Osmotic diuretic
What type of diuretic?
Mannitol
Used to treat cerebral edema
loop diuretics (high ceiling)
What type of diuretic?
Furosemide (Lasix)
Used for fluid overload
Thiazide diuretics
What type of diuretic?
Hydrochlorothiazide
Hypertension treatment
K+ sparing diuretics
What type of diuretic?
Spironolactone, triamterene
Used to offset K+ loss
Furosemide (Lasix fyoo-ROH-seh-mide)
-Mechanism of action Blocks active reabsorption of Na+ Preventing passive reabsorption of water In the ascending limb of Henle's loop ? "Loop" diuretic
�Pharmacokinetics
-Administration: PO, IM, IV PO: 40 mg qD-BID (8am, 2pm) Effective for 8 hours IV: 20m
Hydrochlorothiazide (Hydrodiuril , etc. hy dro klor o THY a zide)
One of the most widely used drugs
-Class: thiazide diuretic
-Mechanism Of Action Inhibits reabsorption of Na+ in early DCT Need normal renal function Ineffective if Creatinine Clearance < 20ml/min
-Therapeutic Use Essential hypertension Mobilization of ed
spironolactone (Aldactone SPEER-oh-no-LAK-tone)
-Class: potassium sparing diuretic
-Mechanism of action Blocks action of aldosterone in DCT Retain K+, lose Na+ Weak diuretic - most of Na+ already reabsorbed Takes 48 hr to see effects Blocking synthesis of new protein pumps
-Therapeutic Uses With loop a
Triamterene (Dyrenium trye-AM-ter-een)
-Mechanism of action Disrupts Na+/K+ exchange in convoluted tubule Directly inhibits pump = effect within hours
-Therapeutic use With other diuretics Hypertension Edema
�New: Vasopressin receptor antagonist
-tolvaptan (Samsca)
�Drug Combinations
-Aldactaz
mannitol (Osmitrol MAN-ih-tole)
-MOA: 6 carbon sugar, this is excreted in urine Increasing solute load in tubules Keeping water from being reabsorbed Filtered freely at glomerulus, minimally reabsorbed Inhibits passive reabsorption of water ? ? urine output Not metabolized, pharmacologi
Hypokalemia (K+ <3.5 mEq/L)
-Causes Insufficient K intake Cellular shifts alkalosis, excessive insulin Loss Thiazide of loop diuretics (most common cause) Increased aldosterone Vomiting, diarrhea, laxative overuse Sweat
-Symptoms Weakness, paralysis, dysrhythmias, Intestinal dilatat
ACE inhibitors
What category are these?
-Captopril (Capoten) KAP-toe-pril Short t? - dose tid-qid
-Enalapril (Vasotec) e-NAL-a-pril PO and IV forms
-Lisinopril (Prinivil, Zestril) ye-SIN-oh-pril
-And many more.....
Angiotensin 2 Receptor Blockers (ARBs)
What category are these?
-losartan (Cozaar) loe-SAR-tan
-valsartan (Diovan) val SAR tan
-candesartan (Atacand) kan de SAR tan
-olmesartan (Benicar) OL me SAR tan
-telmisartan (Micardis) TEL mi SAR tan
Aliskiren (Tekurna a LIS ke rin)
Direct Renin Inhibitor
-MOA: bind renin ? ? Angiotensin II
-Therapeutic use Hypertension � Effect of ACE inhibitors and ARBs
-AE: diarrhea, hyperkalemia
Aldosterone Antagonist
What category of drug does this describe?
Blocks aldosterone receptors
-Retention of K+, excretion of Na+, H2O ?? BP
�Therapeutic uses
-Hypertension - if not responding to other agents
-Heart failure - improves Sx, prolongs life
�Adverse effects
-Hyperkal
Verapamil (Calan)
�First available CCB
�Class: Calcium channel blocker
�MOA: Blocks CCs in BVs and heart
-Direct hemodynamic effects Peripheral arterioles vasodilate ? ? BP Coronary arteries dilate ? ? perfusion Blocks calcium in SA node ? ?HR Blocks calcium in AV node ? ?
