Pharmacokinetics and Absorption

• Pharmacokinetics phases consist of absorption, distribution, metabolism, and excretion.
• Pharmacodynamics describes what the drug does to the body.

Absorption

• This is how drugs enter the bloodstream from the administration site.

• Bioavailability represents the percentage of the drug that reaches circulation, where IV administration is at 100%, and oral is less.

• The first-pass effect involves the liver reducing the drug before it reaches circulation, mainly affecting PO medications.

• Routes of administration include:

  • Enteral (oral): slowest, affected by GI factors
  • Sublingual/Buccal: rapid via oral mucosa, such as nitroglycerin
  • Parenteral (injection): fastest, including IV, IM, subcut
  • Topical/Transdermal: applied to skin, acts locally or systemically
  • Inhaled: direct to the lungs for quick absorption

• Absorption is affected by the medication form (liquid > tablet), dose, route, GI factors (food, pH, motility), and surface area.

Distribution

• Drug movement from the bloodstream to tissues/organs

• Rapid distribution occurs in the heart, liver, kidneys, and brain.

• Slower distribution occurs in the skin, fat, and muscle.

• Affected by:

  • Protein binding (needs albumin)
  • Blood flow/perfusion where poor circulation results in slower delivery
  • Barriers such as blood-brain barrier blocks some drugs

Metabolism

• Drug breakdown primarily occurs in the liver, inactivates or prepares drug for elimination

• Goals include inactivating or preparing the drug for elimination.

• Affected by:

  • Liver function, which is impaired in the elderly, infants, and liver disease
  • First-pass effect where oral drugs lose potency through the liver

Excretion

• Removal of drugs, mostly done by kidneys

• Other routes include liver(bile), lungs, sweat, saliva, feces

• Affected by:

  • Kidney or liver issues
  • Urinary pH
  • Age, with slower excretion in newborns/elderly increasing the risk of toxicity

Receptors and Pharmacodynamics

• Receptor - Bind specific substances (example, drug molecules), and one or more corresponding cellular effects (drug actions) occur because of this drug receptor interaction.
• Agonists are medications that bind to or mimic receptor activity regulated by endogenous compounds, like morphine for analgesia.
• Antagonists block the usual receptor activity that endogenous compounds regulate, like losartan blocking angiotensin II receptors.
• Partial agonists act as both agonists and antagonists with limited receptor affinity, like nalbuphine causing analgesia with minimal respiratory depression.

Medication Interactions

• MAOI food interactions include Tyramine foods like smoked sausage, aged cheese, pepperoni, salami, avocados, figs, bananas, smoked fish, protein supplements, soups, soy sauce, some beer, red wine.

• Warfarin foods to avoid include collard greens, kale, spinach, dark green leafy vegetables.

• Dairy can delay absorption, bind to the drug, and decrease effects.

• Grapefruit juice can decrease the metabolism of the drug and increase the effects.

• Older adults often experience more adverse effects due to slower metabolism and excretion.

Lisinopril

• ACE inhibitor
• Treats hypertension and congestive heart failure
• Competitive angiotensin inhibition, stopping angiotensin II production
• Contraindications include pregnancy, hyperkalemia, and angioedema
• Adverse effects include dizziness, fatigue, headache, persistent cough, and hypotension
• Interacts with NSAIDs, diuretics, and other antihypertensives
• Administer orally and monitor BP regularly

Metoprolol

• Selective beta-adrenergic blocker (beta1) cardioselective
• Immediate and extended release forms exist - tartrate and succinate, respectively
• Used for angina, myocardial infarction, hypertension, dysrhythmias, and as an antianginal
• Contraindications include systolic heart failure, bradycardia, heart block, asthma/COPD
• Adverse effects include bradycardia, decreased cardiac output, bronchoconstriction, and masked hypoglycemia
• Interacts with calcium channel blockers like verapamil and diltiazem
• Monitor BP, ECG, and pulse and taper the dose

Furosemide

• Loop diuretic and antihypertensive
• Treats edema and hypertension
• Blocks sodium reabsorption in the loop of Henle and distal tubule
• Contraindications include sulfa allergy, hepatic coma, severe electrolyte loss, and hypersensitivity
• Adverse effects include hypokalemia, exfoliative dermatitis, and ototoxicity
• Monitor for hypovolemia and electrolyte imbalances

