Pharm test 2 Flashcards
1
Q
Sulfonylureas end in….
A
-ide; GlipizIDE, GlyburIDE, GlimepirIDE
2
Q
What class of hypoglycemics are sulfonylureas?
A
Insulin secretagogues
3
Q
What is the MOA of sulfonylureas
A
promote insulin release from beta cells of pancreas; also reduce hepatic glucose clearance and increase peripheral insulin sensitivity by prolonging half-life
4
Q
What do sulfonylureas do in B cells?
A
close potassium channels leading to depolarization of cell, opening of Ca2+ ion channels and release of insulin
5
Q
Where are sulfonylureas metabolized?
A
liver
6
Q
What are the adverse effects of sulfonylureas?
A
HYPOglycemia, hyperinsulinemia, weight gain
7
Q
Which sulfonylurea options are safer for patients with renal dysfunction and the elderly?
A
Glipizide and glimepiride
8
Q
WHich medications interact with sulfonylureas and can lead to hyperglycemia?
A
glucocorticoids, diuretics, antipsychotics
9
Q
Which medications interact with sulfonylureas and can lead to hypoglycemia?
A
B-blockers, sulfonamides, antifungals
10
Q
Glipizide duration of action and dosing per day
A
14-16 hours and either once or twice a day
11
Q
Glipizide XL duration of action and dosing per day
A
24 hours; once daily
12
Q
Glimepiride duration of action and dosing per day
A
24+ hours; once daily or 4mg BID instead of 8mg once a day
13
Q
MOA of meglitinides
A
prevent ATP-sensitive potassium channels from opening; controls postprandial glucose levels
14
Q
Examples of meglitinides
A
prandin (repaglinide)
starlix (nateglinide)
15
Q
Dosing of meglitinides
A
TID before meals
16
Q
AEs of meglitinides
A
hypoglycemia, weight gain
17
Q
Should meglitinides be taken if a meal is skipped?
A
NO! controls postprandial glucose levels; could lead to hypoglycemia
18
Q
MOA of biguanides
A
decreased hepatic gluconeogenesis (decreased glucose production in the liver); increased glucose uptake by muscles; decreased glucose absorption via GI tract
19
Q
A1C reduction by biguanides
A
approx. 1.5
20
Q
AEs of biguanides
A
N/V, diarrhea, loss of appetite, weight loss, lactic acidosis
21
Q
How do we avoid AEs of biguanides?
A
slow-titration and take with meals
22
Q
Which patients should avoid taking biguanides?
A
Those at risk for lactic acidosis:
impaired renal function
topiramate use
>65 years old
future radiology studies with contrast
excessive alcohol intake
23
Q
How long does a patient need to be off biguanides prior to an imaging test with contrast dye?
A
one week!
24
Q
Which labs need to be checked with biguanide use?
A
eGFR and SCr
25
Renal-dependent dosing for biguanides
eGFR <30mL/min- advanced CKD; contraindicated
eGFR 30-45mL/min- generally not recommended, 500mg QD to BID at most
eGFR 45-60mL/min- max 1.5g/day in BID dosing; renal monitoring every 6 months
eGFR >60mL/min- normal dose up to 2g/day in BID dosing
26
MOA of thiazolidinediones (TZD)
activates PPAR-gamma leading to increased insulin sensitivity in the adipose tissue, muscle, and liver; also decreases hepatic glucose production
27
Examples of thiazolidinediones (TZD)
pioglitazone (Actos)
rosiglitazone (Avandia)
28
What patients should not the use TZDs?
those with symptomatic CHF, NYHA class III or IV heart failure
those with osteoporosis (decreased bone density with use)
29
AEs of thiazolidinediones
fluid retention/CHF
weight gain-edema
increased risk of bladder cancer (pioglitazone)
macular edema
decreased bone density and increased risk of fractures
30
Renal dosing for thiazolidinediones
No renal dosing! ok for use in patient with renal problems
31
MOA of SGLT-2 inhibitors
inhibit the reabsorption of glucose in tubular lumen of kidney
32
A1C reduction with SGLT2 inhibitors
0.4-1.1
33
Contraindications in using SGLT-2 inhibitors
DMI, DMII with low GFR (no use in renal failure!), bladder cancer
34
Avoid SGLT-2 inhibitor use if possible in patients with....
