Pharmacology Flashcards
1
Q
What is carbimazole used for?
A
Hyperthyroidism
2
Q
What is carbimazole’s MOA?
A
inhibit thyroid peroxidase resulting in less T3/T4 precursors –> decreased thyroid hormones output
3
Q
What is carbimazole dosing frequency and ROA?
A
PO once daily
4
Q
What happens to carbimazole after absorption?
A
Converted into active methimazole in the serum
5
Q
What is carbimazole’s (or its metabolites’) half life?
A
Methimazole’s half-life 4-6 hour
6
Q
Does carbimazole (or its metabolites) bind to plasma proteins?
A
No
7
Q
How long does it take for carbimazole to exert its effect?
A
> 90% inhibition achieved within 12 hours, however clinical response may take 3-6 weeks after initiation due to thyroid stores in the body and T4’s long half life.
8
Q
How is carbimazole metabolized?
A
CYP450 and FMO enzymes
9
Q
How is carbimazole excreted?
A
> 90% excreted in urine as methimazole or its metabolites
10
Q
What are adverse effects of carbimazole?
A
Rashes
Joint pains
Nausea
Jaundice
Agranulocytosis (rare)
11
Q
What is levothyroxine used for?
A
Hypothyroidism
12
Q
What is levothyroxine’s MOA?
A
Synthetic thyroid hormone
13
Q
What can affect levothyroxine’s absorption?
A
Increased absorption with fasting
Erratic absorption with dietary fiber
Affected by gastric pH
14
Q
What is levothyroxine’s bioavailability?
A
70-80%
15
Q
How long does it take for levothyroxine to exert its effect?
A
PO: 3-5 days
IV: 6-8H
16
Q
What is levothyroxine’s half-life?
A
7 days
17
Q
Does levothyroxine bind to plasma proteins?
A
Yes, >99%
18
Q
How is levothyroxine being metabolized?
A
Liver - glucuronidation, sulphation
Kidney - deiodination
19
Q
How is levothyroxine being excreted?
A
Primarily by kidneys
20
Q
What are adverse effects of levothyroxine?
A
Reduced appetite
Anxiety, insomnia
Hair loss
Diarrhea
Rare and serious:
Heart issues
Seizures
21
Q
When is IV form of levothyroxine used?
A
Myxoedema coma (severe form of hypothyroidism)
Cannot use PO levothyroxine as there is reduced blood flow to GI
Can also use IV Liothyronine (synthetic T3)
22
Q
What should you monitor after initiation of levothyroxine therapy?
A
Serum TSH every 6-8 weeks after initiation or dose titration
23
Q
What does persistently elevated TSH levels indicate after levothyroxine therapy has been started?
A
Inadequate dosing, poor compliance, malabsorption, DDI or food-drug interaction
24
Q
What is tamoxifen used for?
A
Breast cancer in both pre- and post- menopausal women
25
What is tamoxifen's MOA?
selective estrogen receptor modulator (SERM)
competitively blocks endogenous estrogen binding to the estrogen receptor in the target tissue
26
Does tamoxifen have stereoisomers?
Yes
Tamoxifen exists in cis- (estrogenic) and trans- (anti-estrogenic) stereoisomers
27
How is tamoxifen's absorption profile like?
Rapidly and extensively absorbed in intestine
F ~100%
Css typically reached after 3-4 weeks (max 16 weeks)
Tmax is 3-7 hours
28
Does tamoxifen bind to plasma protein?
>98%
29
What is tamoxifen's Vd?
50-60 L/kg
high concentrations found in tissues especially uterus (2-3 fold higher than serum) and breast (10 fold higher than serum)
30
How is tamoxifen metabolized?
Phase 1: hydroxylation, N-oxidation, dealkylation
Phase 2: glucuronidation, sulphation
Major pathway: N-demethylation
31
What is tamoxifen's major metabolite and its half-life?
