Pharmacology Test 3 Flashcards
1
Q
Monoamine-deficiency theory
A
underlying pathophysiological basis of depression is a depletion of the neurotransmitters serotonin, norepinephrine, or dopamine in the CNS
2
Q
Major mediators of the symptoms of anxiety disorders
A
Norepinephrine, serotonin, dopamine, and gamma-aminobutyric acid (GABA)
3
Q
First generation antidepressants
A
Tricyclic antidepressants (TCA)
Monoamine oxidase inhibitors (MAOIs)
4
Q
Second generation antidepressants
A
Selective serotonin reuptake inhibitor (SSRI)
Serotonin/norepinephrine reuptake inhibitor (SNRI)
Atypical antidepressants
Serotonin modulators
5
Q
Suicidality and Antidepressant black box warning
A
effective 2005 and extended to young adults aged up to 25 years old
6
Q
5HT2A distribution and effects
A
Distribution- platelets and cerebral cortex
Effects- cellular excitation, muscle contraction
7
Q
5HT2B Distribution and effects
A
Distribution- stomach
Effects- Appetite
8
Q
5HT2C Distribution and effects
A
Distribution- hippocampus, substantia nigra
Effects- anxiety, mood
9
Q
SSRIs
A
first line antidepressant
effective, tolerated well, general safety in overdose
Citalopram, Escitalopram, Fluoxetine, Fluvoxamine, Paroxetine, Sertraline
-pram -ine
10
Q
SSRIs MOA
A
decrease the action of the presynaptic serotonin reuptake pump by 60-80%
used for anxiety disorders, premenstrual dysphoric disorder, bulimia
11
Q
SSRIs length of time for benefit
A
takes at least 2 weeks to produce significant benefit and up to 12 weeks
slow titration needed to discontinue due to possibility to precipitate a discontinuation syndrome
12
Q
Withdrawal syndrome with SSRI
A
With abrupt discontinuation usually
usually within 24-48 hours after discontinuation
somatic symptoms- dizziness, chills, light-headedness, vertigo, fatigue, headache, nausea
Psychological symptoms- anxiety, agitation, confusion, insomnia, irritability, mania
13
Q
SSRI side effects
A
QT prolongation, GI effects, weakness and fatigue, sexual dysfunction, serotonin syndrome, bleeding risk if used with antiplatelets or anticoagulants
BLACK BOX: increased suicidal thinking and behavior
14
Q
Serotonin syndrome with SSRIs
A
precipitated by the overactivation of both the peripheral and central postsynaptic 5HT-1A and most notably, 5HT-2A receptor
mental status changes, neuromuscular hyperactivity, and autonomic hyperactivity
usually begins within 24 hours of an increased dose of a serotonergic agent
15
Q
Serotonin-norepinephrine reuptake inhibitor (SNRI) MOA
A
act primarily upon presynaptic serotonergic and norepinephrine neurons, but have little or no effect upon cholinergic or histaminergic receptors
used for depression, anxiety disorders, chronic pain syndromes
16
Q
Examples of SNRIs
A
more inhibition on serotonin reuptake
Duloxetine
Venlafaxine
Desvenlafaxine
more inhibition of norepinephrine reuptake
levomilnacipran
milnacipran
17
Q
Side effects of SNRIs
A
fewer receptor-mediated adverse effects than the TCAs
may increase HR and BP due to increase in noradrenergic activity
relative decreased parasympathetic tone leading to constipation, dry mouth, urinary retention
nausea, dizziness, diaphoresis, sexual dysfunction, serotonin syndrome
give with food
taper off over 2-4 weeks
18
Q
Drug to drug interactions with duloxetine
A
CYP2D6 inhibitor
substrates are tramadol, metoprolol, codeine, celecoxib
19
Q
interaction between MAOIs and SNRIs
A
2 weeks between administration due to possible serotonin syndrome or hypertensive crisis
20
Q
Atypical Antidepressants
A
mixed group of agents that have actions at several different sites
used with major depression who have inadequate responses or intolerable side effects with first line SSRIs or SNRIs
used as mono therapy, initial treatment
Bupropion
Mirtazapine
21
Q
Bupropion
A
a weak dopamine and norepinephrine reuptake inhibitor (no serotonergic effect)
used for major depression, seasonal affective disorder, tobacco dependence
also for ADHD and hyposexual disorder
22
Q
Bupropion for tobacco dependence
A
used for decreasing cravings and attenuating withdrawal symptoms of nicotine
23
Q
Side effects of bupropion
A
dry mouth, sweating, nervousness, tremor, and a dose-dependent increased risk for seizures
24
Q
Avoid bupropion in patients at risk for….