frequent UTIs or yeast infections, low bone density, foot ulcers, factors predisposing them to DKA (alcohol use)
35
When to consider the use of SGLT-2 inhibitors...
patients with inadequate glycemic control on two oral agents OR if metformin and insulin are not a therapeutic option
36
AEs of SGLT-2 inhibitors
volvovaginal candidias, UTIs, urinary frequency, hypotension (particularly in elderly or patients on diuretics), ketacidosis
37
Steglatro (Ertugliflozin) dosing/ renal dosing
once daily in the morning, contraindicated in GFR < 60
38
Canagliflozin (Invokana) dosing/renal dosing
Daily before first meal, contraindicated in GFR <45; no more than 100mg with GFR 45-59
39
Empagliflozin (Jardiance) dosing/renal dosing
Once daily in the morning, contraindicated in GFR <45
40
Which SGLT-2 inhibitor reduces the risk of cardiovascular death in patients with T2DM and CVD?
Empagliflozin (Jardiance)
41
Dapagliflozin (Farxiga) dosing/renal dosing
Daily AT ANY TIME, contraindicated in GFR <30 and active bladder cancer
42
Incretin
gut-driven peptide that are secreted after nutrient intake
43
GLP-1
glucagon-like peptide-1; responsible for 60-70% of postprandial insulin secretion
44
What degrades GLP-1?
DPP-4
45
MOA of GLP-1 agonists
incretin mimetics; enhances postprandial insulin secretion, reduces food intake by enhancing satiety, decreases postprandial glucagon secretion, promotes B-cell proliferation (stimulating more insulin production)
46
A1C reduction on GLP-1 agonists
0.55-1.38
47
Examples of GLP-1 agonists
Long acting: albiglutide (tanzeum), dulaglutide (trulicity), semaglutide (ozempic) liraglutide (victoza),
Short acting: lixisenatide (Adlyxin), exenatide (byetta, bydureon)
48
Which GLP-1 agonist has an oral form?
semaglutide (rybelsus)
49
AEs of GLP-1 agonists
N/V/D/C, weight loss, pancreatitis, increased satiety, possible thyroid tumors so contraindicated in pts with hx of thyroid or other endocrine cancers, hypoglycemia
50
Which GLP-1 agonist should be not be used in renal impairment?
Exenatide (Byetta, Bydureon)
51
Which GLP-1 agonist is approved to reduce the risk of cardiovascular events and cardiovascular mortality?
Liraglutide (Victoza)
52
Instructions for a missed dose of dulaglutide
If at least 72 hours before next scheduled dose- administer ASAP
If less than 72 hours before the next scheduled dose- missed dose is skipped and next dose is administered on regularly scheduled day
Then resume regular once a week dosing schedule
The day of weekly administration can be changed as long as the last dose was 3 days before.
53
MOA of DPP-4 inhibitors
inhibits DPP-4 from breaking down GLP-1 allowing for GLP-1 to exert its effects longer leading to decreased glucose levels; increases release of insulin postprandial and decreases secretion of postprandial glucagon
54
Which medications can be used in combination with DPP-4 inhibitors?
sulfonylureas, metformin, TZDs, insulin
NO COMBO use with GLP-1 agonists
55
All DPP-4 inhibitors require renal dosing EXCEPT...
linagliption
56
Changes in weight with DPP-4 inhibitors
none, they are weight neutral. Also do not cause satiety
57
Dosing of DPP-4 inhibitors
Taken once daily, well-absorbed with oral administration, ok to take with meals
58
AEs of DPP-4 inhibitors
usually well tolerated, nasopharyngitis, headache, pancreatitis, risk of severe joint pain, increased risk of heart failure with alogliptin and saxagliptin
59
Which DPP-4 inhibitors increase the risk of heart failure?
