-
Mechanisms of Adrenergic Receptor
Activation by Agonist Drugs (4)
- Direct Receptor Binding
- Promotion of Norepinephrine (NE) Release
- Inhibition of NE Reuptake
- Inhibition of NE Inactivation-
-
Catecholamines and noncatecholamines differ in three respects:
- Oral usability
- Duration of action
- Ability to act in the CNS
-
Catecholamine's: (Epineherine, Norepinepherine)
3 properties in common
- Cannot be used orally
- Brief duration of action
- Cannot cross the blood-brain barrier
-
Norepinephrine, dopamine, & dobutamine only work if
given by continuous infusion
-
Catecholamine’s are ____ _____, cannot cross the blood-brain barrier
polar molecules
-
Catecholamine's: IV solutions can turn pink or brown over time;
Discard if discolored
-
Adrenergic Agonists affect: (4)
- alpha 1,
- alpha 2,
- beta 1 &
- beta 2 adrenergic receptors
-
Noncatecholamines (4)
- can be given orally &
- have longer half-lives
- less polar,
- can cross the blood brain barrier
-
Alpha 1 Receptors :cause two responses
- vasoconstriction (in blood vessels of skin, viscera, and mucous membranes) &
- mydriasis (dilation of the pupil)
-
Alpha 1 Activation
Hemostasis
Stop bleeding primarily in skin & mucous membranes (Epinephrine)
-
Alpha 1 Activation
Nasal Decongestion
Relieve congestion by vasoconstriction of mucous membranes (phenylephrine & pseudoephedrine)
-
Alpha 1 Activation
Adjunct to Local Anesthesia-
Combined with anesthetics to delay anesthetic absorption, vasoconstriction at the site.(Epinephrine)
-
Alpha 1 Activation
Elevation of BP-
Vasoconstriction can elevate BP, ONLY usedwhen other therapies have failed
-
Alpha 1 Activation
Mydriasis-
facilitates eye exams & ocular surgery
-
Alpha 1 Adverse Effects (3)
- Hypertension
- Necrosis
- Bradycardia
-
Alpha 1 Adverse Effects
Hypertension
- Widespread vasoconstriction can cause HTN, particularly parenteral administration IV:
- Must monitor CV status continuously
-
Alpha 1 Adverse Effects
Necrosis
Extravasation & necrosis with IV infiltrate,(intense vasoconstriction), alpha 1 blocker (antagonist) to minimize damage (phentolamine)
-
Alpha 1 Adverse Effects
Bradycardia
Reflex response to increase in BP, cancause cardiac collapse & impaired tissue perfusion
-
Alpha 2 Activation
Peripherally inhibit NE release (but little clinical relevance)
-
Alpha 2 Activation
In CNS receptors cause
- Reduction of sympathetic outflow to heart & blood vessels
- Relief of severe pain
-
Beta 1 Activation
- Heart Failure
- Shock
- Atrioventricular (AV) Heart Block
- Cardiac Arrest from Asystole
-
Beta 1 Activation
Heart Failure-
Beta 1 receptors increase force of contraction (inotropic effect),improves cardiac Fxn
-
Beta 1 Activation
Shock
- (Shock=profound hypotension) Beta 1’s increase heart rate (HR), force of contraction=increased cardiac output (CO), & improves tissue perfusion
-
Beta 1 Activation
Atrioventricular (AV) Heart Block-
Beta 1’s enhance conduction through AV node (temporarily, until pacemaker )
-
Beta 1 Activation
Cardiac Arrest from Asystole-
Beta 1’s can initiate acontraction in a heart that has stopped, (CPR & TXrequired, Epinephrine)
-
Beta 1 Adverse Effects (2)
- Altered Heart Rate or Rhythm
- Angina Pectoris
-
Beta 1 Adverse Effects
Altered Heart Rate or Rhythm
Overstimulation of beta 1’s can produce tachycardia & dysrhythmias
-
Beta 1 Adverse Effects
Angina Pectoris-
Angina Pectoris- Beta 1’s increase cardiac oxygen demand, which can cause angina in pts with impaired coronary circulation
-
Beta 2 Activation (3)
- Limited to lungs and uterus
- Asthma- Beta 2 receptors promote bronchodilation, Selective beta 2 receptors(albuterol) preferred, (Drugs that activate beta 1 receptors can stimulate tachycardia & angina).Most via inhalation to minimize adverse systemic effects, systemic toxicity with overdosing
- Can Delay Preterm Labor- Relaxes uterine smoothmuscles
-
Beta 2 Adverse Effects (2)
-
Beta 2 Adverse Effects Hyperglycemia
- (highest risk: diabetic pts)
- beta 2 receptors stimulate breakdown of glycogen into glucose
-
Beta 2 Adverse Effects
Tremor
Most common, beta 2;s in muscles cause enhanced contractions, fades over time, minimized by starting at low dose
-
Dopamine Receptor
- Activation of peripheral dopamine receptor causes dilation of renal vasculature
- *Dopamine (the drug) used in shock to dilaterenal blood vessels & reduce risk of renal failure
- Dopamine also enhances cardiac performance
Assess Urinary output (UOP), increases when kidneys are functioning, shock=no/low perfusion to kidenya and low UOP
-
Epinephrine
Receptor specificity:
alpha 1, alpha 2, beta 1 and beta 2
-
Epinephrine
Therapeutic Uses:
- Alpha 1-mediated vasoconstriction
- Beta 1’s - to overcome AV heart block,
- Beta 2’s: promotes bronchodilation
- **Epinephrine is the Tx of choice for anaphylactic shock*
-
Epinephrine Therapeutic Uses: Alpha 1-mediated
vasoconstriction, used to delayabsorption of anesthetics, control superficial bleeding, &elevate BP. (Was used for nasal decongestion) Alsomydriasis.
-
Epinephrine Therapeutic Uses: Beta 1’s -
to overcome AV heart block, & restore cardiac function in pts experiencing cardiac arrest.
-
Epinephrine Therapeutic Uses:Beta 2’s:
promotes bronchodilation
-
Epinephrine ROUTE:
Topical, injection or IV administration only.
-
Epinephrine half-life
Short (due to MAO and COMT)
-
Epinephrine Adverse Effects:
- Can cause Hypertensive Crisis-
- Can cause Dysrhythmias-
- Angina Pectoris-
- Necrosis Following IV Extravasation-
- Hyperglycemia
-
Epinephrine Adverse Effects:Hypertensive Crisis
Can cause Hypertensive Crisis- Alpha 1 stimulation,vasoconstriction, dramatic increase in BP (IV infusion)
-
Epinephrine Adverse Effects: Dysrhythmias
Can cause Dysrhythmias- Beta 1 stimulation
-
Epinephrine Adverse Effects: Angina Pectoris
Angina Pectoris- Beta 1 increases cardiac work & oxygendemand
-
Epinephrine Adverse Effects: Necrosis
Necrosis Following IV Extravasation-alpha-adrenergic antagonist can minimize (phentolamine)
-
Epinephrine Adverse Effects:Hyperglycemia
Hyperglycemia- beta 2’s, typically in diabetic pts only
-
Epinephrine Drug Interactions: (5)
- MAO Inhibitors
- Tricyclic Antidepressants-
- General Anesthetics-
- Alpha-adrenergic Blocking Agents
- Beta-adrenergic Blocking Agents-
-
Epinephrine Drug Interactions:MAO Inhibitors-
Prolong and intensify the effects ofepinephrine & other catecholamines
-
Epinephrine Drug Interactions: Tricyclic Antidepressants-
Block the uptake ofcatecholamines, so can intensify & prolong epinephrineeffects.
-
Epinephrine Drug Interactions: General Anesthetics-
Can cause tachydysrhythmias when used together
-
Epinephrine Drug Interactions:
Alpha-adrenergic Blocking Agents
(antagonists) Can prevent receptor activation by epinephrine(*Phentolamine: antidote used to treat toxicity)
-
Epinephrine Drug Interactions: Beta-adrenergic Blocking Agents-
Can prevent receptoractivation by epinephrine, reduce adverse effectscaused by epinephrine
-
Epinephrine
Catecholamine or Noncatecholamine
Catecholamine
-
Norepinephrine (6)
- Receptor specificity: Alpha 1, Alpha 2, Beta 1
- Catecholamine
- *Same as Epi, except no Beta 2 stimulation
- Does not promote hyperglycemia
- Typically only used in hypotensive states & cardiacarrest
- IV infusion only
-
Isoproterenol (3)
- Receptor Specificity: Beta 1 and Beta 2
- Catecholamine
- *First beta selective medication
-
Isoproterenol Therapeutic Uses:
- Cardiovascular-overcome AV heart block, restart heart following cardiac arrest, increase cardiac output in shock
- Bronchospasm- Not used to treat asthma ONLY bronchospasm, (more selective medications treat asthma)
-
Isoproterenol
Adverse Effects:
- Beta 1 activation- tachy-dysrhythmias & angina
- Beta 2 activation- hyperglycemia
-
Isoproterenol Drug Interactions:
- Effects are enhanced by MAO Inhibitors andtricyclic antidepressants; Reduced by beta-blockers
- Can cause dysrhythmias when given with inhaled anesthetics
-
Inotropic drugs influence the
- strength or contractilty of muscle tissue.
- Increase the force of the heart's contractions
-
Two types of Inotropic drugs
Cardiac Gylcosides and phophodiesterase (PDE) inhibitors
-
-Slow heart rate and slow electrical impulse conduction through the AV node.
-Useful for pts who have artrial fibrillations.
-Can help control HR and prevent it from becoming too fast
- Incrs. perfusion of tissues improves function/help decrease edema (interstitial fld)
Cardiac Glycosides
-
Cardiac Glycosides Prototype
Digoxin
-
Digoxin Actions
- Inhibits sodium-potassium- activated adenosine triphosphas: reg. amt. of Na and K+ inside the cell resulting in increased intracellular levels of Na and K.
- Promotes the movement of Ca from extra cellular to intracellular cytoplasm and strengthens myocardial contraction
- Acts on the CNS to enhance vagal tone, slowing contractions through the SA and AV nodes- provides an antiarrhythmic effect.
