Exam 3 Flashcards
Risk factors for Primary Hypertension aka Essential
Obesity Stress Smoking Age Diet Race
Define Secondary Hypertension
Has definitive cause like stenosis or renal artery, or pheochromocytoma
Complications of HTN
CAD Cardiac/Renal Failure Stroke TIA's MI
Centrally acting hypertensives action
Decrease sympathetic outflow to HRT which decrease HR which decreases myocardial contractility which decreases CO which decreases BP
Centrally acting hypertensives work on which receptor?
A2 receptors in the CNS
Alpha-adrenergic blockers action
Block A1 receptors which cause vasodilation which decreases peripheral resistance which decreases BP
Name an Alpha-adrenergic blocker
Prazosin (Minipress)
Beta-adrenergic Action
Blocks B1 receptors which decreases HR and myocardial contractility with decreases CO which decreases BP
Name Beta adrenergic drugs
Propranolol - B1 &B2 blocker Metoprolol - cardio selective B1 Atenolol - Cardio selective Labetolol - also blocks A receptors Cavedilol - also blocks A receptors
Ganglionic Blocker action
At high doses it blocks ganglia which block the sympathetic outflow to BV’s which decreases BP
Name a Ganglionic Blocker drug
Mecamylamine
Name Postganglionic adrenergic neuronal blockers
Reserpine
Guanethidine
Reserpine Action
Blocks the uptake of dopamine in the synaptic vesicles blocking the formation of norepinephrine (doesn’t work on adrenergic receptors)
Guanethidine Action
Inhibits release of NE
Types of Diuretics?
Thiazide Diuretics
Loop Diuretics
Potassium Sparing Diuretics
Example of Thiazide diuretics?
Hydrochlorothiazide
Example of Loop diuretic?
Furosemide
Example of Potassium Sparing diuretic?
Spironolactone
Structural unit of the kidney?
Nephron
Why are diuretics used?
Decrease blood volume which decreases BP
What’s the action of diuretics?
Blocks reabsorption of NA
Where on the nephron is 65% of Na reabsorbed?
Proximal Convulated Tubule (PCT)
Where on the nephron is 20% of Na reabsorbed?
Loop of Henle
Where on the nephron is 10% of Na reabsorbed?
DCT
Where on the nephron is 1-5% of Na reabsorbed?
Collecting Duct (Spironolactone)
Where on the nephron do Thiazide diuretics work?
DCT = Weak diuretic
Where on the nephron do Loop Diuretics work?
LOH (20%) greater diuresis
Indications of Thiazide Diuretics?
Mild to moderate HTN
MOA of Thiazide diuretics?
Block reabsorption of NA, Cl in the early segment of DCT which blocks reabsorption of H2O (where sodium goes water follow). Will only work with decent renal function
Adverse Effects of Thiazide Diuretics?
- HYPONATREMIA
- HYPOCHLOREMIA
- HYPOKALEMIA (^NA reabsorption at CD, aldosterone secreted, some NA reabsorbed in exchange for K secreted)
- HYPERGLYCEMIA ( inhibition of insulin releases, promotion of glycogenolysis, inhibition of glycogen genesis)
- HYPERURICEMIA (^ urine acid in the blood)
- ALTERATION OF LIPID PROFILE (LDL ^ - high cholesterol, HDL decreases)
Indications of Loop Diuretics?
Pulmonary edema
Edema associated with cardiac, renal or hepatic origin
Adverse effects of Loop Diuretics?
- HYPONATREMIA
- HYPOCHLOREMIA
- HYPOKALEMIA (^NA reabsorption at CD, aldosterone secreted, some NA reabsorbed in exchange for K secreted)
- HYPERGLYCEMIA ( inhibition of insulin releases, promotion of glycogenolysis, inhibition of glycogen genesis)
- HYPERURICEMIA (^ urine acid in the blood)
- ALTERATION OF LIPID PROFILE (LDL ^ - high cholesterol, HDL decreases)
- OTOTOXICITY (damage to ear)
Loop diuretics and other drug interactions?
Patients taking amino glycoside antibiotics (Gentamicin) cause ototoxicity
Potassium sparing diuretics indication?
To avoid side effects, use K sparing diuretics - acts at the level of the Collecting Ducts
Someone on Digoxin what should you give to maintain K levels elevated?
Spironolactone
Action of Spironolactone?
Blocks aldosterone (NA not reabsorbed, is eliminated with H2O, K is retained - K levels should be 3.5-5.5 meq/L)
Name Vasodilators used for HTN?
- Hydralazine
- Minoxidil
- Sodium Nitroprusside
- Calcium Channel Blockers
Hydralazine, Minoxidil MOA?
