Unit 1 Exam Flashcards
Phases of Clinical Trials
Pre-Clinical Trials
Phase I-IV
Pre-Clinical Trials
Animal testing
Phase I
20-100 healthy individuals
Focuses on pharmacodynamics
Most effective administration routes and dosage ranges are determined.
Occurs inpatient (overnight/weekend).
Phase II
Up to several hundred people with the disease the drug is intended to treat.
Same testing focus as phase I.
Performed outpatient. Serum levels, tolerance, side effects, and effectiveness are monitored.
Approval of the application means the drug can be marketed, but only by the company seeking the approval.
Phase III
1000 of patents
It begins once FDA determines that the drug causes no apparent side effects and that the dosing range is appropriate.
Double-blind research methods.
Most risk is discovered in this phase.
Either approved or rejected by FDA after this phase.
Phase IV
Post-marketing studies/surveillance.
Objectives:
1. Compare drugs to other drugs on the market.
2. Monitor long-term effectiveness and impact on QOL.
3. Analyze cost effectiveness.
Drugs can be taken off the market due to additional findings about the drugs and their side effects.
What is the Controlled Substances Act of 1970?
From the FDA
A way to categorize risk for addition and abuse.
What is the Controlled Substances Act of 1970?
From the FDA
A way to categorize risk for addition and abuse.
Drug Schedule
I, II, III, IV, V
Example of Schedule I Drugs
Heroin, cocaine
Highest abuse / addictive potential
Example of Schedule II Drugs
Morphine, dilaudid, methadone
Short interval of use
Example of Schedule III Drugs
Percocet
Low abuse potential / high addictive potential
Example of Schedule IV Drugs
Benzos
Low abuse / some addiction
Those who “NEED” it are likely to abuse it
Example of Schedule V Drugs
Robotussin w/ codeine, adderall
Least abuse / lowest addition
How to monitor adherence to therapy?
Lab testing
Pill count
Patient diary (BP or BG journal)
Therapeutic Window
Range of drug concentration in the blood between a minimally effective level and toxic level.
Pharmacogenomics
Personalized medicine
How genetic variations impact response to therapy
Single nucleotide polymorphism
Enables targeted therapy/focus resources
Expedites clinical improvements
Targeted risk reduction strategies
Area of tremendous amount of research.
Pharmacotherapeutics
Utilization of drugs to diagnose, prevent, or treat disease or illness.
Includes pharmacokinetics and pharmacodynamics.
Pharmacokinetics
What the body does to the drug.
Pharmacodynamics
What the drug does to the body.
Pharmacokinetics includes what 4 phases?
Absorption
Distribution
Metabolism
Excretion
Gender and Pharmacokinetics
Women have a higher % body fat which can alter the pharmacokinetics of different drugs.
Most drugs are tested more on men than women so need to consider hormonal changes and different patterns of fat.
Absorption
How administered drugs are absorbed into the body.
What affects absorption?
Bioavailability and route of administration
Bioavailability
The rate and extent drugs are absorbed from substances and are available at the site of action.
The fraction or % of an administered dose of a drug that reaches the circulation in its unmetabolized form.
What affects bioavailability?
First pass effect
Prodrugs
Drug formulation (Ex. ER vs. IR)
GI motility
Blood flow
First Pass Affect
Metabolism that occurs in the liver before passing into circulation.
PO drugs are subject to first pass effect.
Pro-Drugs
Drugs w/ no biological activity itself
Once metabolised in the liver, it becomes an active metabolite.
Precursor to active drug.
Drug Formulation
IR - Delivered to GI tract quickly for quick onset of action.
ER - Extends activity of drugs in the body to level out the high peaks to low troughs of concentrations.
EC - Slow drug to be dissolved in the intestines rather than the stomach.
GI Motility
Gastric emptying - Increases absorption and bioavailability.
Decreased intestinal motility - Greater absorption and bioavailability.
Increased intestinal motility - Less absorption and bioavailability.