-
Digoxin Indications (3)
- heart failure
- Atrial Fib. and flutter
- Supraventricular tachycardia
-
Digoxin Nursing Considerations
- Monitor pt for adverse effects
- W/hold if apical pulse is less than 60 bpm and notify prescriber
- monitor serum K and digoxin levels
- assess renal function
-
Digoxin Pharmacokinetics
- intestinal asbsorption varies greatly
- cap. most efficent, then elixr then tabs
- absorp. hightest concen. in heart musc., liver, and kideny
- poorly bound to plasma protiens
- Most is excrete from kid. unchanged
-
Digoxin Pharmacodynamics
- boost intracellular Ca at the cell membrane
- enable stronger heart contractions
- may enhance movement of Ca into myocardial cells and stimulate the release for block re-uptake of noreponephrine at the adrenergic nerve terminal
- Works on CNS to slow HR
- Increases refractory period
-
-
Digoxin ______ Cardiac Output:
- Increased:
- -Increases contractilityby restoring cardiac muscle fibers to near health,increases the stroke volume of failing heart =cardiac output rises
-
Digoxin Three major secondary responses due to increased cardiac output:
- – Decreased sympathetic tone
- – Urine production increases
- – Renin release declines
- – These responses can reverse virtually all signs and symptoms of heart failure.
-
Digoxin (Cardiac Glycoside)Adverse Effects 1:
Cardiac Dysrhythmias
-
Digoxin (Cardiac Glycoside) Adverse Effects 1: Cardiac Dysrhythmias:
Digoxin: used in therapeutic doses to slow fastheart rates, but causes dysrhythmias if given inhigh doses or in the presence of hypokalemia
-
Elevated digoxin levels- Narrow therapeutic window/Range:
(0.5-0.8 ng/mL; variance among range, most state no higher than 1.5 ng/ml) levels slightly higher than therapeutic produce toxicity
-
Managing Digoxin-Induced Dysrhythmias:–
- Withdraw digoxin & potassium-wasting diuretics
- – Monitor serum potassium
- – Anti-dysrhythmic drug is sometimes needed (Lidocaine & phenytoin most effective for ventricular dysrhythmias, atropine for bradycardias)
- – Can give reversal agent: Digibind or Digifab, Cost$2,000-$3,000, only use when severe (also can cause arrhythmias as it binds digoxin)
-
Digoxin (Cardiac Glycoside) Adverse Effects 2: Non-cardiac Adverse Effects
- **GI- anorexia, nausea, and vomiting
- **CNS- Fatigue & visual disturbances (blurred vision, yellow tinge to vision, halos around dark objects)
-
Digoxin (Cardiac Glycoside) Drug Interactions:
- *Diuretics- Thiazide and Loop Diuretics promoteloss of potassium (increases risk of dysrhythmias)
- ACE Inhibitors and ARBs- Can increase potassiumlevels (decreases digoxin levels)
- Sympathomimetics- Can add to the inotropiceffects of digoxin
-
Plasma Digoxin Levels:
- Therapeutic Range: 0.5-0.8 ng/mL.
- Anything over 1 ng/mL offers no additional benefit and increases the risk of toxicity.
-
Herbs and Digoxin
St. John's wort and ginseng can ^ levels of digoxin and ^ risk of toxicity
-
S/S of Digoxin toxicity:
- slow to rapid ventricular rhythms
- nausea and vomiting
- blurred vision
- anorexia
- abdomin. discomfort
- mental changes
-
Classification of Antidysrhythmic Drugs
- Class I: Sodium Channel Blockers
- Class II: Beta Bloacker
- Class III: Potassium Channel Blockers
- Class IV: Calcium Channel Blockers
- Other: Adenosine and Digoxin
-
Most Antidysrhythmic Drugs most:
- Slow conduction or part of the cardiac cycle/HR
- Improve Contractility
- Correct Dysrhythmia
-
Sodium Channel Blockers
Slow impulse conduction in the atria, ventricles, and HIS Purkinje system- Largest group
-
Beta Blockers
- Reduce Ca entry & depress phase 4 depolarization
- reduce automaticity in SA node
- Slow Slow conduction velocity in AV node
- Reduce force of contraction
-
Beta-Adrenergic Blockers
Nonselective agents
- Carteolol,
- Nadolol,
- Penbutolol,
- Pindolol,
- Propanolol,
- Sotalol,
- Timolol
- Carvedilol,
- Labetalol
-
Carteolol, Nadolol,Penbutolol, Pindolol,Propanolol, Sotalol, Timolol
Receptors Blocked
Beta 1, Beta 2
-
Carvedilol, Labetalol
Receptors Blocked
Beta1, Beta 2, Alpha 1
-
Beta 1-Selective Agents
- Acebutolol,
- Atenolol,
- Betaxolol,
- Bisoprolol,
- Esmolol,
- Metoprolol,
- Nebivolol
-
Lidocaine (Xylocaine) PT
- limited to short-term
- therapy for ventricular dysrhythmias. Not
- effective against supraventricular dysrhythmias
-
Lidocaine (Xylocaine) PK
If given orally, most of the drug would be inactivated in the first pass.
-
Lidocaine (Xylocaine)Adverse
- CNS effects- drowsiness, confusion, paresthesias, tremor
- Toxic doses- (severe CNS effects), convulsions & respiratory arrest
-
Lidocaine (Xylocaine)Therapeutic range;
1.5-5 mcg/ml
-
Lidocaine (Xylocaine) dose
50-100 mg (1mg/kg) followed by infusion rate of 1-4mg per min
-
Lidocaine (Xylocaine) special instructions
Only the IV form is used , never the lidocain eused as a local anesthetic
-
Propanolol (Inderal, Inderal LA)
- Class II: Beta Blockers for Dysrhythmia
- *nonselective beta adrenergic antagonist
-
Propanolol (Inderal, Inderal LA) Effects on the Heart & ECG-
- Decreased automaticity of SA node,
- Decrease velocity of AV node, &
- Decreased myocardial contractility (force of contraction),
-
**Only four of all beta blockers are approved for treating dysrhythmias:
- propranolol,
- acebutolol,
- esmolol, and
- sotalol
- (All others just for HTN)**
-
Beta Blockers for Dysrhythmia PD:
- *Competitively Blocks catecholamine's at non-CNS beta adrenergic receptor sites,
- particularly the heart to decrease CO,
- central effect decreases sympathetic outflow to periphery,
- prevents release of renin from kidneys.*
-
(Beta Blockers) *Overall Therapeutic Effects*:
- – Reduced Heart Rate
- – Reduced Force of Contraction
- – Reduced Velocity of Conduction through the AV node.
-
(Beta Blockers) for *Heart Failure- Only drugs:
- carvedilol (Coreg),
- bisoprolol (Zebeta), &
- metoprolol (Lopressor).*
-
Propranolol (Inderal/Inderal LA) Therapeutic Uses:
- Hypertension,
- angina pectoris,
- cardiac dysrhythmias, and
- myocardial infarction.
-
metoprolol (Lopressor,Toprol XL) is a
- Beta Blocker
- 2nd-Generation, selective cardiac (beta 1) blockade
-
Beta Blockers: Metoprolol (Lopressor,Toprol XL)• Therapeutic Uses:
- Primarily HTN,
- also angina pectoris,
- heart failure, &
- myocardial infarction.
-
Class III: Potassium Channel Blockers work by
Delay repolarization of fast action potentials
-
Potassium Channel Blockers prototype
Amiodarone (Cordarone),
-
Amiodarone is highly effective for ____ ___& is widely used for this purpose (BUT IT IS NOT APPROVED FOR THIS USE)
atrial fibrillation
-
Amiodarone is Effective against
both atrial & ventricular dysrhythmias
-
Amiodarone (Cordarone, Pacerone)ORAL half life
Extremely long half-life (25-110 days), continuesto act long after it is discontinued
-
Amiodarone (Cordarone, Pacerone) ORAL THERAPY• Adverse Effects:
- **Pulmonary Toxicity- lung damage**,Cardiotoxicity
- Thyroid Toxicity-
- Liver Toxicity-
- Opthalmic Effects-
- Toxicity in Pregnancy & Breast-feeding
- Dermatological Toxicity-
- CNS reactions- ataxia, dizziness, tremor,mood alteration, & hallucinations (Safety). GIreactions- anorexia, N/V
-
Amiodarone ORAL is ineractions
- *increased by grapefruit juice* and CYP3A4(toxicity can result)•
- cholestyramine & agents thatinduce CYP3A4 (St. John’s Wart, rifampin)•
- *Risk of severe dysrhythmias is increased by diuretics(reduced levels of potassium and magnesium) & by drugs thatprolong QT interval• *Combining amiodarone with beta blockers,verapamil or diltiazemcan excessive slowing of heart rate
-
Amiodarone (Cordarone, Pacerone) IV THERAPY• Therapeutic Use-
Approved only for initia ltreatment & prophylaxis of recurrent ventricular fibrillation & hemodynamically unstable ventricular tachycardia in pts refractory to safer drugs.
-
Amiodarone (Cordarone, Pacerone) IV THERAPY• NOT approved uses*
- Also used to treat atrial fibrillation,
- AV nodal reentrant tachycardia and
- shock-resistant ventricular fibrillation (NOT approved uses)
-
CALCIUM CHANNEL BLOCKERS action on muscle
- *Calcium channels regulate muscle contraction in vascular smooth muscle.•
- *If calcium channels are blocked, contraction will be prevented; vasodilation will result•
- *Calcium Channels Blockers act selectively on peripheral arterioles and arteries & arterioles of the heart.•
- *No significant effect on veins.
-
CALCIUM CHANNEL BLOCKERS action on heart:
- In heart, calcium channels help regulate the myocardium,
- sinoatrial (SA) node,
- & atrioventicular (AV) node•
-
If calcium channels are blocked:,
- contractile force will diminish
- heart rate is reduced
-
Calcium Channel Blockers• Three families
- The largest family is dihydropyridines
- Phenylakylamine is next family: Verapamil is the only drug in this family•
- Benzothiazepine is the final family: Diltiazemis the only drug in this family
-
Dihydropyridines act primarily on
arterioles
-
Calcium Channel Blockers• Verapamil and Diltiazem act on
arterioles & the heart
-
Calcium Channel Blockers: Verapamil Used for
- angina pectoris,
- essential hypertension&
- cardiac dysrhythmias*.
