Clinical Pharmacology Study Guide (Pharmacological Treatment)

Pharmacological Treatment of Acute Decompensated Heart Failure (ADHF) Requires hospitalization & management in a cardiac intensive care unit. In these cases, our goal is to keep the patient alive rather than “prevent compensatory mechanisms” as in HF. Dobutamine (Dobutrex ) IV • β1 Adrenergic agonist (discussed earlier); positive inotropic agent; drug of choice for management of ADHF; administration by continuous IV infusion. Dopamine (Dopastat, Intropin ) IV • β1 α1, dopaminergic Adrenergic agonist (discussed earlier); positive inotropic agent; also increases BP if patient is hypotensive; Administration by continuous IV infusion. Other IV positive inotropes used in ADHF • inamrinone (Inocor®) IV • milrinone (Primacor®) IV Vasodilators used for ADHF • nesiritide (Natrecor®) IV • nitroglycerin IV • nitroprussside (Nipride®) IV Loop diuretics • furosemide (Lasix®) & bumetanide (Bumex®) IV 43 Drugs for Diabetes Mellitus Diabetes: elevated blood glucose caused by a lack of or low levels of insulin, or insulin resistance. Type 1 [insulin dependent mellitus, IDDM, juvenile onset] • Most typically develops in childhood or adolescence and onset is abrupt • ~5% of all cases of diabetes • Immune-mediated destruction of pancreatic β cells • Circulating insulin is absent, plasma glucose is elevated • Body composition-thin and undernourished • Treatment: Insulin replacement is mandatory; along with strict dietary control Type 2 [non-insulin dependent mellitus, NIDDM, adult onset] • More than 90% of diabetics have Type 2 diabetes • Typical onset usually over age 40 and onset is gradual • Associated with middle-aged to older adults, abdominal obesity, sedentary lifestyle, genetics • Pancreatic β cells are functioning to some degree • Insulin resistance – exercise & weight reduction will reduce resistance • Body composition-Frequently obese • Treatment: diet, exercise, & usually self-monitoring of blood glucose. Some patients may require oral hypoglycemic agents and/or supplemental insulin injections. Pre-Diabetes • All overweight adults > 45 years old; or < 45 years old with any of the following risk factors: family history, low HDL, HTN, gestation diabetes, African American, Native Indian, or Hispanic should be screened for Type 2 diabetes. • Fasting BG between 110 – 125 mg/dL. • This diagnosis indicates a high risk of developing diabetes within the next 10 years. • Focus is on prevention. Recommend cardiovascular exercise for 30 mins 5 days/week. Even a 5-7% reduction in weight can reduce the risk of developing diabetes by 60%. Gestational Diabetes • Diabetes that appears during pregnancy only. • Often associated with large birth-weight babies (> 9lb). • Placenta produces hormones that block the actions of insulin. Cortisol levels increase. • Treatment: diet, self-monitoring of blood glucose; sometimes insulin; sometimes metformin Long Term Complications of Diabetes (Accounts for 90% of diabetes related deaths) • Cardiovascular disease –leading cause of death: stroke, MI, hypertension • Retinopathy – damage to the retina of the eye (patients need annual eye exam) • Nephropathy – kidney disease (protein in urine, reduced glomerular filtration) • Neuropathy – nerve damage resulting in pain, loss of sensation, & muscle weakness • Amputations – poor peripheral circulation & infections • Gastroparesis – very slowed GI tract resulting in nausea & constipation • Erectile Dysfunction-caused by blood vessel injury and neuropathy Hypoglycemia (BG < 50mg/dl) When in doubt, treat. • Symptoms include tachycardia, palpitations, sweating, anxiety, shakiness, nervousness, headache, irritability, confusion, weakness, & fatigue. If severe, seizures, coma, & death. • Medical alert bracelet, necklace, or wallet card should be encouraged. • BG  60 = milk, crackers and cheese. BG 20-60 = non-diet soda, honey, juice, candy, or oral glucose tablets or glucose gel. 44 • If the patient is unconscious, either IV dextrose or IM glucagon will be administered. Glucagon is a hormone that promotes glycogen breakdown & increases blood glucose levels. Glucagon injection (IM, SQ, IV) is recommended to be kept on hand. Diagnosis: Fasting plasma glucose test: Casual plasma glucose test: Oral glucose tolerance test: HgbA1c: Goal of Therapy: Keep glucose levels as close to normal as possible to avoid fluctuations. Avoid long-term complications associated with uncontrolled blood sugars. Monitoring Treatment • Self-Monitoring of Blood Glucose (finger sticks): 70 – 130 mg/dl before meals & < 180mg/dL after meals (~ 2 hours after a meal) • Glycosylated Hemoglobin, HbA1c: indicates long-term (120 days) glycemic control; goal for most patients is < 7% • Also reported as Estimated Average Glucose (eAG): HbA1C of 7% equivalent to eAG of 154 mg/dl Advantages of Tight Glucose Control Beneficial Medications in Diabetics • • • Disadvantages of Tight Glucose Control Potentially Problematic Meds in Diabetics Insulin (INsulin) Synthesized in the pancreas. Precursor is called proinsulin. A byproduct is called C-peptide. Secretion is stimulated mainly by glucose. Other stimulants = epinephrine, fatty acids, amino acids, ketone bodies. Promotes conservation of energy & increases cellular uptake of glucose, amino acids, & K+. Therapeutic Use: • All patients with type 1 diabetes • Many patients with type 2 diabetes Complications of Insulin Treatment • • Hypoglycemia Lipohypertrophy: Buildup of fat below the surface of the skin, causing lumps; caused by repeated injections of insulin in the same spot Insulin Dosing • Insulin dosing is extremely individualized and variable. • Insulin dosage must closely match insulin needs; based on patients weight, insulin resistance, activity, carbohydrate intake, stress (i.e. infections, pregnancy) Some examples of different insulin regimens • Twice-Daily Premixed: 35 units 70/30 before breakfast and 25 units before supper • Basal/Bolus: Lispro (Humalog®) TID with meals and 15 units Glargine (Lantus®) at bedtime 45 Insulin Concentrations • Insulin is measured in “units” rather than “mg” or “mcg” • In the United States, 2 concentrations are available: U-100 which has 100 units of insulin per ml and U-500 which has 500 units per ml. U-500 is available in only one product, Humulin R. This insulin is available from the manufacturer only by special request. • U-100 is for routine use; U-500 is used in patients with severe insulin resistance Insulin Storage • Unopened vial stored in refrigerator. Discard after expiration date marked on vial. • Avoid freezing or heat. Avoid prolonