HTN Flashcards
Clinical practice guidelines for normal BP? What is normal BP?
<120/80
- Promote optimal lifestyle habits
- reassess in 1 yr
Clinical practice guidelins for elevated BP? What is elevated BP?
120-129/ <80
- Non-pharmacologicla therapy
- Reassess in 3-6 mo
Clinical practice guidliens for Stage 1 HTN? What classifies as stage 1 HTN?
bp 130-139/ 80-89
- Is patient clniical ASCVD or estimated 10 y CVD risk >10%
- yes
- non pharmacological therapy and BP lowerin g meds
- reassess in 1 mo
- BP goal met?
- yes- reassess in 3-6 min
- no- assess and optimize adherence to therapy and consider intensification of therapy
- BP goal met?
- No
- non pharmacologicla therap
- reassess in 3-6 mo
- yes
What classifies as Stage 2 HTN? Clinical Practice Guidelines?
>140/90
- non pharmacologicla therapy and BP lowering meds
- reassess in 1 mo
- Bp goal met?
- yes- reasses in 3-6 mo
- no- assess and optimize adherence to therapy. consider intensification of therapy
What physiologically influences BP?

What are the various sites of action for anti-HTN?
- Brainstem- alpha 2 receptors
- clonidine
- methyldopa
- sympathetic ganglia- not as popular because influence both SNS and PSNS
- mecamylamine
- trimethapran
- Adrenergic terminals- would deplete ALL adrenergic terminals, of vesicales with NT; can cause unwanted s/e such as depression
- guanethidine
- reserpine
- Cardiac B1 receptors
- Propranolol
- metoprolol
- other B blocker
- Vascular alpha 1 receptors
- Prazosin
- Terazosin
- Labetalol
- Vascular smooth muscle
- hydralazine
- minoxidil
- nitroprusside
- diazoxide
- CCB
- Thiazides
- Renal Tubules- Decrease amt Na/H2O reabsorption
- thiazide diuretics
- furosemide
- K sparing diuretics
- Components of the RAAS- huge component is decreasing tone RAAS
- 8A- receptors on juxtaglomerular cells- propranolol, metoprolol
- 8B- Renin- aliskiren
- 8C- ACE- Captopril, enalapril
- 8D- ANGII Receptor- losartan, valsartan
- 8E - Aldosterone receptors- eplerenone, spironolactone

RAAS system and role in BP modulation?
- Renin+ angiotensinogen–> ANG I–> (via ACE)–> ANG II–> SNS activity, tubular NaCl reabsorption and K excretion, adrenal cortex to make aldosterone, arterialar vasoconstriction, ADH secretion
- Renin works to maintain tissue perfusion through increase ECF volume and increase BP
- Renin is secreted by the Juxtaglomerular Apparatus
- renin is the rate-limiting step
- released when less NaCl delivery to juxtaglomerular apparatus or when renal baroreceptors sense decreased flow
- beta 1 receptors on renal tubules also stimulated by circulating NE/Epi
- release renin when dry and BP too low
- Results in 1) vasoconstriction & 2) Na+ retention
- Renin-angiotensin system is synergistic with SNS by increasing the release of noradrenaline from the sympathetic nerve terminals

Role of ACE inhibitors to treat HTN?
- First line therapy
- HTN
- CHF
- Post-MI to reduce CHF progression
- Mitral Regurgitation
- Delay progression of renal disease
- More effective in diabetic patients- ACE inhibitors in DM can delay renal dysfunction
MOA ACE inhibitors?
- Mechanism of Action: Block the conversion of angiotensin I to angiotensin II in the vascular endothelium
- Via an interaction with the zinc ion of angiotensin converting enzyme (peptidyl-dipeptidase)
- Fall in arterial pressure
- Reduced cardiac work load
-
Get less ANGII and subsequent fall in BP
- vasodilation
- decrease blood volum
- decrease cardiac and vascular remodeling
- potassium retention
- fetal injury
-
ACE inhibitors also block bradykinin
- get vasodilation, cough and rare angioedema

What is effect on ANG II on BP? What receptor does ANG II bind to?