Blood Flow
Based on adequate perfusion
Gut and intestinal perfusion is important for absorption.
Shock states affect blood flow and delivery of drugs.
Route of Administration
Enteral vs. Parenteral (all routes not involving GI)
Distribution
How drugs are distributed to the site of action
What affects distribution?
Blood flow
Lipid or water solubility
Protein binding
Passive Diffusion
High-concentration to low-concentration
No energy needed
Facilitated Diffusion
High-concentration to low-concentration
Via carrier proteins
Active Transport
Low-concentration to high-concentration
Utilizes ATP
Protein Binding
After absorption, drugs circulate through the body as unbound (free drug) or bound to proteins (commonly albumin).
Drug unbound (free drug) = Biologically active.
Low albumin states can result in toxicity.
ATBs have higher affinity to albumin than warfarin -> free warfarin -> increased INR.
Metabolism
Biotransformation of the drug from active form to inactive form.
Preparation for elimination.
What organ is primarily responsible for metabolism?
Liver
Also kidneys and intestines
Two Phases of Metabolism
Phase 1 - Enzymatic process that involves oxidation or reduction (hydrolysis).
Phase 2 - Adding a conjugate to the parent drug or metabolized drug to further increase water solubility and enhance excretion.
Cytochrome P-450 System (CYP450)
Composed of superfamilies of more than 100 enzymes.
3 families (15 enzymes) are responsible for drug metabolism in about 90% of cases.
Drugs may be substrate, inducer, or inhibitors of the CYP450 system.
Inducer
Stimulates production of enzymes which increase the amount of enzymes available for metabolism.
Ex. Phenytoin, Rifampin, St. John’s Wort
Inhibitors
Inhibits the production of CYP enzymes, decreasing the metabolism of drugs and increasing circulating levels.
Ex. Grapefruit juice, Azoles, Protease inhibitors.
Excretion
Removal of inactive drug from the body.
Primary organ of excretion
Kidneys
Important to know GFR to help dose drugs.
Other areas include lungs, skin, and GI tract.
Half-Life (t 1/2)
Time required for 50% of a drug to be eliminated from the body.
Ex. If t 1/2 is 10 hrs, then each 10 hrs, 50% of what is remaining will be eliminated.
Drug is considered fully eliminated after 4-5 half-lives.
Factors Interfering w/ Elimination
Renal failure → Increased t1/2 → dose less
Hepatic failure → Impacts prodrugs + CYP450 enzymes → increases t1/2
Exercise (regular vs. intermittent) → Impacts blood flow, GI motility, and body temp.
Factors affecting pharmacodynamics
Receptor abundance
Receptor affinity
Post-receptor changes and sensitivities
Types of receptors
Agonists
Antagonists
Agonist
Creates a response
Dose dependent
Depended on receptor sensitivity
Antagonist
Creates no biological response
Blocks receptors from agonists
Compete for receptor sites
Noncompentative sites.
Autonomic Nervous System receptors
Alpha-1, alpha-2, beta-1, beta-2
Flight or fight
Neurotransmitter is NE
Parasympathetic Nervous System Receptors
Cholinergic and muscarinic receptors
Neurotransmitter is ACH (acetylcholine)
How is pharmacotherapy different in the pediatric population?
Each property of pharmacokinetics is different.
Factors affecting drug delivery in pregnant women
Increased blood volume (30-50%), increased body water (~8lbs), and increased circulation -> Dilutional effect
Decreased serum albumin -> Increased free drug.
Increased progesterone + decreased Gi motility -> Increased absorption + bioavailability.
Maternal fat distribution + GI pH increased.
Factors promoting placental transfer
Lipid solubility.
Smaller, lighter molecules.
Unbound or “free drug”.
Factors Inhibiting placental transfer
Highly ionized molecules (requires active transport).
Larger, heavier molecules.
Drugs with high protein binding.
Beers Criteria
Guidelines for inappropriate medication use in older adults.