-
**Overall effect of verapamil is
simply vasodilation, reduced arterial pressure, &increased coronary perfusion**
-
Calcium Channel Blockers: Verapamil administration
Given IV or orally.
-
Calcium Channel Blockers: Verapamil• Therapeutic Uses
- **Angina Pectoris-
- **Essential HTN-
- **Cardiac Dysrhythmias-
-
Calcium Channel Blockers: Verapamil• Adverse Effects:
- Common effects- *Constipation most common
- **Other common effects – dizziness, facial flushing,headache, & edema of the ankles & feet (all from vasodilation)•
- Cardiac Adverse Effects- *Bradycardia, Sick Sinus Syndrome, and 2nd or 3rd degree blocks (slowed conduction)
-
Calcium Channel Blockers: Verapamil• Drug and Food Interactions:
- Digoxin-
- Beta-Adrenergic Blocking Agents-
- Grapefruit Juice- il
-
Diltiazem
- Similar to verapamil except:
- • Bigger first-pass effect, starts working in minutes,peaks in 30 minutes
- • Diltiazem is less likely to cause constipation
-
Calcium Channel Blockers:
- Dihydropyridines•
- Nifedipine (Adalat CC, Nifedical XL, Nifediac CC,Procardia, Procardia XL)
-
Calcium Channel Blockers: Nifedipine Net Effects–
Lowers BP, increases heart rate, & increases contractileforce
-
Calcium Channel Blockers: Nifedipine• Therapeutic Uses:
- • Angina Pectoris-
- HTN- Essential HTN, *Only sustained release should beused.
-
Calcium Channel Blockers: Nifedipine Adverse Effects–
- Flushing, dizziness, headache, peripheral edema, & gingivalhyperplasia
- – Reflex tachycardia (avoided if with Beta-blocker)
- – Rapid-acting nifedipine is associated with increased mortality and therefore is used with EXTREME CAUTION.
-
Calcium Channel Blockers• Drugs:
- (many end in dipine, but not all)
- amlodipine (Norvasc),
- bepridil (Vascor),
- diltiazem(Cardizem),
- felodipine (Plendil) SR,
- isradipine(DynaCirc) SR,
- nicardipine (Cardene) SR,
- nifedipine(Procardia) SR,
- nimodipine (Nimotop),
- nisoldipine(Sular),
- verapamil (Isoptin, Calan)
-
Digoxin (Lanoxin)•_____ inotrop action:
Positive inotrop action, increases force ofventricular contraction
-
Digoxin (Cardiac Glycoside)• Plasma Digoxin Levels:• Therapeutic Range:
0.5-0.8 ng/mL.
-
Hormones of the Posterior Pituitary– 2
- Oxytocin- facilitates uterine contraction during labor.–
- Antidiuretic Hormone (ADH)- promotes renalconservation of water.
-
Anterior pituitary gland dysfunction:
– Growth hormone (GH) deficiency (short stature) & excess (gigantism)
-
Posterior pituitary gland dysfunction (major disorders):–
- Diabetes Insipidus (DI)
- – Syndrome of Inappropriate Antidiuretic Hormone (SIADH).
-
Thyroid gland dysfunction:–
- Hyperfunction (hyperthyroidism) or
- hypofunction (hypothyroidism)
- – Dysfunction can be congenital defect or by a problem later in life.
-
Parathyroid gland dysfunction:
- – PTH a major regulator of serum calcium and phosphate.
- – Decrease in serum calcium concentration main stimulus/regulator of PTH, response rate in seconds
- – Decrease in serum phosphate causes an indirect effect on PTH by combining with calcium and decreasing serum calcium concentrations
-
Growth Hormones• GH deficiency, causing short stature, was initially treated with:
GH injections extracted from the pituitary glands of cadavers.
-
Growth Hormones• GH deficiency, causing short stature, Now treated
synthetic human GH (rhGH), produced fromrecombinant DNA
-
Growth Hormones Prototype drug:
- somatropin (several brand names).
- In pediatric patients: VERY EXPENSIVE $20,000-$50,000 yr
-
Somatropin (Human Growth Hormone)• Implementation: Daily administration• Routes:
SubQ (preferred) or IM
-
Somatropin (Human GrowthHormone)•
Minimizing Adverse Effects and Interactions:
- *Hyperglycemia- GH can elevate plasma glucose levels in diabetics.Increase insulin dose as needed.•
- *Hypothyroidism- GH may suppress thyroid function. Assessthyroid function before treatment and periodically thereafter. Iflevels of thyroid hormone fall, institute replacement therapy.•
- Interaction with Glucocorticoids- Glucocorticoids can opposegrowth-stimulating effects of GH.
-
GH therapy may induce ____ _____
insulin resistance.
-
Growth Hormone Agonists• GH excess leads to:
-
Growth Hormone Agonists• GH excess
Prototype drug:
Octreotide acetate (Sandostatin)
-
posterior pituitary stores two hormonesproduced in the hypothalamus:
-
____ & _____ are syntheticanalogues of the naturally occurring posteriorpituitary hormone.
Desmopressin & vasopressin
-
Posterior Pituitary Hormone Regulators Prototype drug:
Desmopressin (DDAVP,Stimate, Minirin). [vasopressin (Pitressin)]
-
____a drug identical to natural ADH, can cause _____ _____
Vasopressin, profound vasoconstriction.
-
Desmopressin Routes–
Intranasal, PO, SubQ, and IV–
-
Vasopressin routes
- IM, SubQ
-
ADH (Vasopressin orDesmopressin)• Ongoing Evaluation and Interventions:• Evaluating Therapeutic Effects:– Teach the patient to
monitor and record dailyintake and output of fluid
-
Oxytocins• Interventions:
Baseline and ongoing maternal HR and BP, uterine activity: timing and length of contractions, and fetal heart rate.
-
Oxytocins Drugs-
- *ergonovine (Ergotrate);
- *methylergonovine (Methergine);
- oxytocin(Pitocin, Syntocinon)
- *used post delivery to decrease risk of hemorrage
-
PITOCIN
- P- Pressure is elevated•
- I – Intoxication with water•
- T- Tetanic contractions•
- O- Oxygen decrease in fetus•
- C- Cardiac arrhythmia•
- I- Irregularity in fetal heart rate•
- N- Nausea and vomiting
-
Estrogen• Action-
Development and maintenance for adequate functioning of female reproductive system; affects release of pituitary gonadotropins; promotes adequate use in bone structures.•
-
Estrogen• Indications
- Moderate to severe vasomotor symptoms associated with menopause;postpartal breast engorgement, hormonal replacement therapy; prevention of osteoporosis and cardiovascular disease.
-
(Estratab, Estratest, Menest);
estradiol (Climara, Estrace, Estrace Vaginal Cream,Estraderm, Vivelle);
estradiol cypionate (depGynogen,Depo-Estradiol, Dura-Estrin, etc.) estradiol valerate.–
Esterified estrogens:
-
Premarin, Premarin Intravenous, Premphase, Prempro)
Conjugated estrogens:
-
Progestins Often used with estrogen to:
– stimulate endogenous hormones– Restore hormonal balance– Treat hormone-sensitive tumors (suppress tumor growth)– Contraception
-
Types of Anti-hypertensives
- Calcium Channel Blockers
- • Angiotensin II Receptor Blockers (ARBs)
- • losartan (Cozaar)
- • Beta Blockers• propranolol (Inderal), atenolol (Tenormin)
- • Angiotensin – Converting Enzyme (ACE) inhibitors• captropril (Capoten)
- • Alpha – Beta Blockers• labetalol (Normodyne, Trandate)
-
Angiotensin II Receptor Blockers (ARBs)• Prototype:
Losartan (Cozaar)
-
Losartan (Cozaar) Mechanism of action
Blocks binding of Angiotensin II at receptors, so blocks the actions of Angiotensin II (vasoconstriction & aldosterone secreting effects)
-
Losartan (Cozaar) Adverse effects•
*Most common - Hypotension, diarrhea,*dizziness, Most serious (but rare) *Angioedema
-
ARB’s: Nursing Interventions•
- Do not use for pregnant/Breast feeding patients, (risk of birthdefects and fetal injury)
- those with severe CHF•
- Frequently used for DM patients with kidney damage•
- Assist patients when getting OOB or with position changes, teachabout orthostatic hypotension•
- Assess/Avoid use of prescription potassium/OTC potassiumsupplements, like salt substitutes•
- Lifestyle changes along with pharmacotherapy•
- Avoid giving with grapefruit juice•
- Monitor BUN, Creatnine, BP level* may need combo therapy
-
Angiotensin – Converting Enzyme (ACE)inhibitors• Prototype:
captopril (Capoten) oral
-
Angiotensin – Converting Enzyme (ACE)inhibitors
Uses:
- HTN,
- *CHF,
- diabetic Nephropathy,
- LV dysfuncion post MI, & off label uses *( in combination with others)
-
Angiotensin – Converting Enzyme (ACE) inhibitors Preg.
