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Pharm-Spring > Anti-hypertensives > Flashcards

Anti-hypertensives Flashcards

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1
Q

Angiotensin Converting Enzyme (ACE) Inhibitors

Use

A
  • 1st line therapy: HTN, CHF (Post-MI to reduce CHF progression), Mitral Regurgitation
  • Delay progression of renal disease → More effective in diabetics
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2
Q

Ang II normal physiology effects

A
  • Ang II is potent vasoconstrictor: arterial smooth muscle constriction
    • Main action mediated via AT-1 G-protein coupled receptor
      • Signaling = ↑ Ca2+ release from SR
  • AT-1 receptor effects
    • Generalized vasoconstriction (esp afferent arterioles of renal glomeruli)
    • ↑ NE release
    • Proximal tubular Na+ reabsorption
    • Secrete aldosterone from adrenal cortex
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3
Q

ACE Inhibitors

MOA

A
  • MOA: Block conversion of ang I to ang II in vascular endothelium
    • Via interaction w/ zinc ion of ACE (peptidyl-dipeptidase)
    • ↓ arterial pressure
    • ↓ cardiac work load
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4
Q

ACE Inhibitors

Side Effects

A
  • Highly potent & minimal side effects → good pt compliance
  • Side Effects:
    • Prolonged hypotension intra-op (do NOT take AM of surgery!)
    • Granulocytopenia
    • Hyperkalemia (esp CRI)
    • Angioedema
    • Persistent cough
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5
Q

ACE Inhibitors

Drug Interactions

A
  • NSAIDs antagonize effects
  • Other anti-hypertensives additive effect
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6
Q

ACE Inhibitors

Contraindications

A
  • Pregnancy
  • Renal artery stenosis pts may develop renal failure d/t impaired afferent arteriole constriction
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7
Q

Angiotensin II Receptor Blockers (ARBs)

MOA

A
  • Angiotensin II (AT1) receptor antagonists
  • MOA: Competitive binding to inhibit action of ang II at its receptor
    • Blocks vasoconstrictive actions of ang II w/out effecting ACE activity = ↓ peripheral vasoconstriction
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8
Q

Angiotensin II Receptor Blockers (ARBs)

Side Effects

A
  • Similar to ACEI’s but no significant bradykinin accumulation = no cough side effect
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9
Q

Angiotensin II Receptor Blockers (ARBs)

Contraindications

A

Pregnancy, Renal artery stenosis

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10
Q

Hydralazine

MOA/Dose

A
  • Vasodilation through activation of guanylate cyclase (interferes w/ action of IP3 mediated Ca++ release from SR) and hyperpolarization
  • Produces direct relaxant effect on vascular smooth muscle & ↓SVR
    • arteries > veins
    • Alter Ca2+ transport in vascular smooth muscles
  • Dose 2.5-10 mg IV
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11
Q

Hydralazine

Clinical Uses

A
  • In combo w/ BB and diuretic
  • Also, used in CHF (combo w/ isosorbide mononitrate)
  • Limits increased SNS activity
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12
Q

Hydralazine

Pk

A
  • Extensive hepatic first pass metabolism
  • After IV < 15% appears unchanged in kidney
  • Onset: 15 min, give slowly
  • Peak: 10-20 min
  • DOA: up to 6 hrs
  • E½t = 3 hrs
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13
Q

Hydralazine

Side Effects

A
  • Angina w/ EKG changes
    • DBP reduced >SBP
  • Reflex ↑HR, SV, CO
  • Tolerance & Tachyphylaxis
  • Na+ & H2O retention
  • Lupus-like syndrome
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14
Q

Minoxidil

MOA

A
  • KATP channel opener → hyperpolarization (↓VG-Ca2+ channel activity) & vasodilation
  • Directly relaxes arteriolar smooth muscle; little effect on venous capacitance
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15
Q

Minoxidil

Clinical Use

A
  • In combo w/ BB (offset reflex tachycardia) & diuretic (offset Na+ & H2O retention)
  • Treat most severe forms of HTN d/t: renovascular dz, renal failure, transplant rejection
  • Topically used to treat baldness (side effect hirsutism)
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16
Q

Minoxidil

Pk

A
  • Orally active
  • Very potent; activity via active sulfate metabolite
  • 90% oral dose absorbed from GI tract
  • 10% of drug recovered unchanged in urine
  • Peak levels = 1 hr
  • E½t = 4 hrs
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17
Q

Minoxidil

Side Effects

A
  • Marked ↑ in HR & CO
  • ↑ plasma concentration of NE and Renin
    • Compensatory retention of Na+ & H2O
      • Weight gain, Edema
      • Pulmonary HTN, Pericardial effusion or tamponade
  • Hypertrichosis
  • Abnormal EKG: Flat or inverted T wave, ↑ voltage of QRS complex
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18
Q

