RXRS 200 Finals Review

What is the role of insulin?

insulin opens doors for glucose to access cells

• tells GLUT4 transporter to facilitate diffusion of glucose into cell

What are the two ways liver converts glucose to?

glycogen in muscles (long term energy storage) and triglycerides (fat) in adipose tissue

Explain glucose homeostasis

insulin secreted y beta cells when high levels of glucose detected

• increased glucose = increased metabolism = decreased blood sugar

glucagon secreted by alpha cells when low levels of glucose detected, leading to breaking down of glycogen to produce glucose

What is Type I diabetes?

destruction of beta cells in pancreas that don’t regenerate, leading to manual management of lood glucose levels

what are therapeutics for type I diabetes?

synthetic insulin

• recombinantly generated human insulin tolerated by immune system

• not a cure for T1D

teplizumab

• postpones onset by few years

• immunotherapeutic - daily infusion for two weeks

• very expensive

What is metabolic syndrome?

• associated with risk factors for T2D, heart disease, and stroke

• diagnosed with 3+ risk factors for atherosclerosis + T2D

  • increased fasting glucose levels, increased triglycerides, reduced HDL cholesterol, hypertension, obesity, elevated waist circumference, insulin resistance

What is insulin resistance?

major component of metabolic syndrome

• normal levels of insulin no longer impact glucose transport to cells + blood sugar levels

  • vicious cycle - consume glucose, secret insulin, resisted, stored as fat, cells unfed and consume glucose

• leads to development of other disease like T2D, hypertension, atherosclerosis, dyslipidemia

What are pharmaceuticals to manage insulin resistance?

lower LDL cholesterol levels (alleviate atherosclerosis, etc)

• statins, cholesterol absorption inhibitors

increase body’s sensitivity to insulin

• insulin sensitizing agents

enhance natural insulin secretion

• CLP-1 receptor agonists, DPP-4 inhibitors

SGLT2 inhibitors - block glucose reabsorption in kidneys

agents that slow digestive/absorptive process

bariatric surgery

What are lifestyle changes to manage and prevent metabolic syndrome?

exercise

• increases GLUT4 transporter activity

weight management

• reverse fatty acid infiltration to liver, preventing IR development

nutrition

• low glycemic index foods - decrease spikes in blood sugar

What is Type 2 Diabetes?

not only resistance to insulin

• decreased insulin production + beta cell dysfunction + decreased uptake of glucose in response to insulin

  • increased alpha cell activity in pancreas → increased glucagon activity, hyperglycemic state

  • increase in inflammatory cytokine production

  • increase in circulating white blood cells

  • decrease in adiponectin [reduces plasma cells of free fatty acids]

What are risk factors to T2D?

obesity, hypertension, lack of exercise, low HDL/high triglyceride level, family history

What are pharmaceuticals to manage T2D?

reduce glucose production by liver

• metformin

augment glucose removal from bloodstream

• thiazolidinediones

increase insulin production by pancreas

• secretagogues

slow starch absorption from gut

• starch blockers

slow absorption of food

• incretin therapies, amylin analogs

recombinant insulin

Lifestyle changes for T2D?

preventable

• reduce weight, reduce fat intake, increase fiber, increase physical activity

smoking cessation, exercise, nutrition [improve glycemic control, fiber, good fats], decrease alcohol consumption

What is dyslipidemia?

• abnormal amount of lipids from glucose stored as triglycerides

  • low levels of HDL, high levels of triglycerides and LDL

• most important risk factor for atherosclerosis

Risk factors for dyslipidemia?

genetics, obesity, smoking, increased saturated and trans fats, prolonged high insulin levels, lack of exercise

Pharmaceuticals for dyslipidemia?

main trend - prevent atherosclerosis by lowering LDL and TG

• increase HDL, though rare [fibrates + niacin only]

• statins, intestinal cholesterol absorption inhibitor, niacin, bile acid resins

Lifestyle changes for dyslipidemia?

smoking cessation, exercise, weight loss + nutrition

What is coronary artery disease?

