180 Questions
What is the active moiety of penicillins?
Four-member ring
Which type of antibiotics contain the beta-lactam ring, similar to penicillins?
Cephalosporins
At what concentration are beta-lactam antibiotics bactericidal against most organisms?
Exceeding the minimum inhibitory concentration (MIC)
When are beta-lactam antibiotics most effective?
Against rapidly growing organisms forming cell walls
Where are monobactams and carbapenems commonly used?
In treating serious infections in the hospital
Why are beta-lactamase inhibitors described with penicillins?
Because they are used together as combination products
Why are oral penicillin formulations generally limited to mild to moderate infections?
Higher doses can lead to gastrointestinal distress and diarrhea.
Which statement is true regarding penicillin V and dicloxacillin?
They are recommended for oral administration due to their adequate absorption.
Why is it recommended to use amoxicillin instead of ampicillin for oral administration?
Amoxicillin is more completely absorbed than ampicillin.
Why should penicillin G procaine and penicillin G benzathine depot formulations not be injected near an artery or vein?
IV injection may cause cardiac arrest and death.
What is the primary route of excretion for most penicillins, except nafcillin and oxacillin?
Renal excretion as unchanged drugs in the urine.
How does probenecid affect the pharmacokinetics of penicillins when administered concurrently?
Prolongs the half-life and raises peak plasma concentration.
What is the main mechanism of action of penicillins against bacteria?
Disruption of the bacterial cell wall
Which subclass of penicillins is known for its activity against aerobic, gram-positive organisms like Streptococcus species?
Penicillinase-sensitive penicillins
Why are penicillins considered effective mainly during active cellular multiplication?
They weaken the bacterial cell wall during rapid growth.
Which bacterium is Penicillin G specifically reliable for treating?
Listeria monocytogenes
Which group of organisms has reduced the range of bacterial species that penicillins can effectively treat?
Beta-lactamase-producing bacteria
Why do aminopenicillins have greater activity against gram-negative bacteria compared to natural penicillins?
They have enhanced penetration ability through the outer membrane.
What is a common reason for combining amoxicillin and ampicillin with beta-lactamase inhibitors like clavulanic acid?
To boost the effectiveness against gram-negative bacteria
Which factor contributed to the decreased concern with penicillin-resistant S. pneumoniae strains?
Universal vaccination against Pneumococcus
Why are penicillins considered bactericidal against sensitive organisms?
Because they disrupt the bacterial cell wall synthesis
Why are aminopenicillins considered more effective against gram-negative bacteria than natural penicillins?
They have enhanced penetration through the outer membrane.
How do beta-lactamase inhibitors prevent the destruction of beta-lactam antibiotics?
By acting as a competitive inhibitor of beta-lactamase
What is the result of altering target PBPs on the bacterial cell wall in terms of resistance to penicillins?
Decreased antimicrobial activity
Which organisms are resistant to all penicillins, cephalosporins, and carbapenems, except for ceftaroline?
Methicillin-resistant strains of staphylococci
What is the mechanism by which beta-lactamase inhibitors like clavulanate, sulbactam, and tazobactam work?
Irreversibly inactivating beta-lactamase enzymes by binding to their active site
What type of resistance mechanism is responsible for methicillin resistance in staphylococci and penicillin resistance in pneumococci?
Alteration in target PBPs on the bacterial cell wall
Which group of organisms produce extended-spectrum beta-lactamases (ESBLs) that can hydrolyze both penicillins and cephalosporins?
Enterobacteriaceae like E.coli, Klebsiella species, and Enterobacter species
What role do antipseudomonal penicillins like piperacillin/tazobactam play in antimicrobial therapy?
They have enhanced activity against gram-negative bacilli, particularly Pseudomonas aeruginosa
Which enzymes irreversibly inactivate beta-lactamase enzymes produced by bacteria?
Beta-lactamase inhibitors like sulbactam
What is the main reason for resistance to penicillins due to alteration in the outer membrane of the cell wall?