Sodium Nitroprusside (SNP)

MOA

A
  • Direct acting, nonselective peripheral vasodilator
  • Relaxation of arterial & venous vascular smooth muscle
  • Lacks significant effects on non-vascular smooth muscle and cardiac muscle
  • MOA:
    • SNP interacts with oxyhemoglobin
      • dissociates immediately to form
        • Methemoglobin
        • Releasing Nitric Oxide (NO) and cyanide
    • NO activates guanylate cyclase (in the vascular muscle) = ↑ cGMP
      • cGMP inhibits Ca++ entry into vascular smooth muscle & increases uptake of Ca++ into smooth ER → Results in vasodilation via NO
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19
Q

Sodium Nitroprusside (SNP)

Effects

A
  • CV:
    • Direct venous & arterial vasodilation, ↑ venous capacitance d/t ↓VR
    • ↓SBP, SVR, PVR
    • Baroreceptor reflex = ↑HR
    • ↑contractility
    • Intracoronary steal in MI- damanged areas
  • CNS: ↑CBF, ICP
  • Pulmonary: Attenuate hypoxic vasoconstriction
  • Blood: ↑intracellular GMP→ inhibit platelet aggregation = ↑bleed time
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20
Q

Sodium Nitroprusside (SNP)

Metabolism

A
  • Transfer of electron from 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)
  • Remainder metabolized in liver and kidney; converted to thiocyanate
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21
Q

Sodium Nitroprusside (SNP)

Dosage

A
  • 0.3 mcg/kg/min – 10 mcg/kg/min IV
  • > 2.0 mcg/kg/min ↑risk toxicity
  • Do not infuse max dose >10 min
  • Onset: Immediate
  • DOA: Short
  • Need continuous IV admin to maintain therapeutic effect
  • Extremely potent: use A-line
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22
Q

Sodium Nitroprusside (SNP)

Dosing for different clinical uses

A
  • Controlled hypotension: 0.3-0.5 mcg/kg/min not to exceed 2 mcg/kg/min
  • HTN crises:
    • Infusion 1-2 mcg/kg IV can be given as bolus
    • Infusion not to exceed 10 mcg/kg/min
  • Cardiac disease:
    • ↓ LV afterload, useful for MR, AR, heart failure
    • Consider coronary steal
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23
Q

Sodium Nitroprusside (SNP)

Cyanide Toxicity

A
  • Cyanide Toxicity: toxicity occurs due to effects of high plasma concentrations of thiocyanate
    • At rates >2 mcg/kg/min for long periods
    • Suspect when pt starts demonstrating resistance to hypotensive effects or a previous responsive patient who is unresponsive (tachyphylaxis) at rates >2-10 mcg/kg/min
    • May precipitate tissue anoxia, anaerobic metabolism, and lactic acidosis
    • Caution in pregnancy
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24
Q

