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.
Valproic Acid
Mechanism:
Increase Na+ channel inactivation
Increase GABA concentration by inhibiting GABA transaminase
Clinical Use: Partial (focal) Seizure Tonic Clonic Seizure Absence Seizure Also used for myoclonic seizures, bipolar disorder, migraine and cluster headache prophylaxis
Side Effects: Gastrointestinal upset Tremor Alopecia Pancreatitis Weight gain Teratogenicity Especially neural tube defects (contraindicated in women of childbearing age/pregnancy) Hepatotoxicity (rare) (LFT should be regularly performed in people taking valproate) Cytochrome P450 inhibition Rash Sedation Ataxia Thrombocytopenia Agranulocytosis
Clozapine
Atypical Antipsychotic
Mechanism:
Not completely understood.
Most are 5-HT2 and D2 antagonist.
Varied effects on α- and H1-receptors.
Clinical Use:
Treatment resistant schizophrenia
Schizophrenia associated with suicidality
Adverse Effects:
- Prolonged QT interval
- Decreased risk of extrapyramidal symptoms compared to typical antipsychotics
- Throat and mouth ulcers
- Parotitis
- Myocarditis
- Hypersalivation
“-pines”—metabolic syndrome (weight gain, diabetes, hyperlipidemia).
Clozapine—agranulocytosis (monitor WBCs frequently) and seizures (dose related).
Olanzapine, clOzapine –> Obesity (metabolic syndrome)
Must watch bone marrow clozely with clozapine.
Monitoring guidelines –> fasting glucose and lipids, blood pressure and waist circumference
Warfarin
Mechanism:
Inhibits epoxide reductase, which interferes with γ-carboxylation of vitamin K– dependent clotting factors II, VII, IX, and X, and proteins C and S.
Metabolism affected by polymorphisms in the gene for vitamin K epoxide reductase complex (VKORC1).
In laboratory assay, has effect on extrinsic pathway and increase PT.
Long half-life.
Therapeutic efficacy is delayed until preexisting clotting factors in the plasma are consumed. Although INR tends to slowly increase in the first few days of administration due to the short half Iife of factor VII (4-6 hours), full therapeutic effect does not typically occur for 3 days due to the long half-life of factor II.
Clinical Use:
Chronic anticoagulation (eg, venous thromboembolism and pulmonary embolism prophylaxis, and prevention of stroke in atrial fibrillation).
Not used in pregnant women (because warfarin, unlike heparin, crosses placenta).
Follow PT/INR.
Adverse effects:
Bleeding, teratogenic, skin/tissue necrosis, drug-drug interactions.
Initial risk of hypercoagulation: protein C has a shorter half-life than factors II and X. Existing protein C depletes before existing factors II and X deplete, and before warfarin can reduce factors II and X production –> hypercoagulation.
Skin/tissue necrosis within first few days of large doses believed to be due to small vessel microthrombosis.
For reversal of warfarin, give vitamin K. For rapid reversal, give fresh frozen plasma (FFP) or PCC.
Heparin “bridging”: heparin frequently used when starting warfarin. Heparin’s activation of antithrombin enables anticoagulation during initial, transient hypercoagulable state caused by warfarin. Initial heparin therapy reduces risk of recurrent venous thromboembolism and skin/tissue necrosis.
Cytochrome P-450 inhibitors increase warfarin effect.
Metabolized by cytochrome P-450
Acetylsalicylic acid (Aspirin)
Mechanism:
NSAID that irreversibly inhibits cyclooxygenase (both COX-1 and COX-2) by covalent bonding (via acetylation of a serine hydroxyl group near the active site of the enzyme) –> decrease synthesis of TXA2 and prostaglandins.
Increase bleeding time.
No effect on PT, PTT.
Effect lasts until new platelets are produced.
Clinical Use: Low dose (< 300 mg/day): decrease platelet aggregation. Used in the management of cardiovascular events (e.g., acute MI, angina) and for primary/secondary prophylaxis of cardiovascular disease. Intermediate dose (300–2400 mg/day): antipyretic and analgesic. High dose (2400–4000 mg/day): anti-inflammatory.
Adverse Effects: Gastric ulceration, tinnitus (CN VII), allergic reactions (especially in patients with asthma or nasal polyps). Chronic use can lead to acute renal failure, interstitial nephritis, GI bleeding. Risk of Reye syndrome in children treated with aspirin for viral infection. Aspirin overdose (salicylate toxicity) presents with tinnitus, tachypnea, vomiting, and a characteristic mixed respiratory alkalosis and metabolic acidosis on arterial blood gas.
Heparin
Mechanism: Activates antithrombin (an endogenous anticoagulant), which decrease action of IIa (thrombin) and factor Xa. Predominantly on factor IIa Short half-life.