A
seizures or bulimia
taper off slowly
25
Bupropion dosing for depression
do not exceed 150mg in a single dose
up to 100mg 3x/day
26
Bupropion dosing for smoking cessation
150mg once daily for 3 days; increase to 150mg twice daily
treatment should start while patient is still smoking
patients should stop smoking during second week of treatment
maximum daily dose: 300mg/day
If quit in 2 week, continue meds for at least 12 weeks
If he haven't quit in 7 weeks, consider discontinuing
27
Mirtazapine (Remeron)
major depression
antagonist at central presynaptic a2 receptors
serotonin antagonist
sedating because of potent antihistaminic activity (Histamine 1 receptors)- take at bedtime
does not cause antimuscarinic side effects or interfere with sexual function like SSRIs
28
AEs of atypical antidepressants
sedation, increased appetite, dry mouth, weight gain, withdrawal symptoms
29
Serotonin Modulators
effects upon norepinephrine reuptake are minimal
for depression
nefazodone
trazodone
vilazodone
vortioxetine
30
Nefazodone and trazodone
both are sedating- due to potent histamine H1 blocking activity
Trazodone- off-label use for insomnia
31
AEs of Nefazodone and Trazodone
priapism and orthostatic hypotension (trazodone), hepatotoxicity (nefazodone), orthostasis and dizziness, nausea, somnolence, dry mouth, constipation
32
Trazodone dosing for insomnia
25-50mg at bedtime, 200mg/day
33
Withdrawal syndrome with serotonin modulators
usually appear within a period of 24 to 48 hours after discontinuation
Somatic symptoms
Psychological symptoms
Primarily happen following abrupt discontinuation
34
Tricyclic Antidepressants MOA
inhibits reuptake of serotonin and/or norepinephrine which increases the amount of neurotransmitters in the synaptic cleft
35
Therapeutic index of tricyclic antidepressants
narrow- 5-6x the max daily dose can be lethal
36
Absorption of tricyclic antidepressants
absorbed in the small intestine rapidly and nearly completely
37
Dosing of tricyclic antidepressants
not first line therapy (severe side effects)
usually QD dosing at bedtime due to sedation
ok to give BID to TID with smaller dose
should taper TCA off
38
AEs of tricyclic antidepressants
from interaction with many neurotransmitter systems
muscarinic or histamine receptors, noradrenergic activity
cardotoxic: HR variability, prolonged QT interval, due to noradrenergic activity
Orthostatic hypotension- from blockade of A1 receptors on the blood vessels
decreased seizure threshold
can be fatal in higher doses
39
Monoamine Oxidase enzyme
found in nerve, GI tract, and liver
In the neuron- functions as a "safety valve" to oxidatively dominate and inactive any excess neurotransmitters
40
Monoamine Oxidase Inhibitors
a minimum of 2 weeks of delay must be allowed before starting a different category of antidepressant
Not a first or second-line antidepressant (extensive side effect profile and drug-to-drug interactions)
used for resistant depression
41
AEs of MAOI
potent hypotension effects, dizziness, dry mouth, GI upset, urinary hesitancy, headache, myoclonic jerks, afternoon fatigue, serotonin syndrome, hypertensive crisis
42
Hypertensive crisis with MAOIs (cheese reaction)
increased tyramine (substrate of MAO) causes release of large amounts of stored catecholamines from nerve terminals
increased catecholamines = increased HTN
AVOID tyramine-containing foods (aged cheeses and meats, liver, pickled or smoked fish, red wines)
43
Selegiline
MAO B inhibitor at low doses
no benefit for depression
used for Parkinson's disease
Non-selective MAO inhibitor at high doses
used for depression
44
Dietary restrictions for MAOIs
required if dose is 9mg/24hrs or 12mg/24 hours patch is used
45
MDD DSM V Criteria
Five or more symptoms during the same 2 week period and one of the symptoms is either depressed mood or loss of interest or pleasure
46
Major Depressive Disorder in primary care
collaborative care
primary care clinician- prescriber
case manager
mental health specialist- psychiatrist
47
Severe MDD
should be referred to a psychiatrist for management and generally require hospitalization
48
MDD general approach
aim to induce remission of the major depressive episode
aim to achieve a full return to patient's baseline
choice of medication should be guided by anticipated safety and tolerability, physician familiarity, and history of previous treatments
address possibility of treatment failure
49
Mild to moderate MDD pharmacological treatment
SSRI, SNRI, atypical and serotonin modulator are all ok for initial treatment
improvement may be observed as early as the first 1-2 weeks
Dose: start low to reduce SE and improve adherence
50
Timing of treatment of Mild to moderate MDD
treat for 6-12 weeks before deciding whether antidepressants have sufficiently relieved symptoms
duration of treatment should be 4-9 months once satisfactory response is achieved
longer duration with a history of 2 or more episodes of depression
51
Cross-tapering
gradual reduction of the current antidepressant with the new antidepressant being increased to therapeutic range over the same time period
best technique to minimize the risk of drug-drug interactions while preventing depressive symptoms from abrupt withdrawal
52
Switching antidepressants- SSRI to venlafaxine or duloxetine
SSRI to venlafaxine or duloxetine
switching immediately from most SSRIs to the equivalent does is typically well-tolerated
caution is needed in switching from fluoxetine or paroxetine
53
Switching antidepressants- bupropion to or from antidepressants other than MAOIs
no mitigation needed for possible discontinuation symptoms
when switching from an SSRI, a TCA, venlafaxine, duloxetine, or mirtazapine to bupropion
54
Discontinuation of Antidepressants
typical taper length is 2-4 weeks to minimize symptoms associated with abrupt discontinuation
55
General Anxiety Disorder
excessive worry and anxiety that causes significant distress and impairment and occur on more days than not for at least six months
effectively treated with serotonergic antidepressants, psychotherapy, or a combination of the two
56
Co-occuring depression & other anxiety disorders
effectively treated with SSRIs or CPT
benzodiazepines are not effective
57
Which SSRI or SSNI has superior efficacy in GAD
NONE... selection based on AEs drug-drug interactions and treatment history/preference
58
Timing for GAD medication (SSRI/SSNI) to take effect
4 weeks
59
Second-line anxiety disorder medication
Buspirone 10mg/day and increased weekly or biweekly in increments of 10mg to a max dose of 60mg
60
Buspirone
reduce symptoms of anxiety without risk of dependence
thought to affect the serotonergic system via blockade of 5HT1A autoreceptors
time to onset: 4 weeks
weaker anxiolytic affect than benzos
may be used as mono therapy 10-60mg/day
61
Pregabalin (Lyrica)
second-line anxiety medication
therapeutic range of 50-300mg/day
SE: sedation and dizziness
62
Benzodiazepines
acute management of anxiety during the period before SSRI or SNRI takes effect
used for short term crisis
slow tapering off of medication- 10% dose reduction per 1-2 weeks
63
S/S of withdrawal from benzodiazepines
early signs: anxiety, dysphoria, and tremor
advanced manifestations: perceptual disturbances, psychosis, and seizures
64
Pharmacotherapy for anxiety disorders
should be continued for at least 12 months
after 2 relapses when tapering off medication, ongoing maintenance treatment should be considered
65
Tier 1 contraceptives
intrauterine devices
implants
irreversible methods- vasectomy, tubal ligation
66
Tier 2 contraceptives
pills, patches, vaginal ring, injections
67
Tier 3 contraceptives
condoms, diaphragms, spermicides, sponges, periodic abstinence
68
Only contraceptive to protect against STI
Condoms
69
Three types of estrogen
Estradiol, estrone, estriol
70
Estradiol
most potent estrogen produced and secreted by the ovary
principle estrogen in premenopausal women
71
Estrone
metabolite of estradiol
1/3 the potency of estradiol
primary circulating estrogen after menopause
generated mainly from the conversion of DHEA in adipose
72
Estriol
metabolite of estradiol
significantly less potent than estradiol
present in significant amounts during pregnancy
synthesized by the placenta
73
Ethinyl estradiol
synthetic estrogen
only estrogen used in contraceptives
(ee)
blunts release of FSH and LSH by the pituitary gland = preventing ovulation
74
Progesterone
endogenous steroid and progestogen sex hormone
75
Progestins
synthetic form of progesterone
suppression of LH surge = suppression of ovulation
development of viscous and scant cervical mucus to deter sperm penetration
prevention of proper endometrial growth and development
76
Most common estrogen used in contraceptives
ethinyl estradiol (synthetic estrogen)
77
Most common progestin used in contraceptives
norethindrone, norethindrone acetate, levonorgestrel, desogestrel, norgestimate, and drospirenone
etonogestrel (synthetic long acting)
78
Contraceptive Implant
single rod of ethylene vinyl acetate
progestin contraceptive
contains 68mg of etonestrel
Nexplanon
SubQ in upper arm over area of triceps
visible under skin & palpable
79
How long does the nexplanon last?
3-5 years
80
How long does it take for nexplanon to become effective?
within 24 hours of insertion
if inserted during the first week of menstrual cycle
81
Rate of release of contraceptive implants
begins at 70mcg/24 hours
decreases to an average of 30mcg/24 hours in the latter years of use
82
Contraindications of contraceptive implants
known or suspected pregnancy
active liver disease
current or past breast cancer
83
Do you have to use back up contraception after contraceptive implant insertion?
If inserted day 1-5 of cycle: immediate contraceptive effect
after day 5: back up contraception for 7 days
84
Side effects of contraceptive implant
unpredictable menstrual bleeding pattern
headaches
bloating
weight gain
acne
breast tenderness
85
Copper IUD
no impact on ovulation
works by foreign body effect induced by ICU frame (spermacidal effect)
works for 10 years
86
MOA of Copper IUD
enhances the cytotoxic inflammatory response within the endometrium which impairs sperm migration, viability & impairs implantation of a fertilized egg
87
Menses changes with copper IUD
may be heavier, longer, or more painful for first several cycles after insertion
improves rapidly within six months
88
Levonorgestrel IUD (LNG IUD) MOA
effect of progestin is at the level of endometrium
direct ovicidal effects
changes in cervical mucus
thinning and glandular atrophy of endometrium inhibits implantation
89
Side effects of LNG IUD
bleeding, uterine cramping, or pain
infection or PID
malposition
expulsion
pregnancy
hormone side effects
90
contraindications for LNG IUD
pregnancy
active uterine infection
malignancy in the uterus or cervix
inability to place or retain the device
unexplained abnormal bleeding
adverse reaction to product ingredients
91
First generation combined oral contraceptive pills
norethindrone acetate
not very potent
negligible androgenic side effects
92
Second generation combined oral contraceptive pills
Levonorgestrel
more potent than 1st gen
longer half life
used in mirena
associated with more androgenic effects such as increased LDL, acne, oily skin, facial hair, increased libido
93
Third generation combined oral contraceptives
desogestrel
norgestimate
potent but not designed to reduced androgenic side effects
fuller expression of pill's estrogen effects
treats cystic acne, prevents hirsutism
94
Unclassified combined oral contraception
drospirenone
95
Monophasic COCs
same dose of estrogen and progestin during active pill phase
96
Multiphasic COCs
biphasic or triphasic
different doses or either or both hormones
introduced as a strategy to reduce AEs and unscheduled bleeding
efficacy is similar across all COC types
biphasic formulations may be associated with more unscheduled bleeding
97
cyclic use of COCs- 21/7 regimen
hormones for 21 days followed by 7 day placebo pill
follicles may develop and secrete enough estradiol to "repair" or stimulate proliferation of thin endometrium
will have regular withdrawal bleeding with less breakthrough bleeding
98
cyclic use of COCs- 21/4 regimen
shorter time off hormones with low-dose COCs.
