Pharm Exam 1: Section 2 Flashcards
Renin Angiotensin System
Maintains homeostasis in euvolemic state
Stimulated in low volume or low O2 state –> Sympathetic NS
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
ACEI Benzapril Captopril Enalapril Lisinopril
ARBS
Losartan
Valsartan
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
ACEI and black people
Black people make less renin than other groups
ACEI less effective
ACEI & ARBS
How they work
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
ACEI & ARBS
Pharmacokinetics
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
ACEI & ARBS
Pharmacokinetics
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.
ACEI & ARBS
Adverse reactions
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
ACE & ARBS
Contraindication
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
ACE & ARBS
indications
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%
ACEI & ARBS
Monitoring
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
CCB
Most potent class of BP reduction
Nondihydropyridines: Type 1 receptors
- verapamil and diltiazem
Dihydropyridines: Type 2 receptors
- pines
CCB
Mechanism of action
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
CCB
Pharmacokinetics
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
CCB
Pharmacokinetics
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
CCB
Adverse reactions
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
CCB
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
CCB
Indications
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
Diuretics
Thiazides
Loop diuretics
K+ sparing
Decrease volume
decreased preload
decreased pressure arterial bed
Diuretics
Thiazides
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
Diuretics
Thiazides
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
Diuretics
Loop
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
Diuretics
K sparing
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
Diuretics
Preload reducers
Long term: reduce volume -> decreased SVR and afterload
Diuretics
Pharmacokinetics
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
Diuretics
Adverse reactions
Electrolyte imbalances
Glucose intolerance
Hyperuricemia: concern for gout pt
Dehydration and hypotension -> falls
Drug interactions
Diuretics
C/i
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
Diuretics
Indications
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
Diuretics
Indications
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
Beta adrenergic blocker
“olol”
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
Beta blockers
Mechanism of action
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
Beta blockers
Pharmacokinetics
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
Beta blockers
Adverse reactions
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)
Beta Blockers
Indications
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
Beta Blockers
C/i
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
Alpha Receptors
Sympathetic NS: fight or flight
Parasympathetic: Rest and relax
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)
Alpha Agonists
Mechanism of action
Alpha 1
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
Alpha Agonists
Mechanism of action
Alpha 2
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
Alpha 2 agonists
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
Alpha 2 Agonists
Pharmacokinetics
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
Alpha 1 Agonist
Adverse reactions
Tachycardia Increased cardiac workload Increased O2 demand Dysrhythmias Headache Sedation
Alpha 2 Agonist
Adverse reactions
Xerostomia (dry mouth)
Hypotension
Sedation
Alpha 1 agonist
Indications
Sepsis Anaphylaxis Post CABG hypotension Anesthesia induced hypotension Nasal decongestion
Alpha 2 agonist
Indications
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
Alpha Agonists
C/i
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
Alpha Agonist
indications
Low dose: renal low flow states (dopamine) High dose dopamine: sepsis Nasal decongestion Hypotension ETOH and drug withdrawal Menopause
Alpha blockers
Mechanism of Action
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
Alpha blockers
Non selective
Regitine (Phentolomine)
Dibenzyline (Phenoxybenzamine)
Reflex cardiac stimulation: cause reflex tachycardia
Rarely used except for Pheochromocytoma: tumor in adrenal gland -> dump huge amounts of epi
Alpha blockers
Selective
“osin”
Doxazosin (cardura)* Prazosin (minipress)* Terazosin (Hytrin)* Tamulosin (flomax) Alfuzosin (urizatral) Silodosin (rapaflo)*
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
Alpha blockers
Pharmacokinetics
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
Alpha blockers
Adverse reactions
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
Alpha blockers
C/i
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
Alpha blockers
Indications
HTN (not first line drug)
BPH
Ureteral stones in ureter (off label use)
Doxazosin, terazosin, tamrulosin
Alpha blockers
Monitoring
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)
Heart failure
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
HTN
Treatment goals
> 60: < 150/90
< 60: < 140/90
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
HTN
First line therapy
Black: thiazide and/or CCB
Nonblack: thiazide, ACE or ARB, CCB (alone or in combo)
ACC & AHA
Recommend BP <130/90
HTN
Selecting tx plan
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
Cardiac Glycosides
Bufalin, Oufalin
Digoxin (derived from fox glove plant)
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
Na - K pump
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
Digoxin and K
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
Cardiac glycosides
Mechanism of action
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
Cardiac glycosides
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
Cardiac glycosides
Pharmacokinetics
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
Cardiac glycosides
Interactions
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
Cardiac glycosides
Adverse reactions
Therapeutic level: 0.9-1.2ng/ml
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,
Cardiac glycosides
C/i
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
Cardiac glycosides
Indications
Rapid afib
SVT
HF w/ severe dysfunction (EF <40); not 1st line HF med
Nitrates
IV sublingual inhaled Transdermal: paste; patch ER tabs
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
Nitrates
PO
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
Nitrates
C/i
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
Nitrates
Adverse drug reactions
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
Nitrates
indications
Angina
Post MI
HF: not 1st line
Antiarrhythmics
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
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
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
Serum lipids
Influenced by:
Genes
Diet
Activity
Smoking
Medication
Comorbidities: DM, HTN, arthritis, lupus
Triglycerides
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
Hepatic LDL
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
Antilipidemics
Statins
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
Statins
CYP3A
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
Statins
Adverse drug reactions
HA, fatigue, GI distress, myalgia (order creatinine kinase (CK))
Myopathy
D/c med or reduce dose
Rhabdomyolysis
renal failure
Increased LFTs
Antilipidemics
Indications
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
Statin Treatment
Group 1
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
Statin treatment
Group 2
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
Statin treatment
Group 3
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
Statin treatment
Group 4
Pt w/ no ASCVD or DM; LDL 70-189; >7.5% 10yr ASCVD risk; 40-75 yo
Moderate to high intensity
primary care emphasis
Bile Acid Resin
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
Bile acid resins
Wlchol (colesevelam)
Questran (cholestyramine)
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
Bile acid resin
Adverse reaction
No LFT monitoring required
GI complaints; take stool softener or Metamucil @ different time of day; prune juice
- constipation
- diarrhea
- bloating
- flatulence: simethicone, gas x
Fibric acid derivatives
Mechanism of action
Used to reduce triglycerides by enzymatic destruction of lipoproteins that transport triglycerides
- lower triglycerides
- increase hdl
- little impact on LDL
Fibric acid derivatives
Gemfibrizol (Lopid)
Fenofibrate (tricor)
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
Cholesterol absorption inhibitors
Ezetimibe (Zetia)
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
Niacin
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
Niacin
Adverse reactions
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
Niacin
C/i
Peptic ulcer disease
Gout: bc of uric acid
DM: bc worsens glycemic control
Omega 3 fatty acids
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
Cholesterol Drugs
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