- Angiotensin II is a potent vasoconstrictor responsible for arterial smooth muscle constriction
- Angiotensin II
-
Main action mediated via AT-1 G-protein coupled receptor.
- Signaling results in increased Ca2+ release from the SR
-
Main action mediated via AT-1 G-protein coupled receptor.
-
AT-1 receptor effects
- Generalized vasoconstriction (especially in the afferent arterioles of renal glomeruli)
- Increased norepinephrine release
- Proximal tubular reabsorption of Na+
- Secretion of aldosterone from adrenal cortex
Examples of ace inhibitors?
- Highly Potent with minimal side effects
- Good patient compliance (end in -pril)
- Captopril- [Capoten]
- Enalapril- [Vasotec]
- Ramipril- [Altace]
- Benazepril- [Lotensin]
- Lisinopril- [Zestril, Prinivil]
- Moexipril- [Univasc]
- Quinapril- [Accupril]
- Fosinopril- [Monopril]
- Trandorapril- [Mavik]
S/E of ace inhibitors? Drug interaction? contraindications
- S/E
- prolonged hypotension intra op (prohibit taking on AM of sx)
- granulocytopenia
- angioedema d/t bradykinin
- persistent cough d/t bradykinin
- hyperkalemia (esp CRI)
- Drug interaction: NSAIDs antagonize its effects, other anti-HTN additive effect
- NSAIDs inhibit prostaglandin, which is a vasodilator. Giving NSAIDS stop vasodilation, kind of working against ACE vasodilation.
- Contraindication
- pregnancy
- renal artery stenosis patients may develop renal failure due to impaire efferent arteriole constriction
- renal artery stenosis patients rely on efferent vasoconstriction to maintain GFR
ACE inhibitor pharmacologic effects?
- all affect venous and arterila system evenly
- enalapril and ramipril are prodrugs
- peak times can be 4-8 hours after dose, with duration lasting 18-30 hours (enalapril) or 24-60 hours (ramipril)

MOA Angiotensin II Receptor Blockers? S/E? Contraindications?
- Angiotensin II (AT1) receptor antagonists
- MOA: Competitive binding to inhibit the action of angiotensin II at its receptor
- Blocks the vasoconstrictive actions of angiotensin II without effecting ACE activity
- results in decreased peripheral vasoconstriction
- Side effects similar to ACE inhibitors
- No significant bradykinin accumulation (avoid cough side effect)
- Contraindication:
- renal artery stenosis
- pregnancy
Examples ARBS?
- Losartan-[Hyzaar, Cozaar]
- Valsartan- [Diovan]
- Irbesartan- [Avalide, Avapro]
- Candesartan- [Atacand]
- Telmisartan- [Micardis]
- Eprosartan- [Teveten]
- Olmesartan- [Benicar]
- Tasosartan- [Verdia]
MOA hydralazine? Dose?
- direct arterial vasodilator, second- line
- reserved for cases not responding and in pregnancy
- used in OR frequently when beta blockers are contraindicated
- Vasodilation through activation of guanylate cyclase (interferes with action of IP3 mediated calcium release from SR) and hyperpolarization
- Produces direct relaxant effect on vascular smooth muscle and decrease in SVR
- arteries > veins
- Alter Ca2+ transport in vascular smooth muscles
-
Dosage 2.5-10mg IV
-
10-20minutes peak, can last up to 6hrs
- be careful/patient when titrating hydralazine
-
10-20minutes peak, can last up to 6hrs
Pharmacokinetic hydralazine?
- Extensive hepatic first pass metabolism
- Onset 15 minutes give slowly
- Elimination ½ time 3 hours
- After IV < 15% appears unchanged in the kidney
S/E Hydralazine?