Clinical Use:
Immediate anticoagulation for pulmonary embolism (PE), acute coronary syndrome, MI, deep venous thrombosis (DVT), unstable angina.
Used during pregnancy (does not cross placenta).
Follow PTT.
Treatment and prophylaxis of venous thrombosis.
Adverse effect:
Bleeding, thrombocytopenia (HIT), osteoporosis, drug-drug interactions. For rapid reversal (antidote), use protamine sulfate (positively charged molecule that binds negatively charged heparin).
Low-molecular-weight heparins (eg, enoxaparin, dalteparin) act predominantly on factor Xa. Fondaparinux acts only on factor Xa. Have better bioavailability and 2–4× longer half life than unfractionated heparin; can be administered subcutaneously and without laboratory monitoring. Not easily reversible.
Heparin-induced thrombocytopenia (HIT)—development of IgG antibodies against heparin- bound platelet factor 4 (PF4). Antibody-heparin-PF4 complex activates platelets –> thrombosis and thrombocytopenia. Highest risk with unfractionated heparin
Phenytoin
Mechanism:
Blocks voltage gated Na+ channels
Disrupt the generation and propagation of action potential (in the axon hillock and axon proper, respectively)
Zero-order kinetics
Use:
Partial (focal) Seizure
Tonic-Clonic Seizure
1st line for recurrent Status Epilepticus prophylaxis
First-line treatment for tonic-clonic seizures
Only rarely used for long-term treatment of focal seizures
Treatment of established status epilepticus
Side Effects:
PHENYTOIN: P450 induction, Hirsutism, Enlarged gums, Nystagmus, Yellow-brown skin (hyperpigmentation of skin; melasma), Teratogenicity (fetal hydantoin syndrome), Osteopenia, Inhibited folate absorption, Neuropathy. Rare adverse reactions including Stevens-Johnson syndrome, DRESS syndrome, SLE-like syndrome.
Toxicity leads to diplopia, ataxia, sedation.
Phenobarbital
Barbiturate
Mechanism:
Facilitate GABAA action by increase duration of Cl− channel opening, thus decrease neuron firing (barbidurates increase duration).
Clinical Use: Partial (focal) Seizure Tonic-Clonic Seizure First line in neonates Insomnia Anxiety disorders Alcohol withdrawal Second-line for status epilepticus. Crigler-Najjar syndrome (increase liver enzyme synthesis)
Side Effects:
Sedation, tolerance, dependence, induction of cytochrome P-450, cardiorespiratory depression
Contraindicated in porphyria
Barbiturates
Mechanism:
Bind to GABAA receptors → ↑ duration of the GABA-gated chloride channel opening → ↑ intracellular Cl-flow → hyperpolarization of postsynaptic neurons → ↓ neuronal excitability in the brain
↓ Glutamate signaling
Membrane effects similar to those of inhalational anesthetics
High lipid solubility of barbiturates leads to their rapid onset of action
Accumulation in skeletal and adipose tissue → prolonged duration of action
Clinical Use:
Sedative for anxiety, seizures, insomnia, induction of anesthesia (thiopental).
Dose-dependent effects (from low to higher dose)
Hypnotic
Inducing general anesthesia
↓ Intracranial pressure due to reduced cerebral blood flow
Antiepileptic
Little to no analgesic or muscle relaxant effects
Adverse Effects:
Hypotension (dose-dependent)
Respiratory depression and/or apnea (dose-dependent) (narrower margin of safety than benzodiazepines)
Dependence
Cytochrome P450 induction → variety of possible drug interactions
CNS depression, especially when used with other CNS depressants (e.g., benzodiazepines, alcohol)
Laryngospasm, bronchospasm (due to histamine release)
Myoclonus
Painful injection
IV Anesthetics
Group of drugs used to induce a state of impaired awareness or complete sedation.
Agents include propofol, etomidate, ketamine, and barbiturates (e.g., thiopental, phenobarbital).
Propofol is the standard drug for induction of anesthesia and etomidate is most commonly used in cases of hemodynamic instability.
Ketamine plays a key role in emergency medicine because of its strong dissociative, sympathomimetic, and analgesic effects.
The barbiturate thiopental reduces intracranial pressure, making it useful in patients with high intracranial pressure and/or head trauma.
While the characteristics and side effects of intravenous anesthetics are highly dependent on the substance involved, they all share a strong hypnotic effect.
Solifenacin
Mechanism:
Competitive antagonist of muscarinic acetylcholine receptors that functions as an antispasmodic agent for the bladder.
Tertiary amine
Lipophilic (good oral bioavailability and CNS penetration)
Clinical Use: Urge incontinence (overactive bladder).
Tolteridone
Mechanism:
Competitive antagonist of muscarinic acetylcholine receptors that functions as an antispasmodic agent for the bladder.