Alogliptin (Nesina) and saxagliptin (Onglyza)
60
Examples of DPP-4 inhibitors
Alogliptin (Nesina), Saxagliptin (Onglyza), Sitagliptin (Januvia), Linagliptin (Tradjenta)
61
DPP-4 inhibitors end in
-gliptin
62
Insulin analogues
made by recombinant DNA technology, administered SubQ, IV, or inhalation
63
Concentration of insulins
all have concentration of 100 units/mL except glargine (Toujeo) which is 300 units/mL
64
Regular insulin onset, peak, duration
Onset: 1/2-1 hour
Peak: 2-4 hours
Duration: 6-8 hours
65
Lyspro/Aspart/Glulisine onset, peak, duration
Onset: <15 minutes
Peak: 1-2 hours
Duration: 4-6 hours
66
NPH onset, peak, duration
Onset: 1-2 hours
Peak: 6-10 hours
Duration: 12+ hours
67
Detemir onset, peak, duration
Onset: 1 hour
Peak: around 12 hours
Duration 12-24 hours
68
Glargine onset, peak, duration
Onset: 1.5 hours
Peak: flat, no peak
Duration: 24 hours
69
AEs of insulin
lipodystrophy- may cause wide glycemic oscillations and hypoglycemia
70
Lipoatrophy
large, often deep retracted scar on skin from serious damage to SubQ tissue
71
Lipohypertrophy
thickened "rubbery" tissue swelling; mostly firm but occasionally presents as a soft lesion
72
S/S of hypoglycemia
Headache, anxiety, tachycardia, confusion, vertigo, diaphoresis, shakiness, increased appetite, blurred vision, weakness/fatigue
73
Hypothyroidism
permanent condition requiring lifelong treatment, commonly autoimmune (Hashimoto's)
74
Two conditions that may not require thyroid hormone replacement
Transient hypothyroidism (painless or subacute thyroiditis)
Reversible hypothyroidism (due to a drug that can be discontinued) ex: amiodarone
75
Liothyronine
T3 analogue, takes effect rapidly, Cytomel: 25-75mcg PO QD
76
How soon can a dose of liothyronine be increased?
1-2 weeks
77
Levothyroxine
T4 analogue; standard choice of therapy
78
MOA of levothyroxine
diffueses into cell nucleus and binds to thyroid receptor proteins attached to DNA on the effector organs; bound to thyroxine-binding globulin in the plasma, must dissociate prior to entry into cells, T4 then deiodinated into T3 in the cells
79
When does levothyroxine reach it's steady state?
6-8 weeks
80
What labs do you check for hypothyroidism?
TSH and T4
81
What can decrease the absorption of T4?
calcium, iron salts, aluminum-containing antacids, PPIs, sucralfate
82
How is levothyroxine metabolized?
via conjugation with glucoronides and sulfates and excreted in bile
83
Dose changes to levothyroxine in pregnancy
dose needs to be increased; free T4 is important for normal fetal development
84
AEs of levothyroxine
cardiovascular side effects: palpitations, tachycardia; increased appetite, nervousness, tremor, weight loss, diarrhea, diaphoresis- think hyperthyroid sx's
85
Ways to avoid AEs of levothyroxine
start with low dose and increase gradually
86
Dosing for levothyroxine
1.6mcg/kg/day OR
25-50mcg standard dosing
87
When should T4 be taken
on an empty stomach, ideally 60 minutes before breakfast with water OR three hours after the evening meal
other meds are best 4 hours after dose.
88
When should soft gels be used in treatment of hypothyroidism?
Patients with atrophic gastritis and after bariatric surgery; soft gels may be less dependent upon gastric pH
89
combination T4/T3 therapy
DO NOT USE
physiological ratio of T4:T3 is 13:1-16:1
combo meds such as Liotrix and desiccated thyroid extract are supraphysiologic at 4:1 ratio
90
How does furosemide interact with levothyroxine
Decreases T4 binding to TBG
91
How does amiodarone interact with levothyroxine?
