Pathophysiology And Pharmacology Assignment

Pathophysiology And Pharmacology Assignment

Note: When taking the final exam, read each question carefully. The exam questions have only one answer, unless the question specifically states there is more than one correct answer.

Pharmacokinetics

1. Pharmacokinetics involves ADME (absorption, distribution, metabolism, and elimination).
   1. Absorption: absorption from the administration site either directly or indirectly into the blood/plasma. Pathophysiology And Pharmacology Assignment
      

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The absorption rate depends upon various factors, including the route of administration, drug formulations, and drug-food reactions.

1. Distribution: reversibly or irreversibly move from the bloodstream into the interstitial and intracellular fluid.

Distribution determines the amount of drug that reaches the active site, thus influencing a drug’s efficacy and toxicity. Factors influencing distribution include blood flow, the molecular size of the drug, lipophilicity, and the interaction of the drug with blood components, including plasma proteins.

1. Metabolism: biotransformed via hepatic metabolism or by other tissues.

Cytochrome P450 enzymes in the liver perform most of the metabolism functions. During metabolism, most drugs are converted into inactive products. However, prodrugs are transformed into active products upon metabolism.

1. Elimination: Lastly, the drug and its metabolites are eliminated from the body.

Excretion is achieved through kidneys in most cases or bile in fewer cases.

2. The route of administration with the highest bioavailability is intravenous; putting entire dose into a patient’s vein and bypassing absorption.

Overcoming absorption leads to 100% bioavailability in the systemic circulation to give its effects. Administration of drug route leads to reduced bioavailability due to incomplete absorption with less drug reaching the targeted tissues.Pathophysiology And Pharmacology Assignment

3. Intravenous route avoids first-pass metabolism in the liver.

First pass metabolism occurs in orally administered drugs that are absorbed in the gastrointestinal then transported to the liver for metabolism. This reduces the amount of drugs that reach the circulation or tissues.

4. Rectal administration has variable and erratic absorption.

Rectal absorption is unpredictable due to the small surface area for drug uptake. However, effects are achieved faster with reduced toxic effects.

5. Steady state (SS) is usually reached within 4-5 half-lives of a drug.

A steady state is achieved after repeated administration of a drug. It is reached when the quantity of drug eliminated in the unit of time equals the quantity of the drug that reaches the systemic circulation in the unit of time. Drugs with a short half-life achieve a steady state faster, unlike medications with a long half-life that takes longer. Steady state determines the dosage and frequency of drug administration.

6. Half-life of a drug is how long it takes for half the drug to be excreted from the body.
   1. Determines how frequently the drug must be administered.

Drugs with shorter half-lives need frequently repeated administration, unlike those with long-half life that require less frequencies of administration.

1. Predicts how long toxic effects can last.

7. First-order (linear) pharmacokinetics means the metabolism is directly proportional to the free concentration of the drug.

First order is concentration-dependent, i.e, the higher the concentration, the faster the clearance. Pathophysiology And Pharmacology Assignment

8. Zero-order (nonlinear) pharmacokinetics means a drug is metabolized at a constant rate per unit of time.

Non-linear clearance is independent of concentration.

9. CYP3A4 substrate drugs may have decreased activity if any CYP3A4 inducer drugs are used along with it.

CYP3A4 inducers increase the activities of the enzyme by either binding to it, increasing gene expression, and decreasing enzyme degradation. Examples of inducers include rifampicin, carbamazepine, phenytoin, and phenobarbital.

Drug Development

1. Drug development process involves these steps according to the FDA:
   1. Discovery: laboratory research to develop the new drug.

Researchers discover a new drug by studying the unique insights of the disease process, with the help of new technology, and by carrying out many tests of the molecular compounds to find the beneficial effects. Many laboratory tests are carried out during this time. Laboratory tests are aimed at understanding the pharmacokinetics, potential benefits, side effects, dosage, interactions, administration route, and drug effectiveness compared to the existing ones.

1. Preclinical research with animal testing for safety.

Animal models, including rats, are used in this stage.

1. Clinical research on healthy human subjects to assess medication pharmacokinetics (Phase I).

Clinical trials are made on human subjects. At this stage, healthy volunteers or those with the condition are studied in this stage. Several months are required. Drug safety and dosage are determined.

1. Clinical research in humans primarily for medication safety usually in a population for which the treatment is intended (Phase II).

Individuals with the intended condition are put on trial for several months while efficacy and side effects are determined.

1. Clinical research in humans comparing the new drug to accepted medications or placebo for efficacy and safety (Phase III)Pathophysiology And Pharmacology Assignment.

Up to 3000 volunteers with the condition undertake the trial. The aim is to determine efficacy while monitoring adverse reactions.

1. FDA review of the results to determine approval.

FDA officials look into the original submission. The process protects volunteers who participated from unreasonable and significant risks. Based on its examination, the FDA can either approve or fail to approve the new drug.

1. Postmarketing study to identify adverse effects not found in earlier clinical studies (Phase IV).

FDA continues to examine the new drug for safety while it is in use in the public. If the drug causes more harm than benefit, then it can be withdrawn from the market.