- Class C (1st Tri)
- Class D (2nd & 3rd) *Black box warning forfetal injury and birth defects
-
Angiotensin – Converting Enzyme (ACE)inhibitors Contra:
Hx Angioedema or Hypersensitivity
-
Angiotensin – Converting Enzyme (ACE)inhibitors PD:
prevents conversion of angiotensin I to angiotensin II,decreasing secretion of aldosterone which prevents Na &H2O retention, decreases PVR & BP
-
Adverse effects of captopril (Capoten)
- Persistent nonproductive *cough,
- (*inhibits degradation of Bradykinin) rash
- *first dose hypotension/& hypotension, HyperKALEMIA,
- angioedema,
- neutropenia,
- & dyspnea,
- dysgeusia, others less common
-
captopril (Capoten) Drug/agent Interactions:
- Drugs that raise K level,
- other BP lowering agents such as diuretics & other BP lowerin =increased risk of hypotension,
- lithium,
- NSAIDS
-
captopril (Capoten) Nursing Considerations•
- Administer captopril 1 hour before meals, other ACE inhib’s can be given with food•
- Monitor the patient for at *least 2-3 hours after the initial dose and until blood pressure stabilizes, and intermittently during use•
- Assess blood reports for WBC,
- *Hyperkalemia, Hyponatremia,neutropenia, & assess urine for proteinuria, UOP, BUN & Creatnine(renal insuffic./DM)•
- Body Position changes/safety, *watch closely when used in combo with diuretics, (also watch BP, electrolyte levels, s/s hypovolemia)
-
Other ACE Inhibitors:•
- Lisinipril (Prinivil, Zestril),
- Benazepril (Lotensin),
- *enalapril (Vasotec)
- *asIV form,
- ramipril (Altace),
- quinapril (Accupril),
- moexipril (Univasc),
- moexipril (Monopril),
- perindopril (Aceon).
-
Alpha – Beta Blockers Adverse effects•
Diarrhea, N/V IV dosing, dizziness, weakness, orthostatic hypotension,elevations in BUN and serum creatinine levels, tingling of scalp, andfatigue
-
Alpha-beta blockers• Contras:
- • Patients with bradycardia, 2 or 3rd degree heart block, bronchial asthma, uncompensated CHF, cardiogenic shock (can exacerbate disease)
- • Cautions: preg. Class C no studies, other: (see table 47-8 p 545) CHF,emphysema, bronchitus, DM
-
-
Alpha-beta blockers Drug interaction
- : beta-adernergic agonists,
- cimtieidine,
- nitroglycerine,
- halothane,
- oral antidiabetic agents, others…
-
Alpha-beta blockers Nursing Interventions•
- Administer oral labetalol with food•
- Do not stop drug abruptly•
- Prepare IV infusions of labetalol carefully•
- Patient safety, assist OOB/position changes•
- Observe the patient closely for signs of heart failure.•
- Monitor BP closely of patients receiving IV infusions of labetalol, particularlypost CVA (titrate carefully)
-
Centrally acting Alpha-2 Agonists• Prototype:
Clonidine (Catapress)
-
Clonidine (Catapress) Approved for:
HTN & Severe pain
-
Centrally acting Alpha-2 Agonists PD:
- Stimulates the alpha 2 receptors in the medulla oblongata,
- Inhibits neuron firing,
- suppresses release of NE from sympathetic NS,(so decreased activation of alpha & Beta A. receptors in periphery)
- inhibits sympathetic NS response•
- Reduced sympathetic outflow of NE= decreased HR, BP, decreasedvasoconstriction, decreased renal vascular resistance, but renal blood flowand GFR remain the same•
- Initial mild vasoconstriction when alpha receptors in periphery arestimulated, then sympathetic outflow is reduced (sympatholytic) and result isvasodilation•
- Reduces Renin activity, excretion of aldosterone and catecholamines•
- Little to no orthostatic hypotension, b/c equal positional BP lowering•
- Stimulates growth hormone release
-
Centrally acting Alpha-2 Agonists Transdermal drug: is released at a constant rate for 7 days, reapplyweekly to maintain therapeutic plasma levels (reach therapeutic at at2-3 days), lower level in plasma level from transdermal than oraldosing, half life 19 hours, if patch not replaced plasma level dropsafter 8 hours
Transdermal drug: is released at a constant rate for 7 days, reapply weekly to maintain therapeutic plasma levels (reach therapeutic at at 2-3 days), lower level in plasma level from transdermal than oral dosing, half life 19 hours, if patch not replaced plasma level drops after 8 hours
-
Centrally acting Alpha-2 Agonists PK:
- Well absorbed GI & skin, 40-60%,
- oral onset 30-60 min,
- peak 3-5hours,
- eliminated unchanged in urine,
- metabolized in liver
-
Centrally acting Alpha-2 Agonists PT:
- often a secondary or supplemental medication to lower BP(usually not a monotherapy)•
- Oral, parenteral, transdermal patch•
- Varied off label usage: sympathetic inhibition, *prevention of s/s of alcohol, methadone, or opiate withdraw during detox, constitutional growth delay in children, diabetic diarrhea, menopausal flushing, dxpheochromocytoma, allergen induced extrinsic asthma, others…
-
Centrally acting Alpha-2 Agonists: Clonidine Contras:
- Preg. Class C,
- caution with severe CAD,
- recent MI,
- CVA,
- chronic renal failure,
- very careful dilution of parenteral form (500mcg/ml),
- not recommendedfor epidural/obstetrical use
-
Centrally acting Alpha-2 Agonists: Clonidine Adverse Effects:
*dry mouth, *drowsiness, dizziness, sedation, constipation,*erythema. *Rebound HTN if withdrawn abruptly. (*transdermal) Many othersthat are less common, see textOver dosage: bradycardia, hypotension, CNS & Resp. depression, apnea,seizures, hypothermia, aggitaion, irritability, N/V/D, hypo-ventilationarrythmia….
-
Clonidine Nursing Interventions:
- Nursing Interventions:•
- Assess for cardiac or vascular disease•
- Teach how to monitor BP & pulse rate•
- Apply patch over a hairless area on upper torso/arm, rotate applicationsites when time to change (7 day), if loosens apply adhesive tape/dsg•
- Instruct dosage reduced gradually to prevent rebound hypertension•
- Discard patches safely•
- Ice chips/hard candy for dry mouth•
- Fluids/exercise to avoid constipation•
- Caution with work that requires alertness until effect of drug on person is known (drowsiness)
-
Peripheral Alphas Major differences from central alphas (clonidine)
- is unique therapeutic use:
- terazosin & doxazosin are used to treat benign prosthetic hyperplasia (BPH, relax smooth muscle in bladder neck and prostate gland due to alpha blockade, which increases urine flow)
-
Antihypertensives: General Nursing Care
- Monitor blood pressure and pulse during therapy•
- Some require BP and P before administering and at sometime interval after•
- Observe for orthostatic hypotension (take precautions)•
- Most require periodic monitoring of lab (very with drug)•
- If IV most have additional special precautions•
- Food decreases absorption to some extent
-
Specific Nursing Care• Angiotensin II Receptor Blockers (ARBs)
- • Avoid giving losartan with grapefruit juice, ok with food.
- • Monitor creatinine, BUN, hemoglobin, and hematocrit levels.
- • If taking a potassium supplement, contact prescribingprovider.
-
Specific Nursing Care Beta Blockers
- • Take pulse before each dose•
- Do not stop abruptly•
- Orthostatic hypotension precautions•
- Monitor I & O and daily weight
-
Vasodilator: Nitroprusside(Nitropress)• Mechanism of action
Directly & Rapidly relaxes vascular smooth muscle, allowing dilation of peripheral arteries and veins.
-
Vasodilator: Nitroprusside(Nitropress) Adverse reactions
- Severe hypotension•
- Cyanide toxicity; Particularly if infused too rapidly,•
- Not for patients with liver disease, or low thiosulfate stores in body (thecofactor needed to detoxify cyanide)•
- Can cause sodium retention, may need to administer a loop diuretic suchas Furosemide (Lasix) to excrete sodium
-
Vasodilator: Nitroprusside(Nitropress) Nursing Interventions•
- Must use infusion pump•
- Infusion must be titrated to reduce blood pressure withoutcompromising organ perfusion
- Start nitroprusside at a low infusion rate (0.3 mcg/kg per minute)and increase gradually until the desired effect has been achieved orthe maximum infusion rate (8-10 mcg/kg per minute) is attained.
- *Maximum infusion time 10 minutes Monitor BP continuously during therapy
- Monitor for cyanide toxicity and excessive hypotension
- IV solutions have a *faint brown color if brightly colored (blue,green, dark red, DISCARD)
*SOLUTION is degrade by light, opaqueIV bag needed, never mix with other drugs
-
Nitrates•
- Nitrates improve the circulation to the heart itself by redistributing bloodflow to the collateral vessels
- Nitrates dilate vascular smooth muscle and both venous and arterial vessels (although more relaxation occurs on the venous side).•
- Venous dilation decreases the returning flow of blood to the heart (preload).•
- Arterial dilation reduces systemic vascular resistance and arterial pressure (afterload).•
- These effects decrease the workload on the heart andits oxygen needs.
-
Nitrates Prototype drug:
nitroglycerin (Nitrostat)
-
nitroglycerin (Nitrostat) Admin.
- Topical Linguial spray,
- SL & IV,onset 1-3 min,
- transdermal 30-60 min.
- Duration IV 3-5 min,
- SL: 30-60 min,
- topical/transdermal: up to 24 hours.
- nIV only if all other medications not effective, continuous drip, continuous heart & BP monitoring, glass bottle &special tubing only
-
Treatment and prevention of anginapectoris, NOT used for HTN.
Given SL, 2.5-5mg; oral tablets (chewable orswallow) or capsules, *immediate and *sustained release. Oral 5-40mg,onset 20-40 min, longer duration than nitroglycerin, SL 1-2 hers, Oral 4-6hours. Less rapid relief of chest pain, limited to use of acute angina inpatient’s that are intolerant of SL nitroglycerine
Isosorbide dinitrate (Isordil)
-
Amyl Nitrate:
capsule that is crushed and vapors inhaled, onset 30-60seconds, duration 3-5 min, no effect on coronary arteries, highly flammable
-
Nitrates PD:
• Relaxes vascular smooth muscle and dilates both arterial and venousvessels.
-
Nitrates Patient and family education•
- Explain the purpose and adverse effects of nitroglycerin.•
- Instruct patients to sit or lie down when experiencing angina.•
- Explain that postural hypotension may occur, change positions slowly,sit for dose, refill and store appropriately: light sensitive•
- Explain how to administer SL form for angina attack: Sit/lie down &rest, place one tab under tongue, no eat/drink till after fullydissolved and absorbed, if chest pain not relieved in 5 min call 911and take another SL tab per above, up to three SL tabs in 15 minutes
-
Nitrates Nitrates Patient and family education• Explain how to administer SL form for angina attack
- : Sit/lie down &rest,
- place one tab under tongue,
- no eat/drink till after fully dissolved and absorbed,
- if chest pain not relieved in 5 min call 911 and take another SL tab per above,
- up to three SL tabs in 15 minutes
-
Amyl Nitrate: * Antidote for
Cyanide poisoning.
