Help
Options
Didn't know it?
click below
click below
Knew it?
click below
click below
Don't Know
Remaining cards (0)
Know
retry
shuffle
restart
0:00
Embed Code - If you would like this activity on your web page, copy the script below and paste it into your web page.
Normal Size Small Size show me how
Normal Size Small Size show me how
Pharmacology MT2
| Question | Answer |
|---|---|
| What are adrenergic agonists? | Drugs that mimic the actions of noradrenaline (NA) either by 1) directly binding receptors, 2) indirectly mimicking NA by inhibiting reuptake or 3) indirectly mimicking NA by causing release. |
| What types of drugs are direct adrenergic agonists? | Alpha-1 agonists, Alpha-2 agonists, Beta-1 agonists, Beta-2 agonists, and adrenergic agonists at multiple receptor subtypes (i.e. adrenaline) |
| What are examples of indirect adrenergic agonists? | Cocaine (inhibits reuptake of catecholamines into nerve terminals) and drugs that release NA from sympathetic nerve terminals |
| What are adrenergic antagonists? | Drugs that block effects of NA at various alpha and beta receptors |
| How do direct alpha-1 agonists act? | Stimulate A-1 receptors to activate Gq to activates PLC to produce DAG and IP3. IP3 acts on Ca2+ in the SR, releasing it from stores so to cause vasoconstriction |
| What are direct alpha-1 agonists used for? | Nasal congestion, to dilate pupils, in cold treatments, in combination with freezing agents to prevent diffusion |
| What are the side effects of alpha-1 agonists? | Increased blood pressure (caution for those with high blood pressure!) |
| How do alpha-1 agonists cause pupil dilation? | They activate the SNS to release NA so that the radial muscle in the pupil is stimulated to contract to dilate the pupil |
| How do direct alpha-2 agonists act? | Bind to alpha-2 autoreceptors to activate Gi which inhibits adenylyl cyclase so that cAMP is not produced from ATP, decreasing NT release, blocking Ca2+ channels, and activating K+ channels |
| What are alpha-2 agonists used for? | Hypertension, act centrally in brain to decrease blood pressure |
| What are the side effects of alpha-2 agonists? | Dry mouth and sedation |
| How do beta-1 agonists work? | Stimulate B-1 receptors to activate Gs, stimulate adenylyl cyclase and increasing cAMP to activate PKA. PKA phosphorylates calcium channels causing influx that actons on SR to release more calcium to cause contraction |
| What are beta-1 agonists used for? | Heart failure; to increase heart rate and contractility |
| What are the side effects of beta-1 agonists? | Arrhythmia |
| What is Dantrolene? | Drug used as skeletal muscle relaxant |
| How does Dantrolene work? | Interferes with calcium release from internal stores of SR of skeletal muscle to modify stretch reflexes in spinal cord to decrease muscle spasms |
| What is Dantrolene used for? | Used to treat Malignant hyperthermia |
| What is malignant hyperthermia? | Hereditary skeletal muscle disorder characterized by life-threatening increase in body temperature and lactic acid caused by opening of SR release channels during anesthesia, increasing calcium release and contraction of all muscles |
| What is hemostasis? | Process of blood clotting |
| What are the functions of hemostasis? | 1)Maintains fluidity of blood 2)Limits loss of blood from damaged blood vessel 3)Prevents vessel occlusion |
| What happens when hemostasis fails? | Excessive bleeding and vessel occlusion by excessive clot formation |
| What are the steps of hemostasis? | Vasoconstriction, Platelet plug, Coagulation |
| What is a platelet plug? | Temporary block of a break in vessel wall |
| What are platelets? | Cell fragments produced in bone marrow from megakaryocytes that lack nuclei but have granules; normally do not stick but are triggered be more procoagulant by vessel damage |
| What is the tissue factor pathway? | Main coagulation pathway; After endothelial or vascular injury, tissue factor (a glycoprotein) activates tissue factor VIII producing a cascade that activates prothrombin(II) into thrombin(IIa) which cleaves fibrinogen(I) into fibrin(Ia) |
| What is the contact activation pathway? | Coagulation pathway initiated by contact between blood and negatively charged surfaces that causes a tissue factor cascade that activates prothrombin (II) to thrombin (IIa) which cleaves fibrinogen (I) into fibrin (Ia) |