- Angina with EKG changes
- DBP reduced >SBP- potential impairment coronary perfusion
- Reflex Increase HR, SV, CO
- Tolerance & Tachyphylaxis
- Sodium and H20 retention- from compensatory action of aldosteron from drop in BP. May need to give BB and diuretic with hydralazine
- Systemic lupus like syndrome
Clinically used in combination with BB and diuretic
- Limits the increased SNS activity
- Also, used in CHF (combined with isosorbide mononitrate)
- speicfically helpful in black patients not traiditonally responding to BP meds
Minoxidil MOA and use?
Mechanism of Action
- KATP channel opener: resulting in hyperpolarization (decreased voltage-gated Ca2+ channel activity) and vasodilation
- Directly relaxes the arteriolar smooth muscle little effect on venous capacitance
- Orally active
- Very potent; activity via active sulfate metabolite
Clinically used (2nd line drug with severe forms HTN)–refractory HTN, if patient on this drug, do thorough cardiac w/u)
- To treat the most severe forms of hypertension due to
- renovascular disease
- renal failure
- transplant rejection
- used in combination with beta-blocker (offset reflex tachycardia and compensatory aldosterone activation) & diuretic (to offset sodium and water retention)
- Topical formulation used to treat baldness (side effect hirsutism)
Pharmacokinetics minoxidil?
- Pharmacokinetics
- 90% oral dose absorbed from the GI tract
- Peak levels in 1 hour
- E ½ t 4 hours
- 10% of drug is recovered unchanged in the urine
S/E Minoxidil?
- Marked increase in HR &CO
- Increased plasma concentration of NE and Renin
- Compensatory retention of Na and H20 (aldosterone mediated)
- Weight gain
- Edema
- Hypertrichosis
- Pulmonary HTN
- Pericardial effusion or cardiac tamponade
- Can have abnormal EKG-
- Flat or inverted T wave, increased voltage of the QRS complex
Sodium Nitroprusside Use?
- Direct acting, nonselective peripheral vasodilator
- most potent vasodilator we use in OR
- Relaxation of arterial & venous vascular smooth muscle
- Lacks significant effects on non-vascular smooth muscle and cardiac muscle
MOA Sodium Nitroprusside (SNP)
- SNP interacts with oxyhemoglobin
- dissociates immediately to form
- Methemoglobin
- Releasing Nitric Oxide (NO) and cyanide
- (One good guy and 2 bad guys made…)
- dissociates immediately to form
- Nitric Oxide activates guanylate cyclase (in the vascular muscle) thus increasing cGMP
- cGMP inhibits calcium entry into vascular smooth muscle & increases uptake of Ca2 into the smooth endoplasmic reticulum.
-
Results in vasodilation via NO
- good for pheochromocytoma with extremely high, difficult to control BP
EFFECTS of SNP?
- CV:
- Direct venous and arterial vasodilation, increased venous capacitance due to decreased venous return
- Baroreceptor mediated reflex responses increased HR
- decrease SBP, decrease SVR, decreasePVR, increase contractility,
- causes an intracoronary steal in areas of damage associated with MI- .loosing preferential flow to ischmic areas during MI. can worsen an MI. main difference between nitrate (NTG) and sodium nitroprusside. NTG maintains preferential blood flow during ischemia
- CNS:
- Increase CBF, and ICP.
- Pulmonary:
- Attenuation of hypoxic vasoconstriction.
- problematic in patient in supine with single lung ventilation, won’t have the HPV to maintain ventilation to “good” lung
- Attenuation of hypoxic vasoconstriction.
- Blood:
- Increases in intracellular GMP–> inhibit platelet aggregation and bleeding time.
Sodium Nitroprusside dosage? onset, doa?
- 0.3ug/kg/min - 10ug/kg/min IV
- >2.0ug/kg/min increased risk toxicity
- max dose should not be infused for >10 minutes
- Immediate onset
- Short duration of action
- Requires continuous IV administration to maintain therapeutic effect
- Extremely potent: use A-line
SNP is good choice if someone accidently gave too much NE, helps to dilate arteries.
Metabolism of Sodium Nitroprusside?
- Transfer of an electron from the Iron (Fe) of oxyhemoglobin to SNP yields
- metHGb and an unstable SNP radical where all 5 cyanide ions are released.
