Pharmacology 2 - Exam 2

hemophilia

• patho → failure of hemostasis

  • limited fibrin production which decreases the strength of the plug of made up of platelets

• inheritance pattern

  • recessive gene

  • carried on the X chromosome

  • can be seen in females but most often in men

• clinical features

  • severe → <1% clotting factors

  • moderate → between >1% and <49% clotting factors

  • mild → reduced clotting factors, >50%

hemophilia treatment overview

1. replacement therapy

   1. factor VIII → for hemophilia A

   2. factor IX → for hemophilia B

2. additional therapies

   1. Desmopressin → releases stored clotting factors, only used in mild hemophilia A

   2. anti-fibrinolytic drugs → prevents the breakdown of fibrin, given prior to surgery/dental procedures

   3. activated factor VII recombinant → used if inhibitors are present

   4. Emicizumab → prophylactic treatment of hemophilia A, works even when inhibitors are present

3. pain management

   1. mild pain → Tylenol

   2. severe pain → opioids

   3. aspirin is avoided

   4. NSAIDs are avoided

4. immunizations

   1. follow regular immunization schedule

factor VIII and IX replacement

• production methods and safety

  • plasma derived factor VIII → donated human plasma (increased risk of viral transfers to recipient)

  • recombinant factor VIII → genetically engineered cells (little risk of ciral transfers to recipient)

• adverse effects and allergic reactions possible

• dosage and administration

  • on demand therapy → replacing what has been lost in real time

  • prophylactic therapy → normally ongoing

    • IV infusion 3 times per week for hemophilia A

    • IV infusion 2 times per week for hemophilia B

desmopressin

• releases stored clotting factors

• only used in mild hemophilia A (not effective in severe hemophilia A because it can’t release more clotting factors if there aren’t enough stored up)

Emicizumab

• for hemophilia A

• available as a subcutaneous injection

• effective even when there are inhibitors present

• NOT effective for hemophilia B

Tranexamic acid

• anti-fibrinolytic agent

• MOA → this stabilizes the clot

• best used as an adjunct therapy for mucosal/dental bleeding

• NOT effective as the sole therapy of joint bleeding

inhibitors

• these are antibodies that develop against factor VIII or IX

• this is measured using Bethesda units (BU)

  • low levels <5 = weak inhibitors

  • levels >5 = alternative treatment required

drugs for patients with inhibitors

• inhibitors against factor VIII

  • activated factor VII (factor Vlla)

  • anti-inhibitor coagulant complex (AICC)

  • porcine factor VIII

• inhibitors against factor IX

  • very limited treatment options

  • immune tolerance therapy (ITT) → this often fails

types of anemia

• iron-deficiency anemia

• megaloblastic anemia

• hemolytic anemia

• aplastic anemia

iron deficiency

• patho → results from an imbalance in iron uptake and iron demand

• causes

  • pregnancy

  • infancy and early childhood

  • chronic blood loss

ferrous sulfate

• this is an iron salt

• drug of choice to treat and prevent iron deficiency anemia

• adverse effects

  • GI effects → dark, tarry stools, N/V

  • staining of teeth → from liquid form, use a straw to prevent this

• toxicity

  • N/V, diarrhea

  • shock leading to acidosis, gastric necrosis, hepatic failure, pulmonary edema, and vasomotor collapse

    • ANTIDOTE = parenteral deferoxamine (Desferal)

• drug interactions

  • antacids → decreased absorption of iron

  • tetracycline → decreased absorption of iron

  • vitamin C → increased absorption of iron but more severe GI effects

• nursing considerations

  • best to be taken on an empty stomach

iron dextran

• parenteral form of iron supplementation

• used for patients who have experienced intolerable or ineffective oral dosing

ferric gluconate complex

• parenteral iron product indicated for iron deficiency anemia

• used in patients with CKD who are also undergoing chronic hemodialysis

iron sucrose

parenteral form of iron indicated for iron deficiency anemia in patients with CKD