N-desmethyltamoxifen (t1/2 ~14 days)
32
How is N-demethylation of tamoxifen catalyzed? And what's the consequences?
By CYP3A4
Should not take with grape gruit or CYP3A4 inhibitors
33
What are tamoxifen's minor metabolites?
4-hydroxytamoxifen
4-hydroxy-N-desmethyltamoxifen (endoxifen)
34
Which of the tamoxifen's metabolites has greater affinity for the estrogen receptor?
Minor metabolites
35
What catalyzes metabolism of tamoxifen into its minor metabolites? And what are its consequences?
CYP2D6
Do not take with diphenhydramine or inhibitors of CYP2D6
36
How is tamoxifen excreted?
Mainly through feces
37
What are side-effects of tamoxifen therapy?
Anti-estrogenic
- Hot flushes
- Menstrual irregularities
Estrogenic
- Risk of endometrial cancer
- DVT
- Vaginal bleed and discharge
- Nausea/vomiting
38
Overdose of tamoxifen can lead to?
Acute neurotoxicity eg. tremor, hyperreflexia, unsteady gait, dizziness
39
How do you treat tamoxifen overdose?
Supportive treatment
40
What is pembrolizumab used for?
Breast cancer
41
What is pembrolizumab's MOA?
PD-1 inhibitor
Binds to PD-1 and prevents PD-L1 on tumor cells binding to it, thus allowing activation of immune response to fight the tumor cells
42
What type of antibody is pembrolizumab?
Humanized antibody (-zumab)
43
How is pembrolizumab administered?
IV infusion over 30 mins
44
What is pembrolizumab's dose?
IV 200mg every 3 weeks
45
What is pembrolizumab's Vd?
~7L
46
How is pembrolizumab metabolized?
non-specific catabolism (general protein degradation routes) into small peptides and single amino acids
47
How is pembrolizumab excreted?
No studies done
48
What is pembrolizumab's half-life?
~27 days
49
When will pembrolizumab reach Css?
after ~19 weeks
50
What can cause slower clearance of pembrolizumab?
Cervical cancer in women
51
What are S/E of pembrolizumab?
Infusion-related S/Es, immune-related inflammation, joint pain, fatigue, diarrhea, nausea
52
What are C/I of pembrolizumab?
- On immunosuppressants or corticosteroids
- Pregnancy
- Hypersensitivity
53
List 4 ways to achieve androgen deprivation
- Inhibition of pituitary gonadotropin release (by using GnRH analogs)
- Inhibition of androgen synthesis
- Inhibition of androgen binding (by using androgen receptor blockers)
- Surgical extirpation of the glands (by castration and adrenalectomy)
54
What is leuprorelin used for?
Prostate cancer
55
What is leuprorelin's MOA?
GLP-1 agonist
It is a synthetic GnRH which activates the pituitary GnRH receptors
Continuous GnRH causes negative feedback on the pituitary leading to reduced FSH and LH levels
Reduced FSH and LH levels suppresses testosterone production in the testes and causes prostate cancer cells (androgen-sensitive cells) to undergo apoptosis
56
What should you monitor after starting leuprorelin?
Measure PSA in first few weeks of therapy
Measure LH, FSH, and serum testosterone after 4 weeks of therapy
Reduction in levels of these substances indicates that the treatment works
57
How is leuprorelin administered?
SC or IM, given as single-dose long acting depot (1, 3, or 4 months interval)
58
What is leuprorelin's time to Cmax and Css?
Cmax: 1-3 hours post injection
Css typically after 4 weeks
59
What is leuprorelin's Vd?
~27L after IV
No data after SC or IM
60
Does leuprorelin binds to plasma protein?
~45% plasma protein binding (in vitro)
61
How is leuprorelin metabolized?
degraded proteolytically (peptidases) into inactive peptides
not metabolized in liver CYP450
62
What is leuprorelin's half-life?
~ 3 hours
63
How is leuprorelin excreted?