Decreased permeability to the site of action
What is the unique spectrum of activity of Nafcillin, oxacillin, and dicloxacillin?
Activity against Streptococcus species but not Enterococcus species
How can changes in resting activity occur in organs?
By increasing the activity of either the PNS or the SNS
Which neurotransmitter is associated with the parasympathetic nervous system?
Acetylcholine
Which branch of the autonomic nervous system is targeted by adrenergic agonists?
Sympathetic nervous system (SNS)
What is the primary function of peripherally acting alpha-adrenergic agonists?
Direct receptor binding to organs or tissues in the SNS
Which type of receptor is NOT involved in adrenergic agonists' action?
Delta
Where are intravenous forms of drugs generally NOT used according to the text?
Primary care settings
What is the most common adverse reaction reported in monotherapy trials of the drug discussed?
Somnolence
What percentage of patients experienced adverse reactions that resulted in their being discontinued from monotherapy trials?
12%
What is the most common adverse reaction reported in trials of adjunctive therapy?
Somnolence
What percentage of patients experienced adverse reactions leading to discontinuation from trials of adjunctive therapy?
3%
What is the mechanism of action of the drug's active metabolite, alpha-methyl-norepinephrine?
It stimulates central alpha2 receptors, decreasing sympathetic outflow.
What is the end result from the use of the drug discussed?
Decrease in blood pressure, peripheral resistance, and heart rate with a slight decrease in cardiac output.
What is the primary route of excretion for the drugs in this class?
Urine
What is the main reason for cautious use of these drugs in patients with renal function impairment?
Increased adverse effects due to drug and metabolite accumulation.
What is the primary reason these drugs should be used with caution in populations like older adults?
Increased risk of cognitive impairment.
What is the primary reason guanabenz and clonidine are classified as Pregnancy Category C drugs?
No adequate human studies have been done.
What percentage of the administered dose of tamsulosin is typically eliminated unchanged in the urine?
Less than 10%
What is the main route of elimination for the metabolites of alfuzosin?
Primarily in the feces
Which enzyme is responsible for the metabolism of silodosin?
CYP 3A4
What is the half-life of the active metabolite of silodosin?
Approximately 24 hours
What is the primary consequence of major drug interactions with these alpha-blocker medications?
Increased risk of hypotension
Which of the following is the main reason for using clonidine in combination with a diuretic for hypertension treatment?
To address problems with sodium and water retention
What is the primary reason for the use of the transdermal formulation of clonidine?
To improve adherence to the treatment regimen
Which of the following is the main reason for the reduced sedation with clonidine when the dose is divided?
To minimize the peak serum concentration
What is the primary reason for the use of clonidine in the treatment of ADHD?
To stimulate central alpha2 receptors and improve concentration
Why are smaller doses of clonidine and methyldopa required in patients with renal impairment?
To compensate for the decreased drug clearance
What is the primary advantage of using the low end of the dose range for guanfacine in patients with renal insufficiency?
To minimize the risk of adverse reactions
Why is consultation with a pediatric mental health professional recommended for the safe administration of clonidine for ADHD?
To ensure appropriate dosing and monitoring
Which statement is true regarding the use of clonidine and methyldopa in older adult patients?
They are associated with a higher risk of fluid retention and orthostatic hypotension
What is the primary reason for the increased use of medications other than methyldopa for the treatment of hypertension during pregnancy?
The availability of more options for the management of hypertension
What is the primary purpose of monitoring weight and other indicators of fluid status in patients taking clonidine and methyldopa?
To detect potential adverse effects related to fluid retention
Which receptors are mostly associated with excitation or stimulation?
Alpha1 receptors
What is the primary mechanism of action of centrally acting alpha2 agonists in reducing blood pressure?
Inhibiting cardioacceleration and vasoconstriction centers in the brain
Which class of drugs may be inappropriate for use in geriatric patients, according to the Beers Criteria?
Centrally acting alpha2 agonists
What is the primary reason for gradually tapering the dose when discontinuing centrally acting alpha2 agonists?
