Pharmacology 2 - Exam 4

estrogen

• ovaries are the primary organ that create this

• physiological roles

  • effects on secondary sex characteristics

  • metabolic actions → increase bone mass, decrease bad cholesterol, cause blood coagulation

• therapuetic uses

  • menopausal hormone

  • female hypogonadism

  • acne

• routes of administration

  • oral, transdermal, intravaginal, parenteral

estrogens adverse effects

• cardiovascular thromboembolic risks

  • estrogen increases hepatic synthesis of clotting factors and decreases anticoagulant proteins

• hormone-dependent cancers

  • breast cancer

  • endometrial cancer

• gallbladder disease

• other

  • nausea, fluid retention/weight gain, headaches/migraine

SERMS

• selective estrogen receptor modulators

• MOA → activate in some tissues (bone) and block estrogen selectively in others (breast)

• adverse effects → DVTs, PEs, MIs

• ex. Tamoxifen, toremifene, raloxifene

progestins

• these are compounds that act like progesterone, which is produced by the ovaries and the placenta

• uses

  • postmenopausal hormone therapy

  • dysfunctional uterine bleeding

  • amenorrhea

  • infertility

  • preterm labor prevention (relaxes the uterus)

  • endometrial carcinoma and hyperplasia

• adverse effects

  • teratogenic effects, gynecologic effects, breast cancer, depression, breast tenderness, bloating

safety alert with estrogen + progesterone

• increases the risk for thromboembolic events such as DVT, stoke, pulmonary embolism

• increase the risk of dementia in patients aged 65 and older

• increase the risk of ovarian and breast cancer

hormone therapy approved indications

• treatment of moderate to severe vasomotor symptoms associated with menopause

• treatment of moderate to severe symptoms of vulvar and vaginal atrophy associated with menopause

• prevention of postmenopausal osteoporosis

without a surge of LH…

…an egg will not be released

birth control

interfering with the reproductive process at any step from gametogenesis (production of egg/sperm) to nidation (implantation of a fertilized ovum)

birth control methods

• pharmacologic methods of contraception

  • oral contraceptives

  • etonogestrel implants

  • injectable medroxyprogesterone acetate

  • intrauterine devices

  • vaginal rings

  • transdermal patches

• nonpharmacologic methods of contraception

  • surgical sterilization → tubal litigation/vasectomy

  • mechanical devices → condom, cervical cap

  • avoiding intercourse during periods of fertility

hormonal contraceptives

• these work by manipulating the body’s natural feedback loop between the hypothalamus, pituitary, and ovaries

• they prevent the LH surge that triggers ovulation and they also make the uterus and cervix less receptive to sperm and implantation

• two categories

  • combination (estrogen + progesterone) suppress FSH/LH → no ovulation

  • progesterone-only thickens cervical mucus, thins the endometrium, and may suppress ovulation

• long-acting vs. short-acting

  • long-acting → injections/implants improve compliance and efficacy

  • short-acting → pills require strict adherence

combination oral contraceptives

• ethinyl estradiol + norethindrone

• MOA

  • inhibits FSH and LH → no ovulation

  • thickens cervical mucus → blocks sperm

  • thins endometrium → prevents implantation

• adverse effects

  • nausea, breast tenderness, headache, breakthrough bleeding, increased risk of thromboembolism, hypertension

• benefits

  • regular cycles, decreased cramps, acne

  • decreased risk of ovarian and endometrial cancer

• teaching points

  • take at the same time daily

• interactions

  • Rifampin, anticonvulsants, St. John’s Wort

oral contraceptives drug interactions

• drugs and herbs that reduce the effects of oral contraceptives

  • Rifampin → TB med

  • Ritonavir

  • antiepileptic drugs

  • St. John’s Wort

• drugs whose effects are decreased by oral contraceptives

  • warfarin

• drugs whose effects are increased by oral contraceptives

  • theophylline

  • tricyclic antibiotics

  • diazepam

transdermal contraceptive patch

• brand name → Ortho Evra

• application → once a week for 3 weeks, followed by 1 week off

• adverse effects → breast discomfort, headache, local irritation, nausea, menstrual cramps

vaginal contraceptive ring

• brand name → NuvaRing

• one ring is inserted once each month, left in place for 3 weeks, and then removed and then a new ring is inserted 1 week later