<5% via urine
64
What are side effects of leuprorelin?
- Hot flushes (first few weeks)
- Injection site reaction
- Headache/dizziness
- Altered mood
- Hyperglycemia
- Decreased libido
65
What are C/I to leuprorelin?
Hypersensitivity
Pre-existing heart disease
Pts with risks for osteoporosis
66
What is bicalutamide used for?
Prostate cancer
67
What is bicalumatide's MOA?
Androgen receptor antagonist
Steps:
- Competitive antagonist of androgen receptor
- Inhibits nuclear translocation of the androgen receptors
- Inhibits transcription processes
- Impairing cell proliferation
- Triggers apoptosis of the cancer cells.
68
Can bicalumatide be used as a monotherapy? Why or why not?
No
Can cause initial surge of testosterone levels, which can lead to the prostate tumor flare
To be used in conjunction with GnRH analogue to alleviate those effects
69
Does food interferes with bicalutamide's absorption?
No
70
Does bicalumatide bind to plasma protein?
>99%
71
How is bicalumatide metabolized?
By liver
Active metabolite - slow hydroxylation (CYP3A4) followed by glucuronidation
72
Which isomer of bicalutamide is active? And its half-life?
R-isomer ~6 days
73
How is bicalumatide excreted?
Via bile and urine
74
What is bicalumatide's S/E?
Constipation/diarrhea
Decreased libido
Fatigue
Hot flushes
Mild swelling of ankles/legs/feet
Nausea/vomiting
75
What are C/I to bicalutamide?
Hypersensitivity
Women and children
76
What are oral pharmacotherapy options for managing BPH?
- Alpha adrenergic antagonists (alpha blockers)
- 5-alpha-reductase inhibitors (5ARIs)
- Muscarinic receptor antagonists (MRAs)
- Phosphodiesterase 5 inhibitors (PDE5i)
77
What is tamsulosin's MOA?
reversible alpha-1A adrenoreceptor blocker
blocks the contraction of internal sphincter resulting in relaxation of bladder & urethra's smooth muscle and allowing urine to flow
78
Can tamsulosin be used on patients with enlarged prostate size?
Tamsulosin can be used for symptomatic BPH regardless of prostate size
79
What is tamsulosin's Vd?
0.2L/kg
80
Does tamsulosin bind to plasma proteins?
>90%
81
How is tamsulosin metabolized?
CYP3A4 and CYP2D6
82
What is tamsulosin's half-life?
10-15 hours (OD dosing)
83
How is tamsulosin excreted?
~10% excreted unchanged in urine
84
What are adverse effects of tamsulosin?
Abnormal ejaculation
Back pain
85
What are C/I to tamsulosin?
Concurrent use of another alpha-1-receptor antagonist
86
What is finasteride's MOA?
5-alpha reductase inhibitor (competitive and specific)
Inhibits the conversion of testosterone to DHT, hence decreasing prostate size
87
What is finasteride's bioavailability?
F ~0.65
88
Is there any dose adjustment of finasteride required for renal/liver failure or elderly patients?
No dose adjustment required
89
Is finasteride bound to plasma protein?
~90%
90
How is finasteride metabolized?
CYP3A4
91
What is finasteride's half-life?
~6 hours
92
How is finasteride excreted?
50% unchanged in feces
Metabolites in urine and feces
93
What are S/E of finasteride?
Decreased libido and sexual potency
Gynecomastia (rare)
94
What are C/I to finasteride?
Women and children
Pregnancy
95
What is sildenafil used for?
Erectile dysfunction
96
What is the MOA of sildenafil?
PDE5 inhibitor (specific to PDE5 in penis)
Inhibits PDE5 to decrease degradation of cGMP
Increased cGMP levels results in smooth muscle relaxation and increased blood flow to the corpora cavernosa
97
What is the onset of sildenafil?
30-60 mins
98
What is the bioavailability of sildenafil?