2. Medication safety organizations include the Food and Drug Administration (FDA), the Institute for Safe Medication Practices (ISMP), and the Joint Commission on Accreditation of Healthcare Organizations (JCAHO).
   1. The Institute for Safe Medication Practices (ISMP)

ISMP help in preventing medication errors. This is achieved through; helping healthcare practitioners understand the causes of medication errors, collect a report of errors, and disseminate recommendations to help prevent a similar occurrence.

1. The Institute of Medicine (IOM)

IOM offers unbiased and authoritative advice to decision-makers and the public regarding medicines.

1. The Joint Commission

It continuously evaluates healthcare organizations and inspires them to offer safe and quality care to improve the public’s healthcare.

1. The National Coordinating Council for Medication Error Reporting and Prevention (NCC MERP)

It maximizes the safe use of medication and increases awareness of medication errors through open communication, increased reporting, and promotion of medication error prevention strategies.

1. Food and Drug Administration (FDA) Safe Use Initiative

FDA protects the public health by ensuring the safety, efficacy, and security of veterinary, biological, and human products. Pathophysiology And Pharmacology Assignment

Adverse Drug Reactions (ADRs)

1. Two basic type of ADRs: pharmacological and idiosyncratic.

Pharmacological reactions are unwanted, undesirable effects related to drug use. They can include simple reactions such as skin rashes to more severe consequences such as heart attack. On the contrary, idiosyncratic ADRs are effects not described by the known mechanisms of actions of the agent. It does not occur in many patients but in susceptible individuals only.

2. 85% to 90% of ADRs are pharmacological.

Idiosyncratic is not common, only in susceptible individuals.

3. Adverse drug reactions are usually preventable, frequently occur in a hospital or nursing home setting, and include medication errors, adverse drug effects, and allergic and idiosyncratic type reactions.

Various ways can be used to prevent adverse drug reactions, including avoiding or being vigilant of high-risk drugs; discontinuation of unnecessary drugs; avoiding drug-drug interactions; addressing non-adherence; dose adjustment based on age and creatinine clearance, and avoiding treating side effects of one drug using the other one. Pathophysiology And Pharmacology Assignment

4. ADRs are not commonly reported; the FDA does not mandate that ADRs be reported.
5. Polypharmacy involves using multiple health care providers for care, using multiple medications, and using several pharmacies for prescription filling.

Polypharmacy may lead to an increased risk of adverse drug effects, including harmful drug interactions, cognitive impairment, drug-disease interaction, and falls.

Cardiovascular

1. Angiotensin-converting enzyme inhibitors (ACEIs): lisinopril, captopril, enalapril, ramipril, benazepril, fosinopril.
2. ACEIs reduce blood pressure by suppressing the release of angiotensin-converting enzyme.

ACEIs inhibits the body from producing angiotensin II, a substance that narrows blood vessels and stimulates the release of aldosterone. ACEIs achieve blood pressure control by causing vascular dilatation with a resultant decrease in peripheral resistance.

3. Important side effects of ACE inhibitors include cough and angioedema; discontinue the ACEI if angioedema occurs.

Angioedema can be life-threatening if it occurs in the airway. It can cause respiratory compromise that can lead to death. Dry cough results in increased bradykinin levels as ACEIs inhibit bradykinin breakdown. Other side effects include first-dose hypotension, hyperkalemia, functional renal failure, and loss of taste.

4. Angiotensin II receptor blocking agents (ARBs): candesartan (Atacand), eprosartan (Teveten), irbesartan (Avapro), losartan (Cozaar), telmisartan (Micardis) and valsartan (Diovan)Pathophysiology And Pharmacology Assignment.
5. ARBs reduce blood pressure by blocking angiotensin II receptors.

They competitively inhibit angiotensin II at its receptors.

6. Essential (primary) hypertension accounts for 90% of cases; secondary hypertension may be caused by chronic renal failure.

Primary hypertension develops over a long period. The cause is not known. However, genetics and family history may be associated. Secondary hypertension develops acutely or rapidly due to an underlying condition such as kidney disease and hormonal issues.

7. Nitroglycerin is a nitrate drug that can be administered IV, SL, as a topical ointment, and as a transdermal patch.

Nitroglycerine has various formulations that allow for various routes of administration. It causes vascular dilatation to relieve symptoms of angina pectoris in patients with coronary artery disease.

8. Nitrates are contraindicated with PDE-5 inhibitors (e.g., sildenafil and vardenafil)Pathophysiology And Pharmacology Assignment.

PDE inhibitors and nitrates both cause vascular dilatation. Concomitant administration of both agents can cause severe hypotension, hence contraindicated.

9. Amiodarone is the antiarrhythmic of choice when there is coexisting heart failure; can cause thyroid and pulmonary toxicity.

Amiodarone causes competitive inhibition of both alpha- and beta-adrenergic receptors. It can cause either hypothyroidism or hyperthyroidism, leading to thyroid toxicity.

10. Alpha-1 adrenergic stimulation results in vasoconstriction and increased blood pressure.

Alpha-1 adrenergic receptors are distributed in smooth muscle and myocardium. Their stimulation leads to contraction of these muscles leading to vasoconstriction and a positive inotropic effect leading to hypertension.