| What are the endogenous anticoagulants? | Prostacyclin, NO, Heparin, Antithrombin, Protein C and Protein S |
| What do prostacyclin and NO do? | Secreted from cells to inhibit platelet adhesion to stop coagulation |
| What is heparin? | Endogenous anticoagulant and indirect thrombin inhibitor |
| What does antithrombin do? | Inhibits coagulation by inactivating thrombin (IIa) |
| What do Protein C and Protein S do? | Inactivates Factor Va and VIIIa |
| What is fibrinolysis? | Process that digests fibrin and removes clots; works via plasminogen activated by tissue plasminogen activator from damaged walls |
| What are antiplatelet drugs? | Drugs that target platelets -3 groups: 1)Agents made outside platelet that interact with platelet membrane receptors 2)Agents made within platelet that interact with platelet membrane receptors 3)Agents generated within platelet that act within platele |
| What is Abciximab? | Antiplatelet drug that is a monoclonal antibody that binds glycoprotein IIb/IIIa receptor and prevents fibrin binding and platelet cross-linking to prevent aggregation of platelets |
| When is Abciximab used? | During and after coronary artery procedures |
| What are the adverse effects of Abciximab? | Bleeding, thrombocytopenia with chronic use |
| What is Clopidrogel? | Antiplatelet drug that inhibits ADP pathway by irreversibly binding receptor, reducing aggregating effects |
| What is Clopidrogel used for? | Transient ischemic attacks and ischemic strokes, especially in those who cannot tolerate aspirin |
| What are the adverse effects of Clopidrogel? | Bleeding, stomach irritation, neutropenia |
| What is Aspirin? | Antiplatlet drug that inhibits thromboxane synthesis by irreversibly inactivating cyclooxygenase; inhibition persists until new platelets are formed |
| When is Aspirin used? | To prevent further heart attacks, transient ischemic attacks, ischemic stroke, and other thrombotic events |
| What are the adverse effects of Aspirin? | GI and CNS effects |
| What does Heparin do? | Binds and stabilizes antithrombin to inactivate thrombin and prevent clotting; rapid onset |
| When is Heparin used? | Venous thromboses, embolism, acute MIs |
| What are the adverse effects of Heparin? | Bleeding and thrombocytopenia |
| What is the antidote of Heparin? | Protamine sulfate |
| What is Hirudin? | Direct thrombin inhibitor that directly binds to the active site of thrombin and inhibits activity to prevent clots |
| When is Hirudin used? | In patients with heparin-induced thrombocytopenia |
| What are the adverse effects of Hirudin? | Those on long-term infusions can develop antibodies to thrombin-hirudin complex |
| What is Warfarin? | Coumarin anticoagulant that prevents carboxylation of glutamate residuces of clotting factors in liver to stop clotting; Vitamin K dependent process |
| When is Warfarin used? | For chronic anticoagulation in venous thromboses, embolism, and acute MIs |
| What are the adverse effects of Warfarin? | Bleeding, cross-placental barrier, drug interactions |
| What are the antidotes for Warfarin? | Vitamin K and plasma |
| What are fibrinolytic drugs? | Drugs that break up clots by catalyzing formation of plasmin which breaks down fibrin in clots |
| What is Streptokinase? | Fibrinolytic drug that combines with plasminogen to catalyze its conversion to plasmin |
| What is Urokinase? | Fibrinolytic drug that directly converts plasminogen to plasmin |
| What is Alteplase? | Fibrinolytic drug that is a recombinant human tPA (tissue plasminogen activator) that direct converts fibrin-bound plasminogen to plasmin |
| What are streptokinase, urokinase, and alteplase used for? | Emergency treatment of acute myocardial infarction, acute stroke symptoms given within 3 hours of onset & after bleeding in brain has been removed as possible cause, multiple pulmonary emboli |
| What are the adverse effects of streptokinase, urokinase, and alteplase? | Bleeding, allergies |
| How are venous thromboses treated? | Warfarin is used for prevention; For established disease, Heparin is used for first 5-7 days with overlap of Warfarin |
| How are arterial thromboses treated? | Aspirin, Clopidrogel |
| How do direct Beta-2 agonists work? | Stimulate B-2 receptors to stimulate Gs to activate adenylyl cyclase, increasing cAMP. This promotes inactivation of MLCK which leads to less phosphorylation of MLC so that myson and actin don't interact, leading to relaxation of smooth muscle |
