09 Cardiovascular Flashcards
(23 cards)
What receptors are *sympatholytics acting on?
alpha, beta, mixed
*Methyldopa (Aldomet)
it is metabolized into an alpha 2 agonist that can be used for for treatment of HTN, especially in pregnancy-induced HTN
INHIBITS DOPA decarboxylase which converts DOPA into dopamine > norepi > epi. Effectively lowering catecholamines and BP
Nitroglycerin
- Mainly venous dilation
- NO is released through glutathione-dependent pathway
- Can be used for controlled hypotension, but less potent than SNP
- *Reflex tachycardia
- Cerebral vasodilation (ICP & CBF, headache)
- Can be used for uterine relaxation (50-200 mcg IV bolus)
- Risk of methemoglobinemia but rare due to rapid hepatic metabolism (Tx methylene blue)
o Give sublingually / transmucosally (avoids 1st pass effect), transdermally
- 0.3 mg SL or 2% ointment for angina pectoris
- Increases coronary perfusion to ischemic subendocardium
o IV dosing: 10-100 mcg IV bolus or infuse at 0.5 – 2 mcg/kg/min
- Potential for absorption of drug into plastic tubing
- Tolerance develops within 24 hours of sustained treatment
Non selective alpha antagonists (2)
Phentolamine and Phenoxybenzamine
Metoprolol, atenolol, esmolol
short acting B1 selective
side effects: *bradycardia, AV heart block, CHF exacerbation, *Hypotension (due to decreased myocardial contractility, HR, and Renin release)
*Reduce myocardial O2 demand
*Clonidine
centrally acting alpha 2 agonists
Decreases CNS Output of presynaptic alpha 2 receptors
caution if d/c resulted in *rebound HTN, treat w/ vasodilator
Can also be used for: analgesia, pre-anesthetic medication, regional anesthesia, treatment of opioid withdrawal syndrome, and post-operative shivering
*Inhaled Nitric Oxide (NO)
*selective pulmonary vasodilator, bronchdilation, improved V/Q matching
o Used to treat: pulmonary hypertension, adult respiratory distress syndrome / acute lung injury
o NO combines with Hgb to form met-Hgb (monitor met-Hgb levels)
Propanolol
nonselective B1=B2
side effects: *bronchospasm, CHF, exacerbation
Problems with alpha 2 receptor blockade
Phentolamine and Phenoxybenzamine
-*Side effects: Reflex tachycardia, orthostatic hypotension
- Cholinomimetic side effects: hyperperistalsis, abdominal pain, *diarrhea
- Can treat with atropine / glycopyrrolate
- May have unrecognized volume depletion
Nitric Oxide (NO)
Deliver NO (nitric oxide) to vascular smooth muscle>vasodilation
o NO release is part of normal endothelial function > autoregulation
o Sildenafil (Viagra) increases local availability of endogenous NO
o Inhibits platelet activation/aggregation/adhesion
o NO is *rapidly inactivated by hemoglobin (may explain vasospasm after subarachnoid hemorrhage)
Prazosin, terazosin, doxazosin
alpha 1 selective
used for BPH (benign prostatic hyperplasia), HTN, and pheochromocytoma
Minoxidil
oral medication, action like hydralazine (reflex tachycardia)
Used for the most severe forms of hypertension
Fluid retention, edema, pericardial effusion
Hypertrichosis = hair growth (minoxidil = Rogaine)
*Carvedilol (coreg)
non selective beta antagonists w/ a-1 antagonism (oral formulation)
Sodium Nitroprusside (SNP)
Direct *venous and arterial vasodilation
- Fe–(CN)5(NO) > Release of NO (and 5 CN)
- Used for controlled hypotension, hypertensive emergencies, cardiac disease
- *Reflex tachycardia
- Cerebral vasodilation (increased ICP & CBF, headache)
- Attenuates hypoxic pulmonary vasoconstriction (HPV)
- Potential for coronary steal syndrome
o Concentration: 50 mg in 250 mL = 200 mg/mL = same as nitroglycerin!
- Starting dose: 0.3-0.5 mcg/kg/min = ~10 mL/hr (good rule of thumb!)
- Onset: almost instant; Duration: 1-10 minutes
- Titrate up by 0.2-0.5 mcg/kg/min increments (common dose ~3 mcg/kg/min)
- Max dose: 10 mcg/kg/min (<10 minutes!) or 2 mcg/kg/min (long-term)
- *Breaks down in light (wrap in foil or black plastic)
- Should use continuous arterial BP monitoring
Hydralazine (Apresoline)
Directly causes *smooth muscle relaxation (arteriolesSBP
*Reflex Tachycardia
Dose 2.5-10mg IV
- takes effect in *10-20min slow AF
- last 3-6hrs (unpredictable)
liver metabolism>renal excretion
*Labetalol
mixed antagonist w/ a:B ratio 1:7
No reflect tachy, but less brady than w/ pure antagonists
a-activity leads to decreased PVR and renin release
Phentolamine and Phenoxybenzamine
Non selective alpha antagonists used exclusively for management of *pheochromocytoma
- Block the action of catecholamines
- α2-receptor blockade > enhanced NE release > increased HR
- Unopposed stimulation of beta receptors may lead to *HYPOTENSION
Sodium Nitroprusside (SNP)
Direct *venous and arterial vasodilation
- Fe–(CN)5(NO) > Release of NO (and 5 CN)
- Used for controlled hypotension, hypertensive emergencies, cardiac disease
- *Reflex tachycardia
- Cerebral vasodilation (increased ICP & CBF, headache)
- Attenuates hypoxic pulmonary vasoconstriction (HPV)
- Potential for coronary steal syndrome
o Concentration: 50 mg in 250 mL = 200 mg/mL = same as nitroglycerin!