American Geriatric Society
Medicare Part-D may not pay for some of these meds.
Commonly prescribed meds are on that list.
Ex. Alpha-blockers prescribed for BPH.
Active Immunization
Administration of all or part of a microorganism or modified product of that microorganism.
Live or attenuated.
Evokes a natural immune response that mimics the body’s response to natural infection.
Ex. PNA vaccine/MMR
Passive Immunization
For people who have been exposed or have the potential to be exposed to specific infectious agents.
Administration of a preformed antibody when the recipient has a congenitally acquired defect or is immunodeficient.
Ex. Rabies
Vaccination Rates Across Lifespan
3 y/o = 90% - Infants/peds consistently visit their PCP.
18-64 y/o = 33-70%
Most vaccine series end around 11/12 y/o
Pediatric PNA Vaccine
Under 2 years, receive 4 doses of PCV-13
Elderly PNA Vaccine
> 65 years receive 1 dose of PPSV-23, even if unknown.
Immunocompromised PNA Vaccine
Under or over 65 years may receive bost PPSV-23 + PCV-13 at different times.
Influenza Vaccine Ages
Ages 6 months and up.
Not recommended for ages 6 months or less.
Inactivated Influenza Vaccine (IIV)
Given IM
Healthcare workers + immunocompromised
Live Attenuated Influenza Vaccine (LAIV)
Nasal spray
Recommended for ages 2-49 years.
Contraindicated in immunocompromised, household members of immunocompromised, and healthcare workers.
Tobacco Use Disorder Key Features
Continued use despite wanting to quit.
Prior attempts to quit.
Persistent use despite physical illness.
Tolerance.
Presence of withdrawal symptoms.
APA Criteria for Tobacco Use Disorder (2 or more in 12 month period)
- Tobacco is taken in larger amounts over a longer period of time than was intended.
- There exists a persistent desire to cut down or control tobacco use, or unsuccessful efforts are made to cut down or control tobacco use.
- A significant amount of time is spent in activities necessary to obtain or use tobacco.
- Craving, or a strong desire or urge to use tobacco, exists.
- Recurrent tobacco use results in a failure to fulfill important obligations or responsibilities at work, school, or home.
- Tobacco use continues despite its contribution to persistent or recurrent social or interpersonal problems (e.g., tobacco use causes or contributes to arguments with others).
- Tobacco use results in the individual giving up important social, occupational, or recreational activities.
- Tobacco use recurs in situations that are physically hazardous (e.g., smoking in bed).
- Persistent tobacco use despite knowledge of having chronic tobacco-related physical or psychosocial problems
- Tolerance to tobacco exists, with tolerance being defined as either one of the following: (1) the need for a markedly increased amount of tobacco to produce the intended effect or (2) a markedly diminished effect with the continued use of the same amount of tobacco.
- Withdrawal occurs. Withdrawal is manifested by either one of the following: (1) presence of characteristic co-relate withdrawal symptoms; (2) tobacco, or other nicotine containing products, is taken to relieve or avoid withdrawal symptoms.
Irritability, anxiety, difficulty concentrating, restless, depression, increased appetite, insomnia.
Fagerstrom Tolerance Test (Point System)
Time to first cigarette (TTFC)
Number of cigarettes per day.
Total score should range 0-10
-Score 6-7 suggest high level of physical dependence to nicotine.
-Score of 8-10 suggests a very high level of physical dependence to nicotine.
Nicotine Replacement Therapy
Transdermal patch
Gum
Lozenge
Nasal spray (req. rx)
Inhaler (req. rx)
No concurrent smoking
Buproprion SR (Zyban) MOA
MOA → Unknown
Takes 1 week to take effect → Smoke 1st week of therapy.
Buproprion SR (Zyban) Caution + SE
Avoid other antidepressants → OD could cause delirium
May cause insomnia and dry mouth
Varenicline (Chantix) MOA
Binds to the subunit of the nicotinic acetylcholine receptor.
