PHARM COPY Flashcards
Baclofen
Muscle relaxant
Can be oral or intrathecally administered
Mechanism:
GABA receptor agonist with central nervous system depressant activity. By activating the GABA B receptors, decreases excitatory neurotransmitter release and lessens γ motor neuron excitability, which improves spasticity
Clinical Use:
Muscle spasticity
Dystonia
Multiple sclerosis
Carbamazepine
Mechanism:
Blocks voltage gated Na+ channels
Disrupt the generation and propagation of action potential (in the axon hillock and axon proper, respectively)
Clinical Use:
Partial Seizure
Tonic-Clonic Seizure
First line for trigeminal neuralgia
Acute manic episodes in patients with bipolar disorder.
First-line treatment for focal seizures
Second-line treatment for generalized tonic-clonic seizures
Side Effects: Nausea Rash Hyponatremia, hyperhydration, and edema (due to SIADH) DRESS syndrome Blood count abnormalities (e.g., agranulocytosis, aplastic anemia) Teratogenicity during the first trimester (cleft lip/palate, spina bifida) Diplopia Ataxia Hepatotoxicity Stevens-Johnson syndrome Induces cytochrome P-450
Amitriptyline
Tricyclic antidepressant (tertiary amine)
Mechanism:
Inhibition of serotonin and norepinephrine reuptake in synaptic cleft → ↑ serotonin and norepinephrine levels
Compared to secondary amines, tertiary amines are more effective at blocking serotonin reuptake and have more anticholinergic effects.
Clinical Use:
Major depressive disorder (third- or fourth-line therapy)
Neuropathic pain (e.g., peripheral neuropathy, diabetic neuropathy, postherpetic neuralgia)
Chronic pain (including fibromyalgia)
Migraine and tension headaches prophylaxis
Adverse Effects:
Sedation
α1-blocking effects including orthostatic hypotension
Atropine-like (anticholinergic) side effects due to blockage of muscarinic cholinergic receptors (more common with tertiary amines) (tachycardia, urinary retention, dry mouth)
3° TCAs (amitriptyline) have more anticholinergic effects than 2° TCAs (nortriptyline).
Cardiotoxicity due to Na+ channel inhibition in the myocardium: changes in cardiac conductivity velocity, arrhythmias, prolonged QT interval (predisposes to torsades de pointes), wide QRS complex
Tremor
Respiratory depression
Hyperpyrexia
Contraindications:
Tertiary amines should be avoided in the elderly because of their side-effect profile; Secondary amines (e.g., nortriptyline) are less likely to cause anticholinergic side effects.
SSRIs
Fluoxetine, fluvoxamine, paroxetine, sertraline, escitalopram, citalopram.
Inhibit 5-HT reuptake in cortico-amygdala pathways
Inhibit the serotonin transporter (SERT) protein, which is normally responsible for transporting serotonin out of the synaptic cleft back into the presynaptic neuron. The inhibition of SERT prevents the normal reuptake of serotonin, resulting in increased availability of serotonin in the synaptic cleft.
It normally takes 4–8 weeks for antidepressants to have an effect.
Used to treat a variety of conditions, including depression, generalized anxiety disorder, and obsessive-compulsive disorder.
Adverse effects include serotonin syndrome, gastrointestinal upset, SIADH, and sexual dysfunction (e.g., anorgasmia, decreased libido).
SNRIs
Venlafaxine, desvenlafaxine, duloxetine, levomilnacipran, milnacipran.
A class of drugs that inhibit serotonin and norepinephrine reuptake from the synaptic cleft.
Usually used to treat depression, anxiety, OCD, ADHD, diabetic neuropathy, and chronic pain.
Venlafaxine is also indicated for social anxiety disorder, panic disorder, PTSD, OCD.
Duloxetine and milnacipran is also indicated for fibromyalgia.
Adverse effects include elevated blood pressure (likely secondary to elevated norepinephrine), stimulant effects (e.g., agitation), nausea and sedation.
Bupropion
Atypical antidepressant
Mechanism:
Inhibit reuptake of dopamine and norepinephrine.
Clinical Use:
Major depressive disorder
Smoking cessation aid
Toxicity:
Stimulant effects (tachycardia, insomnia)
Headache
Weight loss
Reduction of seizure threshold (should be avoided in patients at increased risk for seizure (e.g., history of epilepsy, anorexia/bulimia, alcohol or benzodiazepine withdrawal)).
