Pharm_4.txt

Vasodilator (esp arterioles) Stimulation of guanylyl cyclase. Tx of mild/mod htn. Side effects COMMON (headache, nausea, dizziness, sweating, angina/arrythmias w ischemic heart disease, lupus)

Vasodilator (esp arterioles). Activates k channels for hyperpolarization. Reflex increase in cardiac func also fluid retention. Tx of mild/mod htn. Sfx: chf, tamponade, reflex tacycardia, hair growth (ROGAINE)

Vasodilator ( esp arterioles). Activates k channels. Salt and water retention. Tachycardia and increased CO. Tx of htn emergencies and malignant htn). Sfx: fluid retention and hyperglycemia, hyperuricemia

Vasodilator. Generates NO which activates guanylyl cyclase. Acts on arteries and veins to reduce preload and afterload. Use to produce hypotension in surg and htn emergencies (IV in hospital) RAPID decr in MAP

Vasodilator( esp veins). Generates NO which activates guanylyl cyclase. Use for hypotension in surg and htn emergencies. Sfx: headache, short action, tolerance

Vasodilator. Prostacyclin (PGI2). Uses cAMP. Counteracts thromboxane A2. Use as potent antihypertensive but administer continuously thru IV ( use for pulmonary htn).

Non-selective endothelin receptor blocker. Use for pulmonary htn. Sfx: edema, headache, inhibition spermatogenesis, resp tract infection, decrease hematocrit, hepatic effects

Thiazide diuretic. Then use combos. Secondary approach is ACEI, ARBs, Ca channel blockers, or other vasodilators

Sedation w centrally acting drugs, NSAIDs antagonize anti-htns, orthostatic hypotension, sensitivity to catecholamines (adrenergic blockers), dry mouth, gingival hyperplasia (ca channel blockers), angioedema and cough (ACEI)

Heart rate, contractility, wall stress

• Myocardial oxygen consumption (MVO2)
• But also by autoregulation (arterioles constricting/relaxing)
• Wall tension
• Nueral regulation (affect heart rate and contractility)
• Humoral regulation
• Myogenic tone

• Stable (occurs w exercise etc), unstable, acute
• Also variant (aka Prinzmetals) with vasospasm wo stenosis and microvascular angina which occurs in females more and has no stenosis

• Nitrovasodilators (increase supply and decrrease demand)
• B receptor antagonists (decrase demand)
• Ca channel blockers (increase supply and decrease demand)
• Misc drugs ( alleviate causes)

Coronary blood flow and oxyfen extraction

Also increases (myocytes tell arterioles to dilate)

Relax

• Prevents activation of cGMP. No relaxation. Can occur with
• Atherosclerosis
• Diabetes
• Htn
• Ang II
• Inflammation

Large arteries

• Chest pain (substernal vise-like)
• Arm pain
• Back pain
• Dyspnea
• Lasts 5-30 min
• Can have no signs!
• Arm pain

• Nitrovasodilators
• They release NO like normal endothelium
• Reduce O2 demand:
• Venodilator, arterial dilator, reduce wall stress, but have indirect reflex increase in hrart rate and contractility
• Increase O2 supply: dilate conduit arteries at stenosis, increase subendocardial blood flow, increase collateral blood flow, decreased platelet activation

Bc of enzymatic (mtALDH) release of NO. Other nitrovasodilators have similar effect on all size arteries

First pass hepatic metab, short duration

Avoid first pass effect. Rapid onset. (but only ladts 30-60min)

Inhalant (limited use)

3-5 hr duration. Administer 3-4 times/ d

Longer action than ISDN. Dose 2 times/d. Minimal first pass effect.

• Tolerance (interrupt therapy 8-12 hrs)
• Headache
• Orthostatic hypotension
• Reflex tachycardia
• Gi distress (oral) or skin irritation (patch)
• Contraind w PDE5 inhibitors

PDE5 inhibtors increase cGMP too (inhibit breakdown to GMP) so result is hypotension (drop of over 25mm hg)

PDE5 inhibitors used to treat ED

• B-adrenergic blockers
• Blocking B1 effects: decrease heart rate and contractility and decrease renin release
• Blocking B2 effects: potentiate a-adrenergic effects (vasoconstriction) and may exacerbate vasospasm
• Use for ACS in combo w nitrates
• Adverse fx: bronchospasm, hypoglycemia, hyperlipidemia, myocardial depression, bradycardia, reduced exercise tolerance, sleep disturbances, cold extremities, impotence, rebound w discontinuation ( bc upregulation of receptors)