| What are Beta-2 agonists used for? | Asthma (causes bronchodilation) and premature labor |
| What are the side effects of Beta-2 agonists? | Increased heart rate because Beta-2 agonists can bind Beta-1 receptors |
| What is adrenaline? | Direct adrenergic agonist at alpha-1, beta-1 and beta-2 receptors released from adrenal gland, innervated by SNS, and can augment NA released from nerves during fight or flight response |
| What does adrenaline treat? | Anaphylaxis, shock, in combination with anesthetics |
| How does adrenaline work for anaphylaxis (severe allergic reaction)? | It is a bronchodilator and increases blood pressure |
| What are the effects of adrenaline? | Increases heart rate and contractility (B-1 receptors), act as bronchodilator and dilates some blood vessels (B-2 receptors) and constricts other blood vessels (A-1 receptors) |
| What are the side effects of adrenaline? | Large increase in blood pressure (A-1), increased heart rate and contractility (B-1), increased calcium concentration inside heart cells triggering arrhythmia |
| Explain the confusing presence of Alpha-1 and Beta-2 receptors in vasculature. | A-1 R are in BVs of skin and gut which are innervated and release NTs that cause vasodilation. B-2 receptors are in BVs of skeletal muscle and are not innervated and must wait for circulating adrenaline (not activated unless needed) |
| What are indirect adrenergic agonists? | Drugs that act indirectly to increase concentration of noradrenaline (NA) in the synapse by inhibiting reuptake or causing release |
| What kind of drug is cocaine? | Indirect adrenergic agonist |
| What does cocaine do? | Blocks reuptake of noradrenaline to increase concentrations |
| What is cocaine used for? | Drug of abuse, nasal intubation |
| What are the side effects of cocaine use? | Powerful CNS stimulation, CV system stimulation, increased heart rate and contractility (B1), increased blood pressure (A1), possible arrhythmia |
| How do indirect adrenergic agonists that cause release of noradrenaline work? | Release stored catecholamines into synpase to increase concentrations |
| What are the uses for indirect adrenergic agonists that cause release of noradrenaline? | Narcolepsy, ADHD, appetite suppression |
| What are the side effects of indirect adrenergic agonists that cause release of noradrenaline? | Increased blood pressure, heart rate, CNS and CV stimulation (similar to cocaine) |
| What are adrenergic antagonists? | Drugs that block the effects of noradrenaline at alpha and beta receptors in the SNS |
| What are alpha antagonists? | Drugs that block alpha receptors in the SNS; Non-selective forms are not used due to side effects |
| How do alpha antagonists work? | Bind alpha-1 receptors to block binding of noradrenaline; causes vasodilation in blood vessels |
| What do alpha antagonists treat? | High blood pressure |
| What are the side effects of alpha antagonists? | Nasal congestion, orthostatic hypotension |
| What is orthostatic hypertension? | Sudden drop in blood pressure upon standing because there is no vasoconstriction |
| What are beta antagonists (Beta blockers)? | Drugs that block beta receptors in the SNS; there are non-selective and cardio-selective forms |
| What is the difference between non-selective beta blockers and cardio-selective beta blockers? | Non-selective bind both B1 and B2 receptors while cardio-selective block only B1 receptors (preferred) |
| What do beta blockers treat? | Hypertension, angina, arrhythmia, glaucoma, migraines, stage fright |
| How do beta blockers treat glaucoma? | Decrease production of aqueous humor |
| What are the side effects of beta blockers? | Decrease in exercise tolerance because of blocking of B-1 receptors; worsens asthma because of blocking B-2 receptors |
| What are mixed alpha and beta antagonists? | Drugs that bind A-1, B-1, and B-2 receptors in the SNS |
| What are mixed alpha and beta blockers used for? | Congestive heart failure |
| What are the functions of the heart? | 1.Deliver nutrients and oxygen to tissues 2.Remove wastes and carbon dioxide 3.Transport hormones to sites of action 4.Transport system for cells and components of immune system |
| What is the path of pulmonary circulation? | Right atrium to right ventricle, to lungs via pulmonary arteries to exchange oxygen and carbon dioxide, left ventricle, left atrium |