Nifedipine (Adalat, Procardia)
-Class: CCB, dihydropyridine family
-MOA: Calcium channel blocker Effect on VSM CCs blocked ? vasodilation = ?BP Little effect on heart calcium channels Indirect effect - seen with fast acting forms ?BP ? activates baroreceptors ? Sympathetic stimulation
Hydralazine (Apresoline hye DRAL a zeen)
-Class: vasodilator
-Effect Dilates arterioles ? ? vascular resistance & ?BP MOA unknown
-Pharmacokinetics Metabolized by acetylation in liver Rapid and slow acetylators - genetic trait If slow, higher drug levels, more effects PO - 10-100mg qid IV, IM -
Sodium nitroprusside (Nitropress nye troe PRUS ide)
-Fastest acting antihypertensive available
-Class: vasodilator
-Mechanism of action Potent, fast acting vasodilatation of arterioles and veins Broken down to NO + cyanide NO ? relaxes VSM Cyanide ? toxicity
-Pharmacokinetics Cyanide converted to thiocyana
Beta blockers
-Until mid-1990s HF was CI for these because they ? Contractility
-With careful dose they can ? CO and slow progression of remodeling
-Protects against sympathetic stimuli, dysrhythmias
-Adverse effects Worsening heart failure, fatigue, Hypotension, brady
Digoxin (Lanoxin)
Plasma levels: 0.5-0.8 ng/mL
-Class: cardiac glycoside Extracted from foxglove = digitalis
-Therapeutic Uses Heart failure - improves Sx, does not prolong life Treatment of dysrhythmias (Chpt 48)
-MOA: inhibits Na+-K+ ATPase Competes for site on pump that
Stage A
What stage of heart failure is this treating?
No symptoms or cardiac abnormalities
-Have increased risk of developing HF - behaviors, diseases
-Tx goal: ? Risk factors for heart disease hypertension, hyperlipidemia, diabetes, stop smoking, decrease drinki
Stage B
What stage of heart failure is this treating?
No Sx, but structural changes
-LVH, LV dilation, ? contractility
-Goal: Prevent development of Sx HF
-Add ACE inhibitors, ?-blockers
Stage D
What stage of heart failure is this treating?
Advanced changes
-Sx not controlled with maximal medications
-Tx: transplant heart if eligible
Stage C
What stage of heart failure is this treating?
Sx and structural changes
-Sx: dyspnea, fatigue, edema
-Goals Relieve congestion - pulmonary + peripheral Diuretics, aldosterone antagonists Increase functional capacity Digoxin Slow remodeling and progression
Heart Failure
What do these drugs treat?
Diuretics
Drugs that inhibit RAAS (ACE inhibitors, ARBs, Aldosterone antagonists)
Beta blockers
Digoxin
Class 1
What class of antidysrhythmic drug?
sodium channel blockers Slows impulse conduction Subclasses: A, B, C Largest group
Class 2
What class of antidysrhythmic drug?
beta adrenergic blockers Phase 2 of fast; Phase 0&4 of slow Decreases calcium entry ? SA node automaticity ? AV Node conduction velocity Negative inotrope
Class 3
What class of antidysrhythmic drug?
Potassium channel blockers
-Delay repolarization of fast APs Prolongs action potential Prolongs refractory period
Class 4
What class of antidysrhythmic drug?
