REVIEWER FOR PHARMA Chapter 22 Types of Lipids 1.

Triglycerides (neutral fats) major storage form of fat in the body and only type of lipid that serves as an important energy source; 90% of total lipids in the body 2. Phospholipids essential to building plasma membranes (ex. Lecithin) 3. Steroids such as CHOLESTEROL building blocks of vitamin D, bile acids, cortisol, estrogen and testosterone Lipoproteins transports lipids in the body Types of Lipoproteins 1. Low-density lipoprotein (LDL)/bad cholesterol- transports cholesterol from the liver to the tissues and organs. Cholesterol is then stored in tissues (including blood vessels) for later use. (Normal values: <100 optimal; 100-129 near or above optimal; 130-159 borderline high; 160-189 high; >190 very high) 2. Very low-density lipoprotein primary carrier of triglycerides in the body. Can become LDL. (Normal values: <150 normal; 150-199 borderline high; 200-499 high; >500 very high)

3. High-density lipoprotein (HDL)/ good cholesterol- manufactured in the liver and small intestines and assists in the transport of cholesterol away from the body tissues and back to the liver. (Normal value: <40 low; >60 - high)

DRUGS FOR LIPIDS 3 hydroxy 3 methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors/ Statins Clue: ends with STATIN Prototype drug: atorvastatin (Lipitor) Pharmacokinetics Onset: 2 weeks Peak: Plasma concentration: 1-2h Cholesterol reduction: 2-4 wk Half-life: 14 h Duration: unknown Anatomy: HMG-CoA reductase serves as the primary regulatory site for cholesterol biosynthesis. It is regulated by negative feedback (high levels of LDL will shut down its production)

Action: the drug inhibits the HMG-CoA reductase, which results in less cholesterol biosynthesis. The liver will respond by making more LDL receptors, leading to faster excretion of LDL. Use: To decrease cholesterol (for hypercholesterolemia) and LDL levels Side effects: headache, fatigue, muscle or joint pain and heartburn. Serious side effect: Rhabdomyolysis breakdown of muscle fibers usually due to muscle trauma or ischemia. This can lead to acute renal failure. Drug-to-drug interaction: Macrolides, AZOLE antifungals, fibric acid agents and immunosuppressant increase chances of myopathy. Nurses responsibilities: 1. Most should be administered in the evening (with meals) cholesterol biosynthesis is higher at night. (Exception: atorvastatin because of long-half life) 2. Monitor Lipid profile. Instruct patient that he/ she should be NPO for at least 8-10 hours prior to blood collection. 3. Monitor Creatinine phosphokinase indicator of rhabdomyolysis. 4. Monitor Liver function test 5. Do not give to pregnant and breastfeeding woman pregnancy category X 6. Discourage patient from drinking alcohol 7. Assess patient for side effects and Instruct patient to report them Bile Acid Resins/ Sequestrants Prototype drug: Cholestyramine (Questran) approved for use in children How to prepare: Mix cholestyramine powder with 60 to 180 mL of water, non carbonated beverages, highly liquid soups, or pulpy fruits to prevent esophageal irritation. Place the contents of the packet of resin on the surface of fluid. Allow it to stand without stirring for 2 minutes, occasionally twirling the glass, and then stir slowly to prevent foaming Pharmacokinetics Onset: 24-38 h Peak: 1-3 wk Half-life: Unknown Duration: 2-4 wk Action: Binds bile acids, which contain a high concentration of cholesterol, making large molecules that cannot be absorbed by the small intestines, thus, cholesterol will be excreted in the feces. Use: To decrease cholesterol (for hypercholesterolemia) Side Effects: Limited to GI such as bloating and constipation. Drug-to-drug interaction: Binds with digoxin, warfarin, penicillin and others (decrease absorption of the drug) Nurses responsibilities: 1. Assess bowel sounds 2. Generally are not given during pregnancy and lactation (pregnancy category C)

3. Take medication before meals 4. Take other medication 1 hour before or 4 hours after taking bile acid resins. 5. Increase fluid intake and advise high-bulk diet 6. Take vitamin supplements to replace those that are not absorbed in the diet. 7. Monitor patients liver function (AST Aspartate aminotransferase; ALP- Amino phosphatise) Nicotinic Acid/ niacin/ vitamin b complex (except Nicotinamide this brand has no lipid-lowering effects) Dose as a vitamin: 2 mg/day Dose as an antilipidemic: 2 to 3 g/day Use: to decrease level of VLDL, which in turn is synthesized to LDL, thus, reducing LDL levels, triglycerides and increasing HDL levels. Side effects: flushing, hot flashes, nausea, excess gas, and diarrhea. Serious side effects, hepatotoxicity and gout. Nurses responsibilities: 1. Take niacin with or after meals to prevent GI irritation 2. Take niacin with cold beverages warm beverages increases flushing 3. Take aspirin as prescribed 30 minutes prior to niacin 4. Instruct patient to immediately report adverse effects Fibric acid agents Prototype drug: gemfibrozil (Lopid) Pharmacokinetics Onset: 1-2h Peak: 1-2h Half-life: 1.5 h Duration: 2-4 mo Action: Unknown Use: reduces VLDL and increases HDL Side effects: abdominal pain, nausea, diarrhea, and vomiting Drug-to-drug interaction: if use with statins may increase risk of myositis and rhabdomyolysis; if use with warfarin potentiate anticoagulation Nurses responsibilities: 1. Immediately report sign of bleeding 2. Monitor prothrombin time (Normal: 11-16 seconds) and international normalized ratio (Normal:0.8-1.2) (if using warfarin: 2.5) 3. Assess pt. For history of gallbladder disease. 4. Administer drug with meals.