Does not cause sexual side effects
Dry mouth
Oxybutynin
Mechanism:
Competitive antagonist of muscarinic acetylcholine receptors that functions as an anti-spasmodic agent for the bladder.
Tertiary amine
Lipophilic (good oral bioavailability and CNS penetration)
Clinical Use: Urge incontinence (overactive bladder)
Bethanechol
Direct parasympathomimetics
Mechanism:
Bind to muscarinic/nicotinic AChR → direct AChR agonism
No nicotinic agonism
Resistant to AChE
Clinical Use:
Postoperative and neurogenic ileus and urinary retention (↑ bladder smooth muscle tone)
Adverse Effects: Blurred vision due to miosis when applied to the eyes Bradycardia Hypotension Diarrhea Uncontrolled urination ↑ Sweating ↑ Salivation ↑ Gastric secretion Ocular symptoms Hypoventilation Tremor Restlessness Anxiety Ataxia Muscle paralysis → peripheral neuromuscular respiratory failure Muscle spasms Muscle fasciculations
Capecitabine
Mechanism:
Prodrug of 5-fluorouracil.
Inhibit thymidylate synthase –> decrease dTMP –> decrease DNA synthesis.
S-phase specific
5-FUcan bind tothymidylate synthaseonly in the presence ofmethylene-tetrahydrofolate, which a derivative offolic acidand acofactorofthymidylate synthase.
Administration of folic acid (leucovorin) concurrently with 5-FU or capecitabine augments the effects of these drugs by increasing their binding to thymidylate synthase and simultaneously increases the risk of adverse effects (e.g., myelotoxicity).
Clinical Use:
Advanced breast, colorectal, gastric cancer, basal cell carcinoma (topical), actinic keratosis
Adverse Effects:
Myelosuppression, palmar-plantar erythrodysesthesia (hand-foot syndrome).
5-FU
A cytostatic/cytotoxic antimetabolite in the subgroup of pyrimidine antagonists.
Mechanism:
Inhibits thymidylate synthase to block synthesis of thymidine, thus halting DNA replication and promoting cell death. 5-FUcan bind tothymidylate synthaseonly in the presence ofmethylene-tetrahydrofolate, which a derivative offolic acidand acofactorofthymidylate synthase.
S- phase specific
Also inhibits protein synthesis.
Administration of folic acid concurrently with 5-FU or capecitabine augments the effects of these drugs by increasing their binding to thymidylate synthase and simultaneously increases the risk of adverse effects (e.g., myelotoxicity).
Clinical Use:
Colon cancer, pancreatic cancer, actinic keratosis, basal cell carcinoma (topical).
Adverse Effects:
Myelosuppression, palmar-plantar erythrodysesthesia (hand-foot syndrome).
Methotrexate
Mechanism:
Folic acid antagonist (antimetabolite)
Competitively inhibits dihydrofolate reductase and AICAR transformylase → ↓ pyrimidine and purine nucleotide synthesis → ↓ DNA synthesis
Suppress cell mediated and humoral immunity
Folic acid administration would decrease the risk of methotrexate toxicity (leucovorin rescue).
Clinical Use:
Severe psoriasis, rheumatoid arthritis, ectopic pregnancy, medicaI abortion (with misoprostol)
In neoplastic diseases like gestational choriocarcinoma, chorioadenoma, and hydatidiform mole
Adverse Effects: Myelosuppression Hepatotoxicity Mucositis (eg, mouth ulcers). Gastrointestinal side effects (e.g., nausea and vomiting) Diarrhea Pulmonary fibrosis and toxicity Rash Hair loss Increased risk of lymphoproliferative disorders Teratogenicity Folate deficiency, which may be teratogenic (neural tube defects) without supplementation. Nephrotoxicity.
Mycophenolate mofetil
Mechanism:
Reversible inhibition of inosine monophosphate dehydrogenase (enzyme that is responsible for guanosine synthesis) → blockade of purine synthesis → selective inhibition of lymphocyte proliferation
Suppress cell mediated and humoral immunity
Clinical Use:
Most commonly used to prevent graft rejection in renal transplant recipients.