| What is the path of systemic circulation? | Left atrium to left ventricle to body where blood delivers nutrients and oxygen, and picks up waste, back to right atrium and into the pulmonary circulation route |
| What is coronary circulation? | Circulation that supplies the heart muscle itself through coronary arteries at the base of the aorta |
| What does one cardiac cycle consist of? | Diastole plus systole |
| Diastole | Time when heart muscle is relaxed and is filling with blood |
| Systole | Time when heart muscle contracts and heart ejects blood into aorta and pulmonary artery |
| End diastolic volume (EDV) | Volume of blood in the heart right at the end of diastole |
| Afterload | Force that resists contraction of the ventricle; the load blood is ejected against |
| Cardiac output | Amount of blood pumped per minute, determined by number of times/min the heart beats (heart rate) and the volume of blood ejected per beat (stroke volume) |
| Heart rate | Number of times/min the heart beats |
| Stroke Volume | Volume of blood ejected per beat |
| Sinoatrial (SA) node | Node of specialized cardiac muscle in the right atrium that initiates the action potential that causes heart to beat; natural pacemaker |
| Atrioventricular (AV) node | Where atria and ventricles are connected electrically |
| What is the influence of noradrenaline and adrenaline (SNS) on heart rate? | Noradrenaline, released by SNS nerves, and adrenaline, released from the adrenal medulla, accelerate the SA node and increase heart rate |
| What is the influence of beta-1 agonists and blockers on heart rate? | Beta-1 agonists increase heart rate; Beta blockers decrease heart rate |
| What is the effect of acetylcholine (PNS)on heart rate? | Acetylcholine, released by PNS nerves, slows SA node and decreases heart rate |
| What is the influence of muscarinic agonists and antagonists on heart rate? | Muscarinic agonists decrease heart rate; muscarinic blockers increase heart rate |
| Contractility | Force of contraction of the heart |
| Venous return | Amount of blood returning to the heart |
| What modulates stroke volume? | 1. Increased contractility 2. Increased venous return |
| What is Starlin's law of the heart? | Stroke volume increases as a function of end diastolic volume |
| Peripheral resistance | Degree of constriction of the blood vessels |
| What is a healthy blood pressure range? | 120/80 mmHg |
| Blood pressure | Ratio of systolic to diastolic pressure |
| How is blood pressure controlled? | Via fast and slow systems |
| Fast system of blood pressure control | SNS controlled by carotid baroreceptors |
| Slow system of blood pressure control | Renin-angiotensin system related to kidney function |
| What are diuretics? | Drugs that cause diuresis and/or natriuresis to get rid of fluid and sodium by acting on renal tubule cells in nephrons of the kidney |
| What do diuretics treat? | Abnormalities in fluid volume and electrolyte composition - edema caused by congestive heart failure, hypertension |
| Glomerulus | Blind end of nephron where fluid (water and solutes from plasma) move from capillaries into Bowman's capsule (lumen of nephron) |
| Diuresis | Increase in volume of urine associated with loss of water |
| Natriuresis | Increase in renal sodium excretion |
| Secretory systems | Areas of the proximal convoluted tubule where organic acids such as diuretics enter the lumen of the nephron from the blood so that they may be excreted in urine |
| What are loop diuretics? | Drugs that act at thick ascending loop of the Loop of Henle by inhibiting a co-transporter that normally transports Na, K, and Cl back into the body, thus increasing these ions in the lumen and increasing sodium and water excretion; very powerful diuresis |
| What are the side effects of loop diuretics? | Hypokalemia |
| What are loop diuretics used for? | Edema, especially congestive heart failure (too powerful for hypertension) |
| Hypokalemia | Loss of potassium from body due to increased delivery of sodium to collecting tubule; transporter in collecting tubule that is responsible for Na reabsorption is linked to K secretion; alters membrane potentials and therefore causes arrhythmias\ |
| What are thiazide diuretics? | Drugs that block a NaCl transporter in the distal convoluting tubule of the nephron, increasing sodium and water excretion and producing mild diuresis |
