Immunosuppressives, Autonomics

Question 1

Cyclosporine/Tacrolimus

Answer 1

• inhibits calcineurin phosphatase activity
• Dec. dephosphorylation of NFAT
• T-cell selective
• renal toxicity
• hyperglycemia with tacrolimus

Question 2

Sirolimus/Everolimus

Answer 2

• same family as tacrolimus/cyclosporine
• blocks T cell response to cytokines & inhibits a kinase involved in cell-cycle progression
• hyperlipidemia as adverse effect
• Everolimus-closely related to sirolimus; shorter half-life, quicker time to achieve steady-state concentration

Question 3

Azathioprine/6-Mercaptopurine

Answer 3

• Dec. purine biosynthesis
• fraudulent nucleotide
• allopurinol interaction

Question 4

Mycophenolate Mofetil

Answer 4

• inhibits inosine monophosphate dehydrogenase & dec. de novo purine biosynthesis
• T and B cell sensitive due to lack of salvage pathway
• related drug: mizoribine

Question 5

Cyclophosphamide

Answer 5

• alkylates DNA

- effects on rapidly proliferating cells

Question 6

Methotrexate

Answer 6

-inhibition of DHFR

Question 7

Antithymocyte Globulin

Answer 7

• Mixture of cytotoxic antibodies to various CD molecules

- Adverse effects: fever, chills, hypotension

Question 8

Muromonab CD3

Answer 8

• Antibody that blocks binding of APC to T-cell: Blocks T-cell function & Decreases T-cell number
• Initial stimulation of cytokine release syndrome

Question 9

Daclizumab, Basiliximab

Answer 9

• Monoclonal antibodies against IL-2 receptor, Blocks IL-2 mediated T-cell activation
• Potential anaphylactic reactions

Question 10

Cholinergic activating agents - - bethanechol, neostigmine

Answer 10

• stimulate bladder emptying
• treatment of urinary retention problems post surgery
• only used with no obstructive problems

Question 11

Anti-cholinergics - - tolterodine, oxybutynin, darifenacin, solifenacin, fesoterodine

Answer 11

• relaxes bladder, slows voiding

- treatment of bladder spasms post surgery or due to inflammation & treatment of urinary incontinence

Question 12

Alpha-1 agonists - - ephedrine, pseudoephedrine

Answer 12

Used for the Tx of urinary incontinence

Question 13

Alpha-1 antagonists - - prazosin, terazosin, doxazosin, tamsulosin

Answer 13

• treatment of symptoms of urinary obstruction (BPH)

- tamsulosin greater potency in inhibiting contraction in prostate smooth muscle vs. vascular smooth muscle

Question 14

Propanolol

Answer 14

• Nonselective Beta blocker-Competitive block of β receptors, local anesthetic effect
• Beta2-involved in relaxing the detrusor muscle, therefore, beto blockade should increase contractility of detrusor.
• Beta1-involved in the release of renin, therefore, beta blockade should dec. GFR and cause dec. urine production.
• Uses-Angina, arrhythmias (treatment and prophylaxis), hypertension, thyrotoxicosis, tremor, stage fright, migraine
• Oral and IV Duration: 4–6 h. Ready entry into CNS
• Tox-Excessive β blockade: bronchospasm (can be fatal in asthmatics), atrioventricular block, heart failure, CNS sedation, lethargy, sleep disturbances

Question 15

Metoprolol, atenolol

Answer 15

• Competitive block of β1 receptors
• Uses-Hypertension, angina, arrhythmias
• Oral, Duration: 6–9 h
• Tox-Like propranolol with somewhat less danger of bronchospasm
• Metoprolol-like atenolol, oral, shown to reduce mortality in heart failure

Question 16

Autonomic Pharmocology: what are the effects of M3, alpha1, beta1, and beta2 receptors?

Answer 16

• Muscarinic M3 receptor: contracts detrusor muscle of bladder, relaxes trigone and sphincter
• beta2-relaxes bladder smooth muscle
• alpha1-contracts bladder base, urethral sphincter, prostate
• beta1-increases renin release