F ~0.4
99
Is there any dose adjustment of sildenafil required for renal/liver failure or elderly patients?
No
100
What is the maximum duration of action of sildenafil?
~12 hours
101
How is sildenafil metabolized?
Major - CYP3A4
Minor - CYP2C9
102
What is sildenafil's half-life?
~4 hours
103
How is sildenafil excreted?
Metabolites: 80% in feces, 13% in urine
Unchanged: in urine
104
What are S/E of sildenafil?
- Headache
- Flushing
- Dizziness
- Blurred vision
- Blue-green tinting of vision (retinal PDE6 inhibition)
- Priapism
- Back pain
- Dyspepsia
105
What are C/I to sildenafil?
Cardiac patients on GTN or nitrates
106
What is ethinyl estradiol's MOA?
Synthetic estrogen (estrogen receptor agonist)
Causes decreased FSH release from anterior pituitary and hence suppresses the development of ovarian follicle
Make endometrium unsuitable for implantation of ovum
107
What is ethinyl estradiol used for?
- Menopausal symptoms
- Gynecological disorders
- Certain hormone sensitive cancers
108
What is the onset and bioavailability of ethinyl estradiol?
30-60 min
F ~0.45
109
Is ethinyl estradiol protein bound?
~98%
110
How is ethinyl estradiol metabolized?
Phase I - hydroxylation by CYP3A4
Phase II - glucuronidation (ethinyl estradiol glucuronide) and sulfation (ethinyl estradiol sulfate)
Ethinyl estradiol sulfate undergoes enterohepatic recirculation
111
What is the half-life of ethinyl estradiol?
13-27 hours
112
How is ethinyl estradiol excreted?
Feces and urine
113
What are the adverse effects of ethinyl estradiol?
- Breast tenderness
- Headache
- Dizziness
- Nausea
- Fluid retention
- Weight gain
- Risk of VTE
- Risk of MI/stroke
- Liver damage
114
What are C/I to ethinyl estradiol?
- Breastfeeding and <21 days postpartum
- Breast cancer
- Hx of DVT
- Advanced diabetes with vascular disease
- HTN ≥ 160/100
115
What is norethindrone's MOA?
Synthetic progestin (progesterone receptor agonist)
Reduces LH release which prevents ovulation + make endometrium unsuitable for implantation of ovum
116
What is norethindrone used for?
- Endometriosis
- Abnormal periods or bleeding
117
What is norethindrone's bioavailability?
F ~64%
118
Does norethindrone bind to plasma protein?
Yes, highly bound
119
How is norethindrone metabolized?
Phase I - reduction
Phase II - glucuronidation and sulfation
120
What is norethindrone's half-life?
~8 hours
121
How is norethindrone excreted?
Metabolites excreted 50% in urine and 40% in feces
122
What are S/E of norethindrone?
- Headache
- Dizziness
- Bloating
- Weight gain
- Amenorrhea
- Initial spotting and bleeding
123
Why is norethindrone to be used with caution in ppl with cardiovascular risk?
Partial conversion of norethindrone to ethinyl estradiol
124
What is the MOA of metformin?
Biguanides
Decreases gluconeogenesis in the liver
Enhance tissue sensitivity to insulin
125
What is the bioavailability of metformin?
40-60%
126
What is the duration of action of metformin?
8-12 hours
127
Does metformin bind to plasma protein?
Minimal
128
What is the half-life of metformin?
3 hours
129
How is metformin excreted?
Unchanged in the urine
130
What are the S/E of metformin?
Anorexia
GI disturbances
Increased risk of vit B12 malabsorption
131
Does metformin cause weight loss or gain?
Weight loss
132
In which patients should metformin be used cautiously?
Patients who experienced lactic acidosis
Patients with renal problems
133
What is glipizide's MOA?
Sulfonylureas
Binds to SU receptor protein (found at the K(ATP) channels, inhibiting K+ efflux and hence triggering a calcium-dependent exocytosis of insulin granules from the pancreatic beta cells
134
What is glipizide's oral bioavailability?