11. Alpha-1 adrenergic blockade results in vasodilation and reduced blood pressure.

The vasoconstriction effects overcome alpha-1 adrenergic blockade resulting in relaxation of the smooth muscles and myocardium.

12. Beta-1 adrenergic stimulation by beta agonists (e.g., isoproterenol) results in increased heart rate, increased blood pressure, and increased cardiac output.

Isoproterenol potentiates the action of beta-1 and 2 adrenergic receptors by stimulating them. This results in increased heart rate, which increases cardiac output and blood pressure.

13. Beta-1 adrenergic blockade results in reduced heart rate, reduced blood pressure, and reduced cardiac output.

Examples of beta-1 adrenergic blockade agents include metoprolol, atenolol, acebutolol, and timolol.

14. Left heart failure causes reduced delivery of oxygenated blood to the body tissues.

A Weakened left ventricular myocardium leads to pooling of blood in the heart and lungs while there is reduced blood supply to other organs. As a result, there is less oxygen supply to the tissues. Pathophysiology And Pharmacology Assignment

15. Right heart failure is associated with pulmonary disease and increased pulmonary vascular resistance.

Increased pulmonary resistance and pressure cause increased pressure on the right side of the heart leading to reduced cardiac output and weakening of right side chambers.

16. A drug that relieves heart failure symptoms but does not reduce mortality is furosemide.

Furosemide is a loop diuretic that increases water loss and relieves symptoms caused by increased water retention. This relieves lower limb edema and shortness of breath; however, mortality is not reduced.

17. Loop diuretics like furosemide are potent diuretics, can cause diuretic resistance and hypokalemia, and work on receptors in the thick ascending renal loop of Henle.

Loop diuretics inhibit the sodium, potassium, 2 chloride symporter in the thick ascending loop of Henle. This leads to loss of excess water and salts through urine. Potassium and other salts are lost in the process leading to imbalance.

18. Loop diuretics inhibit the reabsorption of sodium and chloride at this site in the kidney.

Reabsorption is inhibited in the thick ascending loop of Henle.

19. Potassium-sparing diuretics: spironolactone, triamterene.

They cause fluid loss while sparing potassium in the body. They can be used in the management of hypertension and liver failure.

20. Milrinone is a phosphodiesterase inhibitor used for acute heart failure.

Acts by inhibiting phosphodiesterase 3 with positive inotropic effects leading to increased cardiac muscles contractility.

21. Children diagnosed with the tetralogy of Fallot can stop hypoxic spells by squatting down (a compensatory mechanism).

Right to left shunting patients with Tetralogy of Fallot leads to hypoxia. Squatting relieves worsening exercise-induced dyspnea while improving oxygenation.

22. Patent ductus arteriosus (PDA) is a congenital heart defect with a continuous machine-like murmur heard over the left upper sternal border in both systole and diastole, a bounding pulse and a thrill on palpation.

The continuous abnormal communication between the aorta and pulmonary artery after birth leads to the presence of murmur over the left upper sternal border.

23. PDA can be effectively treated with IV NSAIDs such as indomethacin.

Indomethacin causes closure of PDA early in life.

24. Raynaud’s disease is a vasospastic disorder typically seen during cold weather.

During cold weather, the body aims to preserve more heat. As a result, blood is shifted from the extremities to the central organs to help in heat conservation. The extremities, in turn, may become ischemic with resultant hypoxia, pain in the extremities.

25. Raynaud’s involves the small arteries and arterioles in the fingers; occasionally, the toes are also involved.

These small vessels undergo vasospasm leading to numbness and reduced blood supply to extremities.

26. Raynaud’s is treated with dihydropyridine-type calcium channel blockers (e.g., nifedipine) because they cause peripheral vasodilation.

Vasodilation improves blood supply to peripheries, reversing the effects of vasoconstriction.

Respiratory

1. Asthma is an obstructive airway disease associated with airflow obstruction, mucus production, hyperreactivity of the bronchial tissue, and inflammation.
   1. Mild persistent asthma is best treated with a short-acting beta-2 agonist (SABA) plus an inhaled corticosteroid.

SABA offers quick and short-term relief of symptoms. They cause vasodilation. Inhaled corticosteroids offer quick relief of inflammation.

1. Moderate persistent asthma is best treated with an inhaled low-dose corticosteroid and a long-acting bronchodilator.

LABA offers long-term relief of symptoms.

1. Severe persistent asthma is best treated with a long-acting beta-2 agonist (LABA), plus a high-potency inhaled corticosteroid, plus an oral corticosteroid drug.

2. Inhaled short-acting beta-2 agonists (SABA) are indicated only for PRN use. Pathophysiology And Pharmacology Assignment

They offer short-term bronchodilation to relieve acute symptoms.

3. Long-acting beta-2 agonists (LABA, e.g., salmeterol) should never be used in an acute asthma exacerbation; use a short-acting beta-2 agonist (SABA, e.g., albuterol).

The use of LABA in acute asthma exacerbations can worsen exacerbation with increased mortality in asthma patients.