• adverse effects → vaginitis, headaches, upper respiratory infection, leukorrhea, sinusitis, weight gain, nausea

long-acting contraceptives

• subdermal etonogestrel implants (Nexplanon)

  • type → progestin-only, subdermal implant

  • primary MOA → suppresses ovulation

  • secondary MOA → thickens cervical mucus, thins the endometrial lining

  • duration → effective up to 3 years

• depot medroxyprogesterone acetate (MPA)

  • type → progestin-only, intramuscular injection every 12 weeks

  • primary MOA → inhibits the secretion of FSH and LH

  • secondary MOA → thickens the cervical mucus, thins the endometrial lining

  • duration → effective for ~3 months per injection

• IUDs

  • type → local progestin release in the uterus

  • primary MOA → thickens cervical mucus

  • secondary MOA → thins endometrial lining, may inhibit ovulation

  • duration → 3-10 years depending on the brand

emergency contraception

• plan B

• MOA → inhibits or delays ovulation if administered before LH occurs, may block inplantation

• adverse effects → nausea, fatigue, headache, menstrual changes

• benefits → post-intercourse option with ongoing hormones

• teaching → take within 72 hours (ideally < 24 hours), does not terminate an existing pregnancy

• interactions → Rifampin, anticonvulsants, St. John’s Wort

spermicides

• chemical surfactants that kill sperm by destroying their cell membrane

• formulations → gel, jelly, suppository, vaginal film, contraceptive sponge

• all formulations can be purchased without a prescription

• when used alone, only moderately effective

• use with a diaphragm or condom increases efficacy

drugs for medication abortion

• Mifepristone with Misopostol

  • blocks uterine receptors and contracts the uterus

  • abortion pill

    • FDA approved through 10 weeks → recommended to get an ultrasound before taking this pill to rule-out that the pregnancy could be in the fallopian tubes

    • Planned Parenthood will give this through 12 weeks

  • adverse effects → bleeding, cramping, nausea, vomiting, diarrhea, headache

• Methotrexate with Misoprostol

• Prostaglandins → Misoprostol, carboprost, dinoprostone

Clomiphene

• MOA → blocks estrogen receptors in the brain which increases the release of LH and FSH which increase estrogen levels in the body

• uses → promote follicular maturation and ovulation

• adverse effects

  • hot flashes, nausea, bloating, abdominal discomfort, breast engorgement, blurred vision, multiple births, ovarian hyperstimulation (rare)

Menotropins

• brand name → Menopur

• used in conjunction with hCG to promote follicular maturation and ovulation

• adverse effects

  • ovarian hyperstimulation syndrome → leads to severe ovarian enlargement, abdominal pain, ascites, ovarian cyst rupture

    • monitor follicular size with ultrasound

  • multiple births

hCG

• a polypeptide hormone produced by the placenta

• uses → promotes follicular maturation and ovulation, promotes spermatogenesis

• adverse effects → ovarian hyperstimulation syndrome, edema, injection-site pain, headache, irritability, restlessness, fatigue

gonadotropin-releasing hormone antagonists

• used to prevent a premature surge of LH in women undergoing controlled ovarian stimulation

• drug examples → Ganirelix, Cetrorelix

hyperprolactinemia

• a condition characterized by abnormally high levels of prolactin, a hormone produced by the pituitary gland

• causes → can result from pituitary tumors (prolactinomas), certain medications, stress, or hypothyroidism

Cabergoline

• used to correct amenorrhea and infertility (when this is related to hyperprolactinemia)

• adverse effects

  • nausea, headache, dizziness, orthostatic hypotension

Tocolytics

• these meds are used to suppress preterm labor (uterine relaxants)

• uses → delays pregnancy for 48 hours

Oxytocics

these meds stimulate labor induction and control postpartum

Terbutaline

• brand name → Brethine

• a tacolytic

• used to prevent preterm labor and relax the uterus

Nifedipine

• brand name → Procardia

• a tacolytic

• blocks calcium from entering into the muscle cells of the uterus which prevents preterm labor

