NSG 533Advanced Pharmacology| Wilkes University
Exam 1
5 alpha reductase inhibitors - ANSWER-Management of moderate to severe BPH in patients
with enlarged prostate glands.
Management of patients who desire medical therapy but cannot tolerate alpha-1-adrenergic
antagonists and do not have predominately irritant symptoms or concomitant erectile
dysfunction (Symptoms are non-bothersome, so the delay in onset would not interfere with Qol)
Reduce prostate size (and PSA) and thus outlet obstruction
Reverse / Slow disease progression
Decrease the risk of disease complications
Note: although dutasteride blocks both the Type I and Type II iso-enzymes of 5-alpha reductase
while finasteride only blocks Type II, there is not a clinically significant difference in outcomes
when either is used
Peak effect 6-12 months, effect is only durable as long as drug is continued (prostate will return
to pre-treatment size (or larger) when / if 5ARIs are stoppedFinasteride & Dutasteride reduces,
but does not stop the prostate from producing PSA
If PSA fails to decline by 50% after 6-12 months or an increase of 0.3 ng/L or more above the
baseline nadir level, patient should be evaluated for prostate cancer. May also indicate
worsening condition or non-compliance with 5 a-reductase inhibitors
A patient with type 1 diabetes reports taking propranolol for hypertension. What concern does
this information present for the provider? - ANSWER-A patient with Type 1 DM is insulin
dependent for glucose control and at high risk for hypoglycemic episodes. Propanolol causes
prolonged hypoglycemic episodes. Needs to switch to ACE or ARB.
A provider teaches a patient who has been diagnosed with hypothyroidism about a new
prescription for levothyroxine. Which statement by the patient indicates a need for further
teaching?
a. "I should not take heartburn medication without consulting my provider first."
b. "I should report insomnia, tremors, and an increased heart rate to my provider."
c. "If I take a multivitamin with iron, I should take it 4 hours after the levothyroxine."
d. "If I take calcium supplements, I may need to decrease my dose of levothyroxine." -
ANSWER-D. Calcium may reduce levothyroxine absorption. Further education is needed if the
patient feels she can take half of a prescribed medication.
ADRs - ANSWER-(androgen insufficiency) decreased libido, impotence & ejaculatory disorder,
breast tenderness & enlargement
Alpha-blockers - ANSWER-fairly rapid onset (2-4 weeks) with relatively rapid symptom
resolution , durable effect (years) with AUA symptom index (AUASI) improving 30-45%. No
effect on prostate size (PSA) or disease progression.
Relax smooth muscle in bladder neck, urethra & prostate(Blue dots indicate the distribution of
alpha receptors surrounding the bladder and prostate). It is clear why these agents would
provide rapid relief of symptoms
New second generation (alfuzosin) and third generation (tamsulosin and silodosin) agents are
,preferred because of uroselectivity, no need for dose titration and limited orthostasis
Alpha-blockers - ANSWER-Older agents also have an indication for hypertension and have
more CV ADRs (e.g. orthostasis, reflex tachycardia, etc).
e.g. terazosin. doxazosin
dose titration should follow the "start low, go slow" paradigm
Most guidelines advocate for the individual management of BPH and hypertension
Note that the ACC / AHA recommends that that for those with the comorbidities of hypertension
and BPH, each of those conditions should be treated independently based on GDMT. For those
with persistent HTN on maximized first line therapies, alpha-blockers with vascular effects may
provide benefit in terms of additional BP lowering
Alprostadil - PgE1 analog administered by intracavernosal injection & intraurethral inserts -
ANSWER-Because PGs bypass many steps in the erectile cascade, they are quite effective at
producing an erection, even in cases where PDE5 inhibitors cannot do so.
Most invasive and low patient acceptance. Reserved as second or third line treatment
Before initiating treatment for ED - ANSWER-a physical examination and thorough medical,
social, and medication histories with emphasis on cardiac disease must be taken to assess for
ability to safely perform sexual activity and to assess for possible drug interactions
Diagnosis should include PE (including a check for signs of hypogonadism), medication review,
Hx, and labs ( HbA1C, PSA, FLP, testosterone)
Beta-blockers role in therapy? - ANSWER-So .. beta blockers are used for Symptomatic relief of
hyperthyroidism until more definative therapy is instituted and thyroid levels retun to normal or
near normal..
Reduction of peripheral manifestations
Tachycardia, sweating, severe tremor, nervousness
Inhibition of peripheral conversion of thyroid hormones at higher doses (propranolol ONLY)
Small therapeutic effect in magnitude
thyrotoxicosis
BPH - ANSWER-BPH increases urethral resistance, resulting in compensatory changes in
bladder function. Obstruction-induced changes in detrusor function, including smooth muscle
hypertrophy, compounded by age-related changes in the functioning of the bladder, lead to
urinary frequency, urgency, and nocturia, the most bothersome BPH-related complaints. Not all
patients with LUTS have BPH and not all men with BPH have LUTS.
BPH combination therapy - ANSWER-◦ a-blocker and PDE-5Is
For men with moderate symptoms of BPH and erectile dysfunction, treatment with daily tadalafil
(5 mg/day) alone or in combination with tamsulosin (0.4 mg/day) can be considered
Addition of PDE-5Is to alpha blockers may improve lower urinary tract symptoms
◦PDE-5i and 5a-RIs
Addition of PDE-5i to 5a-RIs can offset erectile dysfunction commonly seen with 5a-RIs
BPH combination therapy - ANSWER-◦-blocker and anticholinergic (or β3 agonist)
For men with low post-void residual urine volumes and irritative symptoms (e.g., frequency,
urgency) that persist during treatment with an alpha-adrenergic antagonist, combination
treatment with an anticholinergic agent can be tried
◦Improved storage voiding parameters and frequency compared with alpha-1-adrenergic
antagonist therapy alone
, ◦For patients who poorly tolerate anticholinergic adverse effects, an alternative is Mirabegron
The risk of side effects, increased post-void residual urine volume, decreased maximal urinary
flow rate, or acute urinary retention is low
BPH combination therapy - ANSWER-Alpha-blocker offer immediate relief; 5 alpha-RIs reduce
prostate enlargement over time
◦In patients with an enlarged prostate gland and an elevated PSA ≥1.4 ng/mL, combination drug
therapy with an α1-adrenergic antagonist and a 5α-reductase inhibitor is more beneficial than
single drug therapy.
◦Rationale
a-blocker offer immediate relief
5a-RIs reduce prostate enlargement
◦Works better for those with obstructive symptoms
◦May consider stopping a-blocker after 6-12 months, but should continue in those patients with
severe symptoms as long as they are responding
BPH diagnosis - ANSWER-Diagnosis includes components such as symptom assessment
(AUA score), PE and PSA
PSA is present in small quantities in the serum of men with healthy prostates, but is often
elevated in the presence of prostate cancer or other prostate disorders. PSA is not uniquely an
indicator of prostate cancer, but may also detect prostatitis or BPH. PSA correlates with prostate
size and can be used as a prognostic marker
Can be used as monotherapy or as add-on therapy for T2DM .. Presenting A1C of 9 +
symptoms or failure to achieve goal A1C on adequate trial of 2-3 agents at maximally tolerated
doses - ANSWER-Often starting with a long acting insulin
When glycemic goals aren't reached despite basal insulin (Good FBG and pre-prandial BG, but
elevated HbA1C), Consider prandial therapy with fast-acting insulin. Begin fast-acting insulin
before largest meal.Variation exists between ADA and ACCE in their recommendations
If HbA1C still elevated, add fast-acting to another mealSulfonylurea can continue up until the
point where prandial (rapid) insulin is addedMetformin can / should continue !!
Candidate for prophylaxis - ANSWER-History of prior gastrointestinal event
Age over 60 (5x greater risk)
High NSAID dosage
Concurrent use of corticosteroids (4x greater risk)
Concurrent use of anticoagulants, antiplatelets or low dose ASA (12x greater risk)
Treatment: Discontinue NSAID If possibleEradicate H Pylori if (+)H2RAs or PPIsPPIs heal
NSAID-related ulcers more effectively as compared with H2RAs and are therefore the
antisecretory drug of choice for treating NSAID-related ulcers, especially when NSAIDs are
continuedPatients with NSAID-associated ulcers should be treated with a PPI for a minimum of
eight weeksSucralfate is an option for healing only if NSAID will be stopped
Cardioprotective dose ASA (IE baby aspirin or clopidrogel as alternative)For SECONDARY
PREVENTION of CV Events- Use in ALL diabetics with CV diseaseFor PRIMARY
PREVENTION of CV EventsUSE in: high CV risk patients (10-yr CV risk > 10%) - Typically:
male > 50 yo or female >60 yo with 1 additional major risk factor (FH of CVD, HTN, smoker,
dyslipidemia or albuminuria)MAY consider: intermediate CV risk patrients 10-yr CV risk of 5-
10%) - younger patients with 1 or more risk factors, older patients with no risk factorsNOT
recommended: low CV risk patients - men <50 yo or women <60 yo without major CV risk
factors or 10-yr CV risk < 5%Note - Many authorities consider DM to be an ASCVD risk
Exam 1
5 alpha reductase inhibitors - ANSWER-Management of moderate to severe BPH in patients
with enlarged prostate glands.
Management of patients who desire medical therapy but cannot tolerate alpha-1-adrenergic
antagonists and do not have predominately irritant symptoms or concomitant erectile
dysfunction (Symptoms are non-bothersome, so the delay in onset would not interfere with Qol)
Reduce prostate size (and PSA) and thus outlet obstruction
Reverse / Slow disease progression
Decrease the risk of disease complications
Note: although dutasteride blocks both the Type I and Type II iso-enzymes of 5-alpha reductase
while finasteride only blocks Type II, there is not a clinically significant difference in outcomes
when either is used
Peak effect 6-12 months, effect is only durable as long as drug is continued (prostate will return
to pre-treatment size (or larger) when / if 5ARIs are stoppedFinasteride & Dutasteride reduces,
but does not stop the prostate from producing PSA
If PSA fails to decline by 50% after 6-12 months or an increase of 0.3 ng/L or more above the
baseline nadir level, patient should be evaluated for prostate cancer. May also indicate
worsening condition or non-compliance with 5 a-reductase inhibitors
A patient with type 1 diabetes reports taking propranolol for hypertension. What concern does
this information present for the provider? - ANSWER-A patient with Type 1 DM is insulin
dependent for glucose control and at high risk for hypoglycemic episodes. Propanolol causes
prolonged hypoglycemic episodes. Needs to switch to ACE or ARB.
A provider teaches a patient who has been diagnosed with hypothyroidism about a new
prescription for levothyroxine. Which statement by the patient indicates a need for further
teaching?
a. "I should not take heartburn medication without consulting my provider first."
b. "I should report insomnia, tremors, and an increased heart rate to my provider."
c. "If I take a multivitamin with iron, I should take it 4 hours after the levothyroxine."
d. "If I take calcium supplements, I may need to decrease my dose of levothyroxine." -
ANSWER-D. Calcium may reduce levothyroxine absorption. Further education is needed if the
patient feels she can take half of a prescribed medication.
ADRs - ANSWER-(androgen insufficiency) decreased libido, impotence & ejaculatory disorder,
breast tenderness & enlargement
Alpha-blockers - ANSWER-fairly rapid onset (2-4 weeks) with relatively rapid symptom
resolution , durable effect (years) with AUA symptom index (AUASI) improving 30-45%. No
effect on prostate size (PSA) or disease progression.
Relax smooth muscle in bladder neck, urethra & prostate(Blue dots indicate the distribution of
alpha receptors surrounding the bladder and prostate). It is clear why these agents would
provide rapid relief of symptoms
New second generation (alfuzosin) and third generation (tamsulosin and silodosin) agents are
,preferred because of uroselectivity, no need for dose titration and limited orthostasis
Alpha-blockers - ANSWER-Older agents also have an indication for hypertension and have
more CV ADRs (e.g. orthostasis, reflex tachycardia, etc).
e.g. terazosin. doxazosin
dose titration should follow the "start low, go slow" paradigm
Most guidelines advocate for the individual management of BPH and hypertension
Note that the ACC / AHA recommends that that for those with the comorbidities of hypertension
and BPH, each of those conditions should be treated independently based on GDMT. For those
with persistent HTN on maximized first line therapies, alpha-blockers with vascular effects may
provide benefit in terms of additional BP lowering
Alprostadil - PgE1 analog administered by intracavernosal injection & intraurethral inserts -
ANSWER-Because PGs bypass many steps in the erectile cascade, they are quite effective at
producing an erection, even in cases where PDE5 inhibitors cannot do so.
Most invasive and low patient acceptance. Reserved as second or third line treatment
Before initiating treatment for ED - ANSWER-a physical examination and thorough medical,
social, and medication histories with emphasis on cardiac disease must be taken to assess for
ability to safely perform sexual activity and to assess for possible drug interactions
Diagnosis should include PE (including a check for signs of hypogonadism), medication review,
Hx, and labs ( HbA1C, PSA, FLP, testosterone)
Beta-blockers role in therapy? - ANSWER-So .. beta blockers are used for Symptomatic relief of
hyperthyroidism until more definative therapy is instituted and thyroid levels retun to normal or
near normal..
Reduction of peripheral manifestations
Tachycardia, sweating, severe tremor, nervousness
Inhibition of peripheral conversion of thyroid hormones at higher doses (propranolol ONLY)
Small therapeutic effect in magnitude
thyrotoxicosis
BPH - ANSWER-BPH increases urethral resistance, resulting in compensatory changes in
bladder function. Obstruction-induced changes in detrusor function, including smooth muscle
hypertrophy, compounded by age-related changes in the functioning of the bladder, lead to
urinary frequency, urgency, and nocturia, the most bothersome BPH-related complaints. Not all
patients with LUTS have BPH and not all men with BPH have LUTS.