Calcium Channel Blockers
-Phase 2 of fast; Phase 0, 4 of slow
-Only: verapamil, diltiazem
-Effects = to beta blockers
Supraventricular dysrhythmia
-Arise in atria, SA node, AV node
-Not harmful, unless decrease cardiac output If ventricular rate is high, inadequate time for ventricular filling
-Treatment goal Not always to abolish dysrhythmia To slow ventricular rate - decreasing impulses thru AV no
Atrial fibrillation
Most common dysrhythmia ~10% over age 80 Chaotic excitation of atria Multiple pacemakers Ventricular rate may be normal or very rapid Blood trapped in atria may clot Thrombus ? embolus ? stroke Treatment goals Improve ventricular pumping By restoring NSR
Atrial flutter
Reentry around tricuspid valve annulus, 300 bpm ~50% of impulses to ventricle Acute DC cardioversion Control ventricular rate with beta blockers (II) or CCBs (IV) Long term Ablation of site of dysrhythmia Prevent recurrence flecainide (IC) or amiodarone (
Sustained Supraventricular Tachycardia (SVT)
AV nodal reentrant circuit 200/min Treatment Increase vagal tone Drugs: beta blocker (II), CCBs (IV) Prevent recurrence Catheter ablation Beta blockers, CCBs
Ventricular fibrillation
Life threatening - CO = 0 L/min Multiple asynchronous ventricular foci firing Treatment DC countershock Give sodium channel blockers (I) by vein To stop automaticity
Ventricular premature beats (PVCs, VPCs)
Ectopic ventricular foci Spontaneous depolarizations Treat if > 15,000 qD Ablation, beta blockers (II)
Torsades de Pointes
-Can occur when PVC occurs during QT interval See atypical V-tach that may deteriorate into V-fib
-Occurs when QT interval is markedly prolonged Drugs, malnutrition, hypokalemia, hypoxia, acidosis, genetic
Quinidine (Quinaglute KWIH nih deen)
-Most frequently used PO antidysrhythmic
-Class: IA antidysrhythmic, sodium channel blocker
-Mechanism of action Blocks sodium channels Slows impulse conduction: A, V, His = prolongs QRS Delays repolarization by blocking K+ channels = Prolongs QT interval
lidocaine (Xylocaine)
-Class: antidysrhythmic (Class I-B)
-Mechanism of action Blocks sodium channels Slows conduction in A, V, His Decreases automaticity Accelerates repolarization
30
-Pharmacokinetics If PO first pass metabolism ? no drug effect Rapidly degraded in plasma Gi
propranolol (Inderal)
-Nonselective beta blocker (blocks beta-1 and beta-2)
-Therapeutic use Dysrhythmias caused by sympathetic stimulation Sinus tachycardia, PSVT - ?SA discharge Slows AV conduction ?? ventricular rate V-tachycardia
-Administer PO or IV
-Adverse effects Beta-
amiodarone (Cordarone a mee OH da rone)
Class: antiarrhythmic (Class III) Therapeutic use Life threatening, refractory V-Fib & V-Tach Untreatable with safer drugs Converts A-fib to sinus rhythm ? SA automaticity, ? contractility, ? conduction ECG ?s: QRS widens, prolongs PR and QT PK: Administr
Prehypertension
120-139/80-89
? CV risk of 2-3x
Tx: lifestyle changes
Hypertension
Stage I: 140-159/90-99
Stage II � 160/100
Tx: lifestyle changes and drugs
Primary
What kind of hypertension?
90% of cases
Also called essential hypertension
Since BP increased with age it was thought to be essential for perfusion
No identifiable cause
Chronic, progressive = BP raises over time
Risk: age, African-American, Mexican-Ameri
Secondary
What kind of hypertension?
10% of cases
Treat the cause if possible: Renal Disease, Oral contraceptives Aldosteronism, Cushing's, pheochromocytoma Sleep apnea, Thyroid diseases
Brainstem,
Sympathetic ganglia blockers,
Adrenergic nerve terminals,
Beta 1 receptors on heart,
Alpha 1 receptors on BV,
Vascular smooth muscle,
Renal tubules,
RAAS
Name the 8 places anti-hypertensive drugs act on the body.
Combination antihypertensives
What kind of pills are these?