- One of these cyanide ions reacts with metHGb to form cyano-methemoglobin (nontoxic)
- the remainder are metabolized in the liver and kidney
- converted to thiocyanate
Clinical uses of SNP?
- Clinical uses
- Controlled hypotension:
- 0.3-0.5ug/kg/min not to exceed 2 ug/kg/min
- Hypertensive crises:
- infusion 1-2ug/kg IV can be given as bolus
- Infusion not to exceed 10 mcg/kg/min
- Cardiac disease:
- decreases LV afterload, benefits management of MR or AR, CHF, and heart failure.
- Consider coronary steal
Cyanide toxicity with SNP? Treatment?
- At rates >2ug/kg/min for long periods
- Suspect when the pt starts demonstrating resistance to hypotensive effects or a previous responsive patient who is unresponsive (tachyphylaxis) at rates >2-10 ug/kg/min
- May precipitate tissue anoxia, anaerobic metabolism, and lactic acidosis
- Caution in pregnancy
Treatment:
- Immediate discontinuation of SNP
- 100% 02 administration despite normal oxygen saturation
- Sodium bicarbonate to correct metabolic acidosis
- Sodium thiosulfate 150mg/kg over 15 minutes
- Sodium thiosulfate acts as a sulfur donor to convert cyanide to thiocyanate (less toxic)
- Sodium nitrate 5mg/kg if severe toxicity
- Converts hemoglobin to metHgb which coverts cyanide to cyanometHemoglobin
Other toxicities related to SNP besides cyanide toxicity?
Thiocyanate Toxicity
- Rare as thiocyanate is cleared by the kidney in 3-7 days
- Less toxic than cyanide
- Symptoms include:
- N/V, tinnutis, fatigue, CNS hyperreflexia, confusion, psychosis, miosis seizure and coma
Methemoglobinemia
- Rare
- Should be considered as a differential diagnosis in patients with impaired oxygenation despite adequate cardiac output and arterial oxygenation
Phototoxicity
- SNP should be mixed w/ 5% glucose in water and be protected from exposure to light.
- With continuous exposure to light SNP is converted to aquapentacyanoferrate in the presence of light and the release of hydrogen cyanide
- Wrap the solution and tubing in foil or dark plastic bag.
NTG class, main effect?
- Organic Nitrate
- Acts on venous capacitance vessels and large coronary arteries
- Administered IV, SL, PO, transdermal ointment
MOA NTG? What can form from nitrite metabolite?
Similar to SNP
- Generates NO through a glutathione-dependent pathway which involves glutathione S-transferase
- Requires the presence of thio-containing compound to generate NO
- Generation of NO then stimulates cGMP to cause peripheral vasodilation.
- Elimination ½ time is 1.5 minutes
Methemoglobinemia
- Nitrite metabolite oxidizes ferrous ion in Hgb to ferric form which leads to formation of metHgb.
- Caution with high doses
- MetHemoglobinemia can be treated with methylene blue 1-2mg/kg IV over 5min to reconvert metHgb to Hgb.

CV Effects NTG?
CV:
- Venodilation,
- Decrease venous return,
- Decrease L and R ventricular end diastolic pressure,
- Decrease CO,
- No change or only slight increase in HR
- No change in SVR
- Increase in coronary blood flow to ischemic subendocardial areas (opposite of SNP)
Tolerance
- Tolerance is a limitation of the use of nitrates
- Seen after 24 hours of sustained treatment
CNS, Pulm, coag, GI effects NTG?
CNS:
- Vasodilation
- Increased ICP headache
Pulmonary:
- Decreased PVR,
- Bronchial dilation
- Inhibits Hypoxic pulmonary vasoconstriction
Coagulation:
- Dose related prolonged bleeding time
- Inhibits platelet aggregation
GI:
- Relaxes smooth muscles of GI tract
Clinical Uses NTG?