To maintain the homeostatic balance that regulates sympathetic nervous system action
Which medication in the class of centrally acting alpha2 agonists is approved for the treatment of attention deficit-hyperactivity disorder (ADHD)?
Extended-release guanfacine (Intuniv)
Which receptors are associated with relaxation or inhibition of norepinephrine release?
Alpha2 receptors
Which receptors are found mostly in the heart, brain, kidney, and lipocytes, and are associated with stimulation of adenylyl cyclase?
Beta1 receptors
Which receptors are located in the smooth muscle of the eyes, arterioles, venules, bronchioles, liver, pancreas, and GI and GU systems?
Beta2 receptors
Which neurotransmitter stimulates all four types of adrenergic receptors (alpha1, alpha2, beta1, and beta2)?
Epinephrine
Which class of drugs is used mainly for their bronchodilating effects?
Beta agonists
What is the proper way to handle a missed dose of methyldopa?
Skipping the missed dose and taking the next dose as scheduled
What is the most common adverse reaction associated with methyldopa?
Drowsiness
How should patients using the transdermal clonidine system apply the patch?
Using a different site from the previous application
What lifestyle changes are recommended for hypertension management in addition to drug therapy?
Smoking cessation
What should patients do if they experience more than a 2 lb weight gain in a day?
Report it to the healthcare provider
What is the recommended approach to prevent rebound hypertension when withdrawing drugs like methyldopa?
Slowly withdraw over 2-3 days
How can dry mouth be minimized for patients on medications like methyldopa?
Chewing sugarless gum or sucking on hard candy
What should patients do if they suspect hepatotoxicity from methyldopa use?
Report it to their healthcare provider
What is indicated by swelling in the feet and ankles in patients on drugs like methyldopa?
Fluid retention
Which of the following is NOT a recommended approach for decreasing adverse reactions to drugs like methyldopa?
Exercising vigorously in hot weather
Which category does methyldopa fall under in an injectable form?
Pregnancy Category C
What is a major adverse reaction common to all drugs in the category of centrally acting alpha2 agonists?
Hypertension
What is a common adverse effect associated with clonidine use?
Insomnia
Why should all patients given these drugs be warned about a particular possibility?
Rebound hypertension
Which adverse reaction has been associated with guanabenz and clonidine but not with methyldopa?
Gynecomastia
What is the clinical use of centrally acting alpha2 agonists like clonidine and methyldopa?
Second-line therapy for mild to moderate hypertension
Which drug interaction can result in toxicity, psychoses, or excessive SNS stimulation when interacting with centrally acting alpha2 agonists?
Tricyclic antidepressants
Which category do all drugs in this class belong to when it comes to pruritic rashes?
They are known to cause pruritic rashes.
What is recommended if the withdrawal of a drug from this class is necessary?
Gradual tapering
What baseline test should be performed prior to initiating therapy with methyldopa?
Coombs' test and hemoglobin/hematocrit levels
What is a distinguishing characteristic between phenoxybenzamine and phentolamine in terms of their blockade of receptors?
Phenoxybenzamine blocks receptors reversibly, while phentolamine blocks them irreversibly.
Why are nonselective alpha antagonists like phentolamine and phenoxybenzamine not recommended for the treatment of hypertension?
They cause reflex tachycardia due to the blockade of presynaptic alpha2 receptors.
Which class of alpha antagonists is specifically used for relieving symptoms associated with benign prostatic hypertrophy (BPH)?
Selective alpha1 antagonists
How do reversible alpha1 antagonists affect peripheral vascular resistance?
They decrease peripheral vascular resistance.
Which adverse effect is minimal in patients taking tamsulosin, alfuzosin, and silodosin compared to other alpha antagonists?
Reflex tachycardia
Why is prazosin not typically used for treating benign prostatic hypertrophy (BPH)?
It requires frequent dosing and poses a risk of cardiovascular side effects.
How do selective alpha1 antagonists like doxazosin lower blood pressure?