Indomethacin

• brand name → Indocin

• a tacolytic

• used to prevent preterm labor and relax the uterus

magnesium sulfate

• modest tocolytic effects to suppress contraction

• used to prevent preterm labor and relax the uterus

hydroxyprogesterone caproate

• brand name → Makena

• indicated only for women with a singleton pregnancy and a history of at least one preterm birth

• not approved fro women with multiple pregnancy or other risk factors for preterm birth

Dinoprostone

• most widely used agent for cervical ripening (thinning)

• promotes cervical ripening and later stimulates uterine contractions

• formulations → gel, vaginal inserts

Misoprostol

alternative to dinoprostone for cervical ripening before birth

Oxytocin

• brand name → Pitocin

• MOA → increased the force, frequency, and duration of uterine contractions

• physiologic and pharmacologic effects

  • uterine stimulation

  • milk ejection

  • water retention

• precautions and contraindications

  • uterine rupture may occur

    • slow down infusion if they are having more than 5 contractions in 10 minutes, contractions are more than 90 seconds, peak pressure of uterus to exceed 80 mmHg or not relaxing enough (never under 25 mmHg), or fetal distress (HR < 110 bpm)

  • contraindicated in women with active genital herpes

• adverse effects → water retention/intoxication

drugs for postpartum hemorrhage

• Oxytocin (Pitocin) and Misoprostol (Cytotec)

  • powerful uterotonic agents

  • stops postpartum hemorrhage resulting form uterine atony

• Carboprost tromethamine (Hemabate)

  • ONLY after birth

  • adverse effects → nausea, vomiting, diarrhea, fever

testosterone

• formulations → transdermal gel, transdermal patch, buccal tablets, IM

  • never given PO → increased risk of hepatotoxicity

• precautions

  • avoid skin to skin contact (especially with pregnant women and children)

  • do NOT apply to genitals

• adverse effects

  • infertility, increased blood viscosity (increases clotting risk), acne, prostate enlargement, edema, weight gain, increased LDLs

• required monitoring → testosterone levels, CBC, LFTs, lipid panel

sildenafil

• uses → PRN medication for males with ED, pulmonary HTN

• MOA → dilates the blood vessels which allows blood to accumulate in the penis causing an erection

• nursing considerations → advise pt. to take 1-4 hours before sex, only take one tablet in 24 hours, high fat meals decrease absorption (decreases effects)

• adverse effects

  • dizziness, fainting, hypotension, vision and hearing loss, priapism (erection that lasts longer than 4 hours, can cause penile tissue damage)

• drug interactions

  • nitrates → all patients must tell all providers and emergency personnel that they are taking this medication, it causes profound hypotension when combined with nitrates (ex. nitroglycerin for MI/chest pain)

finasteride

• MOA → works by inhibiting Alpha-5, which leads to a reduction in prostate size

  • “F fixes the prostate size”

• uses → BPH

• adverse effects

  • depression, gynecomastia

• nursing considerations

  • this is not considered a first-line treatment for BPH as it takes several months for symptom relief

  • this medication should never be handled by pregnant women

tamulosin

• brand name → Flomax

• MOA → blocks Alpha-1 adrenergic receptors, which then relaxes the smooth muscle in the bladder neck

  • “T is for tube opener“

• adverse effects

  • orthostatic hypotension, dizziness, abnormal ejaculation

local anesthetics

• suppress pain by blocking sodium channels and by blocking impulse conduction along axons

• stops nerve impulse transmission only in neurons located near the site of administration

• suppress pain without generalized depression of the nervous system

• 2 classifications

  • esters → shorter-acting

  • amides → longer-duration, less allergic reactions (these are used more)

epinephrine

• vasoconstrictor that is used with local anesthetics

• MOA → decreases local blood flow, delays systemic absorption of the anesthetic, prolongs anesthesia, and reduces the risk of toxicity

• nursing considerations → avoid areas of poor circulations (fingers, toes, ears, nose, and penis)

systemic effects of anesthetics

• occurs when local anesthetics are absorbed into the bloodstream

• CNS → excitation followed by depression

• CV → bradycardia, heart block, reduced contractile force, cardiac arrest, hypotension

• allergic reactions

• L&D → reduces uterine contractility (makes labor longer)

• methemoglobinemia → hemoglobin cannot carry oxygen, pt. becomes cyanotic

lidocaine

• amide local anesthetic

• most widely used local anesthetic

• effects are extended if given with epinephrine

• also used for cardiac dysrhythmias

• topical preparations → cream, ointment, jelly, solution, patch

• adverse effects

  • cardiac toxicity, CNS toxicity

• nursing considerations

  • absorption risk increases with increased dose, applying on broken skin, and increased skin temperature

  • apply the smallest amount possible, avoid application to large areas

infiltration anesthesia

injecting a local anesthetic directly into the immediate area of surgery or manipulation

nerve block anesthesia

injecting a local anesthetic into or near nerves that supply the surgical field but at a site distant from the field itself

epidural anesthesia

• injecting a local anesthetic into the epidural space

• anesthetic can reach the systemic circulation in significant amounts

• adverse effect → bradycardia, CNS depression in the infant

general anesthetics

• drugs that produce unconsciousness and a lack of responsiveness to all painful stimuli

• loss of pain and loss of all other sensations

• two main groups

  • inhalation anesthetics

  • intravenous anesthetics

properties of an ideal inhalation anesthetics

unconsciousness, analgesia, muscle relaxation, amnesia, induction brief and please, emergence brief and pleasant, depth of anesthesia raised or lowered with ease, minimal adverse effects, large margin of safety

balance anesthesia

• technique used to compensate for the lack of an ideal anesthetic

• combination of drugs to ensure that induction is smooth and rapid and the analgesia and muscle relaxation are adequate

inhalation anesthetics

• MOA → enhances transmission at inhibitory synapses, depresses transmission at excitatory synapses, these two things combined causes sedation

• adverse effects

  • respiratory and cardiac depression → mechanical ventilation is often required to support the patient during surgery (high doses can be lethal)

  • sensitization of the heart to catecholamines → heart is more sensitive to stress hormones (pain must be controlled because it causes stress to the heart)

  • malignant hyperthermia

  • aspiration of gastric contents → use ET tube during surgery and make sure the patient is NPO before surgery to prevent this

  • toxicity to operating room personnel → headaches and spontaneous abortions

  • hepatotoxicity

malignant hyperthermia

• trigger → deadly reaction to an inhaled general anesthetic

  • succinylcholine + inhaled general anesthetic

• risk factors → family history = increased risk (avoid any inhaled anesthetics)

• signs and symptoms → increased temperature (up to 109 degrees), increased muscle rigidity

  • both of these happen VERY quickly

• treatment → DANTROLENE (relaxes the muscles), stop the anesthetic immediately, begin rapid cooling measures

minimum alveolar concentration

• also known as MAC

• low MAC = high potency (less of the drug is needed to produce the desired effects)

• high MAC = low potency (more of the drug is needed to produce the desired effects)

neuromuscular blocking agents

• surgical procedures require skeletal muscle relaxation

• these reduce the amount of anesthesia needed and precent contraction of all skeletal muscles, including diaphragm and muscles of respiration (flaccid paralysis)

• 21 million patients undergo surgery

  • 1 in 2000 wake up during the procedure

• drug examples

isoflourine

• inhalation anaestehtic

• respiraratorydeopresss and hypotension

nitrous oxide

• very low potency → cannot produce full surgical anesthesia

• used primarily for dental procedures and sometimes to provide relief during labor

propofol

• one of the most widely used anesthetics

• used for surgical anesthesia, endoscopies, radiation, bone reductions

• adverse effects → profound respiratory depression (RT should be present), hypotension, increase risk of bacterial infections (must be discarded within 6 hours)

• not a controlled substance

etomidate

• very potent induction of anesthesia

• also used for intubation

ketamine

• dissociative anesthesia → “the lights are on but no one is home“

• this is a controlled substance

• adverse effects → hallucinations, disturbing dreams, and delirium

• uses → anesthesia for young children with minor procedures

benzodiazepines

• primarily used to help with pre-surgical anxiety

• ex. diazepam (Valium)

roles of dopamine

• reward and pleasure → too much in this pathway leads to psychosis

  • blocking dopamine in schizophrenia patients helps with hallucinations

• thinking and focus → low levels in this pathway lead to negative symptoms of schizophrenia (flat affect, reduced motivation)

  • blocking dopamine in schizophrenia patients worsens negative symptom

• movement control → plays a role in parkinson’s disease

  • blocking dopamine in schizophrenia patients causes EPS symptoms

• hormonal regulation → dopamine inhibits prolactin and keeps it in check

  • blocking dopamine in schizophrenia patients causes moobs and nipple discharge

first generation antipsychotics

• also known as conventional antipsychotics

• MOA → block receptors for dopamine in the CNS which helps positive symptoms but worsens negative symptoms

  • this dopamine blockade reduces psychotic symptoms but is linked to movement disorders

• classifications

  • potency → low = higher sedation, high = less sedation, higher risk for EPS

  • chemical classifications

• uses → schizophrenia, delusional disorders, bipolar disorders, depressive psychoses, drug-induced psychoses, suppress emesis, tourette’s syndrome, huntington’s chorea

• adverse effects → cause serious movement disorders known as extrapyramidal symptoms (EPS)

  • acute dystonia, tremors, rigidity, bradykinesia, akathisia, tardive dyskinesia

second generation antipsychotics

• also known atypical antipsychotics

• MOA → produce only moderate blockade of dopamine receptors, stronger blockade for serotonin

• uses → schizophrenia, delusional disorders, bipolar disorders, depressive psychoses, drug-induced psychoses, suppress emesis, tourette’s syndrome, huntington’s chorea

• adverse effects → fewer extrapyramidal symptoms (EPS) because it doesn’t block dopamine as much as first generation, metabolic effects (weight gain, hyperglycemia)

adverse effects of first generation antipsychotics

• acute dystonia

  • early onset (1-5 days), can be managed with medications, uncontrolled muscle spasms mostly over face, tongue, and neck

• parkinsonism

  • early onset (1-4 weeks), can be managed with medications, rigidity, bradykinesia, tremor

• akathisia

  • early onset (5-60 days), can be managed with medications, restlessness, irresistible desire to move around

• tardive dyskinesia

  • occurs later in therapy (after months or years), no satisfactory treatment available, involuntary movements of face and upper limbs

• neuroleptic malignant syndrome (NMA)

  • occurs weeks to months after drug administration, muscle rigidity, fever, unstable BP, myoglobinemia

• anticholinergic effects

• orthostatic hypotension

treatment for adverse effects of first generation antipyshotics

• EPS

  • acute dystonia → administer anticholinergic medications such as benztropine or diphenhydramine immediately

  • parkinsonism → administer benztropine, never use levodopa!

  • akathisia → administer beta blockers, benzodiazepines, or anticholinergics

  • tardive dyskinesia → this is often irreversible, switch to second generation

• NMS

  • treatment for NMS requires immediate withdrawal of the antipsychotic medication, followed by supportive care to manage fever and stabilize vital signs

  • adminster dantrolene (muscle relaxant) and bromocriptine (dopamine agonist)

• anticholinergic effects

  • sip water frequently, chew sugar-free gum, increase intake of fiber and fluids

• orthostatic hypotension

  • change positions slowly

• abrupt withdrawal syndrome

  • taper off drug

haloperidol

• first generation antipsychotic → high potency agents → less sedation)

• brand name → Haldol

• uses → schizophrenia and acute psychosis

• adverse effects → QT prolongation, EPS, neuroendocrine effects

Chlorpromazine, Thiordiazine, Molindone

• first generation antipsychotics → low potency agents

• higher sedation but lower risk of EPS

Clozapine

• MOA → blocks dopamine and serotonin

• uses → schizophrenia, levodopa-induced psychosis

• adverse effects

  • agranulocytosis, seizures, EPS, diabetes, dyslipidemia, weight gain, myocarditis

• black box warning → doubles the mortality rate in older adult patients with dementia

• nursing considerations

  • weekly CBC for the first 6 months of treatment

  • after 6 months → bi-weekly CBC

  • educate patient to report signs of infection

  • if WBC < 3,000 → stop the drug (pause and restart when balanced out)

  • if ANC < 1,500 → stop the drug (pause and restart when balanced out)

  • if WBC < 2,000 → permanently discontinue the drug

  • monitor WBC for 4 weeks after discontinuation

other atypical antipsychotics

• Risperidone (Risperdal), Paliperidone, Olanzapine (Zyprexa), Ziprasidone, Quetiapine (Seroquel), Aripiprazole (Ablify), Asenapine, Iloperidone