Treatment of SNP-Related Cyanide Toxicity

A
  • Immediately d/c SNP
  • 100% O2 despite normal O2 sat
  • Sodium bicarbonate to correct metabolic acidosis
  • Sodium thiosulfate 150 mg/kg over 15 min
    • Acts as sulfur donor to convert cyanide to thiocyanate
  • Sodium nitrate 5 mg/kg if severe toxicity
    • Converts hgb → metHgb, which coverts cyanide to cyanometHgb
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25
SNP: Other Toxicity
* Thiocyanate Toxicityz; Rare → thiocyanate cleared by kidney in 3-7 days * Less toxic than cyanide * Symptoms: N/V, tinnutis, fatigue, CNS hyperreflexia, confusion, psychosis, miosis, seizure, coma * Methemoglobinemia: Rare * Consider as differential diagnosis in pts w/ impaired oxygenation despite adequate CO and arterial oxygenation * Phototoxicity * SNP should be mixed w/ 5% glucose in water and protected from exposure to light. * SNP is converted to aquapentacyanoferrate in presence of light and release of hydrogen cyanide occurs * Wrap solution/tubing in foil or dark plastic bag
26
Nitroglycerin (NTG) MOA
* Organic Nitrate * Acts on venous capacitance vessels and large coronary arteries * Administered IV, SL, PO, transdermal ointment * MOA: * Similar to SNP * Generates NO through a glutathione-dependent pathway which involves glutathione S-transferase * Requires presence of thio-containing compound to generate NO * Generation of NO then stimulates cGMP to cause peripheral vasodilation. * E½t = 1.5 min * Methemoglobinemia * Nitrite metabolite oxidizes ferrous ion in Hgb to ferric form which leads to formation of methgb. * Caution w/ high doses * Treat w/ methylene blue 1-2 mg/kg IV over 5 min to reconvert methgb to hgb
27
Nitroglycerin (NTG) Systemic Effects
* Tolerance → limitation of use of nitrates; seen after 24 hrs of sustained treatment * CNS: Vasodilation = ↑ ICP headache * CV: * Venodilation = ↓ VR, ↓ L&R VEDP, ↓ CO * No change or only slight ↑ HR * No change SVR * ↑ coronary blood flow to ischemic subendocardial areas (opposite of SNP) * Pulmonary: * ↓ PVR and Bronchial dilation → inhibits hypoxic pulmonary vasoconstriction * Coagulation: Inhibits platelet aggregation → Dose-related prolonged bleeding time * GI: Relaxes smooth muscles of GI tract
28
Nitroglycerin (NTG) Clinical Uses
1. Angina 2. Cardiac Failure 3. Controlled hypotension (less than SNP)
29
Nitroglycerin (NTG) Clinical Uses Angina & Cardiac Failure
* Angina: * Venodilation and ↑ venous capacitance ↓VR to heart which ↓RVEDP & LVEDP * ↓ myocardial O2 requirements * Cardiac failure: * ↓ preload * Relieve pulm edema * Limits damage of MI
30
Nitroglycerin (NTG) Clinical Uses Controlled hypotension
* Less potent than SNP * **Start: 10-20 mcg/min** (3-6 mL/hr) * Titrate: ↑5-10 mcg/min every 5-10 min * Usual dosage: 50-200 mcg/min (max 500 mcg/min) * Not recommended in cranial surgery prior to opening dura * Sphincter of Oddi Spasm treatment: Can bolus 200 mcg at a time (1cc) * Spasm can occur during laparoscopic cholecystectomy or w/ opioid use
31
Isosorbide Dinitrate
* Oral nitrate: used to treat angina pectoris and in combo w/ hydralazine to treat CHF * PO: well absorbed from GI tract, DOA = 6 hrs * Sublingual DOA = 2 hrs * Works predominantly on venous circulation, improves regional distribution of myocardial blood flow in CAD pts * SE include: orthostatic hypotension * **Active metabolite- isosorbid-5-mononitrate** more active than parent compound
32
Trimethaphan
* Ganglionic blocker & peripheral vasodilator. * Rapid onset/must be given IV continuous drip 10-200 mcg/kg/min IV * Blocks ANS signals (both SNS & PSNS) between pre-ganglionic and post-ganglionic neurons; relaxes capacitance vessels * ↓ BP, CO, SVR * Can have ↑ HR d/t PSNS blockade, not because of reflex * Mydriasis, ↓ GI activity, urinary retention
33
The 3 Major Classes of Ca2+ Channel Blockers
1. **Dihydropyridines** * Nifedipine (Procardia, Adalat) * Amlodipine (Norvasc) * Nicardipine (Cardene) * Felodipine 2. **Phenylalkylamines** * Verapamil 3. **Modified Benzothiazepines** * Diltiazem
34
The 3 Major Classes of Ca2+ Channel Blockers Their actions
The 3 major chemical classes bind the alpha-1 subunit of L-type VGCaC at distinct/different sites and work allosterically to inhibit Ca entry into myocardial & vascular smooth muscle cells
35
Ca2+ Channel Blockers: Voltage Sensitive L-type Ca2+ Channel Non-competitive Antagonists MOA
* **Block entry of Ca2+(All classes)** * Cardiac muscle: ↓inotropic effect, ↓contractility * Coronary vascular dilation (good choice in variant angina) * Systemic arterial dilation (artery \> veins) → ↓afterload → ↓ wall tension and BP * **Slow Ca2+ channel recovery (Phenylalkylamines)** * SA node: chronotropic effect, HR↓ * AV node: dromotropic effect, decrease conductivity, HR↓
36
Ca Channel Blockers Anesthetic Specific Drug Interactions