By blocking postsynaptic alpha1 receptors.
Which type of patients might experience orthostatic hypotension as a side effect of taking reversible alpha1 antagonists?
Elderly patients
What subtype of alpha1 receptors are approximately 70% localized to the prostatic stroma in the prostate?
Alpha1a
Which alpha1 antagonist demonstrates the highest selectivity for the alpha1a receptor subtype among the listed drugs?
Silodosin
Why is tamsulosin recommended to be administered with food?
To mitigate risk for adverse effects
Which reversible alpha1 antagonist has significant first-pass metabolism?
Doxazosin
Which alpha1 antagonist is eliminated in feces and has plasma elimination which is biphasic?
Doxazosin
What is the primary route of elimination for prazosin?
Feces
Which drug has active metabolites that contribute to its pharmacological effect, especially in the presence of renal failure?
Prazosin
That should be administered with a meal to increase bioavailability and decrease the risk for adverse effects?
Tamsulosin
Which neurotransmitter is associated with the parasympathetic nervous system?
Acetylcholine
How can changes in resting activity occur in organs?
By increasing the activity of either the PNS or the SNS, or by decreasing the activity of the opposing system
Which receptors are located in the smooth muscle of the eyes, arterioles, venules, bronchioles, liver, pancreas, and GI and GU systems?
Alpha1 receptors
Where are intravenous forms of drugs generally NOT used according to the text?
Primary care
Which receptors are NOT involved in adrenergic agonists' action?
Gamma
Which neurotransmitter, along with epinephrine and norepinephrine, is released by the sympathetic nervous system?
Dopamine
What is the primary metabolite of methyldopa that is stored in adrenergic nerve vesicles?
Alpha-methyl-norepinephrine
Which drug in the class of centrally acting alpha2 agonists should be avoided in patients with a history of bradycardia?
Clonidine
Which drug demonstrates significant first-pass metabolism and is metabolized by CYP 3A4 to inactive sulfate metabolites?
Guanfacine
In what way do patients with renal failure experience increased adverse effects related to methyldopa?
Prolonged hypotensive action
Which drug in this class is not completely absorbed in the gut and is absorbed via an aromatic amino acid transport system?
Methyldopa
What is the primary pharmacotherapeutic precaution for the use of methyldopa and clonidine in patients with cerebrovascular disease?
Cautious use in the presence of cerebrovascular disease
Which enzyme is primarily responsible for the metabolism of silodosin?
CYP 3A4
What is the primary route of elimination for the metabolites of alfuzosin?
Feces
What percentage of the administered dose of tamsulosin is eliminated unchanged in the urine?
Less than 10%
What is the half-life of the active metabolite of silodosin?
Approximately 24 hours
Which of the following enzymes is responsible for the metabolism of alfuzosin?
CYP 3A4
What is the primary mechanism by which selective alpha1 antagonists like doxazosin reduce bladder outflow obstruction?
By relaxing the prostate smooth muscle
Which subtype of the alpha1 receptors is the most predominant in the prostate, making up approximately 70% of the alpha1 receptors?
alpha1a
Which alpha1 antagonist demonstrates the highest selectivity for the alpha1a receptor subtype?
Silodosin
Which pharmacokinetic property of tamsulosin is different from the other alpha1 antagonists discussed?
Slower absorption
What is the primary route of elimination for prazosin?
Primarily eliminated via biliary excretion in feces
Which of the following is a common adverse effect associated with the use of centrally acting alpha2 agonists like clonidine and methyldopa?
Sedation
What is the primary reason for the increased use of medications other than methyldopa for the treatment of hypertension during pregnancy?
Methyldopa has a longer elimination half-life and may accumulate in the fetus
What is the primary reason for the use of the transdermal formulation of clonidine?
To provide a more consistent drug delivery
Which class of alpha antagonists is specifically used for relieving symptoms associated with benign prostatic hypertrophy (BPH)?
Reversible alpha1 antagonists
What is the primary consequence of major drug interactions with these alpha-blocker medications?
