Pharm Exam 1: Section 2

Question 1

Renin Angiotensin System
Maintains homeostasis in euvolemic state
Stimulated in low volume or low O2 state –> Sympathetic NS

Answer 1

Kidneys hold onto sodium and create thirst which increases volume and smooth muscle contraction
Increases BP and increases tissue perfusion in arterioles
If local tissue injury, A2 arrives and promotes vascular inflammation
Remodeling of cardiac and vascular tissues in myocardium occurs
Increased fibrous products in tissues –> hypertrophy
Hypertrophy –> CHF

Question 2

ACEI
Benzapril 
Captopril 
Enalapril 
Lisinopril

ARBS
Losartan
Valsartan

Answer 2

ACEI block Ace enzyme to prevent conversion of A1 to A2

ARBS don’t work on A2, work to block receptors for A2 at tissue level

Bradykinin: at high levels in lung –> cough
Prostaglandins: ACEI -> angioedema

Question 3

ACEI and black people

Answer 3

Black people make less renin than other groups

ACEI less effective

Question 4

ACEI & ARBS

How they work

Answer 4

Decrease production of A2 and aldosterone
Prevent vascular smooth muscle contraction -> decrease afterload (arteries)
Decrease Na and H2O retention in kidney -> decrease preload (veins) - less volume in system
Reduce vascular inflammation & remodeling bc A2 and its mechanisms are blocked
Aldosterone tells kidney to hold onto Na and K -> H2O follows salt - > increased volume. ACEI and ARBS block this mechanism

Question 5

ACEI & ARBS

Pharmacokinetics

Answer 5

Well absorbed PO; better on empty stomach. Ok with food
Most are prodrugs (not active in own form but when they get to liver, they break down into metabolites that are active form)
* Must be used in people with intact hepatic system
* lisinopril & captopril not prodrugs

Used alone and in combo with diuretics -> tends to improve efficacy

Question 6

ACEI & ARBS

Pharmacokinetics

Answer 6

Renal protection: decrease arterial resistance in glomeruli; when blood comes through kidney

Mild Insulin sensitization: ACEI & ARBS help cells recognize and use insulin- good for DM

Most excreted renal: used in pts w/ early renal failure and microalbuminuria in DM. If pt has more advanced renal failure, start at low dose, check electrolytes in 1 week to ensure no high K

Distributed to all tissues except CNS
Cross placenta, are in breast milk.

Question 7

ACEI & ARBS

Adverse reactions

Answer 7

No reflex tachycardia bc no impact on CO

Hypotension

High K if dose too high

Cough: dry; don’t give another ACEI, can try ARB
-Cross -sensitivity so can happen with ARBS

Angioedema: typically when combined with other drugs like macrolides (zpack)

• Occurs in face, mainly lips and mouth, sometimes forehead
• If occurs, stop macrolide, stop ACEI for a couple of days
• If just on ACEI, stop and start a different BP med; give antihistamine bc its a localized reaction

Question 8

ACE & ARBS

Contraindication

Answer 8

ARBS excreted fecally more than renal
Cause with other BP meds
C/I in pregnancy; Category C

• avoid K+ sparing diuretics bc ACEI causes changes with Na and K
• If K is high in ACEI, double check, if still high -> reduce dose a little bit

Question 9

ACE & ARBS

indications

Answer 9

HTN (esp w/ DM): 1st line agent
1st line for DM bc of renal protection

CHF: A2 and inflammation, remodeling -> cardiac changes; preload reducer, afterload reducer

Microalbuminuria: >19 is pathological; reason pts with DM but not HTN might be put on low dose ACEI or ARBS –> decrease arterial deconstruction in kidneys; helps improve perfusion bc less pressure in kidneys

Post MI, ACS, LVEF <40%

Question 10

ACEI & ARBS

Monitoring

Answer 10

Potassium: make sure not elevated in first week and check again in 1 month

Angioedema esp w. macrolides
Don’t prescribe macrolide w/ ACEI if pt has infections

Check liver function

Check renal function

Question 11

CCB

Answer 11

Most potent class of BP reduction

Nondihydropyridines: Type 1 receptors
- verapamil and diltiazem

Dihydropyridines: Type 2 receptors
- pines

Question 12

CCB

Mechanism of action

Answer 12

Inhibit Ca+ movement at smooth muscle cell membrane

• Arterial vasodilation
• Decreased contractility
• Decreased afterload
• No impact on preload (no venous impact)