| What are thiazide diuretics used for? | Primarily hypertension where acts like low sodium diet to decrease body's sodium load and thus decrease stiffness of blood vessels, also congestive heart failure |
| What are side effects of thiazide diuretics? | Hypokalemia |
| What are potassium-sparing diuretics? | Drugs that act in the collecting tubule to inhibit aldosterone which normally promotes sodium reabsorption and potassium secretion; inhibition causes sodium excretion and potassium reabsorption causing mild diuresis |
| What are potassium-sparing diuretics used for? | Hypertension, congestive heart failure, used in combinations (i.e. with thiazides) |
| What are the side effects of potassium-sparing diuretics? | Hyperkalemia (high potassium in body) |
| Hypertension | High blood pressure (higher than 140/90mmHg); silent killer! |
| How is blood pressure controlled? | By the SNS (moment by moment changes) and Renin-angiotensin system (RAS) |
| Renin-Angiotensin System | System in the kidney that regulates blood volume and is involved in long-term changes that can alter blood pressure |
| Renin | Enzyme that acts on angiotensinogen to convert it to Angiotensin I which is convereted by Angiotensin Converting Enzyme (ACE) to Angiotensin II, a potent vasoconstricter and increase aldosterone release which increases sodium and water retention |
| What agents are used to treat hypertension? | 1. Diuretics 2. Drugs that affect SNS 3. Vasodilators 4. Drugs that affect RAS |
| How do thiazide diuretics help hypertension? | Deplete sodium stores similar to dietary sodium restriction - lower sodium means decreased vascular stiffness Initial BP decreases due to decreased volume. Over time, volume returns to normal but PR decreases causing decreased blood pressure |
| What is the mechanism of action of centrally acting agents that affect the SNS to treat hypertension? | Binds Alpha-2 receptors BP control center in brain to decrease NT release which decreases SNS outflow |
| How to beta blockers treat hypertension? | Decrease CO, decrease renin, and decrease water and sodium retention (decrease CO to decrease HR, decrease renin to decrease Angiotensin II causing vasodilation and decrease in water and sodium retention which all decrease |
| How to alpha blockers treat hypertension? | Block alpha-1 receptors in VSM cells and cause vasodilation because they decrease the effect of SNS stimulation on BVs, thus decreasing blood pressure |
| What is a side effect of ALL antihypertensive drugs? | Orthostatic hypotension |
| What are vasodilators? | Antihypertensive drugs; Direct forms and calcium channel blockers |
| How do Nifedipine, Diltiazem, and Verapamil treat hypertension? | All block calcium channles so less contraction occurs causing vasodilation Nifedipine - vascular effect Diltiazem, Verapamil - effects heart and blood vessels |
| What are the types of agents that act on RAS to decrease hypertension? | ACE inhibitors and Angiotensin II Antagonists |
| How do ACE Inhibitors treat hypertension? | Inhibit Angiotensin Converting Enzyme (ACE) decreasing Angiotensin II which decreases aldosterone thus decreasing sodium and water retention which decreases volume and decreases BP |
| What are the side effects of ACE Inhibitors | Terotogenic in late pregnancy, cough (not tolerated well) |
| How do AII Antagonists treat hypertension? | Block Angiotensin II receptors on VSM cells and at the adrenal gland therefore blocking biological actions of AII causing vasodilation and decrease in aldosterone release, decreasing BP |
| What are the side effects of AII Antagonists? | Teratogenic in late pregnancy |
| Angina | Chest pain caused by coronary artery disease due to ischemia; oxygen demand and supply problem (there is too little oxygen to meet demands of the heart); caused by atherosclerosis, vasospasms, and other misc. causes |
| Ischemia | Decreased blood flow to heart muscle causing lack of oxygen |
| Effort Angina | Chest pain with effort or stress that can be stable or unstable (sign of MI) |
| Variant Angina | Chest pain at times not associated with exercise, caused by vasospasm |
| What regulates oxygen supply? | Autonomic nerves and autoregulation (when ischemia releases ions (K+) to cause vasodilation) |
| What regulates oxygen demand? | 1. Afterload 2. Preload 3. Contractility 4. Heart rate Increase in these factors cause oxygen demand to increase because heart must work harder |
| Preload | Amount of venous return to heart |