-
HDL Cholesterol LevelCategory
High HDL cholesterol. An HDL of 60 mg/dL and above is considered protective against heart disease
-
HDL Cholesterol
Good Cholesterol
-
IDLs become
- low density lipoproteins
- (“bad cholesterol”)
- These can deliverfat to the liverand by other tissues
-
LDL receptors:
- are necessary for th eliver to take them up
- Some LDLs are taken up by scavenger cells like macrophages
-
High-density lipoproteins -HDL
- (“good cholesterol”)
- are made in the liver
- They go out to the peripheral tissues and pickup lipid
- Then they carry itback to the liver
-
Statins Actions:
- Lower blood cholesterol levels and thus decrease the uptake of modified lipoproteins by vascular cells.
- Can lower LDL cholesterol by 20-60% when given at their maximum recommended dose.
- Raise HDL levels between 5 and 10% and lowertriglycerides between 10 and 33%.
- Evidence exists that statins work in other ways beside lowering cholesterol levels to decrease the occurrence of cardiovascular events
- Often first drug of choice b/c research backs decrease in cardiac related mortality
-
Statins Prototype drug:
lovastatin (Mevacor)
-
Statins Pharmacokinetics (PK)
- High first-pass effect.
- Highly protein bound.
- Excreted primarily through the gastrointestinal tract.
-
Statins Contraindications and precautions (Contras)
Active liver disease and pregnancy
-
Statins Pharmacodynamics (PD)
Competitively inhibits HMG-CoA reductase, which is the enzyme that catalyzes the early rate-limiting step in cholesterol biosynthesis.
-
Statins Pharmacotherapeutics (PT)
Used for primary hypercholesterolemia and combined hyperlipidemia.
-
Statins Adverse effects (AE)
Muscle & joint aches, weakness, cramps, muscle damage, liver damage, and rhabdomyolysis
-
Statins Drug interactions (DI)
- Itraconazole,
- erythromycin, and
- grapefruit juice
-
statins Health status
Assess cholesterol levels & past medical history
-
Statins Life span and gender
Pregnancy category X; assess age of patient.
-
Statins Lifestyle, diet, and habits
Treat elevated
-
Statins Minimizing adverse effects
- Liver function test (AST and ALT) results should be monitored before starting therapy
- Evaluate the patient carefully for muscle soreness,tenderness, or pain and CK levels
-
Statins Maximizing therapeutic effects
- **Most effective when administered in the evening
- *Immediate-release administered after evening meal
- *Extended-release administered at bedtime
-
Statins Ongoing assessment and evaluation
The patient should have liver function tests and CK measurement performed periodically throughout drug therapy.
-
Statins Patient and family education
- Stress the importance of following a lowc holesterol and low-saturated-fat diet.
- **Instruct patients to report any unexplained muscle pain, tenderness, or weakness.
- Photosensitivity may occur.
-
Closely Related to Lovastatin
- Atorvastatin (Lipitor), f
- luvastatin (Lescol),
- pravastatin (Pravachol),
- rosuvastatin
- (Crestor),
- and simvastatin (Zocor).
- All work similarly to lower LDL cholesterol andhave similar adverse effects.
-
Fibric Acid Derivatives: Two frequently used:
- Fenofibrate (Tricor, Lipofen),
- Gemfibrizol (Lopid, Gemcor)
-
Fenofibrate (Tricor, Lipofen),Gemfibrizol (Lopid, Gemcor)
Similar drugs, pharmacodynamics not clearly understood, Fenofibrate: believed to lower plasma triglycerides by inhibiting the synthesis of triglycerides & amount of VLDL released in blood,and helps catabolize VLDL. Gemfibrozilmay inhibitperipheral lipolysis & reduce hepatic triglycerideproduction.
-
Cholesterol Absorption Inhibitors
- Ezetimibe (Zetia) – anti-lipid drug used for hypercholesterolemia
- Pediatric use - restricted to children older than 10years of age with familial homozygous hypercholesterolemia
- Given orally once daily either as mono-therapy or in combination therapy with a statin
- It localizes and appears to act at the brush border of the small intestine, where it inhibits the absorption of cholesterol.
- Decreases LDL about 17% but has no effect on HDL or triglyceride
-
Nicotinic Acid
- Nicotinic acid (niacin or vitamin B3) is used to treathyperlipidemia.
- Reduces levels of triglycerides and LDL cholesterol levelsand raises levels of HDL cholesterol.
- Triglycerides and VLDL levels are reduced by 25% to 30% in1 to 4 days. LDL level reductions may be seen in 5 to 7 days,with the maximal effect seen in 3 to 5 weeks
-
Nicotinic Acid Adverse effects
- The newer sustained-release forms of nicotinic acid have fewer adverse effects
- Larger doses produce peripheral vasodilation, mostly in the cutaneous vessels of the face, neck, and chest(*Teach to take Ibuprofen or an NSAID 30-60 min prior to said prevent this adverse effect*)
-
Nicotinic Acid Contraindications:
- hepatic dysfunction,
- active peptic ulcer,
- severe hypotension,
- and hemorrhaging.
-
Bile Acid Sequestrants
- cholestyramine(LoCholest, Questran, Prevalite) and colestipol (Colestid)
- are used to reduce elevated serum cholesterol levels in patients with primary hypercholesterolemia who have not responded to other drug therapy
- Not absorbed orally but work in the lower GI tract.
- Reduction in LDLs is apparent in 4 to 7 days andranges between 15% and 30%
- promote the oxidation of cholesterol to bile acids
- Constipation is a side effect
-
Unfractionated Heparin•
- Rapid-acting anticoagulant:
- only parenteral
-
Unfractionated Heparin PD:
- suppresses coagulation by helping anti-thrombin inactivate clotting factors, primarily thrombin &factor Xa; which ultimately suppresses formation of fibrin•
- fibrin forms clots in veins, so heparin is useful in preventing & treating venous thrombi
-
Unfractionated Heparin PK:
- • Absorption and Distribution- Unable to cross membranes, (i.e. placental or breastmilk)
- cannot be absorbed orally•
- Protein/Tissue Binding- Binds
- nonspecifically to many cells, to free heparin it highly variable•
- Metab./Excretion- Half-life is short(about 1 ½ hrs) in normal liver/renalfunction; Longer in liver/renal impairment•
- Time Course- IV bolus is given followedby infusion, or given via Subcutaneous
- Adjunct to other thrombolytic therapy in acut emyocardial infarction (MI)
-
Unfractionated Heparin Therapeutic Uses:
- Preferred anticoag. in pregnancy, & in situations requiring rapid onset of anticoagulant effects
- :pulmonary embolism (PE), evolving stroke,and massive deep vein thrombosis (DVT).•
- Used in open heart surgery and renal dialysis to prevent coagulation in heart-lung & dialysis machines•
- Low-dose therapy to prevent post operative venous thrombosis (often SC injection).•
- Can be used to treat disseminated intravascular coagulation (DIC)
-
Unfractionated Heparin Adverse Effects:
- Hemorrhage- bleeding develops in 10% of pt’s, main complication, can occur anywhwere in body, can be fatal.
- If bleeding develops, stop heparin!
- **Antidote: CAN REVERSE BLEEDING WITH **PROTAMINE SULFATESpinal/Epidural Hematoma-pressure on the spinal cord caused by bleeding, results in paralysis (can be permanent)•
- Risk is increased by: use of indwelling epidural catheter, use of other anticoagulants, use of antiplatelet drugs,Hx of traumatic or repeated epidural or spinal puncture, spinal deformity orinjury/surgery
- Heparin-Induced Thrombocytopenia(HIT)- potentially fatal immune-mediated disorder characterized by reduced platelet count & paradoxal increase in thrombotic events. Thrombus formation=risk of DVT, PE, CVA, & MI.
- STOP heparin & give non-heparinanticoagulant, Watch platelet counts,<100,000 should stop heparin.
-
Unfractionated Heparin Precautions/Contras:
- • Use with extreme caution in pts with high likelihood of bleeding(hemophilia, increased capillary permeability, dissecting aneurysm, peptic ulcer disease, severe hypertension or threatened abortion)
- *Caution in severe liver/renal disease•
- Contraindications- NOT for use in pts with thrombocytopenia & uncontrolled bleeding. Avoid during & immediately after eye, brain, or spinal cord surgery,also lumbar puncture & use of regional anesthetics
-
Unfractionated Heparin Drug Interactions
- Caution with in antiplatelet medications
- PROTAMINE SULFATE FOR HEPARIN OVERDOSE
-
Unfractionated Heparin Laboratory Monitoring:
- Activated Partial Thromboplastin time (aPTT,also abbreviated PTT
- normal range 24- 40seconds)
- Therapeutic usually 1.5- 2.5 X the control (normal)
- Heparin increases aPTT to 60-80 seconds
- MUST MONITOR aPTT contant, daily ormore
-
Low-Molecular Weight Heparin(LMW)
- LMWH preparations composed of molecules that are shorter than in unfractionated heparin•
- As effective as unfractionated heparin & easier to use•
- Now considered first-line therapy for prevention and treatment of DVT•
-
Low-Molecular Weight Heparin(LMW)Four products available
- : *enoxaparin(Lovenox),
- *fondaparinux, (Arixtra),
- dalteparin (Fragmin),
- and tinzaparin(Innohep)
-
Low-Molecular Weight Heparin(LMWH)• Therapeutic Use- (Approved)
- • Prevention of DVT following surgery(abdominal, hip & knee replacement)•
- Treatment of established DVT, with or without PE•
- Prevention of ischemic complication inpts with unstable angina, non Q-wave MI and ST-elevation MI.
-
Low-Molecular Weight Heparin admin.