Ipratropium

• Anticholinergic bronchodilator (inhaled short acting)
• Treats asthma and COPD (not for acute symptoms)
• Causes bronchodilation by blocking cholinergic receptors in bronchial smooth muscle
• Contraindications include allergy to atropine, peanuts, or soy
• Adverse effects include dry mouth, urinary retention, and heart palpitations

Albuterol

• Beta 2 agonist (short acting)
• Used for asthma, COPD, and bronchospasm
• Bronchodilator
• Contraindications include allergy, uncontrolled hypertension, and dysrhythmia if high risk for stroke
• Adverse effects include insomnia, hyperglycemia, and tremors

Methylcellulose

• Bulk forming laxative
• Treats constipation, irritable bowel syndrome, and diverticulosis
• Increases water absorption
• Contraindications include GI obstruction and hepatitis

Pantoprazole

• Proton pump inhibitor (IV and PO)
• Treats GERD, heartburn, and Zollinger-Ellison Syndrome
• Inhibits gastric parietal cell hydrogen-potassium ATPase
• Contraindicated with allergy
• Adverse effects like osteoporosis, GI tract infections, and hypomagnesemia possible

Clarithromycin

• Macrolide antibiotic
• Treats H. pylori
• Inhibits protein synthesis
• Contraindicated with drug allergy
• Adverse effects like nausea, vomiting, ototoxicity, and QT prolongation possible

Tobramycin

• Aminoglycoside
• Treats Pseudomonas bacterial infections of the eyes
• Inhibits protein synthesis
• Contraindicated with hypersensitivity and pregnancy
• Adverse effects include nephrotoxicity and ototoxicity

Phentolamine

• Nonselective alpha-adrenergic antagonist (alpha adrenergic blocker)
• Treats hypertension and extravasation
• A reversible alpha receptor antagonist
• Contraindications include allergy, peripheral vascular disease (PVD), and coronary artery disease (CAD)

Cholinergic Blockers

• Includes natural plant alkaloids such as atropine, scopolamine, and synthetic drugs such as benztropine, ipratropium, etc
• Blocks or inhibit acetylcholine
• Indications: decreases muscular rigidity and muscle tremors: treats Parkinson's disease, IBS, incontinence
• Contraindications include allergy, glaucoma, acute asthma, myasthenia gravis, GI or GU obstruction
• Side effects: Dysrhythmias, hallucinations, ataxia, pupil dilation
• Avoid excessive exercise, excessive sweating, and activities that need quick thinking.
• Prevent hyperthermia – stay hydrated, stay in shaded areas, and wear hats and clothing that protects from sun
• Wear dark-tinted glasses

Clozapine

• Atypical antipsychotic (-pine)
• Treats treatment-resistant schizophrenia
• Adverse effects: neutropenia, hemolytic anemia, extrapyramidal symptoms (EPS), and tardive dyskinesia
• Blocks dopamine receptors.
• Contraindications include allergy, CNS depression, liver or kidney disease, uncontrolled epilepsy.

Acetaminophen

• Analgesic and antipyretic
• Treats mild to moderate pain and fever
• COX inhibitor (reversible)
• Contraindicated with hypersensitivity, allergy, liver disease, and major burns
• Adverse effects include rash, fever, chest pain, and liver toxicity

Salicylate

• Toxicity typically from aspirin causes tinnitus
• Antidote = Sodium Bicarbonate
• Inhibits prostaglandin synthesis to decrease inflammation
• Contraindications include pregnancy, peptic ulcer disease, and bleeding disorders

Cholchicine

• Anti-gout medication for short term
• Binds and stabilizes tubulin
• Inhibits microtubule polymerization, impairing neutrophil chemotaxis and degranulation
• Contraindicated with hypersensitivity to colchicine and concurrent use of the CYP3A 4/5 inhibitors
• Adverse effects include GI upset, nausea, vomiting
• Do not consume grapefruit juice

Topical Anesthetics

• EMLA eases pain for needle punctures
• Transdermal Lidocaine patch relieves postherpetic neuralgia
• MOA applied directly to the skin and mucous membranes to relieve pain or prevent it from being sensed.
• Contraindications include vascular disease, aneurysms, hypertension
• Apply to skin one hour before the puncture.