ferumoxytol

• indicated for iron deficiency anemia in all patients with CKD

• does not matter if they are on dialysis or if they use erythropoietin

vitamin B12

• essential for synthesis of DNA

• absorption requires intrinsic factor

• elimination occurs slowly

• this is a daily nutritiona; requirement

• dietary sources → animal products (liver, dairy), fortified foods

vitamin B12 dificiency

• causes

  • usually a result of impaired absorption

  • regional enteritis

  • celiac disease

  • absence of intrinsic factor → pernicious anemia

• consequences

  • megaloblastic anemia

  • neurologic damage → demyelination of neurons

  • GI disturbances

cyanocobalamin

• routes

  • oral, parenteral (primarily for pernicious anemia), intranasal

• adverse effect

  • hypokalemia

• long-term treatment

  • with lack of intrinsic factor, vitamin B12 therapy is lifelong

folic acid

• this is essential for DNA synthesis

  • DNA replication

  • cell division cannot proceed without this

• absorbed in the early segment of the small intestine

• significant amounts excreted daily

• dietary sources → almost all foods

folic acid anemia

• causes

  • poor diet → malnutrition, alcoholism

  • malabsorption syndrome

• consequences for developing fetus

  • neural tube defects

  • adequate intake before conception is crucial

• consequences for all individuals

  • megaloblastic anemia

  • leukopenia, thrombocytopenia, injuring of the oral and GI mucosa

  • increased risk of colorectal cancer and atherosclerosis

folic acid supplements

• inactive form

  • folacin, folate, pteroylglutamic acid, folic acid

• active form

  • leucovorin calcium → often used as an adjuvant therapy for chemo patients or those with methotrexate toxicity (rescue medication for cells)

hematopoiesis

the process by with red blood cells, white blood cells, and platelets are produced in the bone marrow

epoetin alfa

• brand name → Epogen, Procrit

• uses → low RBC related to renal failure and chemotherapy

• adverse effects

  • HTN

  • cardiovascular events → HF, stroke, MI, cardiac arrest

• cardiac risks are greatest if the hemoglobin levels exceed 11g/dL or if the hemoglobin raises 1g/dL in any 2-week interval → if either of these occur, stop EPO treatment and give heparin if on dialysis

• monitor CBC (Hgb and RBC count)

darbepoetin alfa

longer-acting version of epoetin alfa

filgrastim

• brand name → neupogen

• granulocyte colony stimulating factor → stimulates the production of neutrophils

• uses

  • reduces the incidence of severe neutropenia (in CA patients)

  • reduces the incidence of infection, need for hospitalization, and need for IV antibiotics

• adverse effects

  • bone pain → achy but not harmful, give Tylenol!

  • leukocytosis

• monitoring

  • monitor WBC count

sargramostim

• brand name → leukine

• granulocyte-macrophage colony-stimulating factor

• increases the production of granulocytes and macrophages which are essential for immune defense and tissue/bone marrow recovery

• uses

  • adjunct to autologous bone marrow transplantation

  • treatment of failed bone marrow transplants

  • patients with acute myelogenous leukemia (AML)

• adverse effects

  • leukocytosis

  • thrombocytosis

oprelvekin

• brand name → neumega

• not available in the U.S. anymore

• stimulates platelet production

• uses

  • used with myelosuppressive chemotherapy to minimize thrombocytopenia and to decrease the need for platelet transfusions

• adverse effects

  • fluid retention, cardiac dysrhythmias, effects on the eye

romiplostim

indicated for subcutaneous treatment of ITP → a disorder characterized by low platelet counts secondary to immune-mediated platelet destruction and impaired platelet production

anti-ulcer drug classes

• antibiotics

• anti-secretory agents

• mucosal protectants

• anti-secretory agents that enhance mucosal defenses

H. pylori treatment

• minimum to two antibiotics prescribed (sometimes up to 3 may be used) to reduce the risk of resistance developing

  • amoxicillin

  • clarithromycin

  • bismuth compounds

  • tetracycline

  • metronidazole

  • tinidazole

• none of these are effective alone → if used alone, the risk of resistance developing increases

Clarithromycin

• antibiotic that suppresses growth of H. pylori by inhibiting protein synthesis

• common side effects

  • nausea, diarrhea, distortion of take

• enhanced effects when taken with PPI

Amoxicillin

• antibiotic that kills bacteria by disrupting the cell wall

• H. pylori is highly sensitive to this/it responds well

• rate of resistance is low (about 3%)

• common side effect → diarrhea

• enhanced effects when taken with PPI

bismuth compounds

• ex. pepto bismol

• antibiotic that acts topically to disrupt the cell wall of H. pylori causing lysis and cell death

• adverse effects

  • harmless, black coloration of the tongue and stool

  • possible neurologic injury associated with long-term use

Tetracycline

• antibiotic that inhibits bacterial protein synthesis

• highly active against H. pylori

• resistance is rare (<1%)

• contraindication

  • do not use in pregnant patients and young children → this can stain developing teeth

Metronidazole

• brand name → Flagyl

• antibiotic that is very effective against sensitive strains of H. pylori

• common side effects → nausea and headache

• nursing considerations

  • avoid use during pregnancy

  • avoid alcohol → Disulfiram-like reaction can occur (flushing, N/V, palpitations, tachycardia, psychosis)

H2 receptor antagonists

• Cimetidine (Tagamet)

• Famotidine (Pepcid)

• Nizatidine (Axid)