Activates “reward system” without nicotine.
Varenicline (Chantix) Side Effects
Mood changes
Anxiety
Suicidal ideation
Vivid dreams
Normal BMI
18.5-24.9 kg/m2
Obese BMI
> 30 kg/m2
Severely Obese BMI
> 40 kg/m2
Adjunctive weight loss therapy with pharmacotherapy is recommended for…
> 30 kg/m2
> 27 kg/m2 w/ comorbidity (DM2, HTN, HLD)
Weight Loss Drug Therapy
Appetite suppressants
Lipase inhibitors
Glucagon-like peptide-1 receptor agonists
Appetite Suppressants
Benzphetamine
Diethylpropion ER
Appetite Suppressants MOA
Decreases appetite by stimulating the hypothalamus to release norepinephrine.
Appetite Suppressants Caution / SE
Schedule III or IV → Potential for abuse
SE: Increased BP and HR
Avoid in patients taking MAOIs → can lead to hypertensive crisis
Lipase Inhibitors
Orlistat (Xenical, Alli, Zenicol)
Lipase Inhibitors MOA
Acts locally in the GI tract.
GI pancreatic lipase inhibitor that lowers the absorption of dietary fat.
Spread fat throughout the day.
Lipase Inhibitors Contraindications
Malabsorption syndrome
Can increase INR → d/t decreased absorption of vitamin K
Lipase Inhibitors Side Effects
Frequent BMs
Bowel urgency
Fatty stools
Flatulence
Nausea
Abdominal pain
Glucagon-Like Peptide-1 Receptor Agonists
Saxenda (Victoza for DMII)
Glucagon-Like Peptide-1 Receptor Agonists MOA
Stimulates glucose-dependent insulin secretion, decreases glucagon secretion, and slows gastric emptying.
Activates proopiomelanocortin neurons, which results in a feeling of satiety.
Glucagon-Like Peptide-1 Receptor Agonists Side Effects
Nausea/vomiting
Diarrhea
Constipation
***Block box warning = medullary thyroid cancer, endocrine neoplasias type-2 seen in animal studies.
Combination Weight Loss Drugs
Phentermine EF / Topiramate
Naltrexone SR / Bupropion
Blepharitis
Meibomian glands secrete an oily film that prevents tears from evaporating → inflammation of eyelid margin.
Blepharitis Presentation
Present with irritated red eyes, burning sensation, increased tearing, blinking, photophobia, and sticking of eyelids.
Types of Blepharitis
Bacterial
Seborrheic
Meibomian Gland Dysfunction (MGD)
Bacterial/Staphylococcal Blepharitis Presentation
Loss of eyelashes or misdirection with matted, scaling, and crusting.
Seborrheic Blepharitis Presentation
Greasy deposits
MGD Blepharitis Presentation
Fatty foam deposits
First-Line Treatment of Bacterial Blepharitis
Bacitracin or Erythromycin ointment
If undesirable, then…
Moxifloxacin (Vigamox) or Azithromycin (AzaSite) solution.
*Avoid in corneal abrasion, slows wound healing.
Second-Line Treatment of Bacterial Blepharitis
If no improvment to 1st line after several weeks or condition worsens → refer to ophthalmologist.
First-Line Treatment of Seborrheic Blepharitis
Eye care specialist
First-Line Treatment of MGD Blepharitis
Eyelid massage following warm compress is used to remove excess oil, then use eyelid cleaner or baby shampoo.
Bacterial Conjunctivitis Presentation
Purulent discharge
Starts in one eye
First-Line Treatment of Bacterial Conjunctivitis
Erythromycin - 1cm x6 per day for 5-7 days.
Polymyxin B Trimethoprim (Polytrim) - 1 drop q 3-4 hrs for 5-7days
Targeting S. aureus, S. pneumoniae, H. influenzae.