• atherosclerosis of arteries that carry blood to heart, reducing blood flow

  • plaque ruptures when fibrous cap thins, infiltrated by macrophages, accumulation of lipids, platelets rush and form a blood clot that blocks artery

Risk factors for CAD?

high cholesterol/dyslipidemia, obesity, smoking, diabetes, family history, lack of exercise

Pharmaceuticals for CAD?

statins

• decrease liver production of harmful cholesterol

anticoagulants

• reduce ability to form blood clots

beta blockers

• reduce heart rate and blood pressure

antianginals

• reduce chest pain/pressure

Ca2+ channel blockers

• relax blood vessels

procedures → remove blockages and reduce heart attack risk

• angioplasty, stenting

Lifestyle changes for CAD?

diet, cardio exercise, resistance training

What is hypertension?

high blood pressure

• influenced by cardiac output (volume of blood pumped)

• arterial stiffness (increases with age, atherosclerosis)

• systemic vascular resistance

caused by gradual development, lifestyle choices, underlying conditions, therapeutics

Risk factors for hypertension?

age, sex, race, genetics, obesity, inactivity, tobacco, stress, increase in sodium, decrease in potassium, increase in alcohol consumption

Pharmaceuticals for hypertension?

diuretics

• removes excess sodium + water

beta blockers

• reduces heart rate (less work for heart)

ACE inhibitors

• targets endogenous angiotensin production

• narrows blood vessels

angiotension II receptor blockers

• blocks angiotensin binding to receptors

• prevents vasoconstriction

calcium channel blockers

• decrease heart contraction, relaxes and opens blood vessels

vasodilators

• relaxes and opens blood vessels

Lifestyle changes for hypertension?

decrease smoking → most effective to prevent cardio disease

• decrease heart rate, arterial stiffness, blood pressure

nutrition

What is congestive heart failure?

• heart becomes less effective at pumping blood - left ventricle can’t pump enough blood volume to body

• occurs after cardio issues

  • leading causes = dyslipedemia, atherosclerosis, CAD, hypertension, valve conditions

  • treat/prevent these cardio issues → stop/slow progression to CHF

• systemic fluid retention

  • failing left ventricle - wall thickens, heart beats faster to move thicker muscle, increasing heart rate, increasing fatigue

• kidneys notice reduced blood flow - retain more water and salt, congesting left ventricle even more

Pharmaceuticals for congestive heart disease?

diuretics

• removes excess sodium + water

beta blockers

• reduces heart rate (less work for heart)

ACE inhibitors

• targets endogenous angiotensin production

• narrows blood vessels

angiotension II receptor blockers

• blocks angiotensin binding to receptors

• prevents vasoconstriction

calcium channel blockers

• decrease heart contraction, relaxes and opens blood vessels

vasodilators

• relaxes and opens blood vessels

Lifestyle changes for congestive heart disease?

exercise, smoking, diet

What happens in upper respiratory tract infections?

pathogen usually viral

• virus enters, replicating in nasopharyngeal epithelium

• immune system senses presence of virus

  • mucous glands activated, inflammation, bronchial constriction

  • symptoms - fever, sore throat, sneezing, cough

Pharmaceuticals for upper respiratory tract infections?

antihistamines, decongestants, antitussives, analgesics, anticholinergics, antibiotics

Tamiflu → influenza infections

• must be given within 48 hours to be efficacious

• prevent for high-risk patients; not that effective, benefits don’t outweigh risks

What happens in urinary tract infections?

common bacterial infection

• more common in women than men

• bacterial colonization of bladder (usually e. coli)

• infection can spread to kidneys, risking kidney damage, sepsis

infection causes long lasting changes to bladder - risk UTI coming back

Pharmaceuticals for UTIs?

antibiotics, pain relief, topical estrogen [post menopausal women with recurrent UTIs]

Lifestyle changes for UTI?

