Week 6 (test 2) Flashcards
What are the four classes of antihypertensive drugs?
Diuretics
Sympathaoplegics
Direct vasodilators
Anti-angiotensin agents
How do direct vasodilators work?
Relax vascular smooth muscle, thus dilating resistance vessels and sometimes increasing capacitance
How do anti-angiotensin agents work?
Inhibit action/production of angiotensin and thus reduce peripheral vascular resistance (and sometimes blood volume)
How do diuretics work?
Deplete sodium, reduce blood volume, and perhaps by other mechanisms.
Long-term diuretic - decreased TPR
How do sympathoplegics work?
Reduce peripheral vascular resistance. (Also inhibit cardiac function, and increase venous pooling, thus reducing cardiac output)
Where do osmotic agents (mannitol) work on the nephron? Describe how it works.
Mannitol is a diuretic that works on the thin descending limb.
Mannitol is not reabsorbed and thus water is retained
What is mannitol used to treat?
Not HTN. It is used for increased intracranial pressure after head trauma
Where does acetazolamide work on the nephron? What does it do?
On the proximal convoluted tubule.
It is a carbonic anhydrase inhibitor. It shuts down resorption of bicarbonate into interstitial space. Thus less sodium resabsorption. Thus more NA in the lumen remains.
Causes alkaline urine (more bicarbonate in urine)
What are carbonic anhydrase inhibitors used to treat?
Not HTN. Used as a diuretic for glaucoma and other disorders.
Name two loop diuretics. How well do these work?
***Furosemide (lasix)
Bumetanide (bumex)
These are very efficacious
Describe how loop diuretics work.
Inhibit the luminal Na/K/2Cl transporter in the thick ascending limb of the loop of henle. Thus reducing NaCl absorption, thus increasing urine output.
More potent and more side effects
Loop diuretics are inhibited by ___ under certain conditions.
NSAIDs
What is a major side effect of loop diuretics? Why is this an issue?
Hypokalemia - increase luminal sodium and thus stimulates the aldosterone-sensitive sodium pump to increase sodium reabsorption in exchange for potassium which is lost in the urine.
This can cause heart arrhythmias
Where do thiazide diuretics work?
On the distal convoluted tubule of the nephron
Name two thiazides
***Hydrochlorthiazide
Chlorthalindone
How do thiazides work? What is a side effect? What is it inhibited by?
Inhibit NaCl reabsorption by blocking the Na/Cl transporter.
Can cause hypokalemia
Inhibited by NSAIDs under certain conditions
Note that it is often first order elimination
In addition to heart arrhythmias, hypokalemia can also lead to…
Decreased insulin secretion and thus hyperglycemia
*dont give drugs that cause hypokalemia to pts with poor glucose control
Name 3 potassium-sparing diuretics
Spironolactone
Amiloride
Trimterene
Usually combined with other diuretics, especially the thiazides
Describe how potassium-sparing diuretics work
Prevent K secretion by antagonizing effects of aldosterone in collecting tubules (via blockade of mineralocorticoid receptors) (spironolactone)
Or Na+ influx through ion channels in the luminal membrane (amiloride)
Potassium sparing diuretics are often used in combination with ____ to offset hypokalemia. They are not used with ___ because it worsens hypokalemia
Loop diuretics
ACE-1
Describe how ACE-inhibitors work
ACE inhibitors prevent the conversion of angiotensin 1 to angiotensin 2.
Angiotensin 2 normally leads to constriction, so less angiotensin = less constriction and lower BP
ACE normally will breakdown Bradykinin. If ACE is inhibited, bradykinin accumulates which will ultimately lead to vasodilation
What kind of a drug is captopril? How does it work?
ACE inhibitor
Inhibits the converting enzyme (peptidyl dipeptidase) that hydrolyzes angiotensin 1 to angiotensin 2
Increases bradykinin levels (potent vasodilator)
Therefore inhibit renin-angiotensin system and a stimulate the kallikrein-kinin system
Hyperkalemia because little aldosterone (aldosterone promotes Na retention and thus lower plasma K levels)
What is a side effect of increased bradykinin?
Dry cough
What kind of a drug is losartan? How does it work?
Antiotensin 2 inhibitor
Decreases peripheral vascular resistance
No effect on bradykinin metabolism and therefore more selective blocker of angiotensin effects than ACE inhibitors
What kind of drug is hydralazine, verapamil, diltiazem, nifedipine, and minoxidil?
These are all direct vasodilators
What is the mechanism of action of hydralazine, nitroglycerin and nitroprusside direct vasodilators?
Release of nitric oxide form drug or endothelium
Note that hydralazine also hyperpolarizes smooth muscle?
What is the mechanism of verapamil and diltiazem, (direct vasodilators)?
Reduction of calcium influx (causing muscle relaxation)
What is the mechanism of minoxidil and diazoxide (direct vasodilators)?
