bile Acid Sequestrants and Drug interactions |
|
Definition
GI: constipation, gas, indigestion, nausea
May ↓ absorption of fat-soluble vitamins
Drug Interactions
May form complexes with other drugs (affecting the absorption)
Thiazides, digoxin, warfarin (coumadin), some antibiotics
To reduce the chances of forming complexes, adjust regimen timing
give other meds 1 hour before or 4 hours after bile acid sequestrant |
|
|
Term
| Fibric Acid Derivatives (Fibrates) MoA |
|
Definition
Interact with receptors in liver (PPAR-alpha) to increased activity of lipoprotein lipase & increased clearance of triglyceride-rich lipoproteins
The reduction in available triglyceride-rich lipoproteins causes a decreased production of cholesterol/triglycerides
Most effective for lowering TGs, also ↑ HDL |
|
|
Term
| Uses of Fibric Acid Derivatives |
|
Definition
| Reduce high levels of TGs |
|
|
Term
| SE of Fibric Acid Derivatives |
|
Definition
GI upset
Cholelithiasis
Increase in biliary cholesterol excretion, which may cause gallstones
Musculoskeletal
Myositis= inflammation of voluntary muscle
Pts w/renal insufficiency may be at risk
Rash |
|
|
Term
| Cautions and DI of Fibric Acid Derivatives |
|
Definition
Drug Interactions
Warfarin (Coumadin®): ↑ anticoagulant effect due to protein binding
Statins: ↑ risk for myopathy
Cautions
Pregnancy/lactation
Severe hepatic or renal dysfunction
Pre-existing gallbladder disease |
|
|
Term
| Drugs of Fibric Acid Derivatives |
|
Definition
Medications
Gemfibrozil (Lopid®)
Fenofibrate (Tricor®)
Prodrug |
|
|
Term
|
Definition
Acts in small intestine to inhibit cholesterol absorption (both dietary and biliary)
This leads to reduction of hepatic cholesterol stores and ↑ clearance of cholesterol from blood
↓ LDL,TGs,& possibly a small increase in HDL |
|
|
Term
|
Definition
Adjunct to dietary modifications for reducing cholesterol
↓ LDL by 19%
↑ HDL by 1-4%
↓ TGs by 5-10%
As monotherapy or in combination with a statin
In combination with statin: reduction of LDL with combination of Ezetimibe + statin is greater than either drug used as monotherapy– this has not necessarily translated to decreased CV events or change in carotid-artery intima-media thickness |
|
|
Term
|
Definition
Myopathy
Rhabdomyolysis
Hepatitis
Pancreatitis
Thrombocytopenia
Caution in hepatic impairment
Unknown if harmful |
|
|
Term
|
Definition
Statins
↑ risk of liver damage, myopathy
Fibrates
↑ risk of gallstones, myopathy
Bile Acid Sequestrants
↓ absorption of Ezetimibe |
|
|
Term
|
Definition
Consuming fatty fish or fish-oil supplements is associated with a ↓risk of CHD & CHD-related death.
Fish oil may also ↓ risk of thrombotic stroke
Contains 2 beneficial components
DPA
DHA
American Heart Association recommends eating at least 2 servings per week. |
|
|
Term
|
Definition
1st preparation of omega-3 fatty acids approved by the FDA
Contains EPA & DHA
Approved as an adjunct to diet to ↓ very high levels of TGs
May ↓ TGs by 20-50%
Combination with statin produces a further decrease
Large doses may impair platelet function
Caution with anticoagulant use, bleeding disorders
Recommended dosage is 4 g/day (4 capsules) |
|
|
Term
|
Definition
Dietary supplement
Lack of data (safety, efficacy)
Made from red rice yeast
Active ingredient is the same as statins |
|
|
Term
| Class 1 Antiarrhythmics MoA |
|
Definition
MoA: bind to & block fast Na channels that are responsible for the rapid depolarization (phase 0) of fast-response cardiac action potentials
Same mechanism as local anesthetics
The principal effect of reducing the rate & magnitude of depolarization by blocking Na channels is a decrease in conduction velocity in non-nodal tissue |
|
|
Term
| effects of class 1 antiarrhytmics based on clases |
|
Definition
Sodium-channel blockade:
IC > IA > IB
Increasing the ERP:
IA > IC > IB (decreases) |
|
|
Term
| Black Box Warning for Class 1 |
|
Definition
Treatment of atrial fibrillation/atrial flutter with these drugs may cause paradoxical increase in ventricular rate
Black box warning on all class IC antiarrhythmics
CAST –cardiac arrhythmia suppression trial
Found that treating with class IC drugs for asymptomatic non-life-threatening ventricular arrhythmias who had an MI more than 6 days, but less than 2 years had an excessive mortality or non-fatal cardiac arrest when compared to carefully matched placebo control group
Now recommended to reserve these drugs for life-threatening arrhythmias |
|
|
Term
| effect of class 1A antiarrhythmic |
|
Definition
The direct effect of Class IA antiarrhythmic drugs on AP is modified by its anticholinergic actions
Anticholinergic effects cause an increase in sinoatrial rate and atrioventricular conduction (which may offset the direct effects of the drugs)
While IA drugs may effectively depress atrial rate during flutter, it can lead to an increase in ventricular rate because of an increase in the number of impulses conducted through the AV node (anticholinergic effect)
May require concomitant treatment with a BB or CCB to slow AV conduction.