- All LMW heparins are administered subcutaneously
- Dosage is weight-based & adjusted according to aPTT measurements (but doNOT need to follow aPTT daily)
- Typically given once or twice a day
-
Low-Molecular Weight Heparin• Adverse Effects and Interactions:
- *Bleeding (less than unfractionated heparin)• Thrombocytopenia•
- OVERDOSE CAN BE TREATED WITHPROTAMINE SULFATE•
- Severe neurologic injury- including permanent paralysis when given to pts undergoing spinal puncture or spinal or epidural anesthesia.
- –Risk is higher in pts with concurrent use of antiplatelet drugs
-
Warfarin (Coumadin, Jantoven)
- Vitamin K antagonist,
- oldest oral anticoagulant
- Used to prevent thrombosis,
- but has delayed onset (about 2-3 days for peak effects)
- Often used for long-term prophylaxis
-
Warfarin (Coumadin, Jantoven) PD:
- Suppresses coagulation by decreasing production of four clotting factors VII, IX,X & prothrombin
- (Vitamin K dependent clotting factors)
-
Warfarin (Coumadin, Jantoven)• Time Course:•
- Half-life 6 hrs-2.5 days,
- initial response may not be evident until 8-12 hrs after first dose•
- Peak effect takes several days•
- When stopped it takes 2-5 days for new clotting factors to develop adequately.
-
Warfarin (Coumadin, Jantoven) Therapeutic Uses:
- Prevention of venous thrombosis &associated PE
- Prevention of thrombo-embolism in pts with prosthetic heart valves
- Prevent of thrombosis in pts with atrialfibrillation
- Reduce the risk of recurrent transientischemic attacks (TIA) & recurrent MI
- Atrial Fibrillation-high risk of CVA 2nd to clot formation in atrium.
- Warfarin is still widely used, two new drugs: dabigatran (Pradaxa)and rivaroxaban (Xarelto) are easier to use,
-
Warfarin (Coumadin, Jantoven) Monitoring Treatment:
- • Prothrombin Time (PT) the coagulation test sensitive to alterations in vitamin K-dependent clotting factors
- –Average pretreatment clotting time: 12 seconds(average range 10-15 seconds)
- – PT control 12 – 15 sec; Therapeutic 1.5 -2.5 Xcontrol• International normalized ratio (INR) is now the test of choice, but monitor BOTH
- Normal INR – 0.75-1.25; Therapeutic is 2-4.
- Goal of INR 2-3 sec for most pts.
- – Goal of INR 3-4 is sometimes recommended forprosthetic heart valves and a few other conditions•
- INR daily first 5 days of treatment, adjust dose accordingly, then twice a week for the next 1-2 weeks,then once a week for 1-2 months, finally once every
-
Warfarin (Coumadin, Jantoven) Adverse Effects:
- Hemorrhage-Bleeding is the major complication, can occur at any site
- Monitor closely for signs of bleeding(reduced BP, increased heart rate,bruises, petechiae, hematomas, red or black stools, cloudy or discolored urine,pelvic pain, headache, and lumbar pain).
- OVERDOSE CAN BE TREATED WITHVITAMIN K (antidote) Fetal Hemorrhage and Teratogen; Do NOT use in pregnancy, Category X Breast-Feeding- Warfarin enters breastmilk, should NOT breast feed
-
Warfarin (Coumadin, Jantoven) Drug Interactions:
- Drugs that increase the effects of warfarin:– ex: Aspirin
- Drugs that promote bleeding:
- Drugs that decrease the effects of warfarin:– Carbamazepine, phenobarbital, phenytoin, rifampin, oral contraceptives, vitamin K, cholestyramine, colestipol.
-
Warfarin (Coumadin, Jantoven) Nursing Interventions:
- o Educate well
- o Take coumadin same time every day (5-6pm)
- o Can be crushed if needed & can take with food
-
Direct Thrombin Inhibitors• Dabigatran Etexilate (Pradaxa) Therapeutic Uses:
- Atrial Fibrillation- Prevention of stroke or systemic embolism in pts with nonvalvular vatrial fibrillation.(Dose 150 mg BID)
- Knee or Hip Replacement- Prevention of venous thrombo embolism (220 mg Daily)
-
Aspirin PD:
Suppresses platelet aggregation by causing irreversible inhibition of cyclooxygenase (an enzyme needed by platelets to synthesize thromboxane A2)
-
Aspirin Indications for antiplatelet therapy:
- Ischemic stroke (reduce risk of death & nonfatalCVA)
- Transient ischemic stroke (TIA, to reduce the riskof nonfatal/fatal CVA)
- Chronic stable angina(reduce risk MI & suddendeath)
- Unstable angina (reduce combined risk of death/MI)
- Coronary stenting (to prevent re-occlusion)
- Acute MI (reduce the risk of vascular mortality)
- Previous MI(to reduce the combined risk ofMI/death)
-
Aspirin is used for primary prevention, is typically dosed at
81 mg/day
-
Aspirin Adverse Effects:
- Risk of GI bleed◦
- Proton pump inhibitors reduce the risk of GI bleeds, & Peptic ulcer disease
- Risk of hemorrhagic stroke
-
P2Y12 Adenosine Diphosphate Receptor Antagonists
Block the P2Y 12 ADP receptor on platelets and reduce ADP stimulate daggregation
-
P2Y12 Adenosine Diphosphate Receptor Antagonists Four are available:
- Clopidogrel (Plavix),
- prasugrel (Effient),
- ticlopidine (Ticlid),
- and ticagrelor (Brilinta)
- The first three cause IRREVERSIBLE receptor blockage. The last has reversible receptor blockade.
-
P2Y12 Adenosine DiphosphateReceptor Antagonists Clopidogrel (Plavix) Adverse Effects:
- mild GI: dyspepsia (can take with food), abd. pain, diarrhea, rash
- Bleeding- Risk of serious bleeding, but causes less GI bleeding and less intracranial hemorrhage than aspirin.
-
Teach s/s of bleeding Plavix
and to call MD; Do NOT stopp lavix unless MD says to stop (often stopped 5 days before surgeries)
-
Hemorheologic Drugs PD:
- Act on the RBC to increase the flexibilityof RBC and reduce blood viscosity;
- thereby prevent thrombus formation & increase oxygenation of cells through microvasculature
-
Hemorheologic Drugs PT:
PAD, to manage intermittent claudication(many off label uses)
-
Hemorheologic Drugs Prototype:
Pentoxifylline (Trental)
-
Hemorheologic Drugs Metab:
RBC & Liver, 4-8 weeks till full effect
-
Hemorheologic Drugs Adverse:
- CNS, CV &GI: HA, dizziness,tremor, dyspepsia, N/V, (Give with food) others less common; pg.614, No Alcohol(CNS),
- No smoking, (causesvasoconstriction)
- Baseline assessment of
-
Thrombolytic (Fibrinolytic)Drugs
Given to remove (dissolve) thrombi that have already formed. (Anticoagulants are for PREVENTION of thrombi)
-
Thrombolytic (Fibrinolytic)Drugs Three drugs:
alteplase (tPA), reteplase(Retavase), and tenecteplase (TNKase)
-
Absolute Contraindications for Thrombolytics:◦
- Any prior intracranial hemorrhage◦
- Known structural cerebral vascular lesion◦
- Ischemic stroke within last 3 months(except ischemic stroke within 4.5 hrs)◦
- Known internal bleeding◦
- Active internal bleeding (other than menses)◦ Suspected aortic dissection
-
Kidney, 3 functions:
- – Cleansing of extracellular fluid and maintenance of ECF volume and composition
- – Maintenance of acid-base balance
- – Excretion of metabolic wastes and foreign substances.
-
PD:**Diuretics work
by interfering with reabsorption
-
Diuretics PD
- Most diuretics share same mechanism of action: blockade of sodium and chloride reabsorption–
- Creates osmotic pressure inside nephron that blocks passive reabsorption of water
- – If water and solutes are not reabsorbed, they are excretedfrom the body•
- The increase in urine flow is directly related to the amount of sodium & chloride reabsorption blocked•
- Diuretics that act early in nephron block the greatest amount of solute reabsorption (greatest results)•
- Diuretics increase urine output (UOP) by 1.8 L forevery 1% of solute reabsorption that is blocked; if give TOO much, = dehydration
-
Adverse Effect: Impact on ECF• Diuretics can cause:
- – Hypovolemia (from excessive fluid loss)
- – Acid-base imbalance
- – Altered electrolyte levels.
- – Short-acting diuretics minimize these effects.
-
Classification of Diuretics
- High ceiling (Loop) diuretics- Furosemide (Lasix)
- Thiazide diuretics – hydroclorothiazide (HCTZ)
- Osmotic diuretics – mannitol (Osmitrol)
- Potassium-sparing diuretics:
- – Aldosterone antagonists – spironolactone (Aldactone)
- – Nonaldosterone antagonists- triamterene (Dyrenium)
-
High-Ceiling (Loop) Diuretics
- Most effective diuretics available
- Produce more loss of fluid & electrolytes than any other diuretic
- Furosemide (Lasix) is most frequently prescribed loop diuretic
-
Loop Diuretics: Furosemide
- Sulfa based drug* assess hypersensitivity
- Acts in ascending limb, Loop of Henle; blocks reabsorption of sodium & chloride
- Can produce profound diuresis
- Can be given orally (diuresis starts within 60 minutes, lasts 8 hrs), IV (diuresis in 5 minutes,lasts 2 hrs) and IM.
- • *IV therapy is used in critical situations (pulmonary edema)•
- *Typically used when less powerful diuretics no longer (*but not always)
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Loop Diuretics: Furosemide• Therapeutic Uses:•
- Pulmonary edema associated with congestive heart failure•
- Edema of hepatic, cardiac or renal origin that is unresponsive to less efficacious diuretics•
- Hypertension that cannot be controlled with other diuretics
- Especially useful in pts with severe renal impairment, can promote diuresis even when renal blood flow and glomerular filtration rate are low
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Loop Diuretics: Furosemide• Adverse Effects:
- Hyponatremia, Hypochloremia & Dehydration b/c can produce excessive loss of sodium, chloride, & water
- Orthostatic Hypotension – Due to loss of volume and relaxation of venous smooth muscle (reduces venous return to the heart).