4. Short-acting beta-2 agonists (SABA) are used in acute asthmatic attacks, but can increase heart rate, tremors, nervousness, and reduce serum potassium levels.

They potentiate the action of beta-2-adrenergic receptors while increasing heart rate, blood pressure, nervousness, and tremors.

5. Instruct a patient on any inhaled corticosteroid product to rinse the mouth after each use of the inhaled corticosteroid product.

Rinsing the mouth helps to remove inhaled corticosteroids deposited in the oropharyngeal mucosa. This helps prevent oral thrush, sore mouth, and hoarseness related to steroids use.

6. Advair (fluticasone and salmeterol) is an example of a long-acting beta agonist and a corticosteroid.

It can be used to relieve symptoms in patients with asthma and COPD.

7. Anoro ellipta (umeclidium/vilanterol) is an example of a long-acting beta agonist and an anticholinergic agent.

Prevents airflow obstruction and is useful in the management of COPD.

8. Combivent (albuterol/ipratropium) is an example of a short-acting beta agonist and an anticholinergic agent.
9. Tiotropium is long-acting anticholinergic agent, not for acute asthmatic attacks, and is used once a day in asthma and COPD.

Useful in the prevention of wheezing, cough, chest tightness, and shortness of breath in patients with COPD and asthma.

10. Cystic fibrosis (CF) is a pulmonary disorder typically seen in childhood, with an increased production of a protein-producing thick mucus that blocks the airways, pancreatic ducts, sweat gland ducts, and vas deferens.

It can cause damage to these organs leading to difficulty in breathing, coughing, frequent infections, morbidity, and death.

11. CF of the pancreas is also known as fibrocystic disease of the pancreas.

It presents with pancreatic insufficiency, disturbance in sweat and saliva excretion, and chronic pulmonary lesions.

12. Respiratory distress syndrome is a lung disorder characterized by increased pulmonary resistance and caused by a surfactant deficiency.

RDS occurs mostly in premature infants. Lack of surfactant causes collapse of alveoli with a resultant ventilation-perfusion mismatch.

13. Transudative pleural effusions have watery and diffuse fluid due to increased blood pressure or decrease capillary oncotic pressure.

Transudative effusion results from conditions that increase pulmonary hydrostatic pressure with reduced oncotic pressure. Such conditions include CHF, nephrotic syndrome, hypoalbuminemia, and protein-losing enteropathy. The fluid has less protein content.

14. Cystic fibrosis is associated with meconium ileus.

Increased mucus production can cause intestinal blockage in newborns with CF.

Musculoskeletal

1. NSAIDS have anti-inflammatory, analgesic, and antipyretic activity.

NSAIDs inhibit cyclooxygenase enzyme while preventing the conversion of arachidonic acid into thromboxane, prostaglandins, and prostacyclin. Lack of these eicosanoids helps in achieving these effects.

2. Acetaminophen has analgesic and antipyretic activity, but not anti-inflammatory activity.

Acetaminophen blocks the synthesis of prostaglandins, thus achieving pain and fever control.

3. The NSAID considered safe to use by individuals with heart disease is naproxen.

Naproxen has fewer cardiac-related side effects. It has a lower incidence ratio index.

4. Gout is treated with antigout drugs (e.g., allopurinol, colchicine, febuxostat) and uricosuric drugs (probenecid, sulfinpyrazone)Pathophysiology And Pharmacology Assignment.

Various classes used in Gout treatment

• Xanthine oxidase inhibitors, e.g. allopurinol and febuxostat
• Interleukin-1 inhibitor; rilonacept
• Uricosuric agents; probencid, sulfinpyrazone
• NSAIDs; indomethacin, naproxen, sulindac
• Uricase: pegloticase.

5. The only drugs that directly work on the pathophysiological causes of gout are allopurinol and febuxostat.

Allopurinol and febuxostat that competitively inhibit xanthine oxidase enzyme leading to a reduction in purine formation.

6. Renal calculi can occur as a comorbid condition in patients with gout.

Gout is associated with increased uric acid production. During excretion, uric acid causes acidification of urine that favors the formation of renal stones.

7. Colchicine reduces the inflammatory response seen in gout, reduces the pain in an acute gout attack, but does not stop gout from developing into chronic gouty arthritis.

Colchicine is an anti-inflammatory for symptomatic management but does not control the amount of uric acid in the body.

8. Colchicine efficacy is affected by its incidence of adverse effects.

Colchicine adverse effects include diarrhea, nausea, black tarry stool, muscle weakness, vomiting, peeling of the skin, and hematuria.

9. Allopurinol is the only drug that inhibits xanthine oxidase.
10. Urate lowering therapy (ULT) can initiate an acute gouty attack; concomitant colchicine, NSAIDs, or corticosteroids are used with ULT drugs to decrease the incidence of ULT-induced acute gouty attacks.

These medications reduce the inflammation induced by Urate lowering agents.

11. Allopurinol is the agent of choice for individuals with gout and high serum urate levels with underlying renal dysfunction, history of tophaceous gout, or urinary calculi.

Allopurinol inhibits the formation of uric acid, thus lowering incidences of flares caused by increased uric acid.