CARDIOVASCULAR DRUGS FACTORS RESPONSIBLE FOR BP y Cardiac output volume of blood pumped per minute (ml/min) y Is equal to Heart rate (beats/min) x stroke volume (ml/beat) y Stroke volume the amount of blood pumped by a ventricle in one contraction. o Affected by 3 factors: preload, afterload and the contractility of the heart. o As preload increases, stroke volume also increases (Starlings law of the heart). As afterload increases, stroke volume decreases. As contractility increases, stroke volume also increases and vice versa. y Peripheral resistance friction that reduces the velocity of the blood as it flows through the vascular system. y Total blood volume: approximately 5 L PRINCIPLES: y As the heart rate/ stroke volume increases, cardiac output also increases. Thus, blood pressure also increases. As the heart rate/ stroke volume decreases, cardiac output also decreases. Thus, blood pressure also decreases. y As the diameter of the blood vessel increases (vasodilation), the peripheral resistance decreases. Thus, blood pressure decreases. As the diameter of the blood vessel decreases (vasoconstriction), the peripheral resistance increases. Thus, blood pressure increases. y As the blood volume increases, the blood pressure increases. PHYSIOLOGICAL REGULATION OF BLOOD PRESSURE y Baroreceptors have the ability to sense pressure within the blood vessels. y Chemoreceptors recognize levels of oxygen and carbon dioxide, and the pH in the blood. RAAS decrease BP sensed by the baroreceptors/ decrease in Na+ sensed by the chemoreceptors Juxtaglomerular apparati will secrete enzyme renin Once in the blood, renin will convert angiotensinogen, a protein produce by the liver, to angiotensin I When angiotensin I pass the lungs, it will be converted with the help of angiotensin converting enzyme (ACE) to angiotensin II

Receptor sites for angiotensin II is found

Smooth muscles of the Blood vessels Vasoconstriction Increased BP

adrenal cortex

release of Aldosterone reabsorption of Na+, increasing osmotic pressure, thus increasing blood volume Increased BP

Pathophysiology of CHF

Mitral stenosis: Frequent infection in the upper airway (Group A beta haemolytic streptococcus) Ascending infection reaches the mitral valves. Due to phagocytosis, the inflammatory process leads to thickening of the valvular tissue causing narrowing of the passageway of blood

Blood starts to pool in the left atrium and it backflow to the pulmonary circulation. More blood will aggregate due to the blood from the right side of the heart Pulmonary congestion occurs (as manifested by Productive cough, Dyspnea and crackles)

Blood will backflow to the right side of the heart and in turn to the systemic circulation (as manifested by jugular neck vein distention, hepatomegaly, ascites, spleenomegaly and edema in the lower extremities) other causes such as diabetes, hypertension and others

Decrease oxygenated blood flow triggers a positive feedback mechanism that will trigger the heart to increase its heart rate Increase work load of the heart (leading to failure)

ACE INHIBITORS: Clue: pril Action: Block the conversion of Angiotensin I to angiotensin II, thereby, preventing the effects of angiotensin II Angiotensin II Receptor Blockers/ antagonist Clue: Sartan Action: Block angiotensin II in the receptor sites (smooth muscles of blood vessels and adrenal cortex) Uses: y hypertension (lowering peripheral resistance and decreasing blood volume) Prototype drug: Enalapril (Vasotec) Pharmacokinetics: Onset: 1 h PO; 15 min IV Peak: 4-8 h PO; 4 h IV Half-life: 2 h Duration:12 24 h PO; 4 h IV y CHF (reduction of blood volume and decrease peripheral resistance leads to decrease of after load which in turn, leads to increase cardiac output. In turn, this will lead to decrease workload of the heart Prototype drug: Lisinopril (Prinivil) Pharmacokinetics: Onset: 1 h Peak: 6-8 h Half-life: 12 h Duration: 24 h y Myocardial Infarction (decrease workload of the heart Side effects: reflex tachycardia, hypotension, dizziness, headache, dry cough, angioedema leading to laryngeal swelling, neutropenia or agranulocytosis, Hyperkalemia Drug-to-drug interaction: other hypotensive (potentiation); potassium supplements and potassium sparing diuretics (hyperkalemia) Nurses responsibilities 1. Assess/ monitor vital signs. Hold drug if BP is low. 2. Administer first dose at bed-time to avoid hypotension at night time. 3. Monitor CBC (WBC) and assess for signs of infection. 4. Monitor for signs of heart attack (chest pain, shortness of breath) 5. Avoid foods rich in potassium. 6. Do not use in pregnant and breastfeeding woman (Pregnancy category D) Adrenergic drugs Anatomy: I. Central Nervous system