Hyperpolarize vascular smooth muscle by opening up K channels > away form threshold > no contraction of smooth muscle in the blood > vessels dilate (affects mainly the arteries)
Adverse effects of Hydralazine and Minoxidil?
[] Hydralazine - Lupus like reactions (butterfly rash)
[] Minoxidil - Pericardial effusion (fluid in the pericardium) leading to cardiac tamponade (pressure on the heart)
Indications for Sodium Nitroprusside?
Drug of choice for emergency HTN
Sodium Nitroprusside MOA?
- Increases levels of cGMP > dilates BV’s (both arteries and veins)
- When metabolized cyanide is released > can lead to cyanide poisoning (rhodanese reduces level of toxicity for cyanide poisoning > cyanide detoxification)
Name Calcium Channel Blockers Drugs used to treat HTN?
Verapamil (Calan)
Amlodipine (norvasc)
Nifedipine (Aldolat, Procardia)
Action of Verapamil?
- Dilates peripheral arteries to ↓ BP
- Dilates arteries going to myocardium (coronary vessels)
- Has a cardio suppressant effect → ↓HR, ↓AV nodal conductions, myocardial contraction (but body’s baroreceptors ↑ actions on the heart canceling the effects on the heart)
Adverse effects of Verapamil?
- Constipation
- Edema of ankles and feet
Indications for Verapamil?
- Used for angina pectoris, HTN, cardiac dysrhythmias
Nifedipine action?
- Acts like Verapamil, but it doesn’t suppress the heart
- If we get a baroreceptor reflex → reflex tachycardia (give ß blocker to prevent tachycardia)
Name ACE Inhibitors to treat HTN?
- Captopril (Capoten)
- Enalapril (Vasotec)
Antiotensin → Angiotensin II Mechanism?
Angiotensin converting enzyme (ACE) makes Angiotensin II from Angiotensin I
Systemic Vasoconstrictor that increases BP?
Angiotensin II
Stimulates aldosterone secretion and NA retention by kidneys. ( ↑ H2O reabsorption → ↑blood volume → ↑BP)
Angiotensin II
Stimulates ADH. (↑ H2O reabsorption → ↑blood volume → ↑BP)
Angiotensin II
When you give ACE inhibitors BP decreases because?
Angiotensin II is no longer produced?
What else does ACE work on?
Bradykinin
What’s Bradykinin?
A vessel dilator, won’t be broken down when given ACEi it decreases BP
What is ACE called when working on Bradykinin?
Kinase II
What adverse effects can Bradykinin have when accumulated?
- Cough > take patient OFF ACEi, put patient on Angiotensin II receptor blocker - losartan
Adverse effects of ACEi?
- Possible angioedema (swelling of tongue, glottis, pharynx) can be fatal
- Hyperkalemia (normally Angiotensin II stimulates aldosterone secretion, K excreted)
Name an Angiotensin II receptor antagonist?
Losartan
Types of drugs used to treat CHF?
- Cardiac Glycosides
- Bipyridine Derivatives
- Beta-adrenergic Agonists
- Vasodilators
- Diuretics
- ACE inhibitors
- Angiotensin II Receptor Agonists
- Beta-Adrenergic Blockers
Name a Cardiac Glycoside drug
Digoxin
Name Bipyridine Derivative drugs
Inamrinone
Milrinone
Name Beta-adrenergic agonists
Dobutamine
Dopamine
Name Vasodilator Drugs
Nitroglycerin
Sodium Nitroprusside
Hydralazine
Name Diuretic Drugs
Thiazide Diuretics
Loop Diuretics
K Sparing diuretics
Name ACE inhibitor drugs
Captopril
Enalapril
Name Angiotensin II Receptor Antagonist drugs
Losartan
Name Beta-Adrenergic Blocker drugs
Metropolol
Carvedilol
What is CHF?
When CO is inadequate to meet the metabolic demand of the body
Causes of CHF?
- CAD
- MI
- Chronic HTN
Signs of CHF?
- If left sided HF, fluid may build up in lungs causing pulmonary edema which results in SOB
- If right sided HF, fluid may build back up into your abdomen, legs and feet, causing swelling.
How does the body try to compensate for back flow?
- ↑sympathetic outflow to the heart, to arteries, and veins. ↑ venous return.
- ↑H2O retention which ↑ blood volume
Treatments for CHF?
- ↑ Myocardial contractility
- Decrease preload (venous return to the heart)
- Decrease afterfload (dilate arteries)
Digoxin Indications?
- CHF
- Atrial fibrillation
- Atrial Flutter
Digoxin MOA?
- Inhibits Na-K pump leading to ↑ Na & decreased K
- Reverses Na/Ca exchanger
- ↑ in Ca = ↑ myocardial contraction
Digoxin Contraindications?