Tertiary amine
Lipophilic (good oral bioavailability and CNS penetration)
Clinical Use: Urge incontinence (overactive bladder).
Dicyclomine
Mechanism:
Competitive antagonist of muscarinic acetylcholine receptors that ↓ tone and motility of smooth muscle cells
Tertiary amine
Lipophilic (good oral bioavailability and CNS penetration)
Clinical Use:
Antispasmodic (irritable bowel syndrome)
Mirabegron
Mechanism:
Selective beta-3-adrenergic receptor agonist that acts by relaxing the detrusor muscle of the bladder, delaying the need for micturition.
Clinical Use:
Second-line treatment (after antimuscarinic agents) for urge incontinence (overactive bladder).
Rivastigmine
AChE inhibitor
Clinical Use:
Alzheimer disease 1st-Iine treatment.
Dementia associated with Alzheimer disease and Parkinson disease.
Adverse effects:
Nausea, dizziness, insomnia.
Contraindications: Cardiac conditions (e.g., conduction abnormalities)
Acetylcholinesterase inhibitors (eg, donepezil, rivastigmine) are commonly used in the management of Alzheimer dementia. Alzheimer dementia involves dysfunction of cholinergic pathways in the brain; therefore, inhibition of acetylcholinesterase and a consequent reduction in acetylcholine breakdown may improve cognitive function in some patients. However, this mechanism also produces enhanced parasympathetic tone that can lead to adverse effects. Underlying age-related degeneration of the conduction system is common in the elderly, and the effects of acetylcholinesterase inhibition can precipitate bradycardia and atrioventricular block in such patients. These conduction abnormalities lead to reduced cardiac output that may manifest as presyncope (ie, lightheadedness) or syncope.
Midodrine
Selective α1 agonist
Clinical Use:
Autonomic insufficiency
Postural hypotension
Underactive bladder sphincter (stress incontinence), which can occur in patients with multiple sclerosis due to demyelinating lesions below S1 spinal level.
May exacerbate supine hypertension.
Hemodynamical Changes: Increase BP (vasoconstriction), decrease HR, -/decrease CO
Doxazosin
Peripheral α1-blocker
Clinical Use:
Urinary retention due to overactive sphincter and/or benign prostatic hyperplasia
Hypertension
Adverse Effects:
Peripheral edema
Orthostatic hypotension
Nausea, constipation
Intraoperative floppy iris syndrome (IFIS) (complication of cataract surgery characterized by iris prolapse through the surgical incision and intraoperative pupillary constriction; may lead to retinal detachment and endophthalmitis)
Retrograde ejaculation (muscles of the bladder neck are relaxed and cannot prevent retrograde ejaculation)
Urinary frequency
Tiotropium bromide
Long-acting antimuscarinic agent
Mechanism:
Acts by inhibiting type 3 muscarinic (M3) receptors in bronchial smooth muscle, which results in bronchodilation.
Antimuscarinics cause bronchodilation but actually impair mucociliary clearance and thus cause secretions to remain in the lung (only ipratropium bromide causes bronchodilation without impairing mucociliary clearance)
Quarternary amine
Hydrophilic (poor oral bioavailability and CNS penetration)
Clinical Use:
Long term treatment of COPD
Theophylline
Mechanism:
Methylxanthine derivative
Likely causes bronchodilation by inhibiting phosphodiesterase –> increase cAMP levels due to decrease cAMP hydrolysis.
Provides benefit in asthma by stimulating bronchodilation via inhibition of phosphodiesterase-3 and may also create an anti-inflammatory effect via inhibition of phosphodiesterase-4.
Deceleration of fibrotic changes in the lung
Usage is limited because of narrow therapeutic index (cardiotoxicity, neurotoxicity)
Metabolized by cytochrome P-450.
Blocks actions of adenosine.
Clinical Use:
Used as adjunctive therapy for maintenance of asthma and COPD due to its anti-inflammatory and mild bronchodilatory effects.
No longer recommended for use in acute asthma exacerbations.
Side Effects:
Nausea, vomiting, arrhythmias and seizures
Methyxanthines
Includes aminophylline, theophylline, theobromine, and pentoxifylline.
Class of drugs derived from the purine base xanthine. These drugs nonselectively antagonize adenosine receptors and inhibit phosphodiesterase.
Used to treat asthma but have a narrow therapeutic index.
Colchicine
Mechanism:
Binds and stabilizes tubulin subunits → inhibits microtubule polymerization → inhibits phagocytosis of urate crystals, neutrophil activation, migration, and degranulation
Clinical Use:
Primarily used in the treatment of acute gouty arthritis.
Acute and prophylactic value.