Angina:
- Venodilation and increased venous capacitance decreases venous return to the heart which reduces RVEDP and LVEDP
- Reduces myocardial oxygen requirements
Cardiac failure:
- Decreases preload,
- Relieves pulmonary edema
- Limits damage of MI
Controlled hypotension:
- Less potent than SNP
- Start: 10-20 mcg/min (3-6 ml/hour)
- Titrate: Increase 5 to 10 mcg/min every 5-10 minutes
- Usual dosage: 50 to 200 mcg/min (maximum 500 mcg/min)
- Not recommended in cranial surgery prior to opening the dura
Sphinchter of Oddi Spasm
- Can occur with Laparoscopic Cholecystectomy or opioid use
- Can bolus 200ug at a time (1cc)
What is isosorbide dinitrate?
- Oral nitrate- used to treat angina pectoris
- Orally-Well absorbed from the GI tract duration of action 6 hours
- Sublingual duration of action is 2 hours
- Works predominantly on venous circulation, improves regional distribution of myocardial blood flow in patients with CAD
- SE include:
- Orthostatic hypotension
-
Active metabolite- isosorbid-5-mononitrate
- more active than parent compound
What is trimethaphan?
- Ganglionic blocker & peripheral vasodilator.
- Rapid onset/must be given IV continuous drip 10-200ug/kg/min IV
- Blocks the ANS and relaxes capacitance vessels
- Lowers BP, CO, and SVR
- Can have increased HR due to parasympathetic nervous system blockade, not because of reflex
- Mydriasis, decreased GI activity, & urinary retention
- interfering with PSNS activation
What are 3 major classes of CCB? Examples?
Dihydropyridines (mainly vascular)
- Nifedipine (Procardia, Adalat)
- Amlodipine (Norvasc)
- Nicardipine (Cardene)
- Felodipine
Phenylalkylamines (mainly cardiac)
- Verapamil
Modified Benzothiazepines (intermed b/w vascular and cardiac)
- Diltiazem

CCB MOA?
- CCB- voltage sensitive L-type Ca channel non-competitive antagonists- decrease Ca stimulated Ca release!
-
Block entry of Ca2+(All classes)- relaxation of smooth muscle
- Cardiac muscle: ↓ inotropic effect, ↓ contractility
- Coronary vascular dilation (good choice in variant angina)
- Systemic arterial dilation (artery>veins)–>decrease afterload–> decrease wall tension and blood pressure
-
Slow Ca2+ channel recovery (Phenylalkylamines) (Slow phase 4 depol at heart)
- SA node: chronotropic effect, HR↓
- AV node: dromotropic effect, decrease conductivity, HR↓
CCB Anesthetic Specific Drug Interactions?
- Myocardial depression & vasodilation with inhalational agents
- Can potentiate neuromuscular blockers
- Verapamil contraindicated w/ Beta blockers
- Verapamil-increases risk of local anesthetic toxicity
- because you’re already blocking Ca, if you also block Na, risk of dysrhythmia also goes up
-
Verapamil and dantrolene can cause hyperkalemia due to slowing of inward movement of K+ ions can result in cardiac collapse
- avoid in pt with hx MH because Dantrolene and verapamil= hyperkalemia
General drug interaction CCB?
- Digoxin: CCBs can increase the plasma concentration of digoxin by decreasing its plasma clearance
- H2 antagonists
- ranitidine and cimetidine alter hepatic enzyme activity and thus could increase plasma levels of CCB
- Toxicity of CCB
- may be reversed with IV administration of calcium or dopamine
What is verapamil? site of action? clinical uses?
- Synthetic Derivative of papaverine
- Its levoisomer is specific for the slow calcium channel
- Primary site of action is the AV node
- Depresses the AV node
- Negative chronotropic effect on SA node
- Negative inotropic effect on myocardial muscle
- Moderate vasodilation on coronary as well as systemic arteries
- Clinical Uses
- SVT
- Vasospastic Angina pectoris
- HTN
- Hypertrophic cardiomyopathy
- Maternal and fetal tachydysrhythmias
- Premature onset of labor
Who should not receive verapamil?