four days of placebo pills
reduced symptoms associated with hormone withdrawal
less folliculogenesis
may have more unscheduled bleeding in early cycles
99
Missed pills in continuous use with COCs
single pill: take as soon as noticed then take as prescribed
no additional pills needed
two or more pills: take remaining at usual time
use backup contraception
100
missed pills in 28 day pill cycle with COCs
If 2 or more pills missed in first week of cycle: use EC
If pills were missed in last week of hormone pills: finish last week, skip week 4 then start a new pack
if not possible then back up contraception should be used until hormone pills have been taken for 7 days
101
Transdermal patches for contraceptoin
xulane
twirla
102
Xulane
transdermal contraceptive patch
norelgestromin (0.15mg/day)
Ethinyl estradiol (releases 35mcg/day)
may have diminished effect in women over 90kg
new patch applied every 7 days for 3 weeks followed by patch-free week
103
Twirla
transdermal contraceptive patch
levonorgestrel (releases 0.12mg/day)
ethinyl estradiol (30mcg/day)
contraindicated in women with BMI greater than 30 for decreased efficacy and increased risk of VTE
new patch applied every 7 days for 3 weeks followed by a patch free week
104
Vaginal rings for contraception
NuvaRing
EluRyng
Annovera
105
NuvaRing and EluRyng
etonogestrel (0.12mg/day) ethinyl estradiol (15mcg/day)
ring inserted for 3 weeks followed by 1 week without ring in place
new ring at beginning of each cycle
106
Annovera
segesterone (0.15mg/day) and ethinyl estradiol (13mcg/day)
ring inserted for 3 weeks followed by 1 week without ring
ring then reinserted for first 21 days of next cycle
one ring is used for one year
107
Progestin only injectable
depot medroxyprogesterone acetate (DMPA)
progestin-only
highly effective, three month long reversible contraception
a micro-crystalline suspension
eliminates the need for daily user action
can be IM or SubQ
low solubility of microcrystals allows drug level to persist for several months
108
When to initiate DMPA
within 7 days of onset of menses or before discontinuing another method of contraception
can be started almost anytime if not pregnant
repeat every 3 months with up to 2 week grace period
109
Emergency contraception
works by delaying ovulation
Plan B (LNG)
Ulipristal (Ella)
Copper IUD
110
Plan B (LNG: levonorgestrel)
OTC
prevent ovulation
2 high-dose tablets of LNG 0.75mg
1 tablet within 72 hours and another 12 hours later
111
Ulipristal (Ella)
Rx required
prevents ovulation
progesterone receptor modulator
postpone follicular rupture and alter endometrium
greater efficacy than LNG
take within 5 days, 30mg tablet
repeat dose if vomiting within 3 hours
112
Potential side effects of hormonal contraceptives
nausea
breast tenderness
headaches
breakthrough bleeding
amenorrhea
HTN
VTE
MI and stroke
lipid change
some possibility of increased STI
bone loss with progestin only injectables
113
Most common early side effect of hormonal contraceptives
unscheduled bleeding
affect 1/2 of women during first cycle of use
higher with formulations with 20mcg ethinyl estradiol or 24/4 day dosing
114
Amenorrhea with hormonal contraceptives
intended outcome when using continuous methods
happens with lowest dose combined oral formulations
low ethinyl estradiol level (relative to much larger progestin dose) is inadequate to stimulate endometrial growth
can occur even after discontinuation
does not indicate that patient is not ovulatory or patient cannot get pregnant
evaluate if no menstruation after 90 days of d/c
115
Hypertension with hormonal contraceptives
may cause mild elevation
a newer progestin, drospirenone has antimineralocorticoid effects
appears to blunt the BP incresing effect of estrogen
116
VTE with hormonal contraceptives
low risk in young women
greatest risk in first few months of use
risk factors: smoking, obesity, PCOS, older age, and immobilization
117
MI and stroke with hormonal contraceptives
reduced risk with lower estrogen content
rare: absolute risk of stroke in young women is low
increases with higher estrogen doses
does not vary by progestin type
compounds containing levonogestrel and 30mcg of estrogen appear to be safest
118
STI acquisition as a side effect of hormonal contraceptives
increased rates of bacterial vaginosis, trichomoniasis, and candida vaginitis
no data that support any influence of COC use on acquisition of HIV
no restrictions on COC use among women with STI, PID, or HIV
119
Black box warning for Depo-Provera
bone loss that may not be completely reversible even after stopping the drug
studies have contraindicated the warning
120
ACHES acronym
potential side effects of hormonal contraceptives
A: abdominal pain
C: chest pain
H: headaches
E: eye problems
S: severe calf or thigh pain
121
Contraindications to use of hormonal contraceptives
pregnancy
older than 35 and smoker
past or current history of thrombosis
hepatic tumor or liver disease
undiagnosed abnormal genital bleeding