BPH combination therapy - ANSWER-◦ a-blocker and PDE-5Is
For men with moderate symptoms of BPH and erectile dysfunction, treatment with daily tadalafil
(5 mg/day) alone or in combination with tamsulosin (0.4 mg/day) can be considered
Addition of PDE-5Is to alpha blockers may improve lower urinary tract symptoms
◦PDE-5i and 5a-RIs
Addition of PDE-5i to 5a-RIs can offset erectile dysfunction commonly seen with 5a-RIs
BPH combination therapy - ANSWER-◦-blocker and anticholinergic (or β3 agonist)
For men with low post-void residual urine volumes and irritative symptoms (e.g., frequency,
urgency) that persist during treatment with an alpha-adrenergic antagonist, combination
treatment with an anticholinergic agent can be tried
◦Improved storage voiding parameters and frequency compared with alpha-1-adrenergic
antagonist therapy alone
, ◦For patients who poorly tolerate anticholinergic adverse effects, an alternative is Mirabegron
The risk of side effects, increased post-void residual urine volume, decreased maximal urinary
flow rate, or acute urinary retention is low
BPH combination therapy - ANSWER-Alpha-blocker offer immediate relief; 5 alpha-RIs reduce
prostate enlargement over time
◦In patients with an enlarged prostate gland and an elevated PSA ≥1.4 ng/mL, combination drug
therapy with an α1-adrenergic antagonist and a 5α-reductase inhibitor is more beneficial than
single drug therapy.
◦Rationale
a-blocker offer immediate relief
5a-RIs reduce prostate enlargement
◦Works better for those with obstructive symptoms
◦May consider stopping a-blocker after 6-12 months, but should continue in those patients with
severe symptoms as long as they are responding
BPH diagnosis - ANSWER-Diagnosis includes components such as symptom assessment
(AUA score), PE and PSA
PSA is present in small quantities in the serum of men with healthy prostates, but is often
elevated in the presence of prostate cancer or other prostate disorders. PSA is not uniquely an
indicator of prostate cancer, but may also detect prostatitis or BPH. PSA correlates with prostate
size and can be used as a prognostic marker
Can be used as monotherapy or as add-on therapy for T2DM .. Presenting A1C of 9 +
symptoms or failure to achieve goal A1C on adequate trial of 2-3 agents at maximally tolerated
doses - ANSWER-Often starting with a long acting insulin
When glycemic goals aren't reached despite basal insulin (Good FBG and pre-prandial BG, but
elevated HbA1C), Consider prandial therapy with fast-acting insulin. Begin fast-acting insulin
before largest meal.Variation exists between ADA and ACCE in their recommendations
If HbA1C still elevated, add fast-acting to another mealSulfonylurea can continue up until the
point where prandial (rapid) insulin is addedMetformin can / should continue !!
Candidate for prophylaxis - ANSWER-History of prior gastrointestinal event
Age over 60 (5x greater risk)
High NSAID dosage
Concurrent use of corticosteroids (4x greater risk)
Concurrent use of anticoagulants, antiplatelets or low dose ASA (12x greater risk)
Treatment: Discontinue NSAID If possibleEradicate H Pylori if (+)H2RAs or PPIsPPIs heal
NSAID-related ulcers more effectively as compared with H2RAs and are therefore the
antisecretory drug of choice for treating NSAID-related ulcers, especially when NSAIDs are
continuedPatients with NSAID-associated ulcers should be treated with a PPI for a minimum of
eight weeksSucralfate is an option for healing only if NSAID will be stopped
Cardioprotective dose ASA (IE baby aspirin or clopidrogel as alternative)For SECONDARY
PREVENTION of CV Events- Use in ALL diabetics with CV diseaseFor PRIMARY
PREVENTION of CV EventsUSE in: high CV risk patients (10-yr CV risk > 10%) - Typically:
male > 50 yo or female >60 yo with 1 additional major risk factor (FH of CVD, HTN, smoker,
dyslipidemia or albuminuria)MAY consider: intermediate CV risk patrients 10-yr CV risk of 5-
10%) - younger patients with 1 or more risk factors, older patients with no risk factorsNOT
recommended: low CV risk patients - men <50 yo or women <60 yo without major CV risk
factors or 10-yr CV risk < 5%Note - Many authorities consider DM to be an ASCVD risk