Lupus nephritis
Used in combination with cyclosporine or tacrolimus as transplant rejection prophylaxis
Toxicity: GI upset, pancytopenia, hypertension, hyperglycemia. Vomiting and diarrhea Comparatively low neurotoxicity and nephrotoxicity Peripheral edema ↑ Blood urea nitrogen Hypercholesterolemia Back pain Cough Associated with invasive CMV infection.
Azathioprine
Mechanism:
Metabolized to 6-mercaptopurine, which requires further metabolism to thio-inosine monophosphate (TIM) by HGPRT; TIM then directly acts as a cytotoxic agent
An antimetabolite (purine analog) that impairs cell replication. 6-MP inhibits the enzyme PRPP amidotransferase, which normally converts PRPP to 5-phosphoribosyl-1-amine.
Suppress cell mediated and humoral immunity
Clinical Use:
Prophylaxis against renal transplant rejection
Autoimmune disease treatment (e.g., rheumatoid arthritis, Crohn disease, glomerulonephritis)
To wean patients off long-term steroid therapy
Steroid-refractory disease
Adverse Effects:
Myelosuppression
GI, liver toxicity.
Malignancies, including cervical cancer, lymphoma, squamous cell carcinoma, melanoma (rare)
Acute pancreatitis
Azathioprine and 6-MP are metabolized by xanthine oxidase; thus both have increase risk of toxicity with allopurinol or febuxostat.
Leflunomide
Mechanism:
Reversibly inhibits dihydroorotate dehydrogenase (which is an enzyme of the pyrimidine ribonucleotide synthesis pathway that converts dihydroorotate to orotic acid) → impaired pyrimidine synthesis → inhibits proliferation of T cells
Clinical Use:
Rheumatoid arthritis
Psoriatic arthritis
Adverse E:ffects:
Gastrointestinal symptoms, hypertension, hepatotoxicity and teratogenicity.
Tizanidine
α2-agonist (sympatholytic)
Use:
Relief of spasticity
Muscle spasticity, multiple sclerosis, ALS, cerebral palsy.
Adverse Effects:
Xerostomia, orthostatic hypotension, sedation, and bradycardia.
Rocuronium
Mechanism:
Intermediate-acting, nondepolarizing skeletal muscle relaxant.
Competitively antagonizes acetylcholine at the motor junction, which prevents depolarization and causes paralysis.
Clinical Use:
Rapid sequence intubation when the use of succinylcholine is contraindicated (second fastest acting muscle relaxant)
Adverse Effects:
Respiratory depression or apnea (especially in long-acting NMJ blockers; respiratory muscle paralysis (diaphragm and intercostal muscles) → impaired ventilation → decreased oxygen saturation (if unchecked) → compensatory rapid, shallow breaths)
Critical illness myopathy (seen in ICU patients who have received nondepolarizing muscle relaxants for a prolonged period of time to facilitate mechanical ventilation. These patients experience muscle weakness which may last for weeks/months after discontinuing the drug)
Does not cause histamine release
Specifically antagonized by sugammadex
Reversal of blockade - neostigmine (must be given with atropine or glycopyrrolate to prevent muscarinic effects such as bradycardia), edrophonium, and other cholinesterase inhibitors.
Ropivacaine
Mechanism:
Local anesthetics have a lipophilic group linked with a hydrophilic group. The metabolism of the intermediate link determines which group an local anesthetics belongs to.
Metabolized in the liver
Safer than the ester agents
Should be used when patients are allergic to esters
A long-acting amide type local anesthetic agent.
Acts by reversibly blocking the sodium channels of nerve fibers, thereby inhibiting the conduction of nerve impulses.
Benzodiazepines
Mechanism:
Indirect GABAA receptor agonists that bind to GABA-A receptors → ↑ affinity of GABA to bind to GABAA receptors → ↑ GABA action → ↑ opening frequency of chloride channels → hyperpolarization of the postsynaptic neuronal membrane → ↓ neuronal excitability
Decreases the duration of N3 phase in REM sleep, thereby reducing the occurrence of sleepwalking and night terrors
Predominantly used to treat stress and anxiety disorders, sleep disorders, and seizures but can also be used for muscle relaxation in minor orthopedic procedures and perioperative sedation.