Bradycardia
Ventricular Fibrillation
Digoxin Adverse Effects?
- Digoxin toxicity due to decreased K - hypokalemia (K and Digoxin compete for Na-K pump)
Early signs of Digoxin toxicity?
- Blurred vision
- yellow tinged to the vision
- halos around dark objects
What do you give to keep K levels therapeutic?
K sparing diuretics
Digoxin drug-drug interactions?
- Diuretics
- ACE inhibitors (hyperkalemia)
- Angiotensin II antagonist (hyperkalemia)
Bipyridine derivatives MOA?
- inhibit phosphodiesterase (enzyme that breaks cAMP), increases levels of cAMP which ↑ intracellular Ca which ↑ contractility of the heart
- Vasodilate - unclear MOA
Dopamine binds to adrenergic receptors and stimulates B1 receptors increasing what?
↑ myocardial contractility which ↑CO
At high doses what does Dopamine do?
- could stimulate A1 receptors (negative effect because that would cause vasoconstriction which would increase after load on the heart making it difficult for the heart to pump blog out)
Dopamine also works of Dopaminergic Receptors by doing what?
- Dilating renal blood vessels with ↑ renal blood flow which ↑ urinary output which decreases preload (less work for heart)
Dopamine is used to treat?
Acute CHF
Dobutamine MOA?
More selective for B1
Dobutamine treats?
Acute CHF
Define Angina Pectoris?
Sudden intense substernal pain cause by reduced coronary artery flow to the myocardium (imbalance between myocardium needs and what coronary arteries can supply)
Action of Vasodilator Drugs?
Dilate veins - ↓ preload
Dilate arteries - ↓ afterload
Action of Metropolol & Carvedilol?
↓ HR & Myocardial activity which ↓CO which ↓BP
Types of Angina Pectoris?
- Stable Angina: 90% patients, sudden pain brought on by physical exertion, pain stops when patient rests
- Unstable angina: 10% patients
- Ptinzmetal’s angina: spasm of coronary arteries
Treatments strategies for Angina pectoris?
- ↑ O2 delivery to myocardium
- ↓ demand for O2 by myocardium
Antianginal Drug types?
- Nitrates: Nitroglycerin
- Calcium channel blockers: Procarda, Verapamil, Cardizem
- Beta Blockers: Atenolol, Timolol, Metoprolol
Action of Nitrates?
- when metabolized its converted to nitric oxide (NO)
- Nitric Oxide (NO) activates guanylate cyclase system which ↑ cGMP > dilating vessels
Nitrates at Hight doses?
Dilates the arteries ↓ after load
Nitrates at Low doses?
Dilates veins > ↓ preload > ↓ myocardial demands for O2
Indications for Nitrates?
- Acute Attack, give sublingual
- To prevent attack, give orally or transdermal
Adverse effect of Nitrates?
- Orthostatic Hypotension
- Reflex tachycardia
- tolerance common, give drug holiday
Contraindications for giving Nitrates?
Viagra - also dilates vessels, can significantly ↓ BP
Action of Calcium Channel Blockers?
- Inihbits influx of Ca into myocardial cells, ↓ myocardial contractility
- Inhibits influx of Ca into BV’s causing dilation
Action of Beta Blockers?
- Reduce mortality in patients with MI
2. Blocks reflex tachycardia
Antiplatelet Drug types?
- Aspirin
- ADP Receptor Antagonists: Ticlopidine (Ticlid), Clopidrogel (Plavix)
- Glycoprotein IIB/IIIa Receptor Antagonists: Abciximab (Reopro)
- Dipyridamole (Persantine)
Define Arterial thrombus
- platelet rich clot
- tend to form in medium sized arteries
- Fatty plaques (atheromas)
Define Venous Thrombus
- Fibrin rich
- Forms as a result in bed rest patients
- Can lead to pulmonary embolism
Thrombus formation steps (7)
- Damage to endothelial cells → chemical mediators releases (Von Williebrand factors)
- V factor renders vessel wall which becomes sticky
- Platelets adhere “platelet adhesion”
- The exposed collagen fibers of the connective tissue bind to platelet membrane receptors → triggers production of TXA2
- TXA2 leads to platelet degranulation → ADP, serotonin and platelet derived growth factors are released
- ADP (adenosine dipophate) binds to other platelet receptors (aggregin) causing platelet activation of Glycoprotein IIb/IIIa
- Glycoprotein IIb/IIIa change shape. Fibrinogen can now bind to receptors and bridge platelets together (platelet aggregation)
Aspirin action
- irreversibly inhibits COX → blocks production of TXA2 (no degranulation of the platelets)
- Lasts 7-10 days (lifespan of platelets), must stop aspiring before surgery
Aspirin Indications
[] Longterm myocardial prophylaxis (81-162mg/day)
[] Stroke prophylaxis (50-325mg/day)
[] Acute MI (162-325mg/day)
Adverse effects of Aspirin?