-Inderide
-Enoretic
-Capozide
-Apresazide
-Aldactazide
-Teczem
Hypertensive Emergency
Diastolic > 120 mmHg
-If risk of organ damage Papilledema, ischemia, MI, acute HF Lower within 1 hour
-If no risk: lower over 1-2 days Rapid reduction may cause MI, stroke
�IV drugs - vasodilators
-Nitroprusside, others Direct vasodilator of arteries and
Cholesterol
-Used by body for Components of cell membranes Synthesis of certain hormones Synthesis of bile salts Necessary for absorption and digestion of fats Deposited in skin to decrease water loss
-Sources Dietary Manufactured by cells - source of most of this is
Triglycerides
-3 FFA + glycerol Saturated and unsaturated
-Used by body for Phospholipids - components of cell membranes Body's most compact form of energy Stored in fat cells Burned to CO2 + H20 If lacking carbohydrates, broken down to ketones
-Sources Dietary Manufac
Plasma Lipoproteins
�Carry cholesterol and triglycerides in blood
�Structure
- Hydrophobic Core: triglyceride and/or cholesterol
-Hydrophilic Shell Monolayer of phospholipids - water soluble Apolipoprotein ? Structural stability of this Allows cells to ingest it
Activates en
VLDL
#NAME?
LDL
what is left over after VLDL delivers
70% of cholesterol, "bad" (< 160mg/dL)
Delivers cholesterol to nonhepatic tissues
Cells have receptors for this - so they engulf it
If need more cholesterol, cell ? receptors ? this causes atherosclerosis Decreasing l
HDL
(>60mg/dL)
30% of cholesterol, "good"
Carries cholesterol to liver for disposal
?this ? ? CHD
HMG-CoA Reductase Inhibitors(= "statins")
-Competitively inhibits this enzyme in liver
Decreases cholesterol synthesis But hepatocytes make more of this enzyme
So cholesterol levels go back up But they also make more LDL receptors And can remove more LDL from blood
-Effect ? LDL cholesterol - 25-
HMG-CoA Reductase Inhibitors
What kind of drugs are these?
simvastatin (Zocor) SIM va stah tin
rosuvastatin (Crestor) roe SOO va sta tin
atorvastatin (Lipitor) a TOR va sta tin
pravastatin (Pravachol) PRAV a STAT in
lovastatin (Mevacor) LOE va sta tin
fluvastatin (Lescol) FLOO va sta
colesevelam (Welchol KOE le SEV e lam)
Increase cholesterol secretion
Bile acid Sequestrant
Decreases LDL cholesterol (20%)
Inert, insoluble in water, cannot be digested or absorbed
Mechanism of action: Binds bile acids in gut, preventing their reabsorption --> Liver must make more bile acids
ezetimibe (Zetia eh ZEH teh mib)
Inhibit absorption of cholesterol
-MOA: inhibits cholesterol absorption in gut Both dietary cholesterol and that in bile ? LDL (20%), ? Triglyceride (10%)
-AE: myopathy, hepatic toxicity, pancreatitis
-DI: + statins ? 25% more ? in LDL ? Hepatotoxicity, m
nicotinic Acid (Niacor, Niaspan = Vitamin B3, niacin)
Inhibit synthesis of lipoproteins
�Class: lipid lowering agent
�MOA: ? hepatic VLDL production ?? LDLs
�Therapeutic use
-? Triglycerides if risk for pancreatitis
-? LDL(20%), ? HDL (20%) = ? coronary events and mortality
-Niacin deficiency (pellagra)
�PK:
gemfibrozil (Lopid jem FI broe zil)
Inhibit synthesis of lipoproteins
-Class: lipid lowering agent - Fibric Acid Derivative
-Tx Use: Treatment of hypertriglyceridemia
-Mechanism of action ? Synthesis of lipoprotein lipase ? ? clearance of VLDLs
-PK: Administration: PO ? VLDL 2-5 d, peak 4 w
Chronic stable angina (exertional angina)
-Oxygen supply is adequate at rest But CAs are fully dilated
-With exertion diseased coronary arteries cannot ? blood flow CAs are already fully dilated Partial occlusion ? pain = angina Total occlusion ? myocardial infarction
Chronic stable angina (exertional angina)
What does this treat?
-? O2 supply - fix occlusion
-? O2 demand ? Sx relief ? heart rate, ? contractility : BBs, CCBs ? preload: nitrates ? afterload: CCBs
-Avoid factors that precipitate attacks Overexertion, cold, stress
-Correct risk factors Stop smoki
Variant angina (vasospastic, Prinzmetal's angina)
-Spasms of coronary arteries ? ? blood flow
-Pain occurs at rest, without cause
-Usually also have stable angina
-Tx: ? Oxygen supply by vasodilating CCBs, nitrates
Unstable angina
-Angina at rest
-New onset exertional angina
-Intensified stable angina
-Tx: medical emergency
nitroglycerin (Nitrostat, etc.)