Nondihydropines: slow AV node conduction; verapamil can be given sublingual; monitor BP closely; slow HR

Dihydropines: vasodilator; little/no effect on HR; may cause reflex tachycardia if BP drops too low

Question 13

CCB

Pharmacokinetics

Answer 13

All absorb well PO, OK with food

Nondihydropines
- rapid metabolism and bioavailability quickly (verapamil)

Dihydropines: varying ,metabolism and absorption
- Amlodipine 65-90%: well absorbed; high metabolism (works quickly), long half-life
Isradipine 15%: poor absorption and bioavailability

Question 14

CCB

Pharmacokinetics

Answer 14

Rarely cross blood brain barrier; don’t have sedative properties
All cross placenta
Excreted in breast milk, except Nifedipine
Hepatic metabolism: broken down in liver
Fecal and renal excretion
Short 1/2 life if not sustained release formulation; need to be taken multiple times daily
Norvasc (amlodipine): long half life; good agent to use for daily dosing

Question 15

CCB

Adverse reactions

Answer 15

Nondihydropine: chronotropic effect - low HR and arrhythmia related to low HR or alteration in conduction or velocity

Peripheral edema: vasodilation lets blood pool -> vascular permeability; elderly more prone

Constipation: gut is primarily smooth muscle; effects musculature and contraction of gut; peristalsis slows; elderly more prone

Worsen GERD - interferes with muscle contraction of lower esophageal sphincter -> increased reflux

Flushing, HA, low BP, edema, reflex tachycardia

Question 16

CCB

Answer 16

Sustained release formulas are most effective; most predictive metabolism and lowest rate of side effects; most predictive bioavailability; long acting prevents BP fluctuations

Amlodipine: not sustained release; long acting and stable when crushed (good for pt w/ dysphasia); not excreted quickly; can be given once daily

C/I in pt w/ HF!!! Not used immediately post ACS. Can worsen wolf Parkinson white syndrome (conduction disturbance)

Category C
Amlodipine Category D

Check hepatic function before therapy: metabolized almost entirely in liver

Question 17

CCB

Indications

Answer 17

Tachycardia dysrhythmias
-rate control for SVT, afib, (verapamil & diltiazem)

HTN

migraine prophylaxis (30% improvement)

Vasospastic angina (stable) bc of vasodilation effects

Raynauds: peripheral arterial spasms in cold weather; vasodilation

Esophageal spasm: lower esophageal sphincter relaxes w/ vasodilation of smooth muscle

Question 18

Diuretics
Thiazides
Loop diuretics
K+ sparing

Answer 18

Decrease volume
decreased preload
decreased pressure arterial bed

Question 19

Diuretics

Thiazides

Answer 19

Inhibit Na, K, Cl, and bicarb reabsorption in distal tubule of nephron. H2O follows electrolytes out of body.

Effect is increased Ca and uric acid

Electrolyte imbalance: low K
Increased glucose bc of dehydration

Muscle cramps: due to increased Ca, paresthesias, impotence.

Avoid in gout to prevent uric acid buildup

Question 20

Diuretics

Thiazides

Answer 20

Chlorthalidone (Hygroton): very long 1/2 life (~50 hrs), very effective

Hydrochlorothiazide (Microzide, Hyrodiuril)

Indapaminde (Lozol)

Metolazone (Zaroxolyn): not as effective in pt with renal impairment; with gfr < 25 or low creatinine clearance NOT effective

Question 21

Diuretics

Loop

Answer 21

Work in loop of Henle in kidney; action happens sooner in kidneys than later in tubules where thiazides work. Have more substantial diuretic effect; helpful for pt with kidney function impairment and low gfr

Furosemide (lasix)
Bumetanide (Bumex)

More substantial diuresis
0.5 - 1 hr 1/2 life

More K loss; will need to replace K more often than with thiazide

Indicated for edema with CHF

Question 22

Diuretics

K sparing

Answer 22

Alter Na reabsorption in distal tubules in nephron further than where K is reabsorbed; reason K sparing diuretics let go of Na and not K

Triamterene
Spironolactone

Improve edema in CHF
Na depletion: watch for low Na
Avoid in ACE or ARB bc they hold onto K –> hyperkalemia

