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Pharmacy School 2015-16 > PHAR 736 Midterm 2 (Antagonists) > Flashcards

PHAR 736 Midterm 2 (Antagonists) Flashcards

1
Q

General purpose of B-blockers in CHF

A

CHF is cycle of sympathetic activation. Goal of pharmacological intervention is to inhibit progressive deterioration of cardiac function.

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2
Q

B1-selevtive antagonists (general)

A

All are competitive (antagonists, inverse agonists, or partial agonists)

Effects most pronounced under conditions of stress or exercise

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3
Q

B1-selective antagonists therapeutic indications

A

Post MI therapy, Ischemic heart disease, Angina (decrease O2 demand on heart, decrease workload on cardiac muscle)

Prevention of ventricular tachycardic arrhythmias (decrease heart rate, decrease AV nodal conduction, and increase refractory period; classified as Class 2 anti-arrhythmic agents)

Compensatory cardiac hypertrophy (block the overgrowth of the heart muscle - cardiac remodeling - due to excess SNS activity)

Hypertension (see hypertension notecard)

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4
Q

B1-selective antagonists and hypertension

A

NOT FIRST LINE

Decrease in cardiac output (b1 blockade) resulting in decreased systolic BP

Decrease in renin secretion (b1 blockade in kidney) resulting in vasodilation

Other less understood factors may contribute to decrease in BP with use of B receptor antagonists

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5
Q

Contraindications for B1-selective antagonists

A

Insulin-dependent diabetes:
>masks symptoms of hypoglycemia (increased HR, tremors) of vital importance to diabetics

  • *hyperglycemia is the main problem in diabetics and is toxic in the long-term
  • *hypoglycemia, a side effect of insulin treatment, can kill quickly
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6
Q

B1-selective or non-selective antagonists in those with asthma/COPD?

A

B1-Selective

blocking B2 adrenergic receptors would inhibit pulmonary relaxation

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7
Q

B1-selective antagonists side effects

A

Bradycardic arrhythmias (block of B1 in heart, particularly a problem for those with inadequate myocardial reserve)

Fatigue and exercise intolerance (blockade of B1 receptors in the heart)

Withdrawal syndrome

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8
Q

Describe B1-selective antagonists withdrawal syndrome

A

Rebound tachycardia upon abrupt withdrawal due to receptor supersensitization.

MI may ensure in susceptible patients.

Problematic for up to 2 weeks following cessation of therapy.

Discontinue by tapering the dose.

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9
Q

Metoprolol, Atenolol

A

Reduce basal activity of cardiac B1 receptors

Inverse agonists (awful super-sensitization)

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10
Q

Acebutolol

A

Weak B1 partial agonist (and partial antagonist) - used by itself has ~20% efficacy

Moderately decreases cardiac output and heart rate

Very little receptor supersensitivity, better withdrawal profile

Effects of blockade are more apparent under conditions of stress or exercise

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11
Q

Acebutolol is particularly useful in patients that can…

A

Tolerate changes in cardiac output

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12
Q

How does Acebutolol work in the presence of a full agonist?

A

Acts like an antagonist in presence of full agonist (e.g. NE)

Weak partial agonist as NE presence diminishes

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13
Q

Esmolol

A

Very short duration B1 blocker

Used to treat ventricular tachycardic arrythmias and in other situations where brief cardiac blockade is warranted

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14
Q

Pharmacogenomic considerations for B1 blockers

A

People with two Arg alleles more responsive in terms of cardiac stimulation to sympathomimetics than those with at least one Gly allele.

Bucindolol acts as an inverse agonist in patients with the Arg alleles. Acts as a neutral antagonist in patients with at least one Gly allele.
**Effective in HF only if patient has Arg alleles

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15
Q

B2-selective antagonists

A

NONE of therapeutic value currently marketed

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16
Q

Non-selective B adrenergic antagonists therapeutic indications

A

Chronic glaucoma (decrease aqueous humor production by blocking B1 and B2 in eye)

Hyperthyroidism symptoms (blocks symptoms mimicking SNS over-activity, no effect on the disease itself)

Performance anxiety (reduced nervousness through CNS effects and fine motor tremors)

Tremors (drug induced tremors, such as accompany lithium carbonate treatment; Familial palsy (NOT PARKINSONS)

Prophylactic Treatment of migraines (MOA unknown; does not work acutely)

Hypertension

Ventricular tachycardic arrhythmias, Post MI therapy, angina, HF (same as B1 selective blockers, which are generally preferred now for these indications)

17
Q

B non-selective and hypertension

A

Decrease in cardiac output (B1 blockade) resulting in decreased systolic BP

Decrease in renin secretion (B1 blockade in kidney) resulting in vasodilation

Paradoxical effects:
>short term B2 blockade in normotensives will cause a little bit of vasoconstriction (expected)
>B2 blockade in hypertensives leads to decreased systolic AND diastolic BP (may have to do with adrenergic receptors playing a role in tissue remodeling)

18
Q

B Non-selective antagonists contraindications

A

Asthma/COPD (blocks bronchodilation)

Insulin-dependent diabetes (should work by decreasing glucagon release and aiding in lowering blood sugar, BUT can mask symptoms of hypoglycemia)

19
Q

B non-selective antagonists side effects

A

Exercise intolerance:
Reduced airflow, restriction of blood flow to skeletal muscles, reduced cardiac output

Hyperkalemia (generally only a problem for those prone to electrolyte imbalance, but can be a problem during exercise as skeletal muscle uptake of potassium is reduced)

Mast cell degranulation

Bradycardic arrhythmias (blockade of B1 receptors in heart, particularly in patients with inadequate myocardial reserve)

Malaise (sedation, fatigue, depression) - due to CNS effects
**depression may occur in susceptible population

Withdrawal syndrome

20
Q

Describe B non-selective antagonists withdrawal syndrome

A

Rebound tachycardia upon abrupt withdrawal due to receptor supersensitization.