prevent holding urine, tight clothing, sex, douching

acupuncture

pelvic floor therapy

Describe the pathology of allergies

allergy = inappropriate response to innocuous antigen

• responds like there is an infection when there is none

• manifests after second exposure

• results in immune system trying to expel allergen in body

allergic reactions → hypersensitivity, trigger release of inflammatory mediators

What is asthma?

serious reaction to inhaled allergens

• allergens activate inflammatory immune cells in lower airways

• symptoms appear within exposure to allergen → increased fluid and mucus secretion, bronchial constriction, air trapped in lungs

• late phase reaction - 6+ hours later, persistent infiltration of immune cells to lungs, chronic disease if allergen persists

Pharmaceuticals for asthma?

bronchodilators, anti-inflammatory drugs, immunotherapy

What is allergic rhinitis?

• seasonal allergies

• allergens diffuse across mucous membrane of nasal passages

• local edema (swelling), obstruct airways

• discharge mucus thru nose

• inflammation caused by histamine

Pharmaceuticals for allergic rhinitis?

• immunotherapy - prevent binding to immune cells

• allergic desensitization - high risk adverse effects

What is rheumatoid arthritis?

a form of autoimmune disease

• misdirected immune responses against “self” cells and tissues - no great understanding why

chronic episoding inflammation of joints

• relapsing/remitting disease (spontaneous cycle)

Therapeutics for rheumatoid arthritis?

NSAIDS (nonsteroidal anti-inflammatory drug) - reduce pain, not inflammation

gluticorticoid treatment

• decreases inflammation

biologics - target immune cells, surface markers that drive pathology

What is HIV

retrovirus - genetic info stored as RNA, also contains reverse transcriptase and integrase

• attacks and destroys infectin fighting CD4 cells of immune system

  • harder to fight infections, risk acclimating to AIDS

What are transmission and risk factors for HIV?

transmission - sexual, parenteral, perinatal

risk factors - unprotected sex, blood/body fluid exposure, injection drug use, mother to child, multiple partners

What are treatment goals for HIV infection?

maximally and durably suppress HIV RNA and restore+preserve immunologic function

• maintain/increase CD4 count

• start treatment ASAP based on SMART trial

reduce HIV associated morbidity, prolong duration + quality of survivals

What are the stages of HIV replication cycle?

Binding, fusion, reverse transcription, integration, replication, assembly, budding

(HIV) What is binding?

virus binds to molecules on surface of CD4 cell

• must bind to primary CD4 receptor and either CCR5 or CXCR4 coreceptor

medication:

• CCR5 inhibitor → inhibits HIV entry into cells by inhibiting coreceptor

  • patients must undergo testing to determine which type of coreceptor present for medication to be effective

(HIV) What is fusion?

envelope fuses with CD4 cell through glycoprotein interactions

• once inside, virus releases HIV RNA and enzymes

medication

• fusion inhibitor → blocks HIV envelope from merging with host CD4 cell membrane

(HIV) What is integration?

HIV uses integrase to insert viral DNA unto host DNA

Medication

• blocked by class of ARVs called integrase strand transfer inhibitors (INSTIs)

  • side effect - muscle ache but well tolerated

(HIV) What is replication and assembly?

Once HIV integrates into host DNA, virus begins to use machinery to create long chains of HIV proteins

New HIVRNA and proteins made by host move to surface and assemble into immature HIV

(HIV) What is budding?

Part of viral maturation - HIV releases protease

• proteins combine to form mature HIV

medicatoin

• protease inhibitors - targets maturation

Describe sleep architecture

nREM has 4 sleep stages

• Stage 1 - drowsy, drifting in an dout

• Stage 2 - eye movement stops, electrical activity fluctuates, sleep spindles

• Stage 3+4 - deep sleep - delta waves, no eye movement nor muscle activity

REM - eye movement, rapid and shallow breaths, limb muscles paralyzed

Describe the 3 P model

predisposing [at risk]

• dependence on substances like alcohol, caffeine, nicotine, etc.

• long temr use of stimulants, sedative, etc.

• illnesses disturbing sleep onset and quality

precipitating [development of symptoms]

• causes breakout of insomnia

• acute stress

perpetuating [problem persists]

• excessive waking time spent in bed

• irregular sleep schedule

• excessive caffeine, alc, etc.