Question 23

Diuretics

Answer 23

Preload reducers

Long term: reduce volume -> decreased SVR and afterload

Question 24

Diuretics

Pharmacokinetics

Answer 24

Triamterene not absorbed as well as others. All effect electrolytes

Enter blood AND extracellular spaces

Liver metabolizes diuretics; Furosemide is both hepatic and non hepatic

All excreted in urine, some feces

Question 25

Diuretics | Adverse reactions

Answer 25

Electrolyte imbalances Glucose intolerance Hyperuricemia: concern for gout pt Dehydration and hypotension -> falls Drug interactions

Question 26

Diuretics | C/i

Answer 26

No K sparing diuretics in pt with renal impairment -> high K; Creatinine clearance < 25 - 30 avoid Patients w/ gout: high uric acid -> flairup High risk for falls: urge to go to bathroom is high Dehydration

Question 27

Diuretics | Indications

Answer 27

HTN: 1st line Prevent CV complications: decrease volume and likelihood of developing CHF Selection based EGFR > mid 40s ml/min: Thiazides (good egfr) < mid 40s ml/min: Loops (moderately low egfr) If profoundly low send to nephrology

Question 28

Diuretics | Indications

Answer 28

Edematous conditions CHF: in addition to ACE (except K sparing) Hepatic cirrhosis: abd ascites and lower extremity edema due to hepatic congestion Renal impairment: Loop are most effective Premenstrual edema: Gyn prescribes Take 3-5 days before menses; stop once menses begins

Question 29

Beta adrenergic blocker "olol"

Answer 29

Beta 1: CV; SA node, atria, ventricles - increase HR or increase rate of contraction Beta 2: Pulmonary; mediate smooth muscle contraction and constriction Nonselective beta blockers: influence cells in lungs and in heart -> bronchiole smooth muscle contraction will exacerbate asthma symptoms Nebivolol: most selective can affect poor metabolizers and not affect BP --> build up in system (not used often) Atenolol: second most selective Metoprolol: third most selective All 3 have long half lives

Question 30

Beta blockers | Mechanism of action

Answer 30

Prevent catecholamines (epi, norepinephrine) and beta agonists (albuterol) from binding to sites of activity Receptor site located on CV, renal, opthalmologic, and respiratory systems Some effect in pancreas and metabolism of fat -> elevated triglycerides and cholesterol and lower HDL DM pts might have elevated hA1C bc of effect on pancreas SA node to reduce HR to slow automaticity of heart AV junction to reduce conduction velocity so impulse is not conducted quickly through junction Atria and ventricles to reduce contractile force (negative isotropism) to decrease workload and O2 demand of heart

Question 31

Beta blockers | Pharmacokinetics

Answer 31

Well absorbed PO, first pass metabolism Widely distributed into tissues, placenta, and breast milk CNS penetration with Timolol, Metoprolol, and Propranolol -> sedation Nebivolol is very lipophilic, some CNS penetration -> some sedation Hepatic metabolism Excreted in bile, feces, urine Nadolol, atenolol, and nebivolol require dose adjustments in diminished renal function; excreted in urine

Question 32

Beta blockers | Adverse reactions

Answer 32

Bronchospasm: shouldn't prescribe in pulmonary diseases Most are pregnancy category C or D Sotalol, Acebutolol, Pindolol are Category B Metoprolol has very low excretion in breast milk; safer for breastfeeding mom Rebound symptoms with discontinuation; taper slowly Impotence: no erection, inability to maintain erection; beta blocker not first choice in men unless not sexually active (CHF)

Question 33

Beta Blockers | Indications

Answer 33

Long term angina management Rate control in dysrhythmias Heart failure & HTN: reduce workload of heart and decrease O2 demand Post ACS: reduce workload of heart and decrease O2 demand Migraine prophylaxis, hyperthyroidism: tx of racing heart while leveling out thyroid levels

Question 34

Beta Blockers | C/i

Answer 34

Pulmonary disease AV block or sick sinus syndrome: slowed condition and prolonged PR intervals Avoid in pt w/ DM or pre DM: will negatively impact glucose control Children: atenolol and propranolol have approved dosing schedules Induce cytochrome P2D6 which is used to metabolize Prozac and Paxil; pick a different SSRI if pt needs to be on beta blocker

Question 35

Alpha Receptors Sympathetic NS: fight or flight Parasympathetic: Rest and relax

Answer 35

Alpha Receptors stimulated by norepinephrine (SNS) from brain Alpha 1 receptors: - vascular walls, heart, eye, salivary glands, sphincters, Kidney, ureter, bladder, male sex organs - increased HR, increased urgency to void Alpha 2 receptors: - arterioles of the skin and mucosa (dry mouth), pancreas - fat cells (inhibit lypolysis)