Increased risk of orthostatic hypotension
Which class of receptors are mostly associated with excitation or stimulation?
Alpha1 receptors
What is the primary mechanism of action of centrally acting alpha2 agonists like clonidine?
Activation of alpha2 receptors in the brain, reducing sympathetic tone
Why is it important to gradually taper the dose when discontinuing centrally acting alpha2 agonists?
To maintain the homeostatic balance regulating sympathetic nervous system action
Which neurotransmitter stimulates all four types of adrenergic receptors (alpha1, alpha2, beta1, and beta2)?
Epinephrine
Which class of drugs is used mainly for their bronchodilating effects?
Beta agonists
What is the primary reason for using the transdermal formulation of clonidine?
To reduce fluctuations in blood levels
Which class of alpha antagonists is specifically used for relieving symptoms associated with benign prostatic hypertrophy (BPH)?
Alpha1-selective antagonists
Which branch of the autonomic nervous system is targeted by adrenergic agonists?
Sympathetic nervous system
What is the primary function of peripherally acting alpha-adrenergic agonists?
Vasoconstriction
Which statement is true regarding the use of clonidine and methyldopa in older adult patients?
They may be inappropriate for use in geriatric patients according to the Beers Criteria
What is a common adverse reaction associated with clonidine and methyldopa at higher doses?
Orthostatic hypotension
Why are clonidine and methyldopa not well suited for monotherapy?
They produce troublesome adverse reactions in almost all patients
In which age group do clonidine and methyldopa have pediatric doses approved for use?
Both children and adolescents
Which drug is specifically available in a transdermal formulation for better adherence to treatment regimens?
Clonidine
What is the primary reason for starting clonidine and methyldopa at the lowest recommended dose?
To minimize sedation
Which drug works better in adults but should be used cautiously in older adult patients?
Clonidine
How is clonidine now available for children (ages 6 to 17) for treating ADHD?
As an oral extended-release tablet
What has resulted in improved concentration and reduced behavioral symptoms in some children with ADHD?
Stimulation of central alpha2 receptors by clonidine
What should be done for safe administration when using clonidine for treating ADHD?
Consultation with a pediatric mental health professional
What is the primary advantage of using a transdermal system for clonidine administration?
Better adherence to treatment regimen
What is the Pregnancy Category of methyldopa in an injectable form?
Category C
Which symptom has been specifically associated with guanabenz among the centrally acting alpha2 agonists?
Gynecomastia
What is the major adverse reaction related to centrally acting alpha2 agonists like clonidine and methyldopa?
Drowsiness
Which drug interaction can result in potentially life-threatening hypertension if abruptly discontinued with clonidine or methyldopa?
Beta-adrenergic blockers
What is a common adverse reaction associated with guanabenz and clonidine but not with methyldopa?
Gynecomastia
Which drug should be withdrawn first to prevent excessive unopposed stimulation of alpha2 receptors that can result in a hypertensive crisis?
Beta-adrenergic blockers
What is the primary reason for the cautious use of centrally acting alpha2 agonists in patients with renal function impairment?
Hypotensive effects
Which symptom is NOT more commonly associated with guanabenz compared to other centrally acting alpha2 agonists?
Vomiting
What major body system are the adverse reactions related to centrally acting alpha2 agonists mainly affecting?
Gastrointestinal system
In what form has clonidine been associated with a rash that is an allergic reaction to the adhesive on the patch?
Transdermal form
What is the most common adverse reaction associated with drugs that control hypertension?
Hypotension
How should patients on transdermal clonidine systems address a loosened patch?
Use tape to secure it
What action should be taken if a patient on methyldopa experiences significant weight gain within a day?
Report it to the healthcare provider
What is the recommended approach to prevent rebound hypertension when withdrawing drugs like methyldopa?
Withdraw slowly over 2-3 days
What is the primary reason for instructing patients not to cut or trim transdermal clonidine patches?
To maintain drug efficacy
What lifestyle changes are encouraged in addition to drug therapy for hypertension management?