- Hypokalemia- Potassium loss due to increased secretion in distal nephron
- Ototoxicity- Rarely causes permanent deafness/hearing impairment, most hearing impairment is transient, (Usually in high dose, IV,renal impaired)
- Hyperglycemia- Can result from inhibition of insulinrelease. Watch closely in diabetic pts. (uncommon)•
- Hyperuricemia- Frequent, most pts area symptomatic, but for pts predisposed to gout can cause a gout attack
- Pregnancy- Class C,
- Lipids, Calcium & Magnesium- Furosemidedecreases HDL, raises LDL cholesterol &triglycerides. Increases risk of magnesium deficiency, increased excretion of calcium (*elders with Osteoporosis are at risk for fractures)
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Loop Diuretics: Furosemide• Drug Interactions:
- Digoxin- If potassium is low, serious risk of druginduced toxicity (ventricular dysrhythmias)
- Ototoxic drugs- (Especially gentamycin) can causepermanent hearing loss. Avoid combined use ofthese drugs.
- Potassium-Sparing Diuretics- Can reduce the riskof hypokalemia
- Lithium- Can allow lithium levels to accumulate totoxic levels
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Other Loop Diuretics:
- • Ethacrynic acid (Edecrin) Not sulfa based, safe foruse in sulfa allergy, not for use in children, for edema only, not HTN
- Torsemide (Demadex) metab. to active & inactive metabolites
- Bumetanide (Bumex) for edema only, more potent,*black box warning: More profound diuresis (H2O &electrolytes), not for children, *careful dosing
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Loop Diuretics: Furosemide• Drug Interactions:•
- Anithypertensive Agents- Furosemide can cause hypotension, potentiated by antihypertensive drugs•
- Nonsteroidal Aspirin, Anti-inflammatory Drugs(NSAIDS)-
- Decrease the effects of diuretics, ACEinhibitors (1st dose hypotension) others… see table
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Loop Diuretics: Furosemide Contra’s:
Sulfa allergy/hypersensitivity, Precautions:*poor renal function, SLE (lupus) Assess
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Thiazide Diuretics• PD:
- Increase renal excretion of sodium, chloride,potassium, & water•
- Elevates plasma levels of uric acid & glucose•
- Greatest difference between thiazides & loop diuretics: maximum diuresis of thiazides is considerably lower than in loop diuretics•
- Thiazides are not effective when urine flow isscant (anuria, severe renal failure)•
- Sulfa based drug
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Thiazide Diuretics drug
Hydrochlorothiazide (HydroDIURIL, HCTZ) most widely used thiazide diuretic
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Thiazides: Hydrochlorothiazide• Therapeutic Uses:•
- Essential Hypertension- Primary use is for HTN, and is often FIRST DRUG OF CHOICE.•
- Edema- Mild to moderate, heart failure•
- Diabetes Insipidus- Causes fluid retention instead(unsure why)•
- Postmenopausal Osteoporosis Protection, Promotestubular reabsorption of calcium
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Thiazides: Hydrochlorothiazide• Adverse Effects:
- • Hyponatremia, Hypochloremia & Dehydration-Milder than loop diuretics•
- Hypokalemia- Eat potassium rich foods,
- *careful if taking digoxin.•
- Pregnancy and Lactation: Direct and Indirect effects on developing fetus, and impair fetal blood flow– Should not be used routinely during pregnancy,caution
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Thiazides: Hydrochlorothiazide• Adverse Reaction:
- Hyperglycemia- Can elevate glucose in diabetic pts•
- Hyperuricemia- Retention of uric acid, can causegout.•
- Lipid and Magnesium- Increase LDL, total cholesterol and triglycerides. Can cause magnesium deficiency.
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Thiazides: Hydrochlorothiazide• Drug Interactions:
Same as loop diuretics, Slightly different chemical structure, indications for use, PK’s
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Potassium-Sparing Diuretics
- • Produce increased urine production, but limited,so not often used for diuresis•
- Produce substantial decrease in potassium excretion, so these drugs are often used to counteract potassium loss caused by thiazide & loop diuretics.
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Potassium-Sparing Diuretics Two subcategories
- :– Aldosterone Antagonists
- - spironolactone (Aldactone)
- – Non-aldosterone antagonists
- - triamterene(Dyrenium) and amiloride (Midamor)
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Potassium-Sparing Diuretics:Spironolactone• PD:
- Blocks the actions of aldosterone in distal tubule, (blocks all aldosterone receptors:glucocorticoid, mineral corticoid, androgen, &progesterone)•
- Aldosterone promotes sodium uptake in exchange for potassium secretion
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Potassium-Sparing Diuretics:Spironolactone• PD:
Spironolactone causes retention of potassiumand increased excretion of sodium
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Potassium-Sparing Diuretics:Spironolactone (Aldactone)• Therapeutic Uses:
- HTN & Edema- Most commonly used in combination with a loop or thiazide diuretic to counteract the potassium-wasting effects of the more powerful diuretics•
- Heart Failure (CHF) Proven to reduce mortality andhospital admissions•
- Other Uses- Primary hyper-aldosteronism, Offlabel: premenstrual syndrome, polycystic ovarysyndrome, acne * assess what drug is used for
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Potassium-Sparing Diuretics:Spironolactone• Adverse Effects:•
Hyperkalemia- Most likely when spironolactone isused alone, stop use if hyperkalemia develops
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Potassium-Sparing Diuretics:Spironolactone• Drug Interactions
- Thiazide & Loop diuretics- given to counteract the potassium-wasting effects.•
- Agents that raise potassium levels should never be given with potassium supplements, salt substitutes or another potassium-sparing diuretic
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Osmotic Diuretic: Mannitol•
- Mannitol is the only osmotic diuretic on the market•
- Simple, six-carbon sugar
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Osmotic Diuretic: Mannitol•PD:
- Mechanism of Diuretic Action
- :– Freely filtered at the glomerulus
- – Undergoes minimal tubular reabsorption
- – Undergoes minimal metabolism
- – Is pharmacologically inert (no direct effects on biochemistry or physiology of cells)
- – Pulls off fluid by increased osmotic force/pressure
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Osmotic Diuretic: Mannitol• Administered
IV, most of the drug makes it past the glomerulus, creates increased osmotic force that inhibits passive reabsorption of water (Urine flow increases).
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Osmotic Diuretic: Mannitol• Therapeutic Uses:
- Prophylaxis of Renal Failure- (dehydration,severe hypotension, hypovolemic shock) cause slow blood flow to the kidney, causing reduction in filtrate volume. Ceases urine production,=kidney failure•
- Mannitol pulls water into the nephron (even when blood flow is low), preserves urine output & may prevent kidney failure
- Reduction of Increased Intracranial Pressure
- Reduction of Increased Intra-occular Pressure
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Osmotic Diuretic: Mannitol• Adverse Effects:
Sudden increase of ECF / Edema- can leave the vascular space at all capillary beds except the brain. It will draw water with it which causesedema. Watch for *CHF & *pulmonary congestion (most succeptible: pt’s with history of these).
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Osmotic Diuretic: Mannitol• Nursing Interventions
- Administer only on a pump, low test dose on all patients with renal impairment, patient on heart monitor, monitor ECG tracings•
- Monitor UOP constantly & carefully•
- Assess vitals,*BP, pulse•
- Assess lung sounds•
- High risk for major F/E changes, *safety, orthostatic hypotension
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Osmotic Diuretic: Mannitol Contra’s/Prec:
children, CHF pts, Preg class C, elderly with caution, renal failure, electrolyte imbalance, others…
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hypoglycemia is and the CM *BS frequently
- less than 70mg/dl,
- 50-60 start feeling symptoms but varies in each person.
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Regular Insulin Pharmacotherapeutics
All types of diabetes mellitus
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Regular Insulin:Pharmacokinetics
- Administered: SC or IV.
- *Only insulin that can be given IV
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Regular Insulin: Pharmacodynamics
Injected insulin mimics the effect of endogenous insulin
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Regular Insulin: Contraindications and precautions
Hypoglycemia (BG <50)
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Regular Insulin:Adverse effects
Hypoglycemia and lipoatrophy
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Regular Insulin: Drug interactions
- *Alcohol,
- *beta blockers: mask hypoglycemia, dobutamine,
- niacin,
- MAOIs,
- thiazide diuretics, and
- tetracycline,
- *These and other hypoglycemic agents increase risk of hypoglycemia;Hyperglycemic agents (steroids) counteract effects of insulin
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Regular Insulin: Planning & Interventions Maximizing therapeutic effects
- Store opened vials of regular insulin at room temperature.
- Administer regular insulin with an insulin syringe into an appropriate subcutaneous site.
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Regular Insulin: Planning & Interventions Minimizing adverse effects
- Injection-site rotation also helps prevent lipodystrophy.
- Assess blood glucose level prior to administration.
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Three rapid-acting insulins;
- aspart (NovoLog)
- lispro (Humalog)
- glulisine (Apidra).
- Administer within 15 minutes of start of the meal.
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Intermediate Insulin: NPH
- Onset: 1–2 hours.
- Peak: 6–14 hours.
- Duration: up to 24hours
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Glargine (Insulin) Duration:
Onset: 1 hr , 24 hours. No peak.
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Two classes are Oral Antidiabetic agents:
- 1. Sulfonaureas: Glyburide (Diabeta); Glipizide (Glucotrol)
- 2. Meglitinides Repaglinide (Prandin) Nateglinie (Starlix)
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Four classes Antihyperglycemic agents or insulin sensitizers:
- 1.*Biguanides, *Metformin, (Glucophage),
- 2.Thiazolinediones, Rosiglitazone (Avandia) & Pioglitizone (Actos)
- 3. Alpha-glucosidase inhibitors : Acrabose (Precose); Miglitol(Glyset)
- 4. Gliptins: (DPP-4 inhibitors) Sitagliptin (Januvia), linagliptin,Saxagliptin
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Oral Antidiabetic Medications Prototype drug:
Glyburide (DiaBeta), also Glipizide (Glucotrol)
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Glyburide: Core Drug Knowledge PT:
Adjunct TX to lower blood glucose levels in DM type 2.