Question 36

Alpha Agonists Mechanism of action Alpha 1

Answer 36

Alpha 1 agonists: epi and norepi signal heart, smooth muscle and CNS Primary receptor on vascular smooth muscle: potent vasoconstrictor, increase HR Naturally occurring catecholamines: epi, norepi, and dopamine Nasal spray: oxymetazalone: typical decongestant -> spray in nare; phenylephrine PO ephedrine: decreases nasal decongestion and treats bronchospasm in asthma; banned in 2003 due to risk of insomnia, stroke, HTN, urine retention Pseudoephedrine: vasoconstriction in nasal passages and elsewhere in body; decreases nasal congestion but not used with HTN or arrhythmias * must present ID to pharmacist to purchase due to use in making meth

Question 37

Alpha Agonists Mechanism of action Alpha 2

Answer 37

Stimulate alpha 2 receptors in brain that activate inhibitory neurons to prevent release of norepi Prevent/reduce central sympathetic tone Inhibit cardiac acceleration and vasoconstriction centers in brain Decrease peripheral outflow of norepi -> vasodilation Decreased PVR, RVR, HR, BP Compensatory effects: Na and H2O retention to increase volume -> edema in brain

Question 38

Alpha 2 agonists

Answer 38

Clonidine (Catapres): PO or weekly patch; SL in hypertensive crisis; epidural by anesthesia Guanabenz (Wytensin): not typically used Methyldopa (Aldomet): can change central concentration in brain; affect tissue concentration in serotonin, dopamine, epi, norepi * prescribed for mood changes * preferred BP med for pregnant women; Category B

Question 39

Alpha 2 Agonists | Pharmacokinetics

Answer 39

Methyldopa is most poorly absorbed Methyldopa and clonidine enter brain All are renally excreted Methyldopa: Category B for pregnancy Methyldopa and metabolites accumulate in renal failure and prolonged hypotension

Question 40

Alpha 1 Agonist | Adverse reactions

Answer 40

``` Tachycardia Increased cardiac workload Increased O2 demand Dysrhythmias Headache Sedation ```

Question 41

Alpha 2 Agonist | Adverse reactions

Answer 41

Xerostomia (dry mouth) Hypotension Sedation

Question 42

Alpha 1 agonist | Indications

Answer 42

``` Sepsis Anaphylaxis Post CABG hypotension Anesthesia induced hypotension Nasal decongestion ```

Question 43

Alpha 2 agonist | Indications

Answer 43

Moderate of resistance HTN Clonidine: ETOH, opioid, heroine, tobacco withdrawal Epidural Hot flashes, decreases norepi rush to periphery causing vasodilation and decreasing increased HR with hot flashes

Question 44

Alpha Agonists | C/i

Answer 44

``` Dry eye syndrome Antipsych meds TCAs, MAOIs, interact bc central acting Beta blockers can cause malignant HTN ETOH, benzos, antihistamines: poor choice bc central acting; Ok for withdrawal but NOT ok for people actively drinking alcohol ``` ``` Caution: Renal impairment Recent MI Severe CAD Bc HTN and vasoconstriction can be life threatening if given ```

Question 45

Alpha Agonist | indications

Answer 45

``` Low dose: renal low flow states (dopamine) High dose dopamine: sepsis Nasal decongestion Hypotension ETOH and drug withdrawal Menopause ```

Question 46

Alpha blockers | Mechanism of Action

Answer 46

Indirect action: centrally acting in brain * reduce sympathetic secretion of norepi Direct action: peripheral action - block Alpha 1 receptors in blood vessels and relaxing them to decrease SVR - prostate and neck of bladder

Question 47

Alpha blockers | Non selective

Answer 47

Regitine (Phentolomine) Dibenzyline (Phenoxybenzamine) Reflex cardiac stimulation: cause reflex tachycardia Rarely used except for Pheochromocytoma: tumor in adrenal gland -> dump huge amounts of epi

Question 48

Alpha blockers Selective "osin" ``` Doxazosin (cardura)* Prazosin (minipress)* Terazosin (Hytrin)* Tamulosin (flomax) Alfuzosin (urizatral) Silodosin (rapaflo)* ```