Used since 1879: effective, fast, cheap
-Therapeutic use Decrease or prevent pain of angina Treatment adjunct of heart failure
- Pharmacokinetics Abs: highly lipid soluble - crosses membranes Met: rapidly inactivated by liver T? 5-7 min
Administration IV:
Prothrombin time
-Measures effectiveness of vitamin K depend factors I, II, V, VII, and X
-Blood drawn into tube with oxalate to bind calcium
-To run test Ca+2 & tissue factor added to blood Activates "this" ? thrombin via extrinsic pathway Time to clot = "this" in second
Activated Partial Thromboplastin Time (aPTT)
-Effectiveness of clotting factors X, VII, VIII Intrinsic pathway
-Normal 25-35 seconds
Anticoagulants
What kind of drugs are these?
heparin, warfarin
Disrupts clotting cascade ? ? fibrin production Best for preventing venous thrombi
Antiplatelet drugs
What kind of drugs are these?
ASA, clopidogrel Inhibit platelet aggregation
More effective at preventing arterial thrombi
Thrombolytic drugs
What kind of drugs are these?
alteplase, streptokinase
Lyse fibrin ? dissolves clot
heparin (unfractionated HEP a rin)
-Found in mammalian tissue: lungs of cows, intestine of pigs
-Mixture of long polysaccharide chains Pentasaccharide sequences = active regions Highly polar - can't cross membranes
-Mechanism of action Helps antithrombin to inactivate clotting factors Hepa
Low molecular weight heparin
-Shorter molecule, equally as effective as heparin Made by breaking unfractionated heparin into smaller pieces
-Mechanism of action Inactivates Xa, but not thrombin
-Drugs
enoxaparin (Lovenox) ee nox AP a rin
dalteparin (Fragmin) DAL te PAR in
tinzaparin
warfarin (Coumadin)
Oral anticoagulant
-MOA: prevents activation of vitamin K Blocks liver synthesis of VII, IX, X, prothrombin
Does not effect existing clots, but prevents further extension
-Pharmacokinetics Administration: PO qD, 1-5 mg qD based on INR
Distribution: 99% pr
Warfarin Antidote
-Vitamin K (AquaMEPHYTON) Reverses this drug's effects over 36 hours Give PO or IV (anaphylaxis: dilute & give slow) If give too much won't be able to anticoagulate with warfarin for 2 weeks
-Acute bleeding: fresh frozen plasma Contains clotting factors
-
Aspirin
-Pharm Class: COX inhibitor
-Therapeutic Class: Anti-platelet
-Mechanism of action Irreversible inhibition of COX Platelets cannot synthesis TXA2 Effect lasts life of platelet (7-10 days)
-Therapeutic use Primary prevention of MI in high risk clients Seco
ADP receptor antagonists
-Drugs clopidogrel (Plavix) kloh PID oh grel ticlopidine (Ticlid) tye KLOE pih deen
-MOA: Prevents ADP stimulated aggregation
-Tx use: prevention of MI, thromboembolic stroke � Effective as ASA, used if client can't take ASA Used with ASA, if high risk
-
abciximab (ReoPro ab-SIKS-ih-mab)
Glycoprotein IIb/IIIa receptor antagonists
Antibody against glycoprotein receptor
Prevents platelet aggregation by any cause "Super" aspirin
-Mechanism of action Reversible blockage of GP receptor Inhibiting platelet aggregation
-Therapeutic Use - Short t
streptokinase (Streptase STREP-toe-KIN-ace)
Fibrinolytics = "clot busters"
-Remove thrombin that has already formed
-First drug in class
-MOA: Activates plasminogen to plasmin Plasmin is enzyme that digests fibrin clot Also degrades clotting factors = ? risk of bleeding
-Therapeutic use Acute MI -
fibrinolytic drugs
What class of drugs are these?