• increased risk of metabolic effects, lower risk of EPS

depot antipscyhotics

long acting, injectable formulations used for the long-term maintenance therapy of schizophrenia

bipolar drug therapy

• mood stabilizers → lithium, divalproex sodium, carbamazepine

  • relieve symptoms during manic and depressive episodes

  • prevent recurrence of manic and depressive episodes

• antipsychotics

  • given during severe manic episodes

• antidepressants

  • given during severe depressive episodes

lithium

• has a low therapeutic index → monitor lithium blood levels

  • therapeutic levels → 0.6-0.8 mEq/L

• MOA → alters sodium transport in nerve cells to stabilize mood

• uses → bipolar, alcoholism, schizophrenia

• excretion → kidneys

• adverse effects

  • excessive lithium levels → >1.5 mEq/L

  • GI upset, tremors, polyuria, renal toxicity, hypothyroidism, teratogenesis

• drug interactions

  • diuretics → increase lithium levels because of the loss of sodium

  • NSAIDs → impaired kidneys leads to increased lithium levels

salt-lithium inverse relationship

• low sodium = high lithium

  • decreases the excretion of lithium

• high sodium = low lithium

  • increases the excretion of lithium

lithium toxicity

• clinical manifestations

  • moderate → polydipsia, slurred speech, tremors

  • severe → seizures, coma, reduced/no urinary output

• toxicity

  • risk of toxicity → >1.5 mEq/L

  • severe toxicity → >2.5 mEq/L

• risk factors

  • renal impairment, dehydration, low sodium intake, excessive sweating, NSAIDs/diuretics/ACE inhibitor use

• treatment

  • gastric lavage → for OD

  • kidney impairment → dialysis

divalproex sodium, carbamazepine, and lamotrigine

reduces symptoms of bipolar

antipsychotic drugs for bipolar

• used to acutely control symptoms during manic episodes

• used long term to help stabilize mood

• benefit patients with or without psychotic symptoms

• can be combined with mood stabilizer

• ex. Olanzapine, quetiapine, risperidone, aripiprazole

benzodiazepines

• sedative

• MOA → enhances GABA

• adverse effects → respiratory depression

• nursing considerations → can lead to addiction or overdose, do not combine with other agents that cause respiratory depression

• overdose → supportive care, focus on ABCs, administer Flumazenil (may not reverse respiratory depression)

benzodiazepine-like drugs

• ex. Zolpidem (Ambien), Zaleplon (Sonata), Eszopiclone (Lunesta)

• uses → insomnia

• Ambien → short-term, best for those who struggle to fall asleep, may cause daytime drowsiness. and dizziness

Ramelteon

• MOA → activates melatonin receptors

• relatively new hypnotic, not a controlled substance

• uses → chronic insomnia (best for those who struggle falling asleep)

• no risk of rebound insomnia, no risk of dependence, rapid onset (30 minutes)

• adverse effects → hepatic impairment

barbiturates

• MOA → binds to the GABA receptor-chloride channel complex

• high risk of addiction and dependence

• uses → seizure disorders, rarely used for hypnotic

• ex. phenobarbitol

buspirone for generalized anxiety disorder

• brand name → buspar

• use → anxiety

• no risk of dependence or abuse

panic disorder treatment

• cognitive behavior therapy (CBT)

• drug therapy

  • antidepressants → SSRIs, TCAs, MAOIs

• benzodiazepines

  • first-line for panic disorder

OCD treatment

• SSRIs (higher dose than a normal antidepressant dose)

social anxiety treatment

• SSRIs

• SNRIs

PTSD treatment

• psychotherapy/cognitive behavior therapy

• SSRIs

  • fluoxetine, paroxetine, sertraline

• SNRIs

  • venlafaxine

CNS stimulants

• amphetamines

  • Adderall, Dexedrine, Vyvanse, Evekeo, Zenzedi

• Methyphenidate and dexmethylphenidate

  • Ritalin, Concerta, Metadate CD, Daytrana, Focalin, Focalin XR

amphetamines

• uses → ADHD, narcolepsy

• can lead to abuse

• nursing considerations → take in the morning after breakfast

• adverse effects → decreased appetite