| How is angina managed? | 1. Decrease risk factors/alter lifestyle 2. Bypass surgery, angioplasty, stent 3. Drug therapy |
| What are the goals of drug therapy for angina? | 1. Decrease frequency and severity of attacks 2. Increase exercise tolerance and ability Accomplished by decreasing oxygen demand, increasing oxygen supply, and preventing vasospasms |
| What are the 4 types of drugs used in angina? | 1. Nitrates 2. Beta blockers 3. Calcium channel blockers 4. New agents |
| What is nitroglycerin? | Organic nitrate used to treat angina |
| How does nitroglycerin treat angina? | Nitrates are denitrated in VSM cells to NO which activates guanylyl cyclase which converts GTP to cGMP. cGMP dephosphorylates MLC and prevents interaction of mysoin and actin, relaxing vessels (smooth muscle), esp. veins |
| What are phosphodiesterase inhibitors? | Drugs that inhibit phosphodiesterase to prevent breakdown of cGMP to increase it |
| Why are nitrates effective in the treatment of angina? | 1.Decrease preload to decrease oxygen demand 2.Redistribute blood flow to ischemic area to increase oxygen supply 3.Prevent vasospasms to increase oxygen supply |
| What are the 2 routes to overcome the first-pass effect of nitrates? | 1.Sublingual - fast acting but short duration of action 2.Patch - transdermal delivery with slow release over 10-12hrs but tolerance develops so must be used intermittently |
| What are the side effects of nitrates? | Headache, increased heart rate |
| How do beta blockers treat angina? | Decrease attacks of effort angina by blocking beta receptors in the SNS causing decreased heart rate, contractility and blood pressure which causes decreased afterload, thus decreasing oxygen demand by reducing the heart's work |
| Why are nitrates and beta blockers effective in combination? | 1.Benefits add because of different mechanisms of action 2.Side effects cancel out |
| How do Verapamil and Diltiazem treat angina? | Work on heart cells and smooth muscle by decreasing calcium entry which causes vasodilation and decreased contractility of the heart, afterload, heart rate to decrease oxygen demand, and decreases vasospasms to increase oxygen supply |
| How does Nifedipine treat angina? | Decreases afterload which decreases oxygen demand, and decreases vasospasms which increases oxygen supply |
| How is Nifedipine different from Verapamil and Diltiazem? | Chemically different, selective for calcium channels in blood vessels (primarily vascular effect),no effect on heart at therapeutic doses |
| In what patients would Nifedipine be used to treat angina? | Those with high blood pressure and a failing heart |
| Congestive Heart Failure (CHF) | Decreased ability of heart to contract as result of damage to the heart; caused by: 1.MI or coronary artery disease 2.Hypertension 3.Cardiomyopathies 4.Arrhythmias 5.Other conditions |
| How does decreased contractility and CO in CHF make things worse? | Compensatory mechanisms increase SNS activity=increase HR & force (B1-R in heart), vasoconstriction (A1-R in BV), and increase renin&AII (B1-R in kidney)= vasoconstriction (end result - increase preload and afterload) |
| What symptoms arise due to damage to left side of heart? | Pulmonary congestion |
| What symptoms arise due to damage to right side of heart? | Systemic congestion |
| What are the general symptoms of CHF? | 1.Extreme fatigue 2.Short of breath 3.Increased heart rate 4.Hypertrophy 5.Remodeling |
| Hypertrophy | Increase in size of heart because cells in heart have to work so much harder |
| Remodeling | Increase in connective tissues that impairs contractions, fetal-like cells |
| Chronic CHF | Heart failure that develops over time |
| What are the strategies for CHF treatment? | 1. Unload heart by decreasing preload and afterload 2. Increase strength of contraction 3. Block effects of SNS |
| Why are diuretics effective in CHF? | Decrease sodium and water retention thus decreasing preload and edema which reverses hypertrophy |
| Which diuretics are used in CHF? | Loop diuretics in severe cases, thiazides |
| Why are ACE Inhibitors effective in CHF treatment? | 1. Reduce total PR 2. Decrease aldosterone from adrenals 3. Decrease NA release from sympathetic nerve terminals 4.Decrease bradykinin breakdown 5.Decrease remodeling of ventricles |
| What is the overall effect of ACE Inhibitors? | Improve survival!! |