impaired conversion of T4 to T3
92
Hyperthyroidsim
excessive production of thyroid hormones from the thyroid gland; many times autoimmune (Grave's disease)
93
Symptomatic treatment of hyperthyroidism
beta-blockers (atenolol); decrease symptoms from increased sympathetic tones
94
Antithyroid medications
Thioamides
95
Examples of Thioamides
Propylthiouracil (PTU) and methimazole (Tapazole)
96
MOA of thioamides
inhibit thyroid peroxidase; do not inhibit thyroid hormones
97
How long does it take thioamides to attain euthyroid state
3-8 weeks
98
Methimazole (Tapazole)
exclusively used for longer duration of action and less side effects; used during 2nd and 3rd trimesters of pregnancy
99
Prophylthiouracil (PTU)
used during 1st trimester of pregnancy- high binding leads to less crossing of the placenta; not recommended for pediatric patients due to hepatotoxicity; should be a short dose with close patient monitoring; only for those who cannot take methimazole or have surgery or radioactive iodine treatment
100
AEs of Thioamides
skin rash, vasculitis, hypothyroidism, lupus-like syndrome, agranulocytosis (increased risk of infection), hypoprothrombinemia (Increased risk of bleeding), hepatotoxicity
reversible with discontinuation of meds
101
Monitoring on thioamides
periodically assess free T4 and total T3 levels- first check not before 4 weeks then every 4-6 weeks until stabilized and then every 3-6 months
also monitor calcium levels
102
Lugol's solution
potassium iodine (10%) and iodine (5%); inhibits synthesis and release of T3 and T4; used to treat thyroid storms; not used in primary care
103
Absorption changes in children
different water content and degree of vascularization on skin, muscle, and fat leads to erratic absorption via IM and rectal administration
also lower gastric acidity, gastric emptying time, GI motility, pancreatic enzyme activity, and increased GI surface area with younger age can lead to different bioavailability
104
Distribution changes in children
changes in body composition (total body water and adipose tissue) and differing plasma protein binding, tissue binding, and blood flow to organs changes distribution
105
Metabolism changes in children
limited data
106
Elimination and Excretion changes in children
Immature enzyme development and liver/renal function- decreased renal blood flow, GFR, and tubular function
protein binding in neonates is low, the less bound a drug is the more efficient it can transverse cell membranes or diffuse
- affects drugs efficiency
107
Specific changes in premature infants
Incomplete glial development enhances the permeability of the BBB and permits drugs and bilirubin to enter the CNS more readily
108
Specific drug differences in children: valproic acid
higher incidence of valproic acid- associated hepatotoxicity in young infants
109
Specific drug changes in children- valproic acid
higher incidence of valproic acid-associated hepatotoxicity in young infants
110
Specific drug changes in children- diphenhydramine
greater frequency of paradoxical CNS reactions in infants
111
Specific drug changes in children: atypical antipsychotics
higher incidence of weight gain in adolescence
112
Specific drug changes in children: warfarin
altered concentration-versus-effect profiles for warfarin in children with congenital heart disease
113
Important considerations for pharmacology in children
weigh risks vs. benefits
consider long term effects
consider dosage formulations
114
Specific drug changes in children: fluoroqinolones (ciprofloxacin)
risk of severe degenerative arthropathy so contraindicated in children <18 years old
should not be used if alternate treatment exists
115
Specific drugs changes in children: antidepressants
increased risk of suicidality in children however risk of suicide in patients with untreated depression is much higher
116
Specific drug changes in children: controlled substances for ADHD
delayed onset of puberty (conflicting data)
117
Specific drug changes in children: inhaled steroids
conflicting data about height reduction (1cm reduction)
118
APAP gtts vs. APAP liquid
3x as concentrated
119
What should you use for the best dosage recommendation?
manufacturers package insert
DONT use Young or Clark's rules as they are not accurate
physiologically children are not small adults
120
What is the most common form of dosing calculation for children?
body weight-based dosing
mg/kg/day or mg/kg/dose
121
What is the most accurate method of dosing calculation for children?