Cardioselective ca channel blockers. decrease contractility, decrease heart rate, decrease arterial pressure (decr O2 demand) and vasodilate arteries and prevent coronary and cerebral vasospasm (increase O2 supply)

ACS, HTN, supraventricular arrythmias, cerebral hemmorhage or vasospasm

Dizziness, nausea, headache, flushing, hypotension, edema, arrythmias, reflex tachycardia, gingival hyperplasia

Dihydropyridine ca channel blockers. Decrease art pressure, decrease heart rate (reduce O2 demand) and vasodilate epicardial arteries and stenoses and prevent coronary and cerebral vasospasm (increase O2 supply)

New class of antianginal. Piperazine derivative (partial fatty acid ox inhibitor). Shifts ATP production to that from glycolysis. Inhibits late na channel to decrease na and ca inside ischemic myocytes). Minimal effect on heart rate and bp (use w other drugs in refractory pts). Improves exercise tolerance. Works better in males.

B blockers and aspirin (81mg). If contraindiacted to use bb (reynauds, asthma, depression, diabetes, some arrythmias) use ca channel blockers. Nitrates are cheap and safe but tolerance and side fx limit monotherapy (so use in combo). Also, STATINS to reduce high cholesterol

Reduce demand and prevent vasoconstriction with nitrates, b-blockers, ca channel blockers (prevent vasospasm). Stabilize plaques with statins. Prevent platelet aggregation/activation w aspirin, clopidogrel, glycoprotein IIb/IIa blockers. Limit thrombus formation w heparin and THROMBIN INHIBITORS (hirudin, hirulog)

Thienopyridines. Req hepatic biotransformation. Noncomp irreversible ADP antagonist at P2 receptors. Blocks ADP mediated activation of glycoprotein GP IIa/IIb. INHIBITS PLATELET AGGREGATION. Use w aspirin. ACS (esp stents!) MI and sroke. Side fx: neutropenia

MONA. also b blockers blunt increase in heart rate from GTN

Meds should be near (GTN in office), sit before stand, pts taking b-blockers should avoid other cardio depressants and LA w NE, gingival hyperplasia w ca channel blockers

B-blockers, ARBs, ACEIs

• Drugs that: decrease preload (loop diuretics/ thiazides/ spironolactone)
• Decrease afterload (ACEIs, ARBs, vasodilators), improve contractility (adrenergic agonists, phosphodiesterase inhibitors, cardiac glycosides) and interrupting compensatory responses (various)

Complex syndrome where ventricle cannot fill or eject blood properly. Can be structural or functional problem. 80 percent of ppl w HF are over 65.

Dyspnea, fatigue (leads to exercise intolerance), and sometimes fluid retention (may lead to pulmonary congestionand edema)

Increase filling pressure leads to increase stretch and increase SV

Preload, afterload, ionotropic state ( which is influenced by contractile properties of the muscle, autonomic nerves, circulating catecholomines)

Direct sympathetic nervous stimulation, elevated cardiac filing pressures, Ang II, and aldosterone

• Compensatory hemodynamic abnormalities
• Dysreg of Ca homeostasis which impairs contraction and rekaxation (uptake of Ca by Na/Ca exchanger)
• Dysreg of contractile proteins
• Desensitization of B-adrenergic receptors leads to reduced Ca uptakr into SR

• Decrease in CO activates neurohumoral sysrem
• Compensation maintains perfusion to organs
• Increase in volume leads to wall stress and hypertrophic remodeling
• Nuerohumoral activation directly induces apoptosis of myocytes

• Abnormal baroreflex control (interpret high bp as normal)
• Cardiac hypertrophy (at lower ionotropic state)
• Altered renal function (SNS induces constriction of glomeruli and stimulatesrenin release)
• Vasoconstriction (SNS, RAAS, ADH)
• Edema

• Echocardiogram and Doppler flow to see abnormalities of myocardium, heart valves, or pericardium. See whether
• L ventricular ejection fraction is preserved or reduced?
• L ventricle is normal or abnormal?
• Other structural changes of valves, pericardium, or rt ventricle?

Anemias and thyrotoxicosis

• A: risk for HF but no structural abnormalities
• B: structural heart disease but no signs of HF
• C: structural heart disease w prior or current symptoms
• D: refractory HF

• Treat HTN, dyslipidemia, cease drugs and alcohol.
• Drugs: ACEIs, ARBs

• Treat HTN, dyslipidemia, cease drugs and alcohol.
• Drugs: ACEIs, ARBs, B-blockers

• Same as stage A and B but restrict salt intake.
• Drugs: diruretics, ACEIs, B-blockers
• Some pts may take aldosterone antagonists, digitalis, hydralazine/nitrates

• End of life care.
• Heart transplant, mechanical support, experimental surgery/drugs

Juxtaglomerular cells of the kidney

Potent arterial dilators to reduce afterload and increase SV and CO

ACEIs. (Esp for all pts with reduced LVEF). Often combined with a B-blocker.