| Why would ACE Inhibitors be used over Angiotensin Receptor Blockers (ARBs)? | Decrease bradykinin breakdown |
| Why would ARB be used in treatment of CHF over ACE Inhibitors? | To avoid cough side effect |
| Bradykinin | Vasodilator peptide normally broken down by ACE |
| What is Digoxin? | Example of cardiac glycoside found in foxglove |
| What are the major actions of Digoxin? | 1.Increase contractility of failing heart 2.Addresses underlying problem 3.Also used for arrhythmias |
| How does Digoxin work in treating CHF? | Inhibits Na-K ATPase (sodium pump)to increase sodium in cell, increasing calcium via sodium-calcium exchanger; results in increased contraction and therefore contractility of heart |
| Why is Digoxin is effective in treating CHF? | Increases contractility which increases CO, decreases SNS activity, HR, RAS, BP, sodium and water retention, and preload |
| What is the downside of digoxin? | Many toxic side effects; narrow TI |
| AV Block | Side effect of digoxin; block all impulses going through AV node and causes cardiac arrest |
| What are toxic effects of digoxin? | AV Block; causes almost any arrhythmia at ventricles because it increases calcium inside heart cells |
| How can digoxin be a problem in the elderly? | Renal clearance decreases with age so it is easy for it to build up to toxic range |
| How are beta blockers effective in CHF? | Block B receptors and decrease activity so can decrease mortality |
| How does carvedilol treat CHF? | Blocks B1 receptors to decrease heart rate and renin release; Blocks A1 receptors to decrease afterload; thus decreases mortality, reduces signs and symptoms, and slows progression of CHF |
| What is arrhythmia? | Disruption in rate, rhythm, origin, or conduction of heart beat |
| What causes arrhythmia? | MI, ischemia, drug toxicity, electrolyte imbalance |
| Supraventricular arrhythmia | Arrhythmia that arises in atria or AV node |
| Ventricular arrhythmia | Arrhythmia arising in ventricles |
| Bradycardia | Arrhythmia that slows heart rates; not enough beats/min so decreases CO |
| Tachycardias | More common; fast rates (either regular or irregular), ventricles or atria beat too fast so there is no time to fill the ventricles and CO decreases |
| How are bradycardias treated? | Adrenaline, atropine (muscarinic antagonist), implantable pacemaker |
| How does adrenaline treat bradycardias? | Beta agonist that stimulates B1 receptors to increase heart rate |
| How does atropine treat bradycardias? | Blocks acetylcholine's action on heart rate to increase HR |
| How are tachycardias treated? | Antiarrhythmic drugs |
| Class I Anti-arrhythmic drugs | Sodium channel blockers |
| Class II Anti-arrhythmic drugs | Beta blockers |
| Class III Anti-arrhythmic drugs | Increases action potential duration (APD) |
| Class IV Anti-arrhythmic drugs | Calcium channel blocker |
| How do antiarrhythmic drugs act? | Suppress abnormal impulse formation or conduction |
| How does abnormal impulse formation arise? | By damaged cells that create new pacemakers at other sites; can be suppressed with sodium channel blocker |
| Ectopic pacemaker | New pacemaker at abnormal location |
| How does abnormal impulse conduction arise? | Reentry - when 1 action potential activates heart more than 1 time |
| How do Class I Antiarrhythmic drugs act? | Bind and block sodium channels in cardiac tissue that is damaged and firing rapidly to suppress conduction by turning a 1-way block into a 2-way block |
| How do Class II Antiarrhythmic drugs act? | Inhibit SNS activity and heart rate, decreasing conduction velocity through AV node and increasing refractory of AV node |
| When are Class II Antiarrhythmic drugs used? | Atrial tachycardias - suppress and slow ventricular rate so that ventricles can fill |
| How do Class III antiarrhythmic drugs act? | Prolong action potential duration and thus prolong refractory period by blocking K+ channels so that impulse moves through damage but hits a refractory area so that another AP cannot be produced |
| What is the problem with antiarrhythmic drugs? | All are proarrhythmic and can cause arrhythmias, especially sodium channel blockers |
| What are the major types of lipids? | Triglycerides, Cholesterol, Phospholipids, and Fatty Acids |
| Triglycerides | Type of lipid made up of glycerol and 3 fatty acids; major form of energy storage |
| Cholesterol | Essential for cell membranes, synthesized from simpler substances |