Glaucoma Meds

• IOP = 10-21 mmHg
• Pilocarpine MOA – Nonselective muscarinic agonist
• Indication – glaucoma pupils effect the constriction of the eyes.

Apraclonidine

• Alpha 2 agonist direct acting
• For short term therapy of glaucoma
• Adverse effect is burning, eye pain, lacrimation, conjunctival hyperemia

Dipivefrin

• Sympathomimetic
• Indication for chronic open angle glaucoma
• Contraindication is allergy
• Adverse effects – burning, eye pain, and lacrimation, conjunctival hyperemia.

Betaxolol

• Beta 1 selective beta blocker
• Indication– open angle glaucoma immediate treatment of acute angle closure glaucoma, ocular hypertension
• Contraindications – allergy, COPD, asthma, heart block, any ocular conditions
• Adverse effects – discomfort, burning, photophobia, blepharitis, keratitis, corneal sensitivity

Timolol

• Beta blocker
• Acts as beta 1 and beta 2 receptor.
• Indication – elevated ocular pressure
• Timolol contraindications – bronchospams, COPD, asthma, heart failure, bradycardia
• Timolol MOA will reduce both elevated and normal IOP
• Adverse effect is blurred vision and pain photophobia

Glycerin

• Osmotic diuretic
• Indication is acute glaucoma episode
• Glycerin MOA pulls fluid from aqueous and vitreous humors into the bloodstream
• Glycerin contraindication – anuria, acute pulmonary edema, cardiac decompensation, sever dehydration
• Glycerin adverse effects – nausea, vomiting, headache, fluid and electrolyte imbalance

Mannitol

• Osmotic diuretic
• Indications – acute cerebral edema, transfusion reactions, glaucoma
• Adverse effects – edema headache, nausea
• Mannitol MOA: reduces ocular hypertension increasing fluids in intraocular and bloodstream.
• Interactions – lithium excretion.

Latanoprost

• Prostaglandin agonist, antiglaucoma agent
• MOA Increase outflow of aqueous humor. Can be used daily
• Contraindications – allergies
• Interaction admin 5 mins apart another eye drop containing thimerosal

Lispro

• Rapid acting insulin (Subcutaneously)
• Lispro onset - 15-30 minutes 15 minutes before meals
• Adverse effect- hypoglycemia
• Contraindications – hypersensitivity to Colchicine
• Indication - diabetes mellitus type 1 and 2

Sildenafil

• PDE5 Inhibitor (phosphodiesterase 5)
• Treats erectile dysfunction and pulmonary arterial hypertension
• Increase bloodflow to the corpus cavernosum which increases vasodilation of the pulmonary vasculature
• Any medications in the nitrate family, grapefruit juice, caution in clients with cardiovascular disease including QT prolongation

Alendronate

• Bisphosphonate that treats osteoporosis
• MOA: inhabitation of osteoclast medication bone resorption
• Interventions: monitor bone density
• Adverse effects include headaches and bone pain
• Take on an empty stomach in the morning with 6-8 oz of water
• Need to stay upright after taking

Glargine

• Long acting insulin (subcutaneously)
• For type 1 and 2 diabetes mellitus
• Onset 1-2 hours
• Adverse Effects is hypoglycemia

Glipizide

• Second generation sulfonylurea, antidiabetic (PO)
• For type 2 diabetes mellitus
• Adverse effects include hypoglycemia and weight gain
• MOA stimulates insulin release from the pancreatic beta cells, reduces glucose output from the liver; insulin sensitivity is increased at peripheral target sites.
• Contraindication includes sulfa allergy
• Take 30 mins before a meal

Vasopressin

• Antidiuretic hormone (IV) Natural or synthetic ADH– pituitary drugs
• Used to prevent or control polydipsia (excessive thirst), polyuria, and dehydration in patients with diabetes insipidus caused by a deficiency of endogenous ADH. Septic shock.