Hyperpolarization of smooth muscle membrane through opening of potassium channels
What is the mechanism of fenoldopam (direct vasodilator)
Activation of D1 receptors
True or false… sodium nitroprusside also relax veins
True
Why dont direct vasodilators cause orthostatic hypotension?
Decreased arterial resistance and decreased mean arterial BP elicit compensatory responses, mediated by baroreceptors and the sympathetic nervous system. Because sympathetic reflexes are intact, vasodilator therapy generally does not cause orthostatic hypotension.
Where are some locations where sympathoplegics act?
Sympathetic nerve terminals
B-receptors of heart
A-receptors of vessels
Sympathetic ganglia
Vasomotor center (central)
True or false… clonidine has its antiHTN affects based on central mechanisms
True
What is the mechanism of clonidine? What are some side effects?
It is an alpha 2 agonist (recpetors in medulla)
Reduces sympathetic tone, resulting in decreased blood pressure
Dry mouth and sedation are common. Both effects are centrally mediated and dose dependent
What is mecamylamine?
In is a Nn antagonist. It binds nicotinic cholinoceptors and post ganglionic neurons in both sympathetic and parasympathetic ganglia.
Causes both sympathoplegia (excessive orthostatic hypotension) and parasympatheplegia (constipation, urinary retention, glaucoma, blurred vision, dry mouth etc.)
Rarely used
What is guanethidine? How does it work? What is a side effect of it?
Adrenergic blocking agent
Inhibits the release of NE from sympathetic nerve endings by depleting NE stores.
Causes orthostatic hypotension (because of lack of sympathetic compensation), diarrhea
What kinds of drugs are atenolol and metoprolol?
B1 antagonists (cardioselective)
What kind of drug is propranolol and nadolol?
B1 and B2 antagonists. (Non-cardioselective)
Propranolol ___ the stimulation of renin production by ____ and thus it is likely that propranolol’ effect is due in part to depression of the renin-angiotensin-aldosterone system
Inhibits
Catecholamines
What kind of drug is labetalol and carvedilol?
Beta + alpha 1 antagonist
Beta blockers can be used to treat what three things?
HTN
Angina
Open-angle glaucoma
What are beta blockers' effects on the following tissues? Cardiac Vascular Renal Respiratory Metabolic Aqueous humor Arrhythmias
Cardiac: decreased HR and contractility (impairs excerise tolerance)
Vascular: increased TPR (blockade of B2 in skeletal muscle)
Renal: decreased renin release
Respiratory: bronchial constriction
Metabolic**: decreased glycogenolysis in response to hypoglycemia
Decreased aqueous humor production
May block tachycardia associated with hypoglycemia
What kind of drug is prazosin, terazosin, and doxazosin?
Alpha 1 antagonists. (Cardioselective) prevents catecholamines from causing vasoconstriction
What kind of drug is phentolamine and phenoxybenzamine?
Alpha 1 and alpha 2 antagonists. (Non-cardioselective)
What are the effects and uses for alpha 1 antagonists?
Vasodilation (because it prevents vasoconstriction) and thus decreased TPR and decreased BP
Uses: treat HTN. Benign prostatic hypertrophy (use tamsulosin)
What are the side effects of alpha 1 antagonists?
Orthostatic hypotension (if someone is one prazosin, be careful getting them out of the dental chair)
Nasal congestion
What kind of a drug is hydrochlorthizide?
Thiazides
What kind of a drug is furosemide?
Loop diuretic
What is the most common cause of angina pectoris?
Ischemic heart disease
What are the two treatment strategies to treat angina?
Vasodilation (using direct vasodilators) - immediate but short acting relief
Decrease O2 consumption - prevent the pain onset by decreasing the demand of oxygen of the heart (use b-blockers, and calcium channel blockers)
What are the two types of nitrates/nitrites that are used to treat angina? Describe them.
Nitroglycerin (administer sublingually). Volatile -store in closed glass container. Also long-lasting patches (~8hours) tolerance occurs, exposes pt to side effects. If pain goes away with nitroglycerin, it probably isn’t a heart attack
Amyl nitrate - ample crusehd and fumes inhaled. Short acting. Not used much anymore.
What are the side effects of nitroglycerin/amylnitrate?
Toxicity and tolerance (tolerance develops rapidly. Need ~8 hours between use to diminish tolerance)
Orthostatic hypotension
Tachycardia
Throbbing headache
What is the mechanism of calcium channel blockers in the use of treating angina?
Prevent calcium influx through L-type channels and block contraction of smooth and cardiac muscle-reduce O2 demand
Name three calcium channel blocker drugs that are used as prophylaxis for angina (lasts 4-8 hours)
Verapamil
Nifedipine
Diltiazem
(These are also used as antihypertensives)
Describe the toxicity associated with calcium channel blockers
Cardiac depression and bradycardia - heart failure
Flushing and dizziness
True or false.. B-blockers are vasodilators
False. They reduce output by decreasing HR and contractility, decreasing BP and decreasing O2 requirements
Used as a prophylactic
What are the principal B-blockers used for prophylaxis of angina
Propranolol (non selective B antagonist)
Atenolol (B1 selective antagonist. Less risk for bronchospasms)
Toxicity: asthma and acute heart failure
True or false… cigarette smoking raises HDL values
False, it lowers it. Low HDL is a risk factor for atherosclerosis
Hypertriglyceridemia is associated with increased __ and ___
VDL and LDL
What are the non-drug treatments for lower cholesterol?