12. Acute gouty attacks are treated preferentially with NSAIDs (e.g., indomethacin, ibuprofen, naproxen, sulindac)Pathophysiology And Pharmacology Assignment.

NSAIDs reduce pain, inflammation, and fever associated with acute gouty attacks.

13. NSAIDs can cause GI bleeding (indicated by darkening of stools and epigastric pain); one recommendation is switch to a COX-2 inhibitor (i.e., celecoxib).

NSAIDs cause massive GI irritation, which can lead to bleeding from ulcers. Celecoxib is GI-friendly and causes less GI irritation.

14. Ankylosing spondylitis is a chronic inflammatory joint disease characterized by fusion and stiffening of the spine and sacroiliac joints.

Fusion of the spine and sacroiliac joint leads to reduced flexibility resulting in a hunched posture.

15. Acute liver disorders (e.g., acute hepatitis, hepatotoxicity) may be caused by acetaminophen overdose.

Acetaminophen overdose leads to the formation of N-acetyl-p-benzoquinone (NAPQI), a reactive metabolite. NAPQI decreases the liver glutathione and directly damages liver cells.

16. Osteoblast cells on bone cause bone formation; osteoclasts are cells on the bone that cause bone breakdown.

A balance between osteoclast and osteoblasts determines bone strength and stability.

17. Osteomalacia is a condition of insufficient bone mineralization (softening of bone)Pathophysiology And Pharmacology Assignment.

Vitamin D deficiency leads to demineralization. Bones become weaker, increasing the risk of fractures.

18. Osteoporosis is a metabolic disorder with reduced bone mass/density.

Calcium deficiency is implicated in the process of bone weakening.

19. Osteosarcoma is cancer of the bone and is most commonly diagnosed in childhood.

Cancer attacks the bone cells of long bones. Children have active bone growth that makes them susceptible to osteosarcoma.

20. Paget’s disease is a disorder in which abnormal new bone growth occurs at a faster rate than normal, involving increased resorption of spongy bone tissue.

There is overactive osteoclastic activity followed by compensatory osteoblastic activity leading to the formation of woven spongy bones that are weaker and susceptible to fractures.

21. A pathologic fracture is a fracture occurring at the site of a pre-existing bone abnormality and occurs with a force that is considerably less than that which would cause a bone fracture at a different site.

Bone abnormality that predisposes one to pathological fracture may result from osteoporosis; osteomalacia; osteogenesis imperfecta; giant cell granuloma; aneurysmal bone cyst, local tumor growth, and Paget’s disease.

22. In osteoporosis, estrogen exerts antiapoptotic effects on osteoblasts and proapoptotic effects on osteoclasts.

Reduced estrogen levels favor osteoclastic activities leading increased risk of osteoporosis.

23. Myofascial pain syndrome is the result of muscle spasms, tenderness, and stiffness and leads to muscle guarding that limits muscle motion.

Increased pressure in sensitive points of muscles triggers myofascial pain syndrome. Muscle pain follows after trigger events.

24. Dystrophin is absent in muscle cells of patients with Duchenne muscular dystrophy.

The absence of the dystrophin gene leads to progressive muscular weakness, degeneration, and muscle wasting.

Fluid and Electrolytes

1. Antidiuretic hormone (ADH) is synthesized in the hypothalamus and causes the reabsorption of water in the distal tubule and collecting duct of the kidney.

The supraoptic and paraventricular nuclei in the hypothalamus secretes ADH. It is stored in the posterior pituitary gland and then released in the kidneys to cause water retention.

2. An essential treatment for hyponatremia is normal saline IV (0.9%NaCl)Pathophysiology And Pharmacology Assignment.

Normal saline has sodium and chloride essential in replenishing body sodium levels while restoring extracellular fluid volume.

3. Orthostasis can be a significant side effect with use of a diuretic drug.

Diuretics cause loss of water, leading to depletion of extracellular volume that leads to orthostasis.

4. Orthostatic hypotension is defined as a decrease of >20mmHg systolic blood pressure or a decrease of >10mmHgdiastolic blood pressure within 3 minutes of assuming a standing position.

Symptoms include lightheadedness, faintness, headache, dizziness, confusion, and blurred vision on a standing position. Lying down helps to resolve the symptoms.

5. Causes of hyperkalemia: high potassium intake, renal insufficiency, systemic lupus erythematosus, Addison’s disease, use of potassium-sparing diuretics

Excessive intake and excessive potassium retention lead to excess potassium in the body. A deficiency of aldosterone in Addison`s disease causes potassium retention.

6. Treatment of hyperkalemia include calcium gluconate, loop diuretics, patiromer (Veltassa), thiazide diuretics, sodium polystyrene sulfonate (Kayexalate), regular insulin IV, and inhaled albuterol.

Calcium gluconate is used to stabilize the heart and prevent arrhythmias caused by hyperkalemia. Loop diuretics and thiazide diuretics cause an increase in potassium loss through urine. Kayexalate causes the exchange of sodium for potassium in the colon, leading to increased potassium loss.