Aerobic exercise and stress management
Which of the following is a key difference between phentolamine and phenoxybenzamine?
Phentolamine blocks the receptors reversibly, while phenoxybenzamine blocks them irreversibly.
Why are nonselective alpha antagonists like phentolamine and phenoxybenzamine not used for the treatment of hypertension?
They cause excessive reflex tachycardia.
How do selective alpha1 antagonists like doxazosin lower blood pressure?
By blocking postsynaptic alpha1 receptors in vascular smooth muscle, decreasing peripheral vascular resistance.
Which of the following statements is true regarding the use of selective alpha1 antagonists like tamsulosin, alfuzosin, and silodosin?
They have little effect on blood pressure while relieving symptoms associated with BPH.
What is the primary reason the ALLHAT trial found an increased risk of heart failure with the use of the alpha1 antagonist doxazosin?
Doxazosin is not recommended for initial monotherapy in hypertension.
How do selective alpha1 antagonists like tamsulosin, alfuzosin, and silodosin relieve the symptoms of benign prostatic hyperplasia (BPH)?
By blocking postsynaptic alpha1 receptors in the bladder neck and prostate, decreasing urethral resistance.
What is the primary reason that the nonselective alpha antagonists phentolamine and phenoxybenzamine are used in the treatment of pheochromocytoma?
They prevent hypertensive crisis due to the release of norepinephrine from the tumor.
Which of the following is a potential adverse effect associated with the use of nonselective alpha antagonists like phentolamine and phenoxybenzamine?
Reflex tachycardia.
Study Notes
Penicillin Subclasses
- There are four penicillin subclasses:
- Penicillinase-sensitive or natural penicillins
- Aminopenicillins
- Penicillinase-resistant or antistaphylococcal penicillins
- Antipseudomonal or extended-spectrum penicillins
Pharmacodynamics
- Penicillins inhibit bacterial cell wall formation by binding to penicillin-binding proteins (PBPs)
- PBPs include transpeptidase, carboxypeptidase, and endopeptidase enzymes
- Penicillins are bactericidal against sensitive organisms and are most effective during active cellular multiplication
- Human cells lack a cell wall, so there is virtually no action against host cells
Natural Penicillins
- There are four commercially available natural penicillins:
- Penicillin V (administered orally)
- Procaine penicillin and benzathine penicillin (administered intramuscularly)
- Penicillin G (administered intravenously)
- Active against aerobic, gram-positive organisms, including Streptococcus species, Enterococcus, and some non-penicillinase-producing staphylococci
- Only 5-15% of community-acquired Staphylococcus aureus remains susceptible to natural penicillins
Aminopenicillins
- Have reliable activity against gram-positive organisms, including Streptococcus and Enterococcus species
- Have greater activity against gram-negative bacteria due to enhanced ability to penetrate the outer membrane
- Available aminopenicillins:
- Ampicillin
- Amoxicillin
- Often combined with beta-lactamase inhibitors (clavulanic acid and sulbactam, respectively) for enhanced gram-negative and anaerobic activity
- Have excellent activity against methicillin-susceptible Staphylococcus aureus, Streptococcus and Enterococcus species, and others
Penicillinase-Resistant Penicillins
- Active against Streptococcus species, methicillin-susceptible Staphylococcus aureus, and some coagulase-negative staphylococci
- Not active against Enterococcus species, Listeria, gram-negative bacteria, and most anaerobes
- Chemical modifications of penicillin yields this class of antibiotics that is stable in the presence of penicillinase produced by staphylococci
Antipseudomonal Penicillins
- Comprised of piperacillin combined with a beta-lactamase inhibitor, tazobactam
- Has enhanced activity against gram-negative bacilli, particularly Pseudomonas aeruginosa and others
- Retains activity against ampicillin-sulbactam-susceptible organisms
Resistance to Penicillins
- Due to:
- Inactivation by beta-lactamases
- Alteration in target PBPs on the bacterial cell wall
- Alteration in the outer membrane of the cell wall that decreases permeability to the site of action
- Beta-lactamase production is the most common mechanism
- Beta-lactamase inhibitors (clavulanate, sulbactam, and tazobactam) have minimal antibacterial activity but irreversibly inactivate beta-lactamase enzymes produced by bacteria
Pharmacokinetics
- Absorption and distribution of penicillins depend on the specific structure of the antibiotic, pH of the stomach and intestine, and presence of food
- Penicillin V and dicloxacillin are the only natural and penicillinase-resistant penicillins that have oral absorption adequate to be recommended
- Amoxicillin is more completely absorbed than ampicillin
- Penicillins are bound to plasma proteins to varying degrees and are well-distributed to most tissues and body fluids
- Inflammation enhances penetration of the meninges, joints, and eye fluids, which are otherwise poorly penetrated### Centrally Acting Alpha2 Agonists
- Clonidine, guanfacine, and methyldopa are centrally acting alpha2 agonists used to treat hypertension and ADHD.