known or suspected breast cancer
allergy to method
hypertension
ischemic heart disease
history of stroke
migraine with aura
complicated valvular heart disease
122
Drugs and herbs that reduce the effects of OCs
rifampin
ritonavir
troglitazone
antiepileptic drugs
St. Johns wort
123
Drugs whose effects are reduced by OCs
warfarin
insulin
oral hypoglycemics
124
drugs whose effects are increased by OCs
theophylline
imipramine
125
Vasomotor menopause symptoms
hot flashes
sweating
palpitations
the main indication to treat menopause with MHT
126
Genitourinary syndrome of menopause
vaginal dryness, superficial dyspareunia, urinary frequency and urgency
use of vaginal estrogen preferred
127
Types of estrogen therapy
micronized 17-beta estradiol
conjugated equine estrogens
esterified estrogens
estropipate
ethinyl estradiol
128
Micronized 17-beta estradiol
structurally identical to the endogenous estrogen
all commercially available oral 17-beta estradiol products are micronized for better absorption
129
Conjugated equine estrogens
derived from pregnant mares' urine
synthetic derived from plant source is also available
130
Ethinyl estradiol
used in almost all oral contraceptives
more potent than other estrogens used for MHT
used in very low doses (5mcg)
131
Oral estrogen effects on lipid profiles
increased HDL and TG and decreased LDL
132
Potential AEs of oral estrogen
prothrombin effects including reduction in serum fibrinogen, factor VII, and antithrombin III
an increase in hepatic synthesis of vascular inflammatory markers (CRP)
133
Standard-dose estrogen
conjugated estrogen 0.625mg
134
Dosing equivalents of estrogen
0.625mg conjugated estrogen
1mg micronized 17-beta estradiol
0.05mg/24hr transdermal patch
135
Progestin Types
Medroxyprogesterone acetate (MPA)
micronized progesterone
136
Risk of medroxyprogesterone acetate
excess risk of cardiovascular events and breast cancer
137
What is preferred over MPA
micronized progesterone- less risk!
138
Contraindications to menopausal hormone therapy
hx of breast cancer or endometrial cancer
porphyria
severe active liver disease
thromboembolic disorders
unexplained vaginal bleeding
endometriosis
uterine fibroids
139
Avoid oral estrogen with...
hypertriglyceridemia
active gallbladder disease
thrombophilias
migraine with aura
140
Dosing of estrogen for VMS
lower doses
less vaginal bleeding, breast tenderness, fewer effects on coagulation and inflammatory markers and possible lower risk of stroke and VTE
lowest transdermal dose approved for prevention of bone loss (0.014mg)
141
Side effects of estrogen only products for VMS
endometrial CA
endometrial hyperplasia
thromboembolism
retinal thrombosis
MI
stroke
HTN
breast cancer
ovarian cancer
uterine fibroids
vaginal bleeding
abdominal distention/cramping
N/V
breast pain
cervical secretion changes
HA
migraine
fluid retention, weight changes
142
Contraindications to estrogen-only products for VMS
do not use estrogen alone for post-menopausal women with intact uterus
due to endometrial hyperplasia and cancer from unopposed estrogen
use with progestin
143
Vaginal estrogen for genitourinary syndrome of menopause
most commonly used in very low doses for the management of vaginal atrophy
not associated with cardiovascular or oncologic complications
results in less estrogen absorption than oral or transdermal estrogen therapy
use with caution in patients with or at risk for estrogen-dependent tumors
addition of progestin not necessary
144
Examples of vaginal estrogen products for GSM
tablet or capsule
Estring vaginal ring
vaginal cream
145
Dosing of vaginal estrogen tablet
vagifem, yuvafem, imvexxy
estradiol estrogen
10 or 4 mcg
one daily for 1st two weeks then twice weekly
146
Estring vaginal ring
estradiol estrogen
7.5mcg per day over 3 months
insert Q3 months
147
Vaginal cream- Premarin
conjugated estrogen
QD for two weeks and then twice weekly
21 days on, 7 days off
148
Vaginal cream- Estrace
Estradiol estrogen
QD for 1-2 weeks followed by maintenance dose of 1g 1-3 times per week
149
AEs of vaginal estrogen for GSM
breast pain
enlarged breasts
itching of vagina or genitals
headache
nausea
stinging or redness of genital area
thick, white vaginal discharge
feeling of vaginal pressure
uterine bleeding or spotting
vaginal burning or pain
150
Other treatments for genitourinary syndrome of menopause
first line: vaginal moisturizers and lubricants
moisturizer: use routinely, typically two or three days per week
lubricants: only at time of sexual activity: water, silicone, or oil based
oil-based cause breakdown of latex condoms
151
Dose of medroxyprogesterone
2.5mg PO QD
152
Dose of progesterone micronized
200mg/day for 12 days (cyclic)
add progestin in half each month
153
AEs of progestin only products for VMS
headaches
painful or tender breasts
vaginal spotting
stomach cramping or bloating
N/V
hair loss
fluid retention
yeast infection
154
No hyperkalemia in combination estrogen-progestin products with...