MI may ensue in susceptible patients.

Problematic for up to 2 weeks following cessation of therapy.

Discontinue by tapering the dose.

21
Q

Propranolol

A

Precursor of all B-antagonists

CNS penetrating (decreases nervousness and tremors for performance anxiety, familial and drug-induced tremors)

MOST COMMON agent for performance anxiety.

Decreases HR and cardiac output; decreases systolic BP, inhibits renin production, and peripheral resistance with chronic use to treat hypertension

Used topically to treat glaucoma by inhibiting aqueous humor production

22
Q

Sotalol

A

Little or no blood/brain barrier permeability (no sedation)

Used predominantly for cardioprotective effects

23
Q

Pindolol

A

Partial agonist (partial antagonist in presence of full agonist)

Similar advantages to acebutolol

24
Q

Timolol

A

Used topically to treat glaucoma

Be careful in asthmatics, systemically absorbed

25
Q

A-1 selective antagonists indications

A

Benign prostatic hyperplasia (urinary retention and outflow difficulties; blocks a-1 mediated constriction of bladder sphincter and prostate capsule; longterm, may block hypertrophy of the prostate capsule)

Hypertension (blocks a-1 mediated vasoconstriction; decrease peripheral resistance)

Congestive heart failure (decreased peripheral resistance leads to less workload and increases cardiac output; patient MUST be able to tolerate an increase in heart rate)

Frostbite and Reynaud’s syndrome (increased blood flow to the extremities)

Off-label for nightmares in PTSD patients (Prazosin crosses BBB)

26
Q

a-1 selective antagonist side effects

A

Tachycardia (reflex tachycardia due to decrease in MABP)

Syncope and orthostatic or postural hypotension (blocks ability to respond to gravitational effects on BP; dose at bedtime and remain supine for 2 hours to avoid syncope; remind patients to be careful after taking a hot shower or hot tub)

Nasal congestion

Sexual side effect in men (inhibition of ejaculation)

27
Q

Prazosin, Terazosin, Alfuzosin

A

a-1 selective

Antihypertensives, decrease peripheral resistance

Treatments for benign prostatic hyperplasia

28
Q

Unique quality of Prazosin

A

Crosses BBB

29
Q

Unique quality of Alfuzosin

A

Less sexual side effects

30
Q

Tamsulosin, Silodosin

A

a-1 selective (selective for a1A over a1B)
**70% of receptors in the prostate are a1A

treatment for benign prostatic hyperplasia

Not very effective anti-hypertensive, but dizziness and fainting are possible side effects

31
Q

Nebivolol

A

B1 antagonist (10 fold more selective than metoprolol)

Metabolites promote endothelial NO-dependent vasorelaxation (metabolites may have partial B2 agonist properties or act at serotonin receptors on endothelium)

Summative effects include a reduction in HR and a reduction in BP

32
Q

Labetolol

A

Mix of 4 stereoisomers, each with unique properties
>RR: B1 antagonist and B2 partial agonist
>SR,SS: a1 antagonist
>RS: no activity

Uptake 1 inhibitor (indirect agonist)

Overall effect:
>block a1 receptors, decrease peripheral resistance
>block B1 receptors, decrease cardiac output, renin secretion
>partial B2 agonist, increased vasodilation in skeletal muscle

Very effective antihypertensive agent

33
Q

Carvedilol

A

Mix of 2 enantiomers
>S: B antagonist
>R and S: a1 antagonist

Good antihypertensive agent

Additional antioxidant and antiproliferative effects on vascular smooth muscle protect against atherosclerotic complications of hypertension

34
Q

Non-selective a1/a2 antagonists

A

Used to manage pheochromocytoma in combination with propranolol

Considered “dirty” drugs - block serotonin receptors, histamine and muscarinic activity which makes for complex pharmacology

35
Q

Non-selective a1/a2 antagonist side effects

A

Much more tachycardia than with a1 selective agents (block of a2 inhibition of baroreflex leads to greater baroreflex response; blockade of a2 inhibition of NE release onto heart leads to greater NE release)

36
Q

Phentolamine

A

Competitive a-antagonist

Quick reversal of numbness following dental anesthetics (vasodilates to disperse the local anesthetic more quickly)

GI side effects

37
Q

Phenoxybenzamine

A

Irreversible a-antagonist, alkylating agent

Long duration antagonist (effective longer than 24 hours)

Reversal requires synthesis of new receptors

38
Q

How does a1 mediate urinary retention?

A

Controls constriction of prostate smooth muscle and constriction of bladder sphincter

Pharmacy School 2015-16 (34 decks)

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