Body surface area: use for narrow-therapeutic index drugs
122
KIDs List
released in 2020; Key potentially Inappropriate Drugs in Pediatrics; weak and strong recommendations based on evidence
67 drugs and 10 excipients
123
Specific drugs to avoid in children: Salicylates (ASA)
KIDs list shows weak recommendations but AAP recommends against it for <18 years old due to risk of Reye syndrome; however proven benefit for some pediatric populations
124
Specific drugs to avoid in children: Tetracycline
tooth discoloration & enamel hypoplasia <8 years old; delayed skeletal development and bone growth in premature infants
125
Drugs to avoid in children: codeine
respiratory depression; death
126
Guidelines for use of cold and cough medications in children
AAP- no OTC cough or cold medicine should be given to < 6 years old
FDA- children under 2 should not be given medication containing decongestants or antihistamine
Manufactures- no cold products for children <4 years old
127
Pharmacokinetic changes in obese children
changes in tissue compositon; increased blood volume/cardiac output, impaired liver and kidney functions all decrease the volume of distribution and clearance of many medications
physicochemical properties of a drug (lipid solubility and relative protein binding) leads to different effects on PK
128
Other medications not to use in children
benzocaine, ceftriaxone, gentamycin ophthalmic ointment, lidocaine 2% viscous, macrolides, topical corticosteroids, tramadol
129
Current recommendations for weight-based dosing in children
for children <18 who are <40kg (88lbs) use weight-based dosing
for children >40kg use weight-based design unless the dose exceeds recommended adult dose
130
Common errors in prescribing medications
incorrect dosage
incorrect frequency
underdosing or overdosing
inappropriate medication selection for indication
incorrect route of administration
failure to screen drug interactions or monitor side effects
131
Ways to minimize prescribing errors
Use EMR to send prescriptions
Put pts age and weight on prescription is dose is dependent on weight
132
Placenta-and-fetal unit changes in PK
placenta affects the amount of drug that crosses the placental membrane, the amount of drug metabolized
Fetus: affects the distribution and elimination of drug
both are additional compartments for distribution
133
GI absorption in pregnancy
-decreased gastric motility- delayed absorption of medications unless a drug is slow to dissolve
-decreased GI surface area
-reduction in gastric secretions and increase in gastric mucus secretion leads to increased gastric pH- decrease in absorption of medications that need acidic pH
- N/V in pregnancy from increased progesterone levels so meds should be taken when nausea is minimal
BUT OVERALL MINIMAL EFFECT ON BIOAVAILABILITY AND THERAPEUTIC EFFECT OF MOST ORAL DRUGS
134
Lung absorption in pregnancy
Increased cardiac and tidal volume in pregnancy; but not studies have showed increased toxicity of inhaled medications
135
Transdermal absorption in pregnancy
increased during pregnancy but deemed safer than oral or IV (limited data available)
136
Changes in distribution in pregnancy
increase in total body water and body fat leads to increased volume of distribution of hydro and lipophilic drugs
decreased plasma albumin leads to decreased albumin binding which leads to increased free drug concentration leading to more distribution in tissues
Efficacy and toxicity are related to unbound drug concentration in plasma
137
What drugs are significantly affected by changes in distribution in pregnancy?
Tacrolimus and phenytoin
138
Changes in elimination in pregnancy
increased progesterone levels stimulate hepatic microsomal enzyme systems leading to increased elimination of some hepatically eliminated medications decreasing elimination of others
rate of renal blood flow increases by 50% and GFR increases which leads to drugs excreted by the kidney having an increase in elimination (ex: cefazolin and clindamycin)
139
CYP450 changes in pregnancy
from increase in progesterone levels
140
Four factors affecting the ability of a drug to cross the placenta
lipid-soluble drugs cross more freely than water-soluble
ionisation of the drug affects placental transfer
molecular weight of the drug- lighter weigh tor smaller drug molecules cross the placenta easier
protein binding status- unbound drugs cross placenta easier
141
Teratogenicity
ability of a drug to cause defects in fetus
142
Safe antibiotics in pregnancy
penicillin, cephalosporins, erythromycin- considered safe
higher-dose regimens may be needed since they are cleared quicker due to increased GFR
143
Antibiotics to avoid in pregnancy
aminoglycosides and tetracyclines
avoid nitrofuratoin in near term preganancies
chloramphenicol is safe only topically
144
Metronidazole in lactation
may give breast milk an unpleasant taste
145
Pregnancy and lactation labeling rules
Must give information on pregnancy, lactation, and female and male reproductive potential
146
Lactation labeling
If not systemically absorbed- must state that fact
If systemically absorbed, label must include:
relevant information on presence of drug in human milk
effects of drug on breast-fed child
effect of drug on milk production
risk and benefit statement
147
Absorption changes in geriatrics
least affected
possibly slower but still complete
the more drugs a patient takes the higher risk for drug-drug interactions that interfere with absorption
148
Distribution changes in geriatrics
Bady fat increases with age- drugs that are lipid soluble may stay in blood longer since there are more fat stores where it can be distributed
decrease in muscle mass leads to less total body water- blood levels of a drug that this water-soluble may be higher than expected
decrease in albumin- causes lower amount of protein binding and leads to more active drug circulating in the blood
149
Clearance changes in geriatrics
liver and kidneys are affected by age
blood flow to the liver decreases which can reduce the clearance of some drugs by 30-40%
GFR decline is extremely variable
SCr is not reliable but still important to assess (older adults have decreased muscle mass and muscle metabolism so less creatinine production)
150
CYP450 changes in geriatrics
system becomes easily overwhelmed in older patients leading to slower drug metabolism
151
Cockcroft-Gault Equation
calculates creatinine clearance
CrCl (mL/min) = (140-age) x lean body weight (kg)/serum creatinine (mg/dL) x 72 (x0.85 if female)
152
Drugs with decreased hepatic clearance in geriatrics
acetaminophen, codeine, warfarin
153
Drugs with decreased renal clearance in geriatrics
amoxicillin, atenolol, furosemide, hydrochlorothiazide, metformin
154
Drugs associated with falls in geriatrics
antihistamines, antihypertensives
155
Drugs associated with confusion in geriatrics
corticosteroids
156
Drugs with significant anticholinergic effects in geriatrics
antidepressants (tricyclics) and antihistamines
157
Factors leading to polypharmacy
clinical practice guidelines
chronic disease managment
multiple prescribers or pharmacies
direct to consumer marketing
treating surrogate markers
uncertain treatment goals
clinical uncertainty
lack of communication
adverse drug event or new symptom?
treating side effects of another Rx
increased use of OTC, herbal supplements, complementary or alternative medications
158
Consequences of polypharmacy
increased risk of adverse drug reactions
reduced medication adherence
increase risk of serious drug-drug interactions
increased health care costs
reduced functional ability and ability to perform independent ADLs
increased risk of cognitive impairment, falls, malnutrition, urinary incontinence
159
How to streamline the medication review process
define or confirm clinical indications for all meds taken
adjust dosage for renal function
assess relative risks and benefits for each med
identify adverse drug events
evaluate drug-drug and drug-disease interactions
160
9 questions to address pharmacology in the elderly
Is each medication necessary?
Is the drug contraindicated in the elderly?
Are there duplicate medications?
Is the patient taking the lowest effective dose?
Is the medication intended to treat the side effect of another medication?
Can the drug regimen be simplified?
Are there potential drug interactions?
Is the patient adherent?
Is the paitent taking OTC medications, herbal products, or another person's medications?
161
Safe prescibing tips
review medicaiton list at every visit
evaluate patient adherence
consider new symptoms or complaints as possible drug-related problem and investigate
use Beers criteria when considering new presciptions
ensure each medication has a clear indication
ask about use of OTCs
start low and go slow when prescribing
consult other health care professionals
162
Mnemonic to remember polypharmacy principles
TIDE
T: Time
I: individualize
D: drug interactions
E: educate
T; allow sufficient time to addres and discuss medication issues each visit
I: apply PK and PD principles to regimens by adjusting doses for renal and heplatic imparment and starting medications at lowest possible dose
D: consider potential drug-drug and drug-disease interactions
E: educate the patient and caregiver about side effects and monitoring parameters
163
Role of nursing in polypharmacy
Obtain a thorough drug history
teach patietn when to contact prescriber
use one pharmacy
identify risks and develop individualized interventions
teach patient to dispose of old medications
collaborate with patient, family, and prescriber on treatment goals
provide effective teaching on role of drug thearpy in reaching goals
take steps to promote adherance
avoid drugs on Beers list
monitor for desired levels and labs when appropriate
monitor for drug-drug and drug-disease interactions
reduce symptoms and improve QOL
communicate with patient's other providers
164
Ways to promote adherence in geriatrics
simplify drug regimen
provider clear and concise verbal and written instructions
use approprate dosage forms
containers clearly labeled and easy to open
daily reminders, timers, pill dispensers
support systems
frequent monitoring
165
DPP4 inhibitors end in
-gliptin
166
SGLT-2 inhibitors end in...
-flozin