Answer 48

Block effects of catecholamines in smooth muscle receptors: cause vasodilation * treat HTN and BPH Tamulosin and Alfuzosin: very selective for subtypes in neck of bladder and prostate; increase outflow without increasing contraction. Cause smooth muscle at neck of bladder and around prostate area to relax so men with BPH can pee easier

Question 49

Alpha blockers | Pharmacokinetics

Answer 49

Impact both venous and arterial receptors: impact both preload and afterload Reflex tachycardia with some pts Improved lipid profiles and insulin sensitivity Diastolic BP most profoundly effected: orthostatic hypotension common (1st dose): educated to take right before going to bed Well absorbed PO Metabolized in liver Whole drug is inactive and when broken down, metabolites are active. Long lasting effects bc heavily bound to protein Doxazosin has first pass metabolism in liver Prazosin and terazosin have 3-4 active metabolites Heavily protein bound, liver metabolism

Question 50

Alpha blockers | Adverse reactions

Answer 50

All accentuated with ETOH, nitrates or antihypertensive meds Hypotension Syncope Reflex tachycardia Fluid retention in periphery: effect on arterial and venous beds Nasal congestion and dry mouth

Question 51

Alpha blockers | C/i

Answer 51

CHF: venous dilation, decreased preload, not as much volume back to heart Peripheral edema: venous dilation Pregnant or lactating Impaired renal function: doses accumulate -> persistent hypotension over long period of time

Question 52

Alpha blockers | Indications

Answer 52

HTN (not first line drug) BPH Ureteral stones in ureter (off label use) Doxazosin, terazosin, tamrulosin

Question 53

Alpha blockers | Monitoring

Answer 53

Weight: first indication of fluid status change -> weight gain WBC and LFTs at initiation: liver metabolism If BPH: PSA and digital rectal exam (DRE): evaluate size of prostate with DRE to determine effectiveness of alpha blocker on prostate May take weeks for full effect (6-8 weeks)

Question 54

Heart failure

Answer 54

ACE or ARB: reduce afterload, prevent remodeling of cardiac musculature Beta blocker: reduce mortality in pt with CHF bc decrease O2 demand and workload of heart Diuretic: reduce preload to decrease workload of heart; don't want to decrease too low bc don't have venous return Nitrates: for more advanced heart failure; relax cardiac blood vessels, impact O2 supply and demand

Question 55

HTN Treatment goals > 60: < 150/90 < 60: < 140/90

Answer 55

1: >60 yo 150/90 - no need to adjust meds if no s/s 2: <60 yo DBP > 90 - initiate treatment 3: <60 yo SBP > 140 - initiate treatment 4: > 18 yo w/ CKD BP >140/90 - initiate treatment 5: > 18 yo w/ DM BP >140/90 - initiate tx 6: nonblack w/ and w/out DM: tx includes thiazide, CCB, ACEI, or ARB 7: black w/ and w/out DM: tx includes thiazide or CCB 8: > 18 yo w/ CKD: tx includes ACEI or ARB to improve kidney outcomes (regardless of race) 9: If goal BP not met in 1 month, increase dose or add 2nd drug from recommended class. Add up to 3 drugs. Refer to specialist if still not controlled after 3. First is ALWAYS lifestyle choices

Question 56

HTN

Answer 56

First line therapy Black: thiazide and/or CCB Nonblack: thiazide, ACE or ARB, CCB (alone or in combo)

Question 57

ACC & AHA

Answer 57

Recommend BP <130/90

Question 58

HTN | Selecting tx plan

Answer 58

Maximize first drug: start low hydrochlorothiazide, increase from 12.5mg to 25mg until effects work Add 2nd drug before maximizing 1st drug: start lisinopril If not controlled, add diuretic Start 2 drugs in different classes - usually if very uncontrolled ``` If still not controlled with diuretic, ACEI, ARB, CCB add Beta blocker or Aldosterone antagonist or Alpha blocker if also have BPH or Refer to HTN specialist ``` Pt w/ DM should receive ACE or ARB Pt w/ renal failure should receive ACE or ARB

Question 59

Cardiac Glycosides Bufalin, Oufalin Digoxin (derived from fox glove plant)

Answer 59

Increase contractile force of heart Inhibit Na pump of heart via ATPase - permit buildup of Na and Ca intracellulary - cardiac muscle shortens - increased force -> better CO