-alteplase (Activase) AL-teh-PLACE
Human tissue plasminogen activator made by recombinant gene technology = tPA More expensive
-tenecteplase (TNKase) TEN-neck-te-place Human tPA with 3 different amino acids
Longer half life
Myocardial Infarction
This is management of what condition?
�Goal: increase oxygen supply to equal demand
-Minimize necrosis
�Drugs
-Give oxygen
-ASA - suppress platelet aggregation Chew 325 mg tab ASAP
-Morphine Decreases pain Decreases oxygen demand Venodilates = ? preload A
Hypercalcemia
What condition is this?
Causes
-Increased GI absorption of Ca2+ Excessive Vitamin D
-Increased bone reabsorption of calcium Primary hyperparathyroidism: ? PTH from adenoma Secondary hyperparathyroidism: CKD; Malignancy
-Decreased excretion of Ca2+ Thiazid
Hypocalcemia
What condition does this describe?
�Causes
-Cannot mobilize calcium from bone Low Vitamin D Low PTH: Damage from thyroid surgery, congenital absence
-Decreased absorption of calcium Decreased Vitamin D: ? sun, ? intake Impaired activation of Vitamin D phe
Calcium
Needed for:
-Blood coagulation
-Bone integrity
-Muscle and heart contraction
-Release of neurotransmitters and hormones
-Enzyme reactions
�Stored
-99% stored in bone = 1500 g Being actively remodeled - replace 25% q yr Osteoclasts, osteoblasts
-0.9% cells
Antidysrhythmic Drugs
What kind of drugs?
Drugs try and correct the abnormal electrical impulses
� Classification of drugs
- Groups named by Dr. Vaughn Williams in 1970
Group I-IV effect ion movement during AP
- Class I: sodium channel blockers
Slows impulse conduction
Subclas
Quinidine (Quinaglute KWIH nih deen)
- Most frequently used PO antidysrhythmic
- Class: IA antidysrhythmic, sodium channel blocker
- Mechanism of action
Blocks sodium channels
Slows impulse conduction: A, V, His = prolongs QRS
Delays repolarization by blocking K+
channels
= Prolongs QT inter
lidocaine (Xylocaine)
- Class: antidysrhythmic (Class I-B)
- Mechanism of action
Blocks sodium channels
Slows conduction in A, V, His
Decreases automaticity
Accelerates repolarization- Pharmacokinetics
If PO first pass metabolism ? no drug effect
Rapidly degraded in plasma
Giv
propranolol (Inderal)
- Nonselective beta blocker (blocks beta-1 and beta-2)
- Therapeutic use
Dysrhythmias caused by sympathetic stimulation
Sinus tachycardia, PSVT - ?SA discharge
Slows AV conduction ?? ventricular rate
V-tachycardia
- Administer PO or IV
- Adverse effects
B
amiodarone (Cordarone a mee OH da rone)
Class: antiarrhythmic (Class III)
Therapeutic use
Life threatening, refractory V-Fib & V-Tach
Untreatable with safer drugs
Converts A-fib to sinus rhythm
? SA automaticity, ? contractility, ? conduction
ECG ?s: QRS widens, prolongs PR and QT
PK: Administr
Atropine
Used for bradycardia
Adenosine (Adenocard)
nucleotide
Treatment of choice for SVT
MOA: inhibits calcium influx, Phase 0, slow
? SA automaticity,
? AV conduction
ECG ?s: long PR
Tx Use: Give IV bolus, t
1/2 = 5 seconds
Terminate PSVT, WPW syndrome
Brief AE - sinus bradycardia, dyspnea, chest discom
Digoxin (Lanoxin)
Primary indication is HF, but can be used for dysrhythmias
Mechanism of action
Direct effect on AV node increasing sensitivity to ACh
CNS effect: ? parasympathetic impulses to heart
Result
? SA automaticity
? AV conduction
? His-purkinge automaticity ? pr
800-1200 (cell/mm3)
Normal CD4 T-cell count?
(HIV: Good = 500 cell/mm3; bad = 50 cells/mm3)