7. Insulin and beta-2 agonist inhalers are used to treat hyperkalemia because they move potassium from the bloodstream into the cells; insulin also increases the transport of glucose from the bloodstream into the cells.
8. Calcium and phosphate homeostasis is affected by parathyroid hormone, vitamin D, and calcitonin.

Parathyroid hormone decreases phosphate reabsorption at the proximal convoluted tubule. PTH also causes raised calcium levels in bones and increases intestinal absorption of calcium while decreasing phosphate levels.

9. Hypercalcemia causes: bone hyperplasia, neoplasms, and thiazide diuretics.

Thiazide diuretics cause increased calcium reabsorption in exchange of sodium. Neoplasms causes hypercalcemia through various methods include, increasing the secretion of parathyroid hormone-related protein, bone metastasis with an increase in osteoclast activity, and production of calcitriol.

10. Hypercalcemia treatments: calcitonin, pamidronate, zoledronic acid.

Calcitonin reduces serum calcium by increasing renal calcium excretion and interfering with osteoclast activity to decrease osteoclast function. Pamidronate inhibits bone reabsorption. Zoledronic acid inhibits bone resorption and osteoclast proliferation.

11. Insufficient dietary intake of vitamin D can result in cardiovascular disease, osteoporosis, and rickets.

Vitamin D helps in absorption of calcium which helps in bone mineralization to prevent osteoporosis and rickets. Calcium is also required to help in myocardium contraction.

12. Insufficient dietary intake of vitamin B12 can result in pernicious anemia.

Deficiency of Vitamin B12 can result from either reduced dietary intake or reduced absorption. Vitamin B12 deficiency impairs red blood cells formation.

13. A patient with metabolic acidosis and partial respiratory compensation will have symptoms of fatigue, cool pale hands and feet, a new-onset systolic heart murmur, and vomiting coffee-ground looking material.
14. Hypokalemia will increase digoxin toxicity.

In low potassium levels, digoxin binds easily to the ATPase pump without competition from potassium. Digoxin exerts inhibitory effects Pathophysiology And Pharmacology Assignment.

Endocrinology

1. Hyperparathyroidism can cause secondary renal failure.

Increased parathyroid hormone disrupts serum calcium levels that can cause renal failure.

2. Primary hyperparathyroidism is typically caused by a tumor in the parathyroid gland.
3. Hyperglycemia can occur with increased release of cortisol, epinephrine, glucagon, and growth hormone into the bloodstream.

The release of these counter-current hormones increases favor gluconeogenesis and lipolysis while inhibiting insulin release. This leads to hyperglycemia.

4. Hypoglycemia can be caused by starvation and intense exercise.

Starvation depletes the body’s nutrients required for the creation of glucose and glycogen. Intense exercise causes the release of insulin, which causes glucose breakdown.

5. A patient with type 1 diabetes who exercises heavily may have symptoms of hunger, headache, lightheadedness, confusion, tachycardia, and pallor due to hypoglycemia.
6. Obesity is a risk factor for developing type 2 diabetes because of increased insulin resistance.
7. Glucagon stimulates glycogenolysis by the liver.

Glycogenolysis restores blood glucose levels from stored glycogen.

8. Dawn phenomenon (dawn effect) occurs in the early morning hours (i.e., between 2 a.m. and 8 a.m.); blood glucose levels increase in patients with diabetes. There is not nighttime hypoglycemia.

Release of hormones, including growth hormone, cortisol, glucagon, and epinephrine, causes increased blood glucose levels.

9. Somogyi effect occurs after an episode of untreated nighttime hypoglycemia, causing increased blood glucose levels in the morning; treated by increasing food intake near bedtime or reducing the evening insulin dose.

Gastrointestinal:

1. Laxatives: stimulants (e.g., senna, Bisacodyl, magnesium oxide [milk of magnesia], magnesium citrate, castor oil), bulk (psyllium, methylcellulose), stool softeners (e.g., docusate), sugars (e.g., lactulose), osmotic agent trapping water in the GI lumen (e.g., polyethylene glycol), mineral oil

Laxatives help in increasing bowel emptying.

2. Linaclotide (Linzess) for chronic idiopathic constipation (CIC)Pathophysiology And Pharmacology Assignment.

Linzess helps increase fluid in the intestines while improving bowel movement to relieve constipation.

3. The safest laxative for chronic use is methylcellulose (Citrucel, Metamucil).

Methylcellulose is a bulk-forming laxative with minimal adverse effects when used in moderation.

4. Octreotide is a potent vasoconstrictor used in treating acute GI bleeds.

Octreotide binds to somatostatin receptors leading to smooth muscle contraction in the blood vessels to prevent bleeding.

5. Antiemetic agents: antihistamines, phenothiazines (e.g. prochlorperazine), 5HT3 receptor antagonists (e.g., ondansetron [Zofran], granisetron).

They are used in the management or relief of nausea and vomiting.

6. Ondansetron can cause constipation, headache, and heart conduction irregularities (prolonged QT interval).
7. 5HT3 receptor antagonists inhibit serotonin receptors inside the chemoreceptor trigger zone (CTZ) and inhibit serotonin receptors on vagal nerve terminals; these pharmacologic actions reduce nausea and vomiting.
8. H2RAs: cimetidine (Tagamet), ranitidine (Zantac), famotidine (Pepcid), nizatidine (Axid).