Question 60

Na - K pump

Answer 60

ATP is broken down to ADP --> energy released causing Na-K pump to push Na out of cell and K into cell Digoxin binds to ATPase (enzyme breaks ATP-ADP) -> Na builds up in cell. Na leaks out of Ca channel pump -> buildup of K due to buildup of Na. Buildup of Ca and K -> intracellularly -> increased contractile force -> better CO

Question 61

Digoxin and K

Answer 61

ATPase has higher affinity to K than digoxin -> ATPase will bind to K more readily than digoxin If pt has change that might be related to digoxin, ALWAYS check digoxin levels High K -> ATPase binds to K -> digoxin less effective Low K -> digoxin binds to ATPase bc not enough K -> digoxin toxicity Always check K before giving digoxin dose or if pt has change that could be related to digoxin

Question 62

Cardiac glycosides | Mechanism of action

Answer 62

Impact electrical forces of cardiac tissue Decreased automaticity (enhanced vagus nerve stimulation -> decreased automaticity in SA node) Decrease conduction velocity - AV node conduction slows - cardiac muscle cells: decrease ectopic foci in heart that require decreased automaticity - more effective in atrial muscle cells, SA node, and AV node. less effective in ventricular cells perkinje fibers

Question 63

Cardiac glycosides

Answer 63

Decreased renin activity (vasodilation) Effect all smooth excitable muscle and tissue and CNS Chemoreceptor trigger zone (center of brain that cause vestibular disturbances) -> n/v, diarrhea, visual disturbances

Question 64

Cardiac glycosides | Pharmacokinetics

Answer 64

Slower absorption with food/meals Bioavailability varies with brand; can cause therapeutic changes. Ask pt if going to a different pharmacy or if pill looks different Absorbed into all tissues, but highest in heart, kidney and liver Excreted unchanged in urine 36 - 48 hr half life (long half life - toxicity can last for 5-10 days) Steady state after 4-7 days of dosing

Question 65

Cardiac glycosides | Interactions

Answer 65

Nondihydropines: interact bc they adjust HR and effect conduction system of heart. Add onto effects of Digoxin verapamil and diltiazem Antiarrhythmics: work on conduction of heart, potentiate digoxin s/s Quinidine and amiodarone

Question 66

Cardiac glycosides Adverse reactions Therapeutic level: 0.9-1.2ng/ml

Answer 66

Noncardiac s/s occur first bc of penetration into CNS in chemo receptor trigger zone Anorexia, n/v/d Fatigue, malaise, HA, visual changes (yellow tint, green halos) Bradycardia, AV block (assess pt, listen to heart, know rate, rhythm, periodically check EKG to ensure not creating heart block) with medication Toxic level (>2): with diuretics, hypokalemia,

Question 67

Cardiac glycosides | C/i

Answer 67

AV block bc atrial conduction isn't getting through to ventricles Bradycardia Hypertrophic sub aortic stenosis: digoxin increases force of contraction -> worsened hypertrophy Renal failure (low dose ok for impairment) Electrolyte imbalance: high K reduces effect; low K causes toxicity WPW syndrome: increases afib likelihood bc digoxin blocks normal pathway of atria

Question 68

Cardiac glycosides | Indications

Answer 68

Rapid afib SVT HF w/ severe dysfunction (EF <40); not 1st line HF med

Question 69

Nitrates ``` IV sublingual inhaled Transdermal: paste; patch ER tabs ```

Answer 69

Nitric oxide relaxes all blood vessels - arterial and venous - afterload and preload reducers - venous and arterial pooling Decrease myocardial O2 demand Decrease myocardial O2 supply Less impact on atherosclerotic vessels (need higher doses) PO formulation: less potent vasodilation; sustained longer action bc metabolized in liver; metabolites break down and active

Question 70

Nitrates | PO

Answer 70

Pt who require higher or consistent dosing Ex: pt using sublingual nitroglycerin in outpt setting frequently or pt needs lots of refills) Hepatic metabolism: decreases vasodilation potency Iserbidedinitrate and iserbidemonitrate

Question 71

Nitrates | C/i

Answer 71

Increased ICP: Vasodilation of blood vessels in brain; worsens increased ICP Dehydration/volume depletion: preload already low, nitroglycerin worsens preload; if pt has CHF -> worsened Anemia Use of drugs for erectile dysfunction: potentiate vasodilation -> hypotension

Question 72

Nitrates | Adverse drug reactions

Answer 72

HA Hypotension: arterial vasodilation Reflex tachycardia: don't treat tachycardia until BP is taken care of) Skin irritation: patches and creams Educate to rotate site; don't put it on arms and legs bc as you move, blood flow is increased to extremities and drug gets absorbed more