Adverse reactions (angioedema) or impaired renal function (AngII helps perfuse kidney)

Hypotension, hyperkalemia, kidney failure in pts with impaired renal function, angioedema, cough

ACE inhibitors. Stop conversion of Ang I to Ang II. Inhibit breakdown of bradykinin (a vasodilator)

Block actions of Ang II/III: cardiac remodeling, vasoconstriction, release of aldosterone. do NOT prevent brsdykinin breakdown

• Metoprolol
• Carvedilol
• Bisoprolol

• HF pts in atrial fibrillation or severe HF ( also should be on ACEIs or ARBs, bb, and diuretics.
• Also used for arrythmias

• Inhibition of na/k ATPase to increase intracellular Ca andincrease force of contraction
• Sensitizebaroreceptors to decrease SNS
• Inhibit na/k ATPase inkidney which lowers na resorption so lower renin secreted

• Electrical: arrythmias, heart block, etc
• Increased tox w hypokalemia, hypercalcemia, hypothyroidism
• Clarithromycin, quinidine, verapamil increase tox

Aldosterone antag: used in pts w severe HF or L vent dysfunc after MI. Class C or D HF- low dose with ACEI reduces mortaliy. USE W DIRURETICS. Risk of life-threatening hyperkalemia.

• Reduce preload
• Reduce afterload
• Both
• (decrease filling pressures and volume)

T

T

F. Its used in pts who cant tolerate ACEIs

Ionotropic agents: dobutamine, dopamine, milrinone. SHORT TERM USE

Stimulates b adrenergic feceptors on heart. Increases contractility. Stimulates a2 receptors at high doses to venoconstriction (makes HF worse). Tachycardia can provoke ischemia in pts w CAD

B agonist. For pts w systolic dysfunc. Stimulates b1 and b2 receptors (ionotropy dominates)

Tachycardia and arrythmias

• Inamrinone, milrinone
• Used for advanced HF. Accelerate relaxation so more time for ca to enter cells and increase contraction

Slow inward movement of calcium and na. Change it to alter rate of depolarization.

Atrial fibrillation

Connects signal bt SA node and AV

Ultrasonic scalers, composite curing lights, electrosurgical units (anything emitting electromagnetic waves)

• Na blockers (1): slow upstroke of AP and block spontaneous depolarization
• K blockers (3): increase duration of AP
• Ca blockers (4): slowing spontsneous depolarization
• B blockers (2): prolonging AV conduction

Left atria. Risk for brain infarcts.

Warfarin and aspirin to decrease clot risk

Sinus tach, sinus bradycardia, atrial flutter

Premature ventricular contraction (PVCs), ventricular tach, ventricular fib

• First degree: PR interval increased
• 2nd degree: ventricular rate irregular
• 3rd degree: ventricular rate slow but regular

Tachycardia with accessory path

Dangerous. May progress to v-fib. Electrical loops in ventricle. Risk of quinidine and disopyramide

• Electrical loops in atria.
• Causes: HTN, age, HF, autonomic imbalance, channelopathies, atrial stretch, reduced atrial contraction, ca overload

Na channel blockers to treat HF. Oral meds except lido which is given after ischemia through IV. slows upstroke of AP. RISK OF OTHER ARRYTHMIAS, WORSEN HF, and AV BLOCK. cimetidine reduces clearance

K channel blockers. Inhibit repolarization (prolong AP). WARFARIN increases effectiveness. Amiodarone also acts on na channeks. Sotalol is also a bb.

• Ca channel blockers. Decrease conduction thru AV node, decrease firing in the SA node, reduce slope of pacemaker potential.
• Sfx: hypotension (esp w inhlational anesthetics), AV block, bradycardia, gingival enlargment

Slows AV conduction. Inhibitory on nerves (caffeine/theophylline reduce effects) Given IV. short lived side effects are dyspnea, bronchospasm, hypotension. Dipyridamole amplifies.

Bb used in arrythmias. Decrease conduction thru AV node (reduce slope ofpacemaker potential). Side effects are fatigue, worsening of HF, hypotension, ED, bronchospasm

IV for torsades des pointes