Reduces the formation of LTB4
Used to do karyotypes (halts cells at metaphase)
Aute gout, acute and chronic pseudogout
Adverse Effects: Gastrointestinal symptoms (e.g., diarrhea, nausea, vomiting, abdominal pain) are the most common. Myopathy, rhabdomyolysis (monitor creatine kinase in transplant patients, patients on statins, and patients with GFR < 50 mL/min) Polyneuropathy Cardiac toxicity, arrhythmias Nephrotoxicity Myelosuppression CNS symptoms (e.g., fatigue, headache)
Mexiletine
Class IB Antiarrhythmics
Bind to close (inactivated) Na+ channels
Decrease QT
Decrease effective refractory period (ERP)
Decrease AP duration.
Preferentially affect ischemic or depolarized Purkinje and ventricular tissue.
Very lipophilic and easily cross brain blood barrier and enter the CNS
Clinical Use:
Acute ventricular arrhythmias (especially post- MI), digitalis-induced arrhythmias.
IB is Best post-MI.
Adverse Effect:
CNS stimulation/depression, cardiovascular depression.
Flecainide
Class IC Antiarrhythmics
Very pontent, strong blockade, take a lot to dissociate
Bind to open Na+ channel
Significantly prolongs ERP in AV node and accessory bypass tracts. No effect on ERP in Purkinje and ventricular tissue.
Minimal effect on AP duration.
Clinical Use:
SVTs, including atrial fibrillation. Only as a last resort in refractory VT.
Indicated for the prevention of ventricular arrhythmias, paroxysmal supraventricular tachycardia, and atrial fibrillation/flutter. Can also be used for pharmacological cardioversion of atrial fibrillation or flutter (off-label).
Adverse Effect:
Proarrhythmic, especially post-MI (contraindicated).
IC is Contraindicated in structural and ischemic heart disease.
Basiliximab
Chimeric monoclonal antibodies against alpha chain (CD25 antigen) of the IL-2 receptor of T cells
Clinical Use:
Escalation therapy of multiple sclerosis
Formerly used for the prevention of kidney rejection post transplantation (in combination with cyclosporine and glucocorticoids)
Toxicity: Tremor, shaking Hypertension Edema Allergic reaction Nausea, vomiting
Fibrates
Gemfibrozil, bezafibrate, fenofibrate
Decrease LDL
Increase HDL
Decrease a lot TGs
Upregulate LPL –> increase TG clearance
Activates PPAR-α to induce HDL synthesis, reduce hepatic VLDL production and increase LPL activity
Used as second-line treatment for dyslipidemia
Most effective drug for reducing triglyceride levels.
Adverse effect:
Myopathy (increase risk with statins; blocks p450), cholesterol gallstones (via inhibition of cholesterol 7α-hydroxylase, increase synthesis of bile)
Hydrochlorothiazide (HCTZ)
Mechanism:
Inhibition of Na+-Cl- cotransporters in the early distal convoluted tubule → ↑ excretion of Na+ (saluresis) and Cl- → ↓ diluting capacity of nephron and ↑ excretion of potassium (kaliuresis) and ↓ excretion of calcium → diuresis
Increased reabsorption of Ca2+
Hyperpolarization of smooth muscle cells → vasodilation
Hyperpolarization of pancreatic beta cells → decreased insulin release
Clinical Use:
Hypertension
Chronic edema secondary to congestive heart failure, cirrhosis, and kidney disease
Prevention of calcium kidney stones, idiopathic hypercalciuria
Osteoporosis
Nephrogenic diabetes insipidus (paradoxically, thiazide diuretics are able to reduce the volume of urine in patients with diabetes insipidus. The mechanism of action is not yet fully understood)
Sequential nephron blockade
Adverse Effects:
Hypokalemia and metabolic alkalosis
Hyponatremia
Hypomagnesemia
Hypercalcemia
Hyperglycemia (avoid in patients with diabetes mellitus)
Hyperlipidemia (↑ cholesterol, triglycerides) (avoid in patients with metabolic syndrome or hypercholesterolemia)
Hyperuricemia
Allergic reactions (sulfonamide hypersensitivity)
Contraindications:
Hypersensitivity (including hypersensitivity to any sulfonamide medications)
Anuria
Severe hypokalemia
Interactions:
Glucocorticoids → increased hypokalemia
Carbamazepine → increased hyponatremia
Lithium → increased hyponatremia
ACE inhibitors → hypotension (especially first-dose hypotension)
Propranolol → increased hyperlipidemia and hyperglycemia
NSAIDs → decreased diuretic effect
Increased effects of digitalis (due to hypokalemia), methotrexate, and lithium
Enflurane
An inhalational anesthetic with medium speed of onset and recovery that is moderately potent. The exact mechanism of action is not known.
Used in the induction and maintenance of general anesthesia during surgeries and cesarean sections.
Lowers the seizure threshold and may cause nausea, malignant hyperthermia, and postoperative shivering.