Second-Line Treatment of Bacterial Conjunctivitis
Fluroquinolones (“-oxacin”) → Gram (+) coverage
Moxifloxacin (Vigamox) - 1 drop TID for 7 days
Ofloxacin (Ocuflox) - 1-2 drops q 2-4 hrs for 48 hrs, then 1-2 drops QID for 5 days.
Treatment of Chlamydial Conjunctivitis in Newborns
Erythromycin only
First-Line Treatment of DED
Mild → Artificial tears (GenTeal, Systane)
Mod/Severe → PF artificial tear sub as much as hourly
Sjogren’s → Cholinergic Agonists
Cholinergic Agonists
Pilocarpine
Cevimeline
Cholinergic Agonist MOA (DED)
Binds to muscarinic receptors, stimulating the secretion of salivary and sweat glands.
Cholinergic Agonist Contraindications + SE
Uncontrolled asthma, acute iritis, and narrow-angle glaucoma
SE: Excessive sweating
Second-Line Treatment of DED
Cyclosporine solution
Lifitegrast (Xiidra) 5% solution
Topical corticosteriods
Cyclosporine MOA (DED)
Increases aqueous tear production and decreases ocular irritation by preventing T cells from activating and releasing cytokines.
Liftiegrast 5% MOA
Blocks interaction of cell surface proteins LFA-1 and intracellular adhesion molecule 1 and may inhibit T-cell-related inflammation.
Topical Corticosteriods Use
Max use of 2 weeks → to suppress irritation and inflammation
Long-term use → ocular infection, cataract formation, and glaucoma.
Third-Line Treatment of DED
If all other therapies fail → refer to ophthalmology for permanent occlusion or tarsorrhaphy.
Helps eyes stay lubricated longer.
First-Line Treatment of Glaucoma
Prostaglandin Analogs
Prostaglandin Analogs
Bimatoprost (Lumigan)
Latanoprost (Xalatan)
Travoprost (Travatan Z)
“-oprost”
Prostaglandin Analogs MOA
Reduce IOP by improving uveoscleral outflow of aqueous humor, reducing IOP by 25-33%
Prostaglandin Analog Side Effects
Irreversible iris discoloration → periocular hyperpigmentation
Prostaglandin Analog Considerations
Refrigerate
Discard after 6 weeks
Travoprost should not be used during pregnancy
Second-Line Treatment of Glaucoma
Beta-blockers OR add beta-blocker if 1st agent fails to decrease IOP
Non-Selective Beta-Blockers
Timolol (Timoptic)
Levobunolol (Betavan)
Carteolol
Metiproanolol
Non-Selective Beta-Blocker Contraindications
Severe asthma/COPD
Beta-1 Selective Beta-Blockers
Betaxolol (Betopic S)
Beta-1 Selective Beta-Blocker Contraindications
Bradycardia
Heart block
CHF
Cardiogenic Shock
Beta-Blockers MOA
Reduce adenylyl cyclase activity, reducing the production of aqueous humor in the ciliary body, lowering IOP by 20-25%
Third-Line Treatment of Glaucoma
Topical Carbonic Anhydrase Inhibitors
OR
Adrenergic Agonists
Carbonic Anhydrase Inhibitors
Brinzolmide (Azopt)
Dorzolamide (Truopt)
“-zolamide”.
Carbonic Anhydrase Inhibitors MOA
Reduces aqueous humor production by the ciliary body by reducing the production of HCO3 ions and decreasing movement of HCO3, Na, and fluid into the posterior chamber. Reduces IOP by 15-26%.
Carbonic Anhydrase Inhibitors Contraindications
Severe renal impairment
Respiratory acidosis
Electrolyte disorders
Systemic Carbonic Anhydrase Inhibitors
Acetazolamide (Diamox)
Methanzolamide (Neptazane)
Most potent (reduces IOP by 25-40%)
Adrenergic Agonists
Brimonidine (Alphagan P) → Selective alpha-2 agonist → little to no a-1 activity.