• anxiety from trying to control sleep

What are meds + env factors that impact sleep?

Meds

• diuretics - lowers bP, gets rid of excess fluids, when you take at night

• decongestant - constricts blood vessels, stimulant

• antidepressants vary - some sedate, some stimulate

• alcohol, bronchodilators, caffeine, corticosteroids, nicotine, pseeudoephedrine, sympathomimetics, thyroid hormones

environmental

• exposure to ordinary room light before bedtime, disrupt sleep and circadian

• sound, temp, air, bedding

What are common medications used for insomnia?

antihistamines

• induces drowsiness, causes sedation

benzodiazepines

• agonizes GABA-A receptor, enhances inhibitory effect

• z-drugs, similar mechanism, different chem structure

• short term → dependence risk

antidepressants

• increase monoamine signal transduction - some have sedating effects used for insomnia

What are nutritional supplements and botanicals used for sleep?

melatonin, cannabis, kava kava, german chamomile

What is good sleep hygiene?

• establish healthy sleep environment

• follow routine and schedule

• minimize naps throughout the day

• exercise

• vitamin D during day

• watch diet

• decrease substance use

• use bed only to sleep

What is cancer?

uncontrolled division of cells that could spread to surrounding tissues

• accumulation of several mutations that escape safety mechanisms

  • arises from single cell taht acquires enough specific mutations to become cancerous

What are the two genes associated with cancer?

proto-oncogene

• gene with potential to cause cancer

• steps on gas for cell growth, proliferation, inhibition of apoptosis

tumor suppressor genes

• puts brakes on proliferation

• prevent unwanted proliferation of mutant cells

What is metastasis?

when primary tumors leave initial site where first cell transformed and developed

• cancer cells require additional space + resources to grow

• requires primary tumor to change expression of surface proteins to help with migration to new site

• however gene expression profile is from OG tumor

  • ex: breast tissue growing within lungs

What are therapeutic regimens for cancer?

• complex as cancer is heterogeneous

• similar cancers can respond differently to therapy

• off target effects must also be managed

• some chemotherapeutic agents are more nausea inducing than others

• many regimens cause neutropenia (decreased white blood cells)

  • specifically target cells that grow + divide rapidly

• involves large treatment team

• cancers develop resistance to 1st line of therapy

• standards continuously evolve with developing knowledge on oncologic functions

Describe breast cancer

most common cancer for women - 1/8 diagnosed, risk increases with age

heterogenous disease, two main types

• ductal carcinoma in situ

  • starts in milk duct, doesn’t spread to rest of the tissue

  • noninvasive, preinvasive

  • 20-30% of breast cancers

• invasive breast cancer

  • spread to surrounding tissue

  • metastasize to other organs, tissues, lungs

  • 70-80% of breast cancers

hormone driven - express receptors for progesterone/estrogen

• risks with exogenous estrogen → HRT, pesticides

• triple positive breast cancer - hormone receptors + HER2 overexpression (proto-oncogene)

inflammatory → 1-5%, no lump, not on mammogram

What are risk factors for breast cancer?

genetics

• cancer suppressor genes

• 60-80% lifetime risk for breast cancer

HRT

obesity - aromatase expression in fat tissue

disruption of circadian rhythm → decrease melatonin + estradiol levels

nutrition - alc, decreased fruits and veg

What are approaches for chemoprevention?

