HTN Flashcards
1
Q
Clinical practice guidelines for normal BP? What is normal BP?
A
<120/80
- Promote optimal lifestyle habits
- reassess in 1 yr
2
Q
Clinical practice guidelins for elevated BP? What is elevated BP?
A
120-129/ <80
- Non-pharmacologicla therapy
- Reassess in 3-6 mo
3
Q
Clinical practice guidliens for Stage 1 HTN? What classifies as stage 1 HTN?
A
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
4
Q
What classifies as Stage 2 HTN? Clinical Practice Guidelines?
A
>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
5
Q
What physiologically influences BP?
A
6
Q
What are the various sites of action for anti-HTN?
A
- 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
7
Q
RAAS system and role in BP modulation?
A
- 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
8
Q
Role of ACE inhibitors to treat HTN?
A
- 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
9
Q
MOA ACE inhibitors?
A
- 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
10
Q
What is effect on ANG II on BP? What receptor does ANG II bind to?
A
- 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
11
Q
Examples of ace inhibitors?
A
- 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]
12
Q
S/E of ace inhibitors? Drug interaction? contraindications
A
- 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
13
Q
ACE inhibitor pharmacologic effects?
A
- 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)
14
Q
MOA Angiotensin II Receptor Blockers? S/E? Contraindications?
A
- 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
15
Q
Examples ARBS?
A
- Losartan-[Hyzaar, Cozaar]
- Valsartan- [Diovan]
- Irbesartan- [Avalide, Avapro]
- Candesartan- [Atacand]
- Telmisartan- [Micardis]
- Eprosartan- [Teveten]
- Olmesartan- [Benicar]
- Tasosartan- [Verdia]
16
Q
MOA hydralazine? Dose?
A
- 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
17
Q
Pharmacokinetic hydralazine?
A
- Extensive hepatic first pass metabolism
- Onset 15 minutes give slowly
- Elimination ½ time 3 hours
- After IV < 15% appears unchanged in the kidney
18
Q
S/E Hydralazine?
A
- 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
19
Q
Minoxidil MOA and use?
A
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)
20
Q
Pharmacokinetics minoxidil?
A
- 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
21
Q
S/E Minoxidil?
A
- 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
22
Q
Sodium Nitroprusside Use?
A
- 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
23
Q
MOA Sodium Nitroprusside (SNP)
A
- 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
24
Q
EFFECTS of SNP?
A
- 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.
25
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
## Footnote
*SNP is good choice if someone accidently gave too much NE, helps to dilate arteries.*
26
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**
27
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
28
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
29
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.
30
NTG class, main effect?
* Organic Nitrate
* Acts on venous capacitance vessels and large coronary arteries
* Administered IV, SL, PO, transdermal ointment
31
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.
32
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
33
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
34
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)
35
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
36
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*
37
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
38
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↓
39
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*
40
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**
41
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
42
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**
43
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
44
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
45
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
46
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**
47
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
48
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?
49
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
50
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
51
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
* Occur**s 18 hours** after acute discontinuation of drug
* Lasts for 24-72 hours
* Treatment rectal or transdermal clonidine
52
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