Question 73

Nitrates | indications

Answer 73

Angina Post MI HF: not 1st line

Question 74

Antiarrhythmics

Answer 74

Goal: eliminate or decrease ectopic foci or conduction of ectopic impulses -based on action potential and ion exchange (Na, Ca, K) Depressed or accelerated conduction Alternate pathways Re-entry phenomena: Wolf Parkinson White Uni or bidirectional

Question 75

Antiarrhythmic Drug Classes Amiodarone: fibrosis multiple drug interactions: look up if unsure Work in tandem with cardiologist Monitor EKG, ADR, labs Wean; don't stop abruptly

Answer 75

Class 1: Na channel blockers: reduce influx of Na into cells Class 1a: Work in atrial tissue, SA node, AV nodes to reduce rapid firing of ectopic foci; lengthen action potential Norpace, procainamide, quinidine Class1b: work in ventricular tissue; last result for severe refractory ventricular tachycardia; shorten action potential Lidocaine, phenytoin Class 1C: little/no action potential increase Flecainide, propafenone Class 2: prolong refractory period; slightly negative inotropic effect (decreased contraction) Esmolol, metoprolol, atenolol Class 3: block K channels (decreased automaticity of ventricles) Amiodarone, sotalol, dofetilide Class 4: CCB verapamil, diltiazem

Question 76

Serum lipids | Influenced by:

Answer 76

Genes Diet Activity Smoking Medication Comorbidities: DM, HTN, arthritis, lupus

Question 77

Triglycerides

Answer 77

like carbs that have not been metabolized > 300-400 considered pre DM genetic ETOH abuse menopause bc of decreased estrogen Educate to decrease carb intake Beta blockers slow carb metabolism -> high triglycerides

Question 78

Hepatic LDL

Answer 78

made in liver -> arteries and arterioles create plaque HMG-CoA/mevalonate: substance reduced by lipoprotein lipase and converts to mevalonate. Statins block conversion to HMG-CoA to reduce LDL production Liver has receptors for LDL bc receptors pull LDL from blood to make more LDL to be sent out to periphery. Lower LDL level -> liver makes more LDL receptors -> absorb more LDL into liver -> less LDL in circulation LDL receptors take up triglycerides some cholesterol meds will lower LDL and triglycerides too HDL clearance: good cholesterol, removes. some LDL from circulation and back to liver so it can be metabolized or broken down

Question 79

Antilipidemics | Statins

Answer 79

Inhibit HMG CoA reductase -> prevent conversion mevalonate Most effective lipid lowering agent Lowers LDL Raises HDL Lowes triglycerides Pregnancy category X Very strong CYP450 inducers: many interactions

Question 80

Statins | CYP3A

Answer 80

CYP3A metabolism Statin levels increased w/ meds that inhibit CYP3A Nondihydropines (verapamil and diltiazem) Erythromycin Azoles (antifungals, diflucan) Prozac Protease inhibitors (hiv meds) CYP3A inducers: lower statin levels Rifampin (tb and resp infections) Dilantin and phenobarbital

Question 81

Statins | Adverse drug reactions

Answer 81

HA, fatigue, GI distress, myalgia (order creatinine kinase (CK)) Myopathy D/c med or reduce dose Rhabdomyolysis renal failure Increased LFTs

Question 82

Antilipidemics | Indications

Answer 82

1: Pt w/ ASCVD 2: Pt w/ LDL > 190mg/dl (regardless if no other comorbidities) 3: DM 40-75 yo no ASCVD LDL 70-189 4: no ASCVD; no DM LDL 70-189 > 7.5% 10 year ASCVD 5: measure lipids, return LDL to target

Question 83

Statin Treatment | Group 1

Answer 83

ASCVD (includes ACS, MI, angina, CAD, revascularization, TIA, stroke) Age: < 75: high intensity statin therapy - atorvastatin 40-80 - rosuvastatin 20-40mg Age > 75: moderate intensity if not a high intensity candidate bc of hepatic disease, can elevate liver enzymes

Question 84

Statin treatment | Group 2

Answer 84

Pt w/ LDL > 190mg/dl high intensity statin moderate intensity if not a good candidate for high intensity; intended to lower cholesterol by 30-49%-atorvastatin 10-20mg -rosuvastatin 5-10mg