Anticholinergic actions are most prominent at the SA & AV nodes. Different drugs within the IA subclass differ in their anticholinergic actions |
|
|
Term
|
Definition
| Ventricular tachyarrhythmias (VT) |
|
|
Term
|
Definition
| Supraventricular tachyarrhythmias (SVT) & ventricular tachyarrhythmias (VT) |
|
|
Term
|
Definition
Precipitation of arrhythmias, CNS stimulation, Cardiovascular depression, Allergic reactions
Toxicity is worsened by hyperkalemia |
|
|
Term
| Class 2 antiarrhythmic properties of beta blockers |
|
Definition
| Beta-blockers attenuate sympathetic effects & decrease sinus rate, decrease conduction velocity (which can block re-entry mechanisms), & inhibit aberrant pacemaker activity |
|
|
Term
|
Definition
Propranolol (Inderal®): Non-selective B-blocker
Indicated for post-MI mortality reduction (mortality associated with post-MI arrhythmias)
Metoprolol (Lopressor®): B1-selective B-blocker
Esmolol (Breviblock®): very SHORT acting B1 selective B-blocker
Used IV for acute arrhythmias that occur in surgery or emergencies |
|
|
Term
| Potassium channels for antiarrhythmics, Class 3 |
|
Definition
The primary role of potassium channels in cardiac action potentials is repolarization
In non-nodal tissue APs are initiated when a cell is depolarized by an adjacent cell
This leads to rapid opening of fast Na channels & slower opening of L-type Ca channels
As these channels become inactivated, K channels open permitting K ions to leave the cell, causing repolarization of the membrane potential (phase 3)
K channels remain open until the next action potential. |
|
|
Term
| MoA Class 3 antiarrhythmic drugs |
|
Definition
MoA: Bind to & block K channels that are responsible for phase 3 repolarization
Blocking these channels slows repolarization, which leads to an increase in action potential duration and an increase in the effective refractory period (ERP)
ECG changes-increased QT interval
Common effect of all Class III antiarrhythmic drugs |
|
|
Term
|
Definition
| By increasing the ERP, these drugs are very useful in suppressing tachyarrhythmias caused by reentry mechanisms |
|
|
Term
|
Definition
Similar toxicity to Class IA drugs
Precipitation of arrhythmias
Including Torsades
Caution with other drugs that may cause QT prolongation
Some antibiotics, TCAs, antipsychotics |
|
|
Term
|
Definition
MoA-bind to L-type Ca channels located on the vascular smooth muscle, cardiac myocytes, & cardiac nodal tissue
In cardiac nodal tissue, L-type calcium channels play an important role in pacemaker currents & in phase 0 of action potentials |
|
|
Term
| antiarrhytmic properties of CCBs |
|
Definition
Decrease conduction velocity & prolong repolarization (esp. at the AV node)
Help block re-entry mechanisms
Decrease the firing rate of aberrant pacemaker sites |
|
|
Term
|
Definition
| The cardiac selective, non-dihydropyridine CCBs can cause excessive bradycardia, impaired electrical conduction (e.g., atrioventricular nodal block), & depressed contractility |
|
|
Term
| Cautions of CCB's (Class 4) |
|
Definition
| CCBs (especially non-dihydropyridines), should not be administered to patients being treated with a beta-blocker because beta-blockers also depress cardiac electrical and mechanical activity and therefore the addition of a CCB augments the effects of b-blockade |
|
|
Term
| Digoxin as Antiarrhytmic action and use |
|
Definition
MoA: shortens the refractory period in atrial & ventricular cells, while prolonging the refractory period in the AV node
Therapeutic uses: to control the ventricular response rate in a.fib or flutter |
|
|
Term
| Adenosine is antiarrhythmic MoA and use as well as SE |
|
Definition
Decreases conduction velocity, prolongs the refractory period, & decreases automaticity in the AV node
IV adenosine is the drug of choice for aborting acute supraventricular tachycardia
When given IV in large doses: slows or completely blocks conduction in the AV node
Extremely short duration of action (seconds)
Adverse effects: flushing, chest pain, hypotension |
|
|
Term
| Potassium as Antiarrhythmic |
|
Definition
| Depresses ectopic pacemakers but too much K can cause re-entry arrhythmias |
|
|
Term
| Magnesium as Antiarrhythmic |
|
Definition
| Sometimes effective in arrhythmias caused by digoxin toxicity or Torsades |
|
|
Term
| Antianginal drugs Nitratses MoA actions |
|
Definition
↓ coronary vasoconstriction, ↑ perfusion by relaxing coronary arteries
Also relax veins, ↓ preload & cardiac O₂ consumption |
|
|
Term
| SE and Tolerance of Nitrates |
|
Definition
HEADACHE- most common
May also cause postural hypotension, facial flushing and tachycardia
Tolerance
Develops rapidly- blood vessels become desensitized to vasodilation
Overcome by nitrate free periods (10 to 12 hours)- usually at night when demand on hear is ↓ |
|
|
Term
|
Definition
↓ oxygen demands of myocardium by lowering rate and force of contraction
O₂ demand is ↓ both during exercise and at rest
↓ severity & frequency of attacks
Can be used w/nitrates to improve exercise duration & tolerance
β₁ selective drugs (metoprolol, atenolol) are preferred
Avoid β-blockers w/intrinsic sympathomimetic activity |
|
|
Term
|
Definition
| CCBs protect cardiac tissue by inhibiting influx of Ca into cardiac and smooth muscle |
|
|
