Immunosuppressives, Autonomics Flashcards
Cyclosporine/Tacrolimus
- inhibits calcineurin phosphatase activity
- Dec. dephosphorylation of NFAT
- T-cell selective
- renal toxicity
- hyperglycemia with tacrolimus
Sirolimus/Everolimus
- 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
Azathioprine/6-Mercaptopurine
- Dec. purine biosynthesis
- fraudulent nucleotide
- allopurinol interaction
Mycophenolate Mofetil
- inhibits inosine monophosphate dehydrogenase & dec. de novo purine biosynthesis
- T and B cell sensitive due to lack of salvage pathway
- related drug: mizoribine
Cyclophosphamide
- alkylates DNA
- effects on rapidly proliferating cells
Methotrexate
-inhibition of DHFR
Antithymocyte Globulin
- Mixture of cytotoxic antibodies to various CD molecules
- Adverse effects: fever, chills, hypotension
Muromonab CD3
- Antibody that blocks binding of APC to T-cell: Blocks T-cell function & Decreases T-cell number
- Initial stimulation of cytokine release syndrome
Daclizumab, Basiliximab
- Monoclonal antibodies against IL-2 receptor, Blocks IL-2 mediated T-cell activation
- Potential anaphylactic reactions
Cholinergic activating agents - - bethanechol, neostigmine
- stimulate bladder emptying
- treatment of urinary retention problems post surgery
- only used with no obstructive problems
Anti-cholinergics - - tolterodine, oxybutynin, darifenacin, solifenacin, fesoterodine
- relaxes bladder, slows voiding
- treatment of bladder spasms post surgery or due to inflammation & treatment of urinary incontinence
Alpha-1 agonists - - ephedrine, pseudoephedrine
Used for the Tx of urinary incontinence
Alpha-1 antagonists - - prazosin, terazosin, doxazosin, tamsulosin
- treatment of symptoms of urinary obstruction (BPH)
- tamsulosin greater potency in inhibiting contraction in prostate smooth muscle vs. vascular smooth muscle
Propanolol
- 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
Metoprolol, atenolol
- 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
Autonomic Pharmocology: what are the effects of M3, alpha1, beta1, and beta2 receptors?
- 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