drospirenone
155
Duration of MHT
the standard recommendation is 5 years or less and not beyond age 60
less recurrent sx with tapering method
decrease estrogen by one pill per week every few weeks over 3-6 months
if unsuccessful, repeat tapering over one year
progestin is tapered on same schedule
156
Transition from OC to MHT
age 40-50 still candidates for OCS (low-estrogen)
Age 50- discuss stopping OC or changing to MHT if necessary
157
Antiresorptive agents for osteoporosis
decrease osteoclasts activity
biphosphonates
alendronate
risedronate
ibandronate
zoledronic acid
denosumab
selective estrogen receptor modulators
estradiol
158
Anabolic agents for osteoprosis
directly stimulate bone formation
parathyroid hormone/parathyroid hormone-related protein analog
Teriparatide
Abaloparatide
Romosuzamab
159
Biphosphonates
first-line drugs
suppress respiration by preventing osteoclast attachment to bone matrix
reduction of fracture risk by approx 50%
160
AEs of biphosphonates
esophagitis
osteonecrosis of the jaw
161
Osteonecrosis of the jaw
exposed, nonmetal bone involving the maxillofacial structures
162
Antiresportive agents
recommended to be off meds for 2 months before having a dental procedure
163
Drug holiday for biphosphonates
no supportive clinical data
may be considered after 5 years of treatment
164
Denosumab (Prolix) MOA and dosing
binds to RANKL and blocks the interaction between RANKL and RANK preventing osteoclast formation leading to decreased bone resorption and increased bone mass
approved for women receiving aromatase inhibitors and men receiving gonadotrophin reducing treatment
60mg SubQ q6 months
165
Denosumab AEs and contraindications
AEs: peripheral edema, eczema, hypocalcemia, headache, arthralgia
Contraindications: hypocalcemia, pregnancy, hypersensitivity
166
Selective Estrogen receptor modulators
Tamoxifen: hormone receptor-positive breast cancer
Raloxifene
MOA: act as an estrogen agonist in the bone to prevent bone loss and increase bone mineral density
Antiresorptive effects are less than those of biphosphonates
no effect on non-vertebral fractures
decreases risk for BRCA
167
AEs for SERMs
increased risk of VTE
hot flashes
leg cramps
168
Parathyroid Hormone analog
Teriperatide
MOA: stimulates bone remodeling by increasing bone formation
20mcg SC QD
moderate to severe osteoporosis
should not be given for more than 2 years over life-time
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AEs and contraindications of Parathyroid Hormone analog
mild, transient hypercalcemia, orthostatic hypotension, dizziness, HA, nausea, arthralgia, rhinitis, increased uric acid, hypercalciuria, osteosarcoma (animal studies)
Contraindications: hypercalcemia, hyperparathyroidism, multiple myeloma, bone mets, skeletal tumor, do not use in children with growing bones
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Monoclonal antibodies for osteoporosis
Romososumab
inhibits sclerostin, a regulatory factor in bone metabolism
210mcg SC Qmonth x 1 year
171
Contraindications and side effects of monoclonal antibodies for osteoprosis
contraindications: hypocalcemia
side effects: hypocalcemia, MI, stroke, ONJ, arthralgia, headache, insertion site erythema
172
Calcium and vitamin D for osteoporosis
Post-menopause: 1200mg of calcium QD and 800 units of Vitamin D
Pre-menopause: 1000mg calcium and 600 units of Vitamin D daily
Calcium carbonate taken with meals
calcium citrate is recommended for those taking PPIs or H2 blockers
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Neurotransmission in CNS
an impulse in the presynaptic terminal cause the release of the neurotransmitter
molecules bind to transmitter-gated ion channels in the postsynaptic membrane
Na enters postsynaptic cell and depolarizes the membrane
results in changing the membrane potential
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Alzheimer's disease
progressive loss of cholinergic in discrete brain areas
impaired cognition, movement, or both and behavior problems
175
Current therapies for Alzheimer's Disease
Acetylcholinesterase Inhibitors
NMDA receptor antagonists
Monoclonal antibody
176
Acetylcholinesterase Inhibitors
aim to improve cholinergic transmission within the CNS
inhibits acetylcholinesterase within the CNS
improves cholinergic transmission at functioning neurons
Galatamine, Donepezil, Rivastigmine
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NMDA receptor agtagonists
prevent cytotoxic actions resulting from overstimulation of NMDA receptors in selected areas of the brain
Memantine, Dextromethorphan/quinidine, Eketamine
178
Goals of pharmacological treatment for Alzheimers
modest short-term benefit
none of the available therapeutic agents alter the underlying neurodegenerative process
179
Monoclonal antibodies for Alzheimers
Aducanumab
Laboratory-made proteins that mimic the immune system's ability to target specific antigen on cell surface
180
Acetylcholinesterase
a cholinergic enzyme primarily found at postsynaptic neuromuscular junctions (muscles and nerves)
breaks down or hydrolyzes acetylcholine into acetic acid and choline
181
Donepezil (Aricept)
acetylcholinesterase
starts at 5mg in Qhs
Adjust the dose in 4-6 weeks
max dose 23mg
182
Max dose of donepezil
23mg (may not give additional benefit) but does increase side effects
183
AEs of Donepezil
possible irregular or slow heart rate or fainting
ok to give in am if it causes nightmares
GI symptoms
symptomatic bradycardia, QT prolongation
rhabdomyolysis (rare)
neuroleptic malignant syndrome (rare)
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Galantamine (Razadyne)
acetylcholinesterase inhibitors
start at 8mg QDay
adjust dose in 4-6 weeks
give with meals due to GI AEs
should not be used in patients with end-stage kidney disease or severe hepatic impairment
185
Who should galantamine not be used for?