GI Bleeding
Aspirin drug interactions
[] Don’t use enteric coated. Ask patient to chew it
[] Other NSAIDS have anti platelet properties too
[] Don’t take while taking Ibuprofen
Indication for Ticlopidine?
Prevent stroke
Adverse effects Ticlopidine?
Agranulocytosis
TTP (Thrombotic Thrombocytopenic Purpura)
What is TTP?
Blood disorder that causes blood clots to form in small blood vessels around the body, and leads to low platelet count
TTP characterized by?
Fever Anemia Renal dysfunction Thrombocytopenia Neurobiological disturbances
Indications for ADP receptor Antagonists?
Prevent thrombolytic events following a recent MI, stroke, or unstable angina
Action of Plavix?
- Blocks ADP receptor → no platelet activation → no aggregation
- Blocks glycoprotein IIb/IIIa
ABCiximab MOA?
Inhibit binding of fibrinogen to the Glycoprotein IIb/IIIa receptor
Indication for Glycoprotein IIb/IIIa receptor antagonist?
Prevent thrombolytic events following a recent MI, stroke, or unstable angina
Dipyridamole MOA?
[] Inhibits Phosphodiesterase → ↑ cAMP → prevents platelet degranulation
[] mimics actions of prostaglandin known as PGI2 (prostacyclin) which prevents platelet degranulation
Thrombin inhibitor types?
Parenteral: Heparin, Lovenox
Oral: Warfarin
Heparin action?
- Binds to antithrombin III (AT), inhibits active factors 2 & 10
- Activated AT then inactivates thrombin
Heparin Indication
↬ Pulmonary Embolism
↬ evolving stroke
↬ DVT
↬ DIC
↬ Prevent post op venous thrombus
↬ Adjunct to thrombolytic therapy of acute IM
↬ in dialysis machines to prevent thrombus
↬ Anti-coagulant of choose for pregnant women (doesn’t cross placenta)
Heparin Limitations?
↬ given IV, subQ
↬ prevents thrombus BUT doesn’t break down preexistent ones
↬ Monitor lab tests closely. aPTT
Heparin contraindications?
↬ Thrombocytopenia
↬ Bleeding
↬ During surgery and after surgery of eye, brain, spinal cord
For Heparin OD give?
Protamine Sulfate (antidote)
LOVENOX differs from Heparin how?
⇥ binds to Antithrombin III to inactivate factor 10 only
⇥ dosage is fixed, as opposed to based aPTT with Heparin
⇥ administered Orally, no constant monitoring needed
⇥ greater bioavailability, longer 1/2life than heparin
⇥ less likely to cause thrombocytopenia
Liver needs vitamin K to produce what?
Clotting factors 2,7,9,10
Warfarin Action?
Interferes with actions of VIT. K → liver doesn’t produce clotting factors
Warfarin indications?
Longterm anticoagulant therapy
Drugs that ↑ effects of warfarin?
➻ anti-seizure drugs
➻ oral contraceptives
➻ Vitamin K (also used for Warfarin OD)
➻ Lipid/cholesterol lowering drugs
Contraindications of warfarin?
same as Heparin
Differences between Warfarin & Heparin?
➻ W is a small lipid soluble molecule (crosses placenta - Teratogenic) ➻ H is a large lipid insoluble molecule ➻ W delayed onset of action (HRS) ➻ H rapid onset of actin ➻ W orally ➻ H subQ or IV ➻ W monitor prothrombin time (PT) ➻ H monitor aPTT
Action of Fibronolytic type drugs?
Breaks down actual clot, administered IV
Types of Fibrinolytic drugs?
- Streptokinase (streptase)
- Tissue Plasminogen Activator (Alteplase)
- Tenectaplase (TNKase)
Define Plasmin
Enzyme in blood that degrades fibrin clots (Plasminogen is a pre-cursor to plasmin)
Streptokinase MOA?
⇝ Binds plasminogen - leads to rapid conversion to Plasmin
⇝ Degrades fibrinogen in systemic bleeding
Tissue Plasminogen Activator action?
Endothelial cells put out TPA
Indications for Fibrinolytic drugs?
⇝ Acute MI
⇝ DVT
⇝ Pulmonary embolism
Fibrinolytics contraindications?
⇝ Intracranial hemorrhage
⇝ Recent surgery
⇝ GI bleeding
⇝ aneurysm (weakening of BV walls)
Tx of Fibrinolytic OD?
Aminocaproic Acid (prevents Plasmin from binding to the fibrin mesh - clot)
Where does Streptokinase come from?
Bacteria