Apraclonidine (Iopidine) → Selective Alpha-2 Agonist → Some A-1 acivity
Adrenergic Agonist MOA
Inhibits the release of norepinephrine, which reduces the formation of aqueous humor. Reduces IOP by 18-27%.
Nitric Oxide Donating Prostaglandin Analogs
Lantanoprostene Bunod (Vyzulta)
Nitric Oxide Donating Prostaglandin Analogs MOA
Prostaglandin analog improves uveoscleral outflow of aqueous humor, and NO reduces cellular contractility and volume, facilitating outflow of aqueous humor through trabecular meshwork and Schlemm’s canal.
Nitric Oxide Donating Prostaglandin Analogs Considerations
Requires refrigeration
May cause iris discoloration
Cholinergic Agonists
Pilocarpine (Isopto Carpine)
Cholinergic Agonists MOA (Glaucoma)
Stimulates the parasympathetic muscarinic receptor site to increase aqueous outflow through the trabecular meshwork.
Reduces IOP by 20-30%.
Rho Kinase Inhibitors
Netarsudil (Rhopressa)
Rho Kinase Inhibitors MOA
Increases aqueous humor outflow by relaxing cells that line Schlemm’s canal, reducing resistance to the flow of aqueous humor.
Reduces IOP by 14-22%.
Glaucoma Combination Products
Promotes adherence to therapy.
Combination therapy provides additional reduction in IOP than a single drug alone.
Ex.
Brimonidine + Timolol (Combigan)
Dorzolamide + Timolol (Cosopt)
Education Regarding Glaucoma Ophthalmic Solutions
Wash hands.
Make sure contacts are removed.
Apply medication to the inner aspect of the lower eyelids.
Tip of the container should not touch any part of the eye.
Multiple drops should be separated by at least 10 minutes.
Otitis Media
Occurs when the eustachian tube is obstructed due to inflammation of mucous membranes.
OTC Treatment of Otitis Media
OTC → NSAIDS/Tylenol
Topical benzocaine/procaine for pain relief for children >5 years old.
First-Line Treatment of Otitis Media
PCN (Amoxicillin) or Cephalosporins (Cefdinir if allergic to PCNs)
Second-Line Treatment of Otitis Media
Failure to improve in 72 hrs, change to Augmentin
Failure of augmentin, change to ceftriaxone single IM or IM x3 days.
Third-Line Treatment of Otitis Media
For reoccurrence, refer to ENT for tympanostomy tubes.
Amoxicillin Dosing for Children with Otitis Media
80-90 mg/kg/d PO BID
Amoxicillin-Clavulanate Dosing for Children with Otitis Media
Augmentin 80-90 mg/kg/d PO BID
Cephalosporin Dosing for Children with Otitis Media
Cefdinir - 14 mg/kg/day PO BID
Cefpodoxime - 10 mg/kg/day PO QD
Cefuroxime - 30 mg/kg/day PO BID
Ceftriaxone - 50 mg/kg/day IM QD 1-3 days
Antibiotic Duration for Children with Otitis Media
Age <2 = 10-day course
Age 2-5 = 7-day course
Age >6 = 5-day course
Medications No Longer Recommended for Otitis Media
Macrolides and clindamycin
Due to the ineffectiveness to S. pneumoniae and H. influenzae
First-Line Treatment of Otitis Externa
Fluoroquinolones
Fluoroquinolones
Ofloxacin (Floxin Otic)
Ciprofloxacin 0.3% - Dexamethasone 0.1% (Ciprodex)
Second-Line Treatment of Otitis Externa
Aminoglycosides
Aminoglycosides
Neomycin-Polymyxin B
Neomycin Sulfate-Polymyxin B-Hydrocortisone Acetate (Cortisporin)
Aminoglycosides Side Effects
Superinfection
Contact dermatitis
Ototoxicity with prolonged use
Aminoglycoside Contraindications
Herpes, fungal or viral otic infections
Perforated eardrum
Caution in breastfeeding / pregnancy