Dietary (doesn’t help more than 10%) Reduce fat, avoid alcohol if VLDL elevated, avoid red meats, include complex carbohydrates and fiber
Exercise
True or false. Cholesterol-lowering drugs should be avoided in pregancy. Why or why not?
True. The fetus needs cholesterols to develop the brain
What is the mechanism of statins?
Competitive inhibitors of HMG-COA reductase (enzyme that synthesizes cholesterol)
Name three statins
Lovastatin
Atorvastin
Simvastatin
Statins reduce synthesis of ___ and have most effect on ___.
Cholesterol
LDL (some decrease in triglycerides)
Doesn’t really have an impact on HDLs. These drugs will reduce coronary events
What are the toxic effects of statins?
Liver damage
Weakness and pain in skeletal muscles
What is the mechanism of fibrates?
Increases lipolysis in liver and muscles
Reduces VLDL most. Modest effect on LDL. Some reduction in triglycerides. Moderate increases in HDL.
What kind of a drug is fenobrate?
Fibrate (used to decrease cholesterol)
What are the toxic effects of fibrates?
Primarily GI symptoms (gas and cramps)
What is the mechanism of niacin (nicotinic acid)? What are its side effects?
Decreases triglyceride and LDL
Side effects: flushing. Tolerance develops
What kind of a drug is cholesteramine? Describe its mechanism and its toxicity.
Bile acid-binding agent
Reduces reabsorption of biles acids and metabolites
Toxicity: constipation and bloating
What kind of a drug is ezetimibe? How does it work?
Inhibitor of intestinal sterol absorption
Inhibits intestinal absorption of cholesterol and reduces LDL
What is the main goal with drugs that treat heart failur?
Control symptoms and slow progression
Symptoms such as... Tachycardia Reduced exercise tolerance Myocardial hypertrophy Shortness of breath Peripheral and pulmonary edema
Name two positive ionotropic drugs. What is their mechanism and side effects?
Digitalis and milrinone
Increases intracellular calcium and cardiac contractility - in turns increases blood ejection
Side effects: premature depolarization- arrhythmias. Ectopic beats. Affects all excitable tissues
True or false.. positive ionotropic drugs are orally effective
True
What kind of a drug is dobutamine? What is a side effect?
B-1 adenoceptor agonist
Used to treat heart failure
Side effect: can cause arrhythmias
Diuretics, especially ___ are useful in treating heart failure. It has no positive ionotropic effect but how does it work?
Furosemide
Reduces salt and H2O retention
Reduces venous pressure and ventricular preload
How are ACE inhibitors such as ___ useful in treating heart pain?
Captopril
Reduces peripheral resistance by reducing salt and water retention
Vasodilators such as ___ are used to treat heart failure because it…
Hydralazine
Reduces pre- and post- load/smooth muscle relaxant
B-adenoceptor blockers such as ___ are used to treat heart failure because it…
Metoprolol
Reduces heart rate and blocks sympathetic NS
What is a non drug treatment for treating heart failure?
Eat less salt!
80% of pateints with arrhythmias have a history of ___
Myocardial infarction
Note that treatment of arrhythmias can precipitate serious arrhythmias itself
Name 7 treatments for heart failure
Positive ionotropic drugs
B1 adenoceptor agonists
Diuretics
ACE inhibitors
Vasodilators
B-adrenoceptor blocker
Eat less salt
How do sodium channel blockers treat arrhythmias?
Slows action potential conduction
Effective for most atrial and ventricular arrhythmias
Can precipitate new arrhythmias
Usually not first choice drug
Name 3 sodium channel blockers used to treat arrhythmias
Procainamide (never first choice)
Quinidine
Lidocaine (low toxicity, first choice for ventricular arrhythmias)
What is the first choicedrug for treating ventricular arrhythmias?
Lidocaine
Name one beta blocking drug used for treating arrhythmias
Propranolol (class 2)
Describe the 4 different classes of drugs that are used to treat arrhythmias
Class 1 - sodium channel blockers
Class 2 - block sympathetic autonomic effects on heart
Class 3 - prolong refractory period
Class 4 - calcium channel blockers
Name one drug that prolongs the refractory period used for treating arrhythmias. What is a side effect?
Amiodarone (treats ventricular arrhythmias and atrial fibrillation)
Causes pulmonary fibrosis
Name two calcium channel blockers (class 4) used to treat arrhythmias
Verapamil
Diltiazem
Prolongs refractory time and causes vasodilation (antihypertensive effect)