They are useful in suppressing acid release. They are used to manage peptic ulcer disease and gastroesophageal reflux disease.

9. Lactulose is used in hepatic encephalopathy; works by ion trapping of ammonia.

Lactulose acidifies the colon to favor the conversion of ammonium to ammonia. Ammonia is easily passed from tissues into the lumen.

10. Proton pump inhibitors (PPIs): esomeprazole (Nexium), lansoprazole (Prevacid), omeprazole (Prilosec), pantoprazole (Protonix), rabeprazole (Aciphex)Pathophysiology And Pharmacology Assignment.

They inhibit gastric acid secretion. Helpful in the management of PUD

11. Heart patients taking clopidogrel (Plavix) should avoid omeprazole; it blocks enzymatic conversion of clopidogrel to its active metabolite.

Omeprazole inhibits CYP2C19, a cytochrome P450 enzyme required in the metabolism of clopidogrel. This leads to increased plasma concentration of clopidogrel, leading to toxicity.

12. Clopidogrel does not interact with pantoprazole, rabeprazole, or lansoprazole.
13. Overuse of PPIs can result in Clostridium difficile infection (CDI).

PPIs inhibit gastric acid synthesis. Lack of acid favors proliferation and growth of C. deficile to cause diarrhea.

14. Adverse effects of opioid analgesic agents include constipation, addiction, overdose, sedation, and impaired daily functioning.

Opioids cause inhibitory effects. They can cause depression of the CNS, respiratory, and GI. Addiction and dependence impair functioning.

15. Docusate, a stool softener, is the preferred laxative for prophylaxis of opioid-induced constipation (OIC).
16. Gluten-sensitive enteropathy (celiac sprue) is an autoimmune disorder of the small intestine in which the affected patient cannot absorb certain cereal proteins.

Eating gluten-containing foods such as wheat, barley, and rye triggers an autoimmune attack in the small intestine. Intestinal damage causes malabsorption.

17. Dumping syndrome (rapid gastric emptying) can occur after a partial gastrectomy and has symptoms of rapid pulse, hypotension, pallor, weakness, sweating, and faintness.
18. Dumping syndrome can cause a high osmotic gradient in the small intestine, resulting in a rapid movement of fluid from blood vessels into the intestinal lumen.
19. The liver is the one internal organ that can regrow back to its original size depending on the area of tissue removed; this is a type of compensatory hyperplasia.

Compensatory hyperplasia is the proliferation of cells while maintaining their differentiated structure and function. The liver and kidneys are organs with this ability.

20. Vitamin B12 deficiency can occur after a partial gastrectomy; this may cause the patient to develop a pernicious anemia.

Partial gastrectomy impairs intrinsic factor production that leads to vitamin B12 malabsorption.

21. Know the characteristics of congenital aganglionic megacolon.

Congenital aganglionic megacolon results from failure of descent of neural crest into the distal colon. Passage of stool is impaired. Clinical features include failure of bowel movement 48 hours after birth, abdominal distension, gradual onset vomiting, fever, and constipation. Males are more affected than females. Imaging reveals distal distention of the colon.

22. Know the characteristics of Hirschsprung’s disease

Also called congenital aganglionic megacolon.

23. Know the characteristics of Periduodenal band.

Periduodenal bands represent the pancreatic tissue surrounding the duodenum, and there are barely any structures that can imitate it. The presence of a periduodenal band and a positive double bubble sign (simultaneous dilatation of stomach ad duodenum) is highly suspicious of annular pancreas. Annular pancreas presents with features of duodenal or intestinal obstruction early in life Pathophysiology And Pharmacology Assignment

Hematology

1. UFH: unfractionated heparin.

UFH is a fast-acting blood thinner that works with antithrombin to inhibit clot formation.

2. LMWH: (low molecular weight heparin) enoxaparin (Lovenox); inhibits factor Xa.

Most are subcutaneous anticoagulants. Act by activating antithrombin III, which inhibits thrombin and factor Xa.

3. Heparin produces rapid anticoagulation by binding with antithrombin III, and inhibits factors IXa, Xa, XIIa, and XIII.

Antithrombin III inhibits serine protease leading to the inactivation of thrombin and various factors named in the intrinsic coagulation pathway, thereby decreasing fibrin formation. Heparin potentiates the functions of antithrombin III to achieve anticoagulation.

4. Monitor heparin with aPTT (low dose SC heparin [5000 units BID] does not require aPTT monitoring).

To ascertain how well the intrinsic and common final pathways are working.

5. Warfarin inhibits vitamin K-dependent blood factors II, VII, IX and X; takes several days for its anticoagulant effect.
6. Monitor the International Normalized Ratio (INR) when warfarin is used.

To ascertain the efficacy and safety of warfarin. Normal INR is between 2-3. Very low INR has a risk of forming blood clots, while higher INR has a risk of massive bleeding.

7. Blood factor IIa inhibitor (direct thrombin inhibitor): Pathophysiology And Pharmacology Assignment dabigatran (Pradaxa).
8. An antidote to dabigatran-induced hemorrhage is idarucizumab.