- Starting dose: 0.3-0.5 mcg/kg/min = ~10 mL/hr (good rule of thumb!)
- Onset: almost instant; Duration: 1-10 minutes
- Titrate up by 0.2-0.5 mcg/kg/min increments (common dose ~3 mcg/kg/min)
- Max dose: 10 mcg/kg/min (<10 minutes!) or 2 mcg/kg/min (long-term)
- *Breaks down in light (wrap in foil or black plastic)
- Should use continuous arterial BP monitoring
Nitroprusside Metabolism
Sequestration of CN
- Normally 1% of Hb is naturally met-Hb
- CN + met-Hb cyanmet-Hb
CN > liver / kidney conversion to thiocyanate by rhodanese enzyme
- Requires a sulfur donor: usually thiosulfate
- Excreted in urine
*Cyanide toxicity (esp. w/ hepatic dysfunction)
Treat early if suspicious – don’t wait for lab results
*Acidosis – *early sign – due to inactivation of cytochrome oxidase
- Uncoupling of mitochondrial oxidative phosphorylation, inhibits cellular respiration
- Leads to *anaerobic metabolism, *lactate formation
- May need NaHCO3 to treat acidosis
- CN also decreases affinity of O2 to Hb
Tachycardia, Δ mental status, seizures; HTN (tachyphylaxis)
Treatment
1) STOP nitroprusside
2) Cyanide buffers: Sodium nitrite IV (OR Amyl nitrite inhaled)
- ————————————————
a) Converts ~10% of Hb > met-Hb which sequesters the cyanide
b) >10% met-Hb indicates no further need for nitrite therapy
c) THEN give sodium thiosulfate IV
d) Rhodanese continues converting CN > thiocyanate > renal excretion
- ————————————————
3) Vit B12a (Hydroxocobalamin): chelates cyanide > vit B12 > renal excretion
*ACE Inhibitors
- Renin-Angiotensin-Aldosterone (RAA) Pathway
- Free from many common side effects seen with other anti-hypertensive agents (depression, insomnia, sexual dysfunction, electrolyte imbalances)
- First-line therapy for *systemic hypertension, *CHF
o May reverse LV hypertrophy
o Improved outcomes in diabetics
o *Decreased plasma aldosterone = reduced Na and water retention
-Prolonged hypotension observed under general anesthesia
o Consider holding medication for 24+ hours before surgery
o “Vasoplegic syndrome”
——————————————–
1. Dysregulation of NO synthesis and vascular guanylate cyclase (GC) activation
2. May require vasopressin if unresponsive to fluid bolus or sympathomimetic
3. *Methylene blue: inhibits NO synthesis and GC, decreasing GMP and vascular smooth muscle relaxation
—- Especially after cardiac surgery: Bolus 1-2 mg/kg over 15-30 min (0.25-2 mg/kg/hr infusion may be needed)
Enalapril (Vasotec), Quinapril (Accupril), Lisinopril (Zestril), Ramipril (Altace)
Angiotensin Converting Enzyme Inhibitors (ACEIs)
o Side effects: *cough, allergic-like symptoms (due to bradykinin accumulation?)
o Decreased glomerular filtration in renal dysfn
o Possible *hyperkalemia due to aldosterone
o Allergy: *angioedema
o Renal excretion
Losartan (Cozaar), Valsartan (Diovan)
Angiotensin II Receptor Blockers (A2RBs)
Act later in the Renin-Angiotensin-Aldosterone pathway
o Inhibit hypertensive effect of Angiotensin II
o Less incidence of cough
o *Hyperkalemia – especially if used together with K-sparing diuretics
o Drug and its active metabolites – hepatic metabolism
o Otherwise *similar to ACEIs – may want to discontinue prior to major surgery
*Digoxin (Cardiac Glycoside)
1) Management of supraventricular tachydysrhythmias (ATach, AFlutter, AFib) with rapid ventricular rate
o Slows conduction through AV node > reduce ventricular rate
o Increased parasympathetic nervous system activity, decreases SA node activity
o Some risk of ventricular fibrillation
2) Originally: treatment of congestive heart failure, *but no longer a first-line therapy
o Positive inotropic agent
o Inhibit Na-K-ATP transport system
o Increased intracellular Na > increased intracellular Ca > increased contractility
3) Pharmacokinetics
o Renal clearance
o *Protein bound (25%)
4) *Toxicity: narrow therapeutic range
o Therapeutic effects at 35% of fatal dose
- Therapeutic range: 0.5-2.5 ng/mL; Toxic range > 3 ng/mL
o K+ depletion (ex: from diuretics, alkalosis)
o Symptoms: N/V, vision changes (yellow-green halos); atrial/ventricular dysrhythmias
o Treatment:
a) Identify / correct inciting cause (hypoK, hypoMg, hyperCa)
Treat dysrhythmias (phenytoin, lidocaine, atropine)
b) Artificial pacing if complete heart block is present
c) Fab fragments (digitalis antibodies)
o Drug interactions:
a) Quinidine: displace digoxin from tissue binding sites
b) Sympathomimetics could precipitate dysrhythmias