• screening

• risk reducing surgery - mastectomy → ovary and fallopian tube removed

• prophylactic to modulate estrogen

• exercise

• prolonged breastfeeding [reduce lifetime estrogen]

What are traditional approaches for breast cancer?

post-op use of cytotoxic chemo + anti-estrogen agents

• greater survival post surgery

shift to breast preservation + lumpectomy + radiation

surgery

• only 5% metastatic eligible

• surgery + radiation successful in eliminating

radiation

• whole breast radiation common post lumpectomy

• reduce risk for cancer recurrence

chemo

• before/after surgery

• modulate hormonal environment to reduce recurrence

• cytotoxic → genomic profiling = more targeted

• inhibit cell growth

• use immune system to attack cancer cells

  • monoclonal antibodies conjugated to chemotherapeutic drug

Ways to manage side effects for breast cancer therapy?

vasomotor instability (hot flashes)

• non-hormonal interventions - relaxation, acupuncture, SSRI, SNRI, gabapentin

osteopenia + osteoporosis

• strenth trainig, weight bearing yoga

• supplement with vitamin D + calcium

What are the different kinds of lung cancer?

non-small cell lung cancer (80-85)

• adenocarcinoma → most common, non-smokers

  • starts in mucus secreting cells

• squamous cell carcinoma → smokers

  • start in flat cells that line inside of airways

• large cell → anywhere, grows quickly

small cell lung cancer (10-15)

• grows and spreads quickly, usually already upon diagnosis

What are risk factors for lung cancer?

smoking - largest risk factor

environmental carcinogens - radon, secondhand smoke, asbestos, etc.

What are common therapeutics for lung cancer?

surgery

• better for early NSCLC when localized [best opportunity for care]

• not good option for metastatic cancer

• pneumonectomy, lobecomy, segmentectomy

radiofrequency ablation

• tumors in periphery - can’t tolerate surgery

• a probe is inserted thru skin and heated to destroy tumor

• outpatient procedure, few complications

radiation therapy

• brachytherapy - directly to tumor via catheter to lung (NSCLC)

chemotherapy

• NSCLC - platinum based therapy, monoclonal antibodies, KRAS inhibitors, receptor tyrosine kinase inhibitors

• SCLC - platinum based therapy, Bi-specific T cell engager antibody therapy, immune checkpoint inhibitor monoclonal antibody therapy

What is the difference between mood and affect?

mood: emotional state patient tells you they efel

• feeling/tone prevailing over time

• quoted

• subjective and not static

affect: behavioral/observable manifestation of mood

What is major depressive disorder? What are common signs and symptoms

at least 2 weeks depressed mood or loss of interest or pleasure in daily activities

• depressed mood, insomnia, decreased interst, decreased self esteem, fatigue, lowered concentration and appetite, suicidal ideations

What are common nondrug therapies for MDD?

psychotherapy → CBT

electroconvulsive therapy

light therapy

lifestyle - alcohol, exercise, diet, mindfulness

What are common pharmacotherapies for MDD?

typically involes altering monoamines

• multiple therapies increase serotonin - could lead to toxicity

selective serotonin reuptake inhibitors (SSRIs)

• block presynaptic serotonin reuptake

• treat both GAD + MDD

• decreased risk for cardiotoxicity

serotonin/norepinephrine reuptake inhibitors (SNRIs)

• inhibit reuptake in synaptic cleft

• increased BP, nausea, tachycardia

trycyclics

• similar to SNRI - inhibit serotonin + norepinephrine reuptake

monoamine oxidase inhibitors

• bind irreversibly preventing inactivation of norepinephrine, dopamine, serotonin → increased synaptic levels

• very effective

• orthostatic hypotension, weight gain, dry mouth, sedation

Why are mood stabilizers more effective for bipolar disorder?

SSRI/SNRU would induce mania due to increase in serotonin

• modulate neurotransmitter activity

  • lithium, valproate, atypical antipsychotics

What is generalized anxiety disorder? Common signs and symptoms?

comorbid conditions - major depression, social phobia

• excessive/unrealistic about 2+ aspects of life - often accompanied by symptoms → palpitations, dizziness

• psychological → anticipatory, exaggerated response to danger cues

• neurobiological → amygdala

Common pharmacotherapy for generalized anxiety disorder

1st line of therapy = antidepressants

• SSRIs, SNRIs

• when comparing impact, all antidepressants considered equal

How does pharmacogenetics affect metabolism?