- Should not be given to patients with heart failure severe bradycardia, sinus node dysfunction, or AV node block.
- Verapamil can precipitate ventricular dysrhythmias in a patient with WPW. Less pronounced effects of vascular smooth muscle so less decrease in BP
Pharmacokinetics Verapamil
- 90% protein bound (presence of other agents such as lidocaine, diazepam, propranolol increase its activity)
- Orally almost completely absorbed with extensive hepatic first pass metabolism (PO dose 10X higher than IV)
- Active metabolite - norverapamil.
- Oral Peaks in 30-45 minutes/IV 15 minutes
- E ½ t is 6-12hrs
What is nifedipine? uses? site of action?
- Dihydropyridine derivative (vascular selective)
- Clinical uses
- Angina pectoris
- Hypertension
- Primary site of action is peripheral arterioles
- Coronary and peripheral vasodilator properties > verapamil
- Little to no effect on SA or AV node (esp. with baroreceptor responses)
- Decrease SVR, BP,
- Reflex tachycardia
- Can produce myocardial depression in pts with LV dysfunction or on beta blockers
Nifedipine pharmacokinetics?
- Pharmacokinetics
- IV, oral or sublingual
- Oral –effects in 20 minutes/peaks 60-90 minutes
- 90%Protein Bound/near complete hepatic metabolism/ metabolites excreted in the urine
- E ½ t is 3-7hrs
Diltiazem? uses? site of action? dose?
- Benzothiazepines derivative- intermediate b/w cardiac and vascular
-
Principle site of action is the AV node
- 1st line tx SVT
- HTN
- Intermediate potency between verapamil & nifedipine
- Minimal CV depressant effects
-
Other Clinical Uses
- Similar to verapamil
- Vasospastic Angina pectoris
- Hypertrophic cardiomyopathy
- Maternal and fetal tachydysrhythmias
- PO or IV
- Dose is 0.25-0.35mg/kg over 2 minutes can repeat in 15 minutes
- IV infusion 10mg/h
Diltizem pharmacokinetics?
- Oral onset is 15 minutes and peaks in 30 minutes
- 70-80% protein bound/excreted in the bile and urine (inactive metab)
- E ½ t is 4-6 hours
- Liver disease may require a decrease dose
What are the effects of verapamil, nifedipine, nicardipine, diltiazem on:
BP?
HR?
Myocardial depression?
SA node drepression?
AV Node conduction?
Coronary artery dilation?
Peripheral artery dilation?

MOA of centally acting alpha 2 agonists?
- MOA: Reduce sympathetic outflow from vasomotor centers in the brain stem. Centrally acting selective partial alpha-2 adrenergic agonist
- Site of action: CNS a2 receptor agonist (clonidine)
- Clinical Uses
- Hypertension- second line agents because sedative effects as well
- Induce sedation
- Decrease anesthetic requirements
- Improve peri-operative hemodynamics
- Analgesia
Clonidine? s/e?
Result in:
- BP reduction from decreased CO due to decreased HR and peripheral resistance
- Rebound hypertension with abrupt cessation
Side Effects
- Bradycardia
- Sedation
- Xerostomia (Dry mouth)
- Impaired concentration
- Nightmares
- Depression
- Vertigo
- EPS
- Lactation in men
Pharmacokinetics clonidine? withdrawal syndrome?
Pharmacokinetics
- Available as PO or transdermal patch
- 50/50 hepatic metabolism and renal excretion
Withdrawal Syndrome
- Occurs in pt on doses of >1.2mg/day
- Occurs 18 hours after acute discontinuation of drug
- Lasts for 24-72 hours
- Treatment rectal or transdermal clonidine
Preop continuation HTN therapy?
BB? CCB? ACE?
Beta blockers
- continue
- bb therapy reduces perioperative MI.
- document dose within 24 hours!
CCB
- Continue periop
- benefits outweight risks unless severe LV dysfunction
- if worried about EF, hold
ACE
- NO admin preop
- withholding for 1 dosing interval