Question 85

Statin treatment | Group 3

Answer 85

Pt w/ DM; 40-75yo; no ACVSD; LDL 70-189 Tx bc usually have metabolic syndrome (HTN, DM, HLD) DM pt: increased risk for stroke and MI Higher incidence of first fatal MI Age 40-75: moderate intensity statin - atorvastatin 10-20mg - rosuvastatin 5-10mg If DM and hypercholesterolemia- perform risk assessment If risk >7.5% -> high risk statin

Question 86

Statin treatment | Group 4

Answer 86

Pt w/ no ASCVD or DM; LDL 70-189; >7.5% 10yr ASCVD risk; 40-75 yo Moderate to high intensity primary care emphasis

Question 87

Bile Acid Resin

Answer 87

Not absorbed in GI tract Bind with bile acids and cholesterol in intestine -> form insoluble product that is excreted w/ cholesterol. Stops bile acid from returning to liver to make more cholesterol Liver makes bile acids from cholesterol; bile is stored in gall bladder Eat fatty meal, gall bladder releases bile acids to break down fats -> fats go to liver -> synthesized into cholesterol When LDL goes down, liver increases LDL receptor sites -> more LDL is taken out of blood and into liver to be broken down Decrease LDL Increase HDL Can increase triglycerides Used for people with liver disease who can't take statins

Question 88

Bile acid resins Wlchol (colesevelam) Questran (cholestyramine)

Answer 88

Powders that are mixed and taken with meal Safest agent for pt w/ hepatic disease Oatmeal and shredded wheat (soluble fibers) decrease bile acids bc soluble fiber travel slowly through intestine and absorb H2O, bile acids, and cholesterol -> reduced cholesterol absorbed for cholesterol synthesis Don't take w/ other meds for 2 hrs before or after bc will get excreted with insoluble waste

Question 89

Bile acid resin | Adverse reaction

Answer 89

No LFT monitoring required GI complaints; take stool softener or Metamucil @ different time of day; prune juice - constipation - diarrhea - bloating - flatulence: simethicone, gas x

Question 90

Fibric acid derivatives | Mechanism of action

Answer 90

Used to reduce triglycerides by enzymatic destruction of lipoproteins that transport triglycerides - lower triglycerides - increase hdl - little impact on LDL

Question 91

Fibric acid derivatives Gemfibrizol (Lopid) Fenofibrate (tricor)

Answer 91

GI adverse reactions: myopathies when take w/ statin hepatic toxicity esp w/ statins gall stones bc so much cholesterol coming back to liver Interactions: anticoagulants

Question 92

Cholesterol absorption inhibitors | Ezetimibe (Zetia)

Answer 92

Decrease absorption of cholesterol in the small intestine Decreased storage of cholesterol in liver -decreased LDL Very effective in combo w/ statins No impact on CV events; unclear if helpful Adverse reactions mostly in combo w/ statins

Question 93

Niacin

Answer 93

B vitamin 100-300x recommended daily dose improved cholesterol; never use it to lower LDL Increases HDL lowers LDL slightly Lowers triglycerides Start at low dose: 50-100mg did Titrate slowly up to 1.5g.day

Question 94

Niacin | Adverse reactions

Answer 94

Flushing of face and neck; similar to hot flashes Can take ASA to reduce prostaglandins -> reduced flushing Acanthosis Nigricans: hyperpigmentation of neck, groin, axilla. Indicates pre-DM -> niacin altering metabolism profoundly Can't give to people who already have disorder Check uric acid, glucose, LFTs check before beginning therapy and check 6-12 weeks after completing titration

Question 95

Niacin | C/i

Answer 95

Peptic ulcer disease Gout: bc of uric acid DM: bc worsens glycemic control

Question 96

Omega 3 fatty acids

Answer 96

Lowers triglycerides Increases HDL slightly ``` Lovazza: concentrated fish oil; less GI s/s, less fish breath FDA approved (insurance might cover) ``` OTC flaxseed/fish oil - antiplatelet effects - fish breath Need to be taken at high doses to be effective; minimum of 3g/day

Question 97

Cholesterol Drugs

Answer 97

``` First: lifestyle changes Almost all: metabolized by liver Many interactions: grapefruit juice Most are c/I in pregnancy Monitor LFTs and lipids before q 4-6 weeks for several months Not for use during pregnancy and breastfeeding Diet and exercise before medicating Less fatty food Exercise 30min/day 5x/week ```