CYP 450 - enzyme family responsible for drug metabolism

individuals have variation in CYP functioning phenotypes

• poor metabolizer - 2 inactive alleles

• intermediate - decreased activity / 1 active, 1 inactive

• normal - 2 functional (wild type)

• ultra-rapid - multiple copies of functional alleles

affects how much drug gets into blood stream to have effect

• little active drug - decreased effect

• too much drug - increased adverse effects

What is the difference between active drugs and pro-drugs?

active = pharmacologic effect without activation

prodrugs = activation step required for drug to have effect

• typically metabolizing enzyme

• activation → active metabolite with pharmacologic effect

What is a vaccine?

bioproduct defending against infection/disease upon subsequent exposure to pathogen

• takes advantage of immunological memory

  • vaccines simulate primary response to make immune system think it is infected to establish memory

  • prophylactic - presented before actual pathogen causes infection

What are various kinds of vaccines?

live attenuated vaccines

• pathogenic virus isolated from patient mutated to work ineffectively in human cells

• can’t replicate

• high adverse effects

killed/inactivated virus

• inactivated chemically or physically

• can’t replicate following immunization

subunit vaccines

• individual pathogen antigens seleced for formulation

• adjuvants enhance immune response

toxin vaccines (for bacterial)

• purify and inactivate toxin

• induce high affinity antibodies against toxin

nucleic acid vaccines

• inject nucleic acid to be expressed in a person using own transcription + translation machinery to produce antibodies of virus

nonreplicating viral vector

• genetically engineering virus to express proteins of other virus → stimulates general immune response

What are essentials to vaccine design?

• generates sterilizing immunity

• limited/safe side effects

• confers protection with smallest number of doses

• limited/no cold chain required

What is the history of pharmacy practice?

early 20th century

• apprenticeship model, on the job

• emphasis on compounding

• no distinction between prescription and non-prescription

mid 20th

• area of expansion - drugs dispensed w limitations

• seen more as merchants than healthcare workers

• shifts in drug safety, legal distinction between prescription and OTC, efficacy and clinical trials

• shift from compounding to dispensing manufactured drugs

modern

• push for clinical pharmacy

• mandated counseling for Medicaid

• pharm imunizations, CPA, MTM

What are educational requirements to practice pharmacy?

education = typically undergrad then PharmD

What is the law allowing pharmacists to conduct clinical allowed in scope of practice?

California Senate Bill 493 (SB493)

• pharmacists = healthcare providers

• expand scope of practice

  • contraceptives, travel meds, nicotine replacements, immunizations, order + interpret testing, consultations, drugs + biologics

• established advanced practice pharmacist

What are CPAs?

collaborative practice agreements

established between physician and pharmacist

• defines scope of pharmacist under physicians’ supervision

may have advanced scope of practice

• prescribing privileges

• ability to order lab tests to monitor outcomes

• authority to adjust meds on basis of exam data

What is an advanced practice pharmacist’s roles?

• patient assessment

• order + interpret drug therapy related test in coordination with patient’s primary care provider to monitor process

• evaluation and management of disease + health conditions w other healthcare providers

• initiate, adjust, discontinue drug therapy upon referral when necessary/appopriate with protocol

What are various career paths to pharmacy?

hospital pharmacy

• ensure safe and appropriate use of drugs in hospital setting

• involvement in all aspects of drug use

• provide med management services

• reduce med errors, readmission rates

community pharmacy

• ensure safe and appopriate use of drugs in community setting

• founded on shoulders of independent owners

• patient care → consulting, home health, long term

ambulatory care pharmacy

• integrated, accessible healthcare services

• address medication related problems

  • any undesirable event involving drug therapy interfering with achieving goals requiring professional judgment to resolve

managed care therapy

• developing and applying evidence based med use strategy enhancing population health outcomes while optimizing health resources

• decisions for many people in particular category

What is the patient care process?

collect - before, during, after appointment

• past history, diagnoses, current med, habits

assess - info collected matches presentation?

• medication safety? drug interactions?

plan - develop individualized plan w team

• current condition? improved/optimized? goals

implementation - incorporate plan to life

follow up - monitor + evaluate → see effectiveness of plan