First-line for status epilepticus
Second-line treatment for eclampsia
Adverse Effects: Anterograde amnesia Addictive potential Drug tolerance Drowsiness, sleepiness, or dizziness Blunted affect ↑ Appetite Hangover effect Paradoxical excitability (this occurs most frequently in elderly patients and includes symptoms such as increased talkativeness, excessive movement, anxiety, irritability, and aggression) Respiratory depression.
Metyrapone
A medication that inhibits cortisol synthesis in the adrenal cortex by inhibiting the enzyme 11β-hydroxylase which converts 11-deoxycortisol to cortisol in the zona fasciculata.
Used as an adjunct treatment in Cushing disease.
Tacrolimus
Mechanism:
Calcineurin inhibitor
Binds FK506 binding protein (FKBP).
Blocks the translocation of nuclear factor of activated T-cells (NFAT), resulting in reduced transcription of IL-2.
Blocks T-cell activation by preventing IL-2 transcription.
Clinical Use:
Indications for systemic administration include prevention of organ rejection after allogeneic transplantation and ulcerative colitis.
Indications for topical administration include immune-mediated disorders, such as atopic dermatitis and cutaneous graft versus host disease.
Toxicity:
Similar to cyclosporine (nephrotoxicity, hypertension, hyperlipidemia, neurotoxicity)
NO gingival hyperplasia or hirsutism
Increase risk of diabetes and neurotoxicity
Highly nephrotoxic, especially in higher doses or in patients with decreased renal function.
Can inducenephrotoxicity, which is caused by glomerularand tubular dysfunction and manifests with a slow decrease of renal function.Biopsytypically shows tubular vacuolization. In addition,glomerularscarring andfocal segmental glomerulosclerosismay also be present.
Sirolimus (rapamycin)
Mechanism:
Binds to the immunophilin FK binding protein (FKBP), forming a complex that inhibits mTOR. This leads to interrumption of IL-2 signal transduction, preventing G1 to S phase progression and lymphocyte proliferation.
Blocks T-cell activation and B-cell differentiation by preventing response to IL-2.
Synergistic with cyclosporine.
Clinical Use:
Immunosuppresant also used in kidney transplant rejection prophylaxis specifically.
Also used in drug-eluting stents to reduce the rate of restenosis.
Adverse Effects: Pancytopenia Insulin resistance Hyperlipidemia No nephrotoxicity Infection (e.g., respiratory or urinary tract) Peripheral edema Hypertension Stomatitis
Fluoxetine
Selective serotonin reuptake inhibitor (SSRI)
Mechanism:
Inhibit 5-HT reuptake in cortico-amygdala pathways
It normally takes 4–8 weeks for antidepressants to have an effect.
Clinical Use:
Depression, generalized anxiety disorder, panic disorder, OCD, bulimia, social anxiety disorder, PTSD, premature ejaculation, premenstrual dysphoric disorder.
Adverse Effects:
Fewer than TCAs.
Seroronin syndrome
GI distress, SIADH, sexual dysfunction (anorgasmia, decrease libido).
Mirtazapine
Mechanism:
Presynaptic α2-antagonist (increase release of NE and 5-HT), potent 5-HT2 and 5-HT3 postsynaptic receptor antagonist and H1 antagonist.
Clinical Use:
Second-line treatment for major depressive disorder.
Toxicity:
Sedation (which may be desirable in depressed patients with insomnia), increase appetite, weight gain (which may be desirable in elderly or anorexic patients), dry mouth, increase serum cholesterol.
Lithium
Mechanism:
Not established; possibly related to inhibition of phosphoinositol cascade. It is believed to alter cation transport in neurons and myocytes, affecting serotonin and norepinephrine levels.
Clinical Use:
Mood stabilizer for bipolar disorder; treats acute manic episodes and prevents relapse.
Adverse Effects:
Tremor, hypothyroidism, polyuria (causes nephrogenic diabetes insipidus), teratogenesis. Causes Ebstein anomaly in newborn if taken by pregnant mother.
Narrow therapeutic window requires close monitoring of serum levels.
Almost exclusively excreted by kidneys; most is reabsorbed at PCT with Na+.
Antagonizes ADH in collecting duct
Thiazides (and other nephrotoxic agents) are implicated in lithium toxicity.
Monitoring guidelines –> BUN, creatinine and thyroid function
Long-term treatment reduce the risk of suicide attempts and deaths.