| Cholesterol Synthesis/Daily intake | 1g/d; 0.2-0.3g/d |
| How are lipids transported throughout the body? | Lipoprotein particles |
| Lipoprotein particles | Macromolecular complexes of lipid and protein (Chylomicrons, VLDL, LDL, HDL) |
| Chylomicrons | Transport dietary lipids from intestine to other parts of body; largest lipoprotein made mostly of TGs |
| What happens to the Chylomicron remnant? | Taken up by liver via endocytosis |
| VLDL | Very low density lipoprotein; transport endogenous lipids from liver to other parts of body; made up mostly of TGs |
| What happens to VLDL remnant? | Aka intermediate density lipoprotein (IDL); remains after TG removal and can be endocytosed by liver so hepatocytes can remove IDL OR can be converted to LDL by losing apoE and lipolysis of remaining TGs |
| LDL | Low density lipoprotein; primary means of delivering cholesterol to peripheral tissues; mostly made up of cholesterol; cholesterol uptake is via LDL receptor-mediated endocytosis |
| HDL | High density lipoprotein; transports cholesterol from peripheral tissues to liver; smallest with greatest density; secreted from liver as immature lipid poor HDL and takes cholesterol from tissues to liver |
| How does HDL transfer cholesterol to liver? | Either directly via scavenger receptor-BI-dependent lipid selective uptake OR indirectly by transferring cholesterol to VLDL and chylomicron remnants |
| Hyperlipidemia | Metabolic disorder marked by elevated levels of lipoprotein species |
| What are the clinical consequences of hyperlipidemia? | Acute pancreatitis and atherosclerosis |
| What causes atherosclerosis? | Repeated damage to vessel wall > LDL enters intima layer > oxLDL > increased MPs engulf oxLDL > foam cell! > death - release cholesterol > increased release of pro-inflammatory cytokines > amplification of inflammatory response |
| What are the effects of LDL and HDL on risk of atherosclerosis? | LDL increases risk; HDL decreases risk |
| What types of drugs are used to treat hyperlipidemia? | 1. Statins; 2. Niacins; 3. Bile Acid Binding Resins; 4. Cholesterol Absorption Inhibitors; 5. Fibrates |
| Statins | HMG CoA reductase inhibitors; reduce endogenous cholesterol biosynthesis, decrease intracellular cholesterol stores, increase hepatocyte LDL receptor levels (an indirect effect of cholesterol depletion); fist choice for those with high LDL |
| What are the adverse effects of statins? | Reversible liver toxicity, cardiomyopathy, drug interactions |
| Niacin | Water-soluble vitamin (B3); inhibits lipolysis in adipose tissue at high concentrations (decreases circulating fatty acids, hepatic TG biosynthesis, hepatic VLDL synth and secretion, serum LDL, and moderately increases HDL |
| What are the adverse effects of Niacin? | Flushing, Hot flashes, GIT irritation, hepatotoxicity |
| Bile Acid Binding Resins | Bind bile acids (cholesterol metabolites) in intestinal lumen, preventing reabsorption and thus increasing excretion; diverts cholesterol to synthesis of bile acids causing compensatory increase in LDL receptors |
| What are the adverse effects of Bile Acid Binding Resins? | Bad taste, GI effects, impairs absorption of some vitamins and drugs at higher doses |
| Cholesterol Absorption Inhibitors (CAIs) | Inhibits cholesterol absorption from small intestine, decrease serum total cholesterol and LDL, hepatic cholesterol, and increases LDL receptor expression |
| What are the adverse effects of Cholesterol Absorption Inhibitors? | Reversible impaired liver function, myositis |
| Fibrates | Ligands for PPAr-alpha to regulate transcription of genes for lipid metabolism; upregulate LPL, apoA1, apoA2; downregulate apoC3; speeds clearance of TG-rich chylomicrons and VLDL from serum, increases serum HDL |
| What are the adverse effects of fibrates? | Itchy eyes, rash, liver toxicity, GIT irritation, increased risk of gallstones, cardiomyopathy |
| Familial Hypercholesterolemia | Type of hyperlipidemia; genetic defect in LDL receptors where heterozygotes have half of normal receptor function and homozygotes have none |
| What drugs are best for heterozygous Familial Hypercholesterolemia? | Statins or bile acid binding resins; combinations are more effective |
| What drugs are best for homozygous Familial Hypercholesterolemia? | TLC plus niacin is most effective but limited (minimal effect of statins, resins, and combinations) |
Created by:
shaymacleod
Popular Pharmacology sets