* Myocardial depression & vasodilation with **VA’s** * Potentiate **NMB’s** * **Verapamil contraindicated w/ Beta blockers** * Verapamil ↑ risk **LA toxicity** * Verapamil & **Dantrolene** can cause hyperkalemia d/t slowing of inward movement of K+ ions → can result in cardiac collapse
37
Ca Channel Blockers Drug interactions General
* **Digoxin**: CCBs can ↑ plasma concentration of digoxin by decreasing its plasma clearance * **H2 antagonists**: Ranitidine and Cimetidine alter hepatic enzyme activity and could ↑ plasma levels of CCB
38
Can CCB's toxicity be reversed?
Yes. May be reversed with IV admin of Ca++ or dopamine.
39
Nifedipine MOA
* Dihydropyridine derivative * **Primary site of action is peripheral arterioles** * Coronary and peripheral vasodilator properties \> verapamil * Little to no effect on SA or AV node (esp. w/ baroreceptor responses) * ↓SVR, BP * Reflex tachycardia * Can produce myocardial depression in pts w/ LV dysfunction or on BB’s
40
Nifedipine Pk
* 90% PB/near complete hepatic metabolism/ metabolites excreted in urine * IV, oral or sublingual * PO onset = 20 min * PO peak = 60-90 min * E½t = 3-7 hrs
41
Nifedipine Clinical Uses
* Angina pectoris * HTN
42
Verapamil MOA
* Synthetic papaverine derivative * Its levoisomer is specific for slow Ca++ channel * **Primary site of action is AV node** * Depresses AV node * Negative chronotropic effect on SA node * Negative inotropic effect on myocardial muscle * Moderate vasodilation on coronary & systemic arteries
43
Verapamil Pk
* 90% PB (presence of other agents such as lidocaine, diazepam, propranolol ↑ its activity) * PO almost completely absorbed w/ extensive hepatic first pass metabolism (PO dose 10X higher than IV) * Active metabolite: Norverapamil * PO peak = 30-45 min * IV peak = 15 min * E½t = 6-12 hrs
44
Verapamil Clinical Uses
* Vasospastic Angina pectoris * Hypertrophic cardiomyopathy * Maternal & fetal tachydysrhythmias * Premature onset of labor * SVT * HTN
45
Diltiazem MOA
* Benzothiazepines derivative * **Primary site of action is AV node** * 1st line tx SVT * HTN * Intermediate potency b/t verapamil & nifedipine * Minimal CV depressant effects
46
Diltiazem Pk/Dose
* 70-80% PB/excreted in bile and urine (inactive metab) * PO or IV * PO onset = 15 min * PO peak = 30 min * E½t = 4-6 hrs * Liver disease may need ↓ dose * Dose: 0.25-0.35 mg/kg over 2 min, can repeat in 15 min * IV infusion 10 mg/h
47
Diltiazem Other Clinical Uses
* Similar to verapamil: * Vasospastic Angina pectoris * Hypertrophic cardiomyopathy * Maternal & fetal tachydysrhythmias
48
Nifedipine Selectivity
Vascular
49
Verapamil Selectivity
Cardiac
50
Diltiazem Selectivity
Vascular, Cardiac
51
Nifedipine Adverse Effects
* Reflexive tachycardia * Headache * Dizziness, Palpitations * Flushing, Hypotension * Leg edema
52
Nifedipine Contraindications/Cautions
* Hypotension * Severe aortic valve stenosis
53
Nifedipine Drug Interactions
BB's OK
54
Verapamil Adverse Effects
* Hypotension * Facial flushing * Constipation * Nausea * Headache * Dizziness * Gingival hyperplasia
55
Verapamil Contraindications/Cautions
* Sick sinus syndrome * AV block * LV dysfunction * Digitalis/Quinidine toxicity
56
Verapamil Drug Interactions
* Beta-blockers * Cimetidine * Carbamazepine * Cyclosporine * Digoxin
57
Diltiazem Adverse Effects
"Relatively infrequent"
58
Diltiazem Contraindications/Cautions
* Sick sinus syndrome * AV block * LV dysfunction
59
Diltiazem Drug Interactions
* Beta-blockers * Ecainide * Cimetidine * Cyclosporine * Carbamazepine Lithium carbonate * Disopryramide * Digoxin
60
Centrally Acting Agents MOA/Site of Action
* MOA: ↓ sympathetic outflow from vasomotor centers in brain stem. Centrally acting selective partial alpha-2 adrenergic agonist * Site of action: CNS a2 receptor agonist (clonidine)
61
Centrally Acting Agents Clinical Uses
* HTN * Induce sedation * ↓ anesthetic requirements * Improve peri-op hemodynamics * Analgesia
62
Clonidine Action/Pk
* Result in: * ↓ BP from ↓CO due to ↓HR and peripheral resistance * Rebound HTN w/ abrupt cessation * Pk * Available as PO or transdermal patch * 50/50 hepatic metabolism and renal excretion
63
Clonidine Side Effects
* Bradycardia * Lactation in men * Impaired concentration * Nightmares * Depression * Sedation * EPS * Xerostomia (Dry mouth) * Vertigo
64
Clonidine Withdrawal Syndrome
* Occurs in pt taking \>1.2 mg/day * Occurs 18 hrs after acute d/c of drug * Lasts for 24-72 hrs * Treatment: rectal or transdermal clonidine
65
Pre-op Continuation of Therapy Beta Blockers
Yes, ↓ peri-op MI
66
Pre-op Continuation of Therapy CC Blockers
Yes, benefits outweigh risks unless severe LV dysfunction
67
Pre-op Continuation of Therapy: ACEI's
No, withold for 1 dosing interval

Pharm-Spring (7 decks)

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