A. Brain B. Spinal Cord II. Peripheral Nervous system A. Sensory 1. Sight 2. Smell 3. Hearing 4. Taste 5. Touch B. Motor 1. Somatic/ Voluntary 2. Autonomic/ Involuntary a. Sympathetic/ fight or flight b. Parasympathetic/ rest or relaxation SNS Neurotransmitter Epinephrine/ Norepinephrine Eyes/ pupils dilates Salivary glands inhibit Heart rate Increase rate and contractions Bronci/ dilate bronchioles GI/GU Inhibit (but increase glucose release in the liver) PNS Acetylcholine Constrict Stimulate Decrease rate and contractions constrict Stimulate

Receptor sites: Alpha 1 all sympathetic target organs except the heart; constriction of blood vessel, dilation of pupils Alpha 2 presynaptic adrenergic nerve terminals; inhibition of the release of norepinephrine Beta 1 heart and kidneys; increased heart rate and contracton; release of renin Beta 2 - all sympathetic target organs except the heart; inhibition of smooth muscle Beta 1 adrenergic receptor blockers Clue: olol Action: block norepinephrine in the receptor sites leading to decrease heart contractility [(-) inotropic], decrease conductivity [(-) dromotropic] and decrease heart rate [(-) chronotropic]. Uses:

y Hypertension y CHF Prototype drug: Metropolol (Lopressor) Pharmacokinetics: Onset: 10-15 mins; unknown if sustained release Peak: 1.5-4 h; 6-12 h if sustained release Half-life: 3-4 h Duration:6h; 24 h if sustained release y Angina Prototype drug: Atenolol (Tenormin) Pharmacokinetics: Onset: 1h Peak: 2-4h Half-life: 1-4min Duration: 24 h y Dysrhytmias Prototype drug: Propanolol (Inderal) Pharmacokinetics: Onset: 0.5 1 h Peak: 1-2 h (6 h extended release) Half-life: 3-5 h Duration:6-12h; 24 h if extended release

Alpha 1- adrenergic receptor blockers Clue: osin Action: block norepinephrine in the receptor sites (arterioles) leading to vasodilation Uses: y Hypertension (with other hypertensives because they are not first line antihypertensives) Prototype drug: Doxazosin (Cardura) Pharmacokinetics: Onset: 2h Peak: 2-6h Half-life: 9-12h Duration: 24 h Alpha 2- adrenergic agonist Prototype: Clonidine (CAtapres) Action: stimulates presynaptic adrenergic nerve terminals, thereby inhibiting release of norepinephrine. Use: hypertension

Side effect: bradycardia, bronchoconstriction, hypotension (orthostatic),dizziness, headache, hypoglycaemia Drug-to-drug interaction: Use cautiously with other (-) inotropic agents, anti-hypertensive and oral hypoglycaemic agents and insulin (potentiation); Nurses responsibilities 1. Use cautiously with breastfeeding woman because drug is distributed in the breastmilk (Pregnancy Category C) 2. Assess vital signs. Do not give if BP is less than 90/60 and if apical pulse rate is less than 60 bpm. 3. Assess for presence of asthma and COPD (drug is contraindicated) 4. Assess urine output 5. Assess for decrease libido and impotence (priapism painful penile erection) 6. Assess for side effects Calcium Channel Blockers Clue: pine( specially selective; non selective sometimes does not end with pine) Anatomy: Changes in the permeability of the electrolyte channels (plasma membrane) results in formation of electrical impulses. When calcium enters the cell through channels in the plasma membrane, muscular contraction occurs. Action: Selective CCB: blocks calcium channels in the arterioles thereby limiting muscular contraction, which in turn, leads to relaxation of the arterial smooth muscle. Prototype: Nifedipine (Procardia) Pharmacokinetics: Onset: 10-30 min Peak: 30 min Half-life: 2-5 h Duration: 4-8h (24 h extended release) Non-selective CCB: arterioles and heart (myocardium):inhibits the transport of calcium in myocardial cells thereby causing decrease heart contractility [(-) inotropic], decrease conductivity [(-) dromotropic] and decrease heart rate [(-) chronotropic] Uses y Hypertension (decrease peripheral resistance) y Angina (decrease workload of the heart. Side effects: selective (especially if fast acting) reflex tachycardia, hypotension, dizziness, light-headedness Drug-to-drug interaction: Use cautiously with other (-) inotropic agents and anti-hypertensive (potentiation) Nurses responsibilities: responsibilities

1. Use cautiously with breastfeeding woman because drug is distributed in the breastmilk (Pregnancy Category C) 2. Assess vital signs. Do not give if BP is less than 90/60 and if apical pulse rate is less than 60 bpm. 3. Report weight loss or gain of 2 lbs and more in 24 hours. 4. Monitor for signs of CHF edema, crackles, dob