ESRD or hepatic impairment
186
AEs of galantamine
gastrointestinal symptoms
symptomatic bradycardia
CNS depression
skin reactions
187
Rivastigmine (Exelon)
transdermal patch is preferred (tolerated better with similar effect)
adjust the dose Q4 weeks
Oral meds with meals (start at 1.5mg BID)
188
Who requires dose adjustments for Rivastigmine
hepatic impairment and low body weight
189
AEs of Rivastigmine
N/V
anorexia
headaches
dizziness
190
Contraindications of Acetylcholinesterase inhibitors
bradycardia or known cardiac conduction system disease, increased risk of syncope, falls, and fractures
191
Use acetylcholinesterase inhibitors in caution with...
combination therapy with other drugs that cause bradycardia or alter AV conduction (beta blockers, calcium channel blockers, lacosamide)
192
NMDA
an amino acid derivative that acts as a specific agonists at NMDA receptor site mimicking the action of glutamate
193
NMDA receptor
a glutamate receptors
mostly exist in the CNS
194
NMDA receptor antagonist MOA
blocks overstimulation of glutamate receptors in extra-synaptic area that causes excitotoxic effects on neurons that is caused by neurodegenerative or apoptotic processes
blocks activities in extra synaptic NMDA receptors
195
AEs of NMDA receptor antagonists
hallucinations, lightheadedness, dizziness, fatigue, headache, out of body sensation, nightmares, sensory changes
196
Memantine
indicated for moderate to severe Alzheimers disease
Dose adjustment Q weekly or longer
often given in combination with an AChE inhibitor
197
AEs of memantine
well tolerated with few dose-dependent AEs
confusion, agitation, and restlessness
198
Aducanumab
clinical trails saw no benefit
AEs included headache, diarrhea, change in mental status
severe: cerebral edema, micro brain bleeding
majority went to normal after stopping meds
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Parkinson's Dease
progressive neurological disorder of muscle movement
tremors, muscular rigidity, bradykinesia, postural and gait abnormalities
dementia is a late symptom
correlated with destruction of dopaminergic neurons in the substantial nigra
consequent reduction of dopamine actions in the corpus striatum (motor control)
200
Drugs Used in Parkinson's disease
MAO-B inhibitors
Antiviral (Amantadine): NMDA receptor antagonist
Anticholinergics (Trihexyphenidyl)
Levodopa
Dopaminergic agonist
aim to maintain constant CNS dopamine levels
temporary symptom relief
do not arrest or reverse neuronal degeneration
201
MAO-B inhibitors
for patients with mild symptoms/minimal impact on daily life
selegiline
rasagiline
safinamide
202
Selegiline
MAOB inhibitors
5mg QD: irreversibly binds to MAO B and a single dose is sufficient to achieve enzymatic inhibition for longer than 24 hours
morning and mid-day dosing
may be able to reduce dose of levodopa/carbidopa by 10-30%
do not use higher than 10mg daily
203
AEs of Selegiline
headache dizziness, nausea, suicidal ideation (transdermal)
insomnia
exacerbation of hypertension
orthostatic hypotension
204
Use selegiline with caution in patients with...