Levothyroxine

• Synthetic thyroid hormone
• Treats hypothyroidism
• Acts as a synthetic form of thyroid hormones
• Contraindicated with acute mycardial infraction
• Education: Take on an empty stomach before Breakfast

Hydrocortisone

• Corticosteroid (glucocorticoids)
• For adrenal insufficiency, anaphylaxis, asthma, COPD, distributive shock
• MOA Synthetic steroid with structure identical to cortisol
• Contraindication includes active infection

Prednisone

• Corticosteroid (glucocorticoids)
• Indication for allergic states, dermatologic diseases, endocrine disorders, neoplastic diseases, hematologic disorders, neoplastic diseases, nervous system, renal diseases, respiratory diseases, and rheumatic disorders.
• Prednisone contraindications – hypersensitivity to prednisone, or other glucocorticosteroids, administration of live vaccines, fungal infections

Echinacea

• Stimulates immune system
• Indication for upper respiratory tract infections

Ginko Biloba

• Herbal supplement
• Indication for memory issues
• Has antioxidant and antiinflammatory properties

Kava

• Herbal supplement; depressant type of drug
• Treats stress and anxiety
• MOA: similar to Benzodiazepines- alter limbic system

Flaxseed

• Herbal supplement
• Indication is chronic heart failure, hypertension, diabetes and constipation

Fluorouracil

• Pyrimidine antagonists (antimetabolites)
• Palliative treatments of cancers of the colon, rectum, stomach, esophageal, head, neck, cervical, breast, renal and pancreas. This drug inhibits DNA and RNA synthesis

Vincristine

• Mitotic inhibitor
• MOA - blocks microtubule polymerization & spindle formation – stops cell division during mitosis, not bone marrow toxic
• Vincristine contraindications – pregnancy or lactation, radiation therapy, liver disease, neuromuscular disease, hepatic impairment

Methotrexate

• Folic acid analog (folate antagonist analogue) -antimetabolite
• solid tumors such as breast, head and neck, and lung cancers and for the management of acute lymphocytic leukemia and non – Hodgkins lymphomas, gestational choriocarcinoma
• Methotrexate MOA – stops cell reproduction needed for the synthesis of DNA by inhibiting folic acid conversion
• Renal and hepatic failure can be contraindications

Irinotecan

• Topoisomerase 1 inhibitor
• treats metastatic colorectal cancer & small & cervical cancer
• Irinotecan MOA – Camptothecins inhibit proper DNA function in the S phase by binding to the DNA by binding to the DNA topoisomerase 1 complex.

Topotecan

• Topoisomerase 1 inhibitor
• Indications include ovarian and small lung cancer.
• Topotecan MOA - Camptothecins inhibit proper DNA function in the S phase by binding to the DNA by binding to the DNA topoisomerase 1 complex.

Asparaginase

• Other antineoplastic agents
• Kills cancer by interrupting protein synthesis in leukemia cells; deprives the cell of asparagine.
• Assess for: pancreatic function, mod- severe abdominal pain; hyperglycemia.

Cyclophosphamides

• Alkylating agents:
• treats lymphomas, solid tumors.
• prevents cancer cells from reproducing.

Doxorubicin

• Anthracyclines is the drug class
• Treats multiple cancers including breast, bone, and leukemia
• MOA Binds to DNA altering its structure, inhibits synthesis and prevents repair of DNA
• Contraindications – hypersensitivity, cardiotoxicity, pregnancy

Imatinib

• Targeted antineoplastic (miscellaneous Antineoplastics)
• Indications - chronic myeloid leukemia
• MOA - inhibiting the action of key enzyme bcr- abl tyrosine kinase responsible for causing CML. Stops cancer growth by inhibiting intracellular enzymes.

Tamoxifen

• Hormonal agents; breast cancer medications, estrogen blockers
• Stops growth of breast cancer cells, which are estrogen dependent cancers
• Contraindications include pregnancy, taking Warfarin

Leuprolide

• Hormonal agents
• Prostate cancer medications; GnRH agonists
• Palliative therapy of advanced prostate cancer in clients who do not want surgical castration.
• Prevents the release of luteinizing and follicle stimulating hormones to prevent production by the testicles.