Idarucizmab firmly binds to dabigatran, forming a complex to reverse anticlotting effects of dabigatran.

9. Blood factor Xa inhibitors: apixaban (Eliquis), edoxaban (Savaysa), rivaroxaban (Xarelto), fondaparinux (Arixtra).
10. Eptifibatide binds to GPIIb/IIIa receptor sites on platelets. Eptifibatide reversibly inhibits platelet aggregation by preventing the binding of fibrinogen, Von Willebrand factors and other adhesive ligands to GPIIb/IIIa
11. One symptom of hemolytic anemia is jaundice, caused by the destruction of heme that is greater than the hepatic conjugation and excretion of bilirubin.
12. Jaundice can be caused by hemolytic anemia, sickle cell anemia, pancreatitis, cholecystitis, and multidrug therapy used to treat pulmonary tuberculosis.

Essentially conditions that increase bilirubin concentration through increasing hemolysis of RBCs.

13. Erythropoietin is a substance manufactured in the kidney; the anemia of chronic renal failure reduces erythropoietin production and should be used to correct the anemia of chronic renal failure.

Erythropoietin stimulates the bone marrow to increase the production of RBCs as well protecting the RBCs against destruction.

CNS/Neurology/Psychiatry

1. Sumatriptan is the only triptan available as an injection, as well as tablets and a nasal spray.

Sumatriptan binds and activates serotonin 5-HT1D receptors in the CNS, causing vasoconstriction of cerebral blood vessels. This leads to relief of headaches of vascular origin.

2. Sumatriptan and zolmitriptan are the only triptans available as nasal sprays.

They are effective in the management of migraine.

3. Intravenous anesthetics: ketamine, thiopental, fentanyl, propofol, dexmedetomidine.

Ketamine- NMDA receptor antagonist used in the induction phase.

Thiopental- barbiturate is used to induce anesthesia, treat convulsions, and reduce intracranial pressure.

Fentanyl: opioid analgesic.

Propofol; sedative hypnotic used in induction and maintenance of anesthesia.

Dexmedetomidine; sedative; alpha-2 adrenergic agonist.

4. Propofol has a rapid onset, does not usually cause nausea, and poor analgesia.
5. Propofol can affect triglycerides; monitor triglyceride levels.

Propofol increases the risk of hypertriglyceridemia. High triglycerides are a risk factor for pancreatitis.

6. ICU delirium commonly occurs in elderly patients, is treated with haloperidol, although dexmedetomidine (Precedex) is the preferred drug for sedation in the elderly.
7. If respiratory depression is a concern, dexmedetomidine (Precedex) is the preferred anesthetic; however, it should not be used longer than 24 hours, per the FDA-approved product information.
8. Selective serotonin reuptake inhibitors (SSRIs): citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac), fluvoxamine (Luvox), paroxetine (Paxil), sertraline (Zoloft), vortioxetine (Trintellix). Pathophysiology And Pharmacology Assignment
9. Side effects of SSRIs include weight gain, decreased sexual libido, and insomnia.

Other effects include dizziness, blurred vision, anxiety, indigestion, diarrhea, dry mouth, diarrhea, and drowsiness. Patients on SSRIs should be monitored for various parameters to ascertain side effects.

10. Olanzapine, a second-generation antipsychotic, has the advantage of being available as a long-acting injection for acute psychotic reactions.
11. Drugs most effective in alcohol withdrawal are lorazepam (Ativan) and phenobarbital; if liver dysfunction is present, lorazepam is the preferred agent because of its different metabolic pathway than other benzodiazepines.

Lorazepam does not undergo metabolism by cytochrome P450. On the contrary, it undergoes metabolism via glucuronidation.

12. All benzodiazepine drugs (e.g., diazepam, lorazepam, clonazepam, midazolam) can increase falls in the elderly and other people unsteady on their feet.

Benzodiazepines cause drowsiness and dizziness that can lead to falls.

13. Drugs acting on the sympathetic nervous system include epinephrine, norepinephrine, dopamine, and dobutamine.

They stimulate the nervous system, increase heart rate, decrease intestinal motility, dilate pupils, constrict blood vessels, raise blood pressure, and diaphoresis.

14. Drugs acting on the parasympathetic nervous system include atropine, oxybutynin, and ipratropium.

They stimulate the parasympathetic system leading to decreased heart rate, increased digestion, and decreased respiration. They essentially maintain the body at a resting position.

15. Arachnoid villi absorb excess cerebrospinal fluid (CSF) that accumulates in the cerebral venous sinuses that surround the brain; the villi maintain normal CSF volume and pressure.
    

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Normal CSF volume produced a day is 400-600mls. 150-200mls is the normal circulating volume in adults.

16. The circle of Willis supplies collateral blood flow to the brain.

A group of arteries form the circle; they include;

• Anterior cerebral artery (left and right)
• Anterior communicating artery.
• Internal carotid artery (left and right)
• Posterior cerebral artery (left and right)
• Posterior communicating artery (left and right) Pathophysiology And Pharmacology Assignment