cerebrovascular disease, hypovolemia, or concurrent medication which may predispose to hypotension/bradycardia
205
Rasagiline (Azilect)
adjective therapy with levodopa
0.5mg daily and may increase to 1mg/day (max dose)
when adding to levodopa therapy, a dose reduction of levodopa may be required to avoid exacerbation of dyskinesias, typical dose reduction of 9-13%
206
Do not use Rasagiline with
Meperidine, methadone, propoxyphene, tramadol
cyclobenzaprine, dextromethorphan, St. Johns wort
207
AEs of Rasagliline
headache, ecchymosis, GI symptoms, melanoma, aggressive behaviors or agitation
208
Safinamide (Xadago)
mono therapy possible
usually given as adjective therapy with levodopa to help with motor fluctuations
209
Safinamide (Xadago)
mono therapy is possible
usually given as adjunctive therapy with levodopa to help with motor fluctuations
210
AEs of safinamide
dyskinesia, HTN, orthostatic hypotension, insomnia
211
Amantadine
antiviral NMDA receptor antagonists
for patients with mild symptoms/minimal impact on daily life
weak, uncompetitive NMDA receptor antagonists
may increase dopamine release and inhibit dopamine reuptake
Monotherapy is alternative (for tremor and dyskinesia)
very well tolerated
transient benefits in some patients and often limited to a year or two
212
AEs of amamtadine
orthostatic hypotension, pre-syncope, peripheral edema, dry mouth, constipation, hallucinations, delusions
213
Amantadine ER (Gocovri) dosing
QHS
concentration rises slowly overnight and achieves their peak in the morning
use with or without dopaminergic medications
can be added in addition to levodopa/carbidopa when experiencing "off" episodes
214
Amantadine ER (Osmolex) dosing
combination of extended-release and immediate-release amantadine for treatment of Parkinson's and drug-induced extrapyramidal reactions in adults
immediate-release outer layer and an extended-release inner core
makes concentration higher in the day and lower during the night
215
Anticholinergics for patients with Parkinsons
patients with mild symptoms/ minimal impact on daily life
monothearpy for patients <65 years with increased tremor but no bradykinesia or gait disturbance
avoid this in older patients due to significant cognitive impairment due to the increased risk of adverse effects
216
What is the most widely prescribed anticholinergic agent?
Trihexyphenidyl
217
AEs of anticholinergics
dry mouth, blurred vision, constipation, nausea, urinary retention, impaired sweating, tachycardia
caution is advised in patients with known prostatic hypertrophy or closed-angle glaucoma
cognitively impaired may be more susceptible to memory impairment, confusion, hallucinations
218
Levodopa
the preferred therapy for patient with moderate to severe symptoms
penetrates the blood brain barrier and converts to dopamine by amino acid decarboxylase enzyme
rapid conversion of levodopa to dopamine in GI and peripheral tissues by decarboxylase enzyme
219
What is levodopa administered with?
Carbidopa to inhibit rapid conversion to dopamine in peripheral tissues- reduces needed dose of levodopa by 75%
at the beginning take with meal or snack to avoid nausea
with more advanced disease it is more effective if taken on an empty stomach 30 minutes before or one hour after meals
220
Carbidopa
dopamine decarboxylase inhibitor
does not pass BBB
diminishes the metabolism of levodopa in the periphery
increase the availability of levodopa to the CNS
given with levodopa
decreases severity of AEs from peripherally formed dopamine
221
Reasons to use levodopa
for mild symptoms in older adults and younger adults
initial therapy
intolerant of other drugs
222
AEs of levodopa
nausea, somnolence, dizziness, and headache
older patients: confusion, hallucinations, delusions, agitation, psychosis, and from overactivity of dopamine in the basal ganglia, orthostatic hypotension
223
Drug interactions of levodopa
vitamin pyridoxine (B6)
nonselective monoamine oxidase inhibitors (MAOIs)
caution in psychotic patients
low doses of atypical antipsychotics (quetiapine or clonazapine) can be used to treat levodopa-induced psychotic sympotms
use with caution in cardiac patients- monitor for the possible development of arrhythmias
224
Dosing for carbidopa/levodopa
careful upward titration over several weeks to a full tablet three times daily (taken every 4-6 hours during waking hours)
2x daily, at intervals not less than 6 hours
may adjust no faster than 3 days to max dose of levodopa 2.4g/day
not recommended as initial therapy
225
Max daily dose of carbidopa/levodopa
200/2000mg dosing > 4x daily may be required
if not responsive to levodopa at 1000-1500mg think other diagnoses
carbidopa needs to be 70-100mg/day to reduce n/v
226
Should carbidopa/levodopa be discontinued abruptly
no! risk of neuroleptic malignant syndrome
227
Dopaminergic agonist
Ropinirole, Rotigotine, Pramipexole
adjective therapy for wearing off effect
dose of levodopa should be lowered or adjusted accordingly
228
Pramipexole
dopaminergic agonist
switch from IR to ER overnight at same daily dose: >80% successful rate
229
New generation anti seizure medications
Gabapentin, lamotrigine, pregabalin, topiramate, levetiracetam, oxcarbazepine
simple pharmacokinetics
more limited effects on liver metabolism
reduced need for serum monitoring
once or twice daily dosing for some
few drug-drug interactions
230
Benzodiazepines
Clobazam, clonazepam, clorazepate, diazepam, lorazepam
bind to the GABA (A) receptor and facilitate the attachment of GABA to its binding site on the receptor
231
What is most often used for myoclonic and atonic seizures?
clonazepam
232
Low voltage-gated calcium channel blockers
Ethosuximide
Pregabalin
Gabapentin
Levetiracetam
233
Ethosuximide
blood level should be checked initially after 1-3 weeks
time to steady state 12 days in adults, 6 days in children
check right before the scheduled dose
234
Pregabalin dosing
150mg with or without food in BID or TID up to 600mg
Dose adjustment Q weekly is ok
235
Gabapentin
300mg three times daily or 300mg first day, 300mg twice daily second day, 300mg three times daily on the third day
up to 1800-2400mg/day
236
Antiseizure medication interactions with other medications
phenytoin, carbamazepine, phenobarbital, primidone, and oxycarbazepine and topiramate are the most problematic for drug interactions with warfare, oral contraceptives, and anticancer and anti-infective drugs