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Glyburide: Core Drug Knowledge PK: Administered:
oral.
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Glyburide: Core Drug Knowledge
Metabolism:
Excreted:
Metabolism: liver.
Excreted: urine and feces.
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Glyburide: Core Drug Knowledge Onset:
2 hours. Protein bound.
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Glyburide: Core Drug Knowledge Onset:PD:
- Hypoglycemic action of glyburide results from the stimulation of pancreatic beta cells.
- * Not effective intype 1 DM,
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Glyburide: Core Drug Knowledge Contraindications and precautions◦
- Hypersensitivity,
- & Hypersensitivity to Sulfa drugs,
- not foruse in pregnancy/lactation
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Glyburide: Core Drug Knowledge Adverse effects◦
Hypoglycemia, anorexia, nausea, vomiting, heartburn, metallictaste/mouth, rare: research about possible CV toxicity
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Glyburide: Core Drug Knowledge Drug interactions◦
- Drug interactions are possible because these drugs are metabolized by the CYP3A3/4 system, *Alcohol,
- beta blockers
- 9block insulin release, mask hypoglycemia), & drugs that can intensify Hypoglycemia:
- *, sulfa antibiotics,
- NSAIDS
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Glyburide: Planning & Interventions Maximizing therapeutic effects
- Administer glyburide before breakfast or the first main meal of the day
- A second dose may be given before dinner if needed
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Glyburide: Planning & Interventions Minimizing adverse effects
- Monitor the patient’s blood glucose levelsvperiodically throughout therapy to detecthypoglycemia, why?
- Monitor patients with renal and hepatic impairment for signs of adverse effects
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Glyburide: Teaching, Assessment &Evaluation Patient and family education
- Teach about patient/family diabetes management
- Teach the S/S of hypoglycemia
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Glyburide: Teaching, Assessment &Evaluation Ongoing assessment and evaluation
Interview the patient and family and observe for therapeutic and adverse responses to glyburide and adherence to TX(s)
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Meglitinides Repaglinide (Prandin):PT:
Adjunct TX to lower blood glucose levels in DM type 2.
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Meglitinides Repaglinide (Prandin): PK:
Admin.: oral before each meal. Metab.: liver. Excreted:primarily in feces., therefore preferred in patients whoare elderly or w/decreased renal function. Onset: 30minutes. Protein bound.
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Meglitinides Repaglinide (Prandin): PD:
(similar to sulfonylureas, differ chemically) Hypoglycemic action similar, stimulates beta cells, but more rapid absorption & shorter duration, than glyburide, advantage: rapid excretion prevents beta cells from being overly stimulated=Less like to cause hypoglycemia. Only taken if food is eaten
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Nonsulfonylureas/Antihyperglycemics Prototype drug,
1. Biguanide: *Metformin:(Glucophage
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Metformin:PK:◦
Administered: oral. Metabolism: liver. Excreted: kidneys.
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Metformin:Pharmacodynamics◦
Decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake in skeletal muscle and adipose tissue cells
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Metformin:Contraindications and precautions
- Hepatic disease,
- *Renal disease,
- *Uncompensated Heartfailure,
- *Lactic acidosis (most often in renal disease, CHF )
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Metformin: Adverse effects
- Anorexia,
- nausea and vomiting,
- weight loss,
- abdominal discomfort,
- dyspepsia,
- flatulence,
- diarrhea,
- and a metallic taste sensation
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Metformin:PT:
- Adjunct to lower blood glucose in type 2 DM.
- Also lowers Triglyceride and LDL Levels, promotes weight loss.◦
- Other (off label)uses: trials promising for Gestational Diabetes,Polycystic ovarian disease, (lowers androgen levels) others…
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Metformin:Drug interactions
- May react with contrast media used for radiographicprocedures
- *held for at least 48 hours, Alcohol*
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Metformin: Core Patient Variables
- Assess medical hx/current medical status,
- Pregnancy category B.
- Lifestyle, diet, and habits
- Assess diet, exercise and alcohol intake
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Metformin: Planning & Interventions Minimizing adverse effects◦
Taking the drug at mealtimes and using gradual dosage increments minimize these effects.
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Metformin: Planning & Interventions Maximizing therapeutic effects◦
- Administer metformin twice a day with the morning and evening meal.◦
- Adherence with the recommended diabetic diet and daily exercise help in the control of type 2 DM
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Metformin: Teaching, Assessment &Evaluation
- Patient and family education
- Teach patients to take metformin with meals, morning and evening.
- Emphasize that patients should not use alcohol while taking metformin.
- Ongoing assessment and evaluation
- Monitor blood glucose levels (fasting and hemoglobin A1C)throughout metformin therapy.
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Nonsulfonylurea # 2 ThiazolidinedionesPK /Mode of action:
- Improves insulin sensitivity in muscle & adipose
- suppresses glucose production in liver
- Decreases intestinal absorption of glucose
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Nonsulfonylurea # 2 Thiazolidinediones Prototype drug:
Rosiglitazone (Avandia)& Pioglitazone (Actos)
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Rosiglitazone (Avandia):PT:
- Adjunct TX to diet and exercise lower BG in type 2 DM.◦
- Does not promote weight loss◦
- Used alone, with sulfonylurea, metformin, or insulin
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Rosiglitazone (Avandia): PK:
Adm oral. Metab.: liver through the P-450 system—2C8& 2C9 (not major pathways). Protein bound. Excreted:kidneys and GI tract
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Rosiglitazone (Avandia):PD:
- ◦ Activates receptor PPAT gamma in nucleus which turnson insulin responsive genes to regulate carb & lipidmetabolism to:
- Decrease hepatic glucose production,and improves insulin sensitivity by increasingperipheral glucose uptake in muscle & adipose tissues
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Rosiglitazone (Avandia):Contra’s
Heart failure, Hepatic disease, may increase LDL,triglyceride levels and elevate HDL
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Rosiglitazone (Avandia):Adverse effects
- URI, HA, Moderate weight gain, *edema/fluid retention (rare but can exacerbate Heart Failure) mild anemia, hepatic toxicity,women—increased risk of falls & fractures; lactic acidosis,
- *Hypoglycemia,
- *women may resume ovulation and will need alternate birth contro
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Rosiglitazone (Avandia):Drug interactions
Rifampin & Cimetidine decrease blood level o frosiglitazone; Gemfibrizol, Atorvastatin & ketoconazoleincrease levels & risk of hypoglycemia, insulin alsopromotes fluid , caution when used together
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Alpha-glucosidase Inhibitors.
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Alpha-glucosidase Inhibitors.Prototype drug: Acarbose (Precose) also Miglitol (Glyset)
Acarbose (Precose) also
Miglitol (Glyset)
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Alpha-glucosidase Inhibitors.Mode of action:
- Improves insulin action
- Delays the digestion of carbohydrates
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Acarbose (Precose), & Miglitol (Glyset) PT
: Adjunct to type 2 DM Tx, results in substantial reduction inpost prandial glucose levels, can be used alone incombination with sulfonylurea, metformin or insulin.
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Acarbose (Precose), & Miglitol (Glyset)PK:
Administered: oral with first bite of food. Slows downenzymes that digest CHO in the small intestine, inhibitspancreatic alpha amylase—reducing rate of digestion ofcomplex CHO = less glucose absorption. Metabolism: GItract Excreted: kidneys and GI tract.
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Acarbose (Precose), & Miglitol (Glyset)PD:
Inhibits alpha glucosidase, enzyme on the brush borderof small intestine needed to break down sugars andcomplex carbs into monosacharides that can beabsorbed, slows digestion of CHO=*Lowers postprandialserum glucose
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Acarbose (Precose), & Miglitol (Glyset) Contra’s:
Diseases of the bowel, hiatal hernia or conditions exacerbated by increased formation of gas, chronic liver disease, renal impairment. Treat hypoglycemia with oral glucose tablets, not table sugar WHY?
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Acarbose (Precose), & Miglitol (Glyset) Adverse effects
Flatulence, diarrhea, abdominal pain; does not causehypoglycemia, hyperinsulinemia or weight gain; lacticacidosis.
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Acarbose (Precose), & Miglitol (Glyset) Drug interactions
Increase blood glucose levels with steroids; effects decreased with intestinal absorbents—activated charcoal, pancreatic enzymes.
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Glucose-Elevating Agents
- Glucagon is a hyperglycemic polypeptide hormone produced by the alpha cells of the pancreatic islets of Langerhans.
- Its physiologic effect is generally the opposite ofthat of insulin.
- Glucagon is the body’s first line of defense against hypoglycemia.
- Main stimulus to glucagon secretion: decrease inintracellular glucose concentrations when adrop in serum blood sugar.
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Glucagon: PT:
Hypoglycemia
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Glucagon: PK:
T½: 3 to 10 minutes.
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Glucagon:PD:
Increases blood glucose levels by stimulating glycogenolysis in the peripheral tissues
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Glucagon:Adverse effects
- Hypotension,
- respiratory distress,
- nausea and vomiting
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Glucagon:Drug interactions:
Oral anticoagulants
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Glucagon:Nursing Diagnosis:
- • Risk for Injury related to hypotension from the adverse effects of glucagon•
- Desired outcome: substantial hypotension will not resultfrom glucagon treatment.
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Glucagon: Planning & InterventionsMaximizing therapeutic effects
- Use reconstituted glucagon immediately
- A dose of 0.5 to 1 mg is usually effective
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Glucagon: Minimizing adverse effects
Administer supplemental carbohydrates as soon as possible once consciousness has been achieved,followed by protein, Why?
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Glucagon: Teaching, Assessment &Evaluation
- Education (Pt. & Family)
- Emphasize measures to prevent hypoglycemicreactions from insulin
- Instruct on proper technique for emergency administration of glucagon
- Ongoing assessment and evaluation
- Monitor blood glucose levels before, during, & after glucagon administration
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