- They decrease sympathetic outflow from the CNS, leading to decreased blood pressure and heart rate.
Pregnancy and Lactation
- Clonidine crosses the placenta, but no well-controlled studies have been done in pregnant women.
- Methyldopa and guanfacine are Category B in oral form, but methyldopa is Category C in injectable form.
- Methyldopa appears in breast milk and should be used with caution in nursing women.
- Long-term follow-up of children born to women treated with methyldopa did not find any significant effects.
Adverse Drug Reactions
- Major adverse reactions include:
- Drowsiness
- Dry mouth
- Constipation
- Urinary retention
- Impotence
- Nightmares and insomnia (associated with clonidine)
- Cardiac symptoms (hypotension, chest pain, bradycardia)
- GI symptoms (abdominal pain, vomiting, anorexia, altered taste)
- Gynecomastia (associated with guanabenz and clonidine)
- Life-threatening rebound hypertension (HTN) after sudden withdrawal
- All patients should be warned about the possibility of rebound HTN and should be tapered gradually.
Drug Interactions
- Additive sedative effects with CNS depressants
- Additive hypotensive effects with other drugs that reduce blood pressure
- Tricyclic antidepressant (TCA) agents decrease the antihypertensive effects
- Beta-adrenergic blockers interact with clonidine and methyldopa to produce potentially life-threatening HTN
Clinical Use and Dosing
- Centrally acting alpha2 agonists are used to treat mild to moderate HTN and are second-line drugs.
- Methyldopa is first-line therapy for pregnant patients.
- Clonidine and methyldopa can be used effectively with a diuretic to address sodium and water retention.
- Doses vary with each drug, but adverse reactions occur at higher doses and with older adults.
Unlabeled Uses of Clonidine
- Clonidine has been evaluated for many off-label uses, including:
- Lowering adrenergic stimulation associated with alcohol, heroin, and nicotine withdrawal
- Reducing symptoms of withdrawal
Rational Drug Selection
- Age: Only clonidine and methyldopa have pediatric doses and are approved for use in children.
- Pregnancy: Methyldopa was traditionally the drug of choice for pregnant women, but now other medications are also selected.
- Route of administration: Clonidine is available in a transdermal formulation.
Monitoring
- Clinical monitoring of blood pressure is appropriate for all drugs in this class.
- Baseline blood pressure should be taken before initiating therapy and with each change in dosage.
- Weight and other indicators of fluid status should also be monitored.
Patient Education
- Administration: Take the drug exactly as prescribed, at the same time each day.
- Missed doses: Take as soon as remembered, unless it's almost time for the next dose.
- Withdrawal: Must be withdrawn slowly over 2-3 days to prevent rebound hypertension.
- Interactions: Avoid concurrent use of alcohol or other CNS depressants.
- Adverse reactions: Report any weight gain, swelling, or other symptoms to the healthcare provider.
Adrenergic Antagonists
- Act directly by blocking adrenergic receptors or indirectly by decreasing NE release within SNS terminals.