>95% (delayed with food intake)
135
What is glipizide's onset of action?
0.5 hours
136
What is glipizide's duration of action?
12-24 hours
137
Does glipizide bind to plasma proteins?
Yes, 99%
138
What is glipizide's half-life?
4 hours
139
How is glipizide metabolized?
Hydroxylation in the liver
140
How is glipizide excreted?
<10% excreted unchanged in urine and feces
Metabolites are excreted in urine and feces
141
What is the S/E of glipizide?
Weight gain
Hypoglycemia (less than 1st gen, more likely in elderly)
142
What is the MOA of sitagliptin?
DPP-4 inhibitor
Inhibit DPP-4 to prevent enzymatic degradation of GLP-1 and prolong the action of endogenous incretins
Incretins stimulate insulin secretion at the beta pancreatic cells WHEN there is presence of hyperglycemia, suppresses alpha pancreatic cells mediated glucagon release and hepatic glucose production
Incretins also delay gastric emptying at the gut and induce satiety
143
What is the oral bioavailability of sitagliptin?
F = 87%
144
What is sitagliptin's half-life?
10-12 hours
145
How is sitagliptin metabolized?
low liver metabolism
146
How is sitagliptin excreted?
80% excreted unchanged in urine, rest in feces
147
What are S/E of sitagliptin?
GI disturbances
Flu-like symptoms
Skin reactions
148
In which patients should sitagliptin be used cautiously?
In patients with history of pancreatitis
149
What is liraglutide's MOA?
GLP-1 agonist
Activates GLP-1 receptor on pancreatic beta cells to increase insulin secretion, and on alpha cells to decrease glucagon release (GLUCOSE DEPENDENT)
Delays gastric emptying and induces satiety (reduce appetite)
It is a long acting peptide (C16 fatty acid) and hence is resistant to degradation by DPP-4 enzymes in the body.
150
What is liraglutide's bioavailability after SC injection?
F = 55%
151
How is liraglutide dosed?
Week 1 - 0.6 mg SC daily
Week 2 - 1.2 mg SC daily
Week 3 - 1.8 mg SC daily
Week 4 - 2.4 mg SC daily
Week 5 onwards - 3 mg SC daily
152
Does liraglutide bind to plasma protein?
Yes (C16 fatty acid binds to plasma protein)
153
What is the half-life of liraglutide?
13 hours (due to plasma protein binding)
154
How is liraglutide metabolized?
Non-specific, similar to endogenous polypeptides
155
How is liraglutide excreted?
Little or none excreted unchanged
156
What are S/E of liraglutide?
Nausea, vomiting
Diarrhea, constipation
Headache, tiredness
157
Who should liraglutide not be used on?
Pregnant women
158
What are other benefits of liraglutide?
- Weight loss
- Reduces risk of CV death, non-fatal MI, and HF (IN DM2 LECTURE SAY NEUTRAL EFFECT) among T2DM patients
159
What is the MOA of empagliflozin?
SGLT2i
Binds to SGLT2 at the proximal tubule of the nephron and decrease reabsorption of filtered glucose, increasing urinary glucose excretion
160
What is the oral bioavailability of empagliflozin?
60-80%
161
When is the Cmax achieved for empagliflozin?
1-2 hours
162
What is the half-life of empagliflozin?
12 hours
163
Does empagliflozin bind to plasma protein?
~90%
164
How is empagliflozin metabolized?
Minimal metabolism
Glucuronidation in the liver
165
How is empagliflozin excreted?
40% unchanged in feces
27% unchanged in urine
166
What are the S/E of empagliflozin?
- UTI
- increased urination
- female vaginal thrush
- diabetic ketoacidosis
167
What are additional benefits of empagliflozin?
- Reduced risk of major cardiac event (ASCVD and HF)
- Reduced risk for composite endpoint of worsening renal function (CKD)