Cimetidine

• H2 blocker

• pharmacokinetics

  • absorption is slowed down when taken with meals → take on empty stomach

  • may cause some CNS effects → in elderly and CKD patients

• therapeutic uses → GERD, peptic ulcer disease

• adverse effects → ED, decreased libido, breast development in men

• drug interactions → antacids decrease absorotion (take 1 hour apart)

PPIs

• -prazole

  • ex. Omeprazole, Esomeprazole, Lansoprazole, Dexlansoprazole, Rabeprazole, Pantoprazole

• most effective drugs for suppressing secretion of gastric acid

• therapeutic uses → short term

  • gastric/duodenal ulcers

  • GERD

• generally well tolerated short-term

• serious adverse effects associated with long-term use

  • fractures, pneumonia, acid rebound, hypomagnesemia, C. diff

Sulcrafate

• creates a protective barrier for up to 6 hours by coating the stomach lining

• therapeutic uses

  • acute ulcers and maintenance therapy (helps promote time for healing)

• adverse effects → constipation

• drug interactions → antacids interfere with effects

Misoprostol

• therapeutic uses

  • only approved GI indication is the prevention of gastric ulcers caused by long term NSAID therapy

• adverse effects

  • diarrhea and abdominal pain

  • contraindicated during pregnancy → category X = will cause fetal harm

antacids

• these react with gastric acid to produce neutral salts or salts of low acidity

• use with caution in patients with renal impairment

• adverse effects

  • aluminum hydroxide → constipation

  • magnesium hydroxide → diarrhea

• drug interactions

  • Cimetidine and Sucralfate

magnesium hydroxide

• brand name → Milk of Magnesia

• rapid-acting antacid, high acid-neutralizing capacity that produced long-lasting effects

• adverse effect → diarrhea

• avoided in patients with undiagnosed abdominal pain

• frequently used as a laxative

• used with caution in patients with renal failure

aluminum hydroxide

• slow-acting antacid but effects have long duration

• rarely used alone

• adverse effects → constipation

• includes high amounts of sodium

• drug interactions

  • tetracyclines, warfarin, digoxin

calcium carbonate

• brand name → Tums

• rapid acting antacid with long duration effects

• adverse effects

  • acid rebound, constipation, belching, flatulence

sodium bicarbonate

• antacid that is rarely used

• useful for treating acidosis and elevating urinary pH to promote excretion of acidic drugs after OD

• inappropriate to be used toe treat peptic ulcer disease

laxative effect

• production of soft, formed stool over 1 or more days

• relatively mild

catharsis effect

• prompt, fluid evacuation of the bowel

• fast and intense

indications for laxative use

• diagnostics uses

  • obtain fresh stool sample

  • empty bowel before treatment or procedure

• therapeutic uses

  • expel dead parasites after treatment

  • modify effluent form ileostomy or colostomy

  • constipation → causes include pregnancy and opioid use

  • prevent fecal impaction in bedridden patients

  • remove poisons

contraindications to laxative use

• abdominal pain, nausea, cramps, or other symptoms of appendicitis, regional enteritis, diverticulitis, or ulcerative colitis

• acute surgical abdomen

• fecal impaction or bowel obstruction

• habitual use

• use with caution in pregnancy and lactation

classification of laxatives

• bulk-forming laxatives

  • Psyllium (Metamucil)

• surfactant laxatives

  • Docusate sodium (Colace)

• stimulant laxatives

  • Bisacodyl (Dulcolax)

• osmotic laxatives

  • Milk of magnesia (MOM)

  • Polyethylene glycol (Miralax)

bulk-forming laxatives

• ex. Psyllium (Metamucil)

• functions similarly to dietary fiber → swells with water to form a gel that softens and increases fecal mass

• uses → preferred temporary treatment of constipation, IBS, diverticulosis

• adverse effects → minimal effects, esophageal obstruction (take with a full glass of water, do not lie down for 30-60 minutes)

surfactant laxatives

• ex. Docusate sodium (Colace)

• produce a soft stool several days after the treatment

• alters stool consistency by lowering surface tension, which allows more water to absorb into the stool

• uses → avoid straining (post-op, pregnant, post-partum, cardiovascular conditions)

stimulant laxatives

• ex. Bisacodyl (Dulcolax), Senna

• two effects on the bowel

  • stimulate intestinal motility → peristalsis

  • increase amounts of water and electrolytes in intestinal lumen

• widely used and abused → can lead to dependency because it weakens natural bowel function

• uses → opioid-induced constipation, constipation from slow intestinal transit

• avoid antacids within 1 hour of administration

osmotic laxatives

• ex. Milk of magnesia (MOM), Polyethylene glycol (Miralax)

• MOA → poorly absorbed salts that draw water into intestinal lumen

  • fecal mass softens and swells, wall stretches, and peristalsis is stimulated

• low doses → results in 6 to 12 hours

• high doses → results in 2 to 6 hours

• adverse effects

  • dehydration, acute renal failure, sodium retention → can exacerbate HR, HTN, and edema

Miralax

• an osmotic laxative

• given in 17g once a day

lactulose

• osmotic laxative

• other uses → reduces ammonia levels

glycerin suppository

• osmotic laxative

• may also stimulate rectal contraction

• evacuation occurs about 30 minutes after suppository insertion

• useful for re-establishing normal bowel function after termination of chronic laxative use

lubiprostone

• selective chloride channel activator

• result is spontaneous evacuation of semisoft stool, usually within 24 hours

mineral oil

• normally added to an enema to treat fecal impaction

• mixture of indigestible and poorly absorbed hydrocarbons

• laxative action is produced by lubrication

bowel prep

• Miralax + electrolytes most common to clear colon before procedure

• require ingestion of large volume of bad-tasting liquid

laxative abuse

• causes

  • misconception that bowel movements must occur daily

  • can perpetuate their own use

  • bowel replenishment after evacuation can take 2 to 5 days, often mistaken ofr constipation

• consequences

  • diminished defecatory reflexes, leading to further reliance on laxatives

  • electrolyte imbalance, dehydration, colititis

antiemetics

• given to suppress nausea and vomiting

• these target one or more receptors to block or reduce the vomiting response

• classes

  • serotonin receptor antagonists → Zofran

  • glucocorticoids

  • substance P/neurokinin1 antagonists → Aprepitant

  • benzodiazepines → Ativan (help with anxiety related to N/V)

  • cannabinoids (cannabis) → Dromabinol and Nabilone (not 1st line)

  • dopamine antagonists → Compazine, Phenergan, Haldol

serotonin receptor antagonists

• ex. Granisetron, Dolasetron, Palonosetron

• Ondansetron (Zofran)

  • first approved for chemotherapy-induced nausea and vomiting

  • also used to prevent nausea and vomiting associated with radiotherapy and anesthesia

  • MOA → blocks type 3 serotonin receptors on afferent vagal nerve

  • most effective when used with dexamethasone (corticosteroid)

  • adverse effects

    • headache, diarrhea, dizziness, prolonged QT interval, risk of torsades de pointes

  • contraindications → pts. with prolonged QT interval

dopamine antagonists

• Phenothiazines

  • Prochlorperazine (Compazine) → can cause EPS symptoms

  • Promethazine (Phenergan)

    • can cause severe respiratory depression → contraindication in less than 2 years

    • local tissue injury (use large bore IV)

• Butyrophenones

  • Haloperidol (Haldol)

    • risk for fatal dysrhythmias due to a QT interval prolongation

    • ECG evaluation required

• Metoclopramide (Reglan)

  • helpful for patients with N/V with delayed gastric emptying (gastroparesis, GLP-1s)

drugs for motion sickness

• scopalamine

  • this is a muscarinic antagonist

  • side effects → dry mouth, blurred vision, drowsiness

• antihistamines

  • ex. Dimenhydrinate, Meclizine, Cyclizine

  • side effects → sedation, dry mouth, blurred vision, urinary retention, constipation

non-specific antidiarrheal agents

• opioids → most effective antidiarrheal agents

• ex. Diphenoxylate (Lomotil) and Loperamide (Imodium)

• MOA → acts directly on GI tract

• Diphenoxylate (Lomotil) → high doses can elicit typical morphine-like subjective responses

• Loperamide (Imodium) → no potential for abuse

non-specific drugs for IBS

• Antispasmodics

• Bulk-forming agents

• Anti-diarrheals

• Tricyclic antidepressants

drugs for IBD

• glucocorticoids

  • Budesonide → anti-inflammatory actions beneficial for crohn’s disease (not for long-term use)

• immunosuppressants

  • azathioprine and mercaptopurine → increase infection risk

• immunomodulators

  • infliximab → IV infusion reaction possible

• 5-aminosalicylates

  • Sulfasalazine → reduces inflammation seen with ulcerative colitis

• prokinetic agents

  • Reglan → can cause irreversible tardive dyskinesia, avoid in pt. with GI obstruction

Palifermin

• brand name → Kepivance

• first drug approved for decreasing oral mucositis (mouth ulcers)

• MOA → stimulates proliferation, differentiation, and migration of epithelial cells in the mouth

• uses → ONLY indicated for patients with hematologic malignancies (ex. leukemia, lymphoma)

• adverse effects → vision changes

• precautions

  • STOP Palifermin at least 24 hours before chemo and do not restart until at least 24 hours after chemo (if this isn’t done, it worsens symptoms)

  • NO heparin mixing

  • educate about taste distortion