- Most clinically useful actions result from the blockade of alpha1 receptors in blood vessels, beta1 receptors in the heart, and alpha1 receptors in the bladder neck and prostate gland.
Alpha1 Antagonists
- Nonselective alpha antagonists: Phentolamine and phenoxybenzamine
- Selective alpha1 antagonists: Doxazosin, prazosin, terazosin, tamsulosin, alfuzosin, and silodosin
- Used to treat hypertension and relieve outflow obstruction secondary to benign prostatic hypertrophy (BPH)### Alpha1 Receptors and Selective Blockers
- Alpha1 receptors are found in the prostate, bladder, and other smooth muscles, and are involved in the regulation of bladder outflow obstruction and prostate smooth muscle contraction.
- Three subtypes of alpha1 receptors have been identified: alpha1a, alpha1b, and alpha1d.
- Approximately 70% of alpha1 receptors in the prostate are of the subtype 1a, which are localized to the prostatic stroma.
- Development of a selective alpha1a receptor antagonist would be advantageous in treating BPH, as it would reduce ADRs theoretically mediated by alpha1b and alpha1d receptor subtypes.
Alpha1 Antagonists
- Alpha1 antagonists are used to treat BPH and reduce bladder outflow obstruction without affecting bladder contractility.
- Large numbers of alpha1 receptors are found in the base of the bladder and prostate.
- Doxazosin, terazosin, and alfuzosin are selective for alpha1a, alpha1b, and alpha1d receptors, respectively.
- Silodosin demonstrates a 583-fold selectivity for the alpha1a receptor subtype and 56-fold selectivity for the alpha1d receptor subtype.
Pharmacokinetics and Pharmacodynamics
- Five of the alpha1 antagonists are well absorbed after oral administration, except for silodosin.
- Absorption of alfuzosin is reduced by 50% in a fasting state, and taking tamsulosin in a fasting state increases bioavailability and Cmax.
- All drugs in this class are widely distributed in the body and are highly protein bound.
- Doxazosin accumulates in breast milk, while prazosin is found in small amounts, and it is not known if terazosin is excreted in breast milk.
- Reversible alpha1 antagonists are extensively metabolized by the liver and excreted in both feces and urine.
Adrenergic Agonists
- Adrenergic agonists target the sympathetic nervous system (SNS) by direct receptor binding to organs or tissues, promotion of NE release, or mimicking the action of NE or epinephrine.
- The four main receptor types involved in this process are alpha1, alpha2, beta1, and beta2.
Centrally Acting Alpha2 Agonists
- Centrally acting alpha2 agonists are used to treat hypertension and ADHD.
- They activate alpha2 receptors in the brain, reducing sympathetic tone and increasing parasympathetic tone.
- They decrease peripheral resistance, heart rate, blood pressure, and renal vascular resistance.
- Examples of centrally acting alpha2 agonists include clonidine, guanabenz, and guanfacine.
Clonidine
- Clonidine is used to treat hypertension, ADHD, and symptoms of opioid or alcohol withdrawal.
- It is available in oral and transdermal forms.
- It is used off-label to treat symptoms of nicotine withdrawal and to reduce adrenergic stimulation associated with heroin withdrawal.
- It is used as an adjunct therapy or monotherapy to treat ADHD in children and adults.
Methyldopa
- Methyldopa is used to treat hypertension, especially in pregnant women.
- It is used off-label to treat ADHD and symptoms of opioid or alcohol withdrawal.
- It is used in combination with a diuretic to address sodium and water retention.
Guanabenz and Guanfacine
- Guanabenz and guanfacine are used to treat hypertension and ADHD.
- They are used off-label to treat symptoms of opioid or alcohol withdrawal.
- Guanfacine is available in an extended-release form and is used to treat ADHD in children and adults.
Test your knowledge on antibiotics containing the beta-lactam ring, such as penicillins, cephalosporins, carbapenems, and monobactams. Learn about their mechanism of action, clinical effects, and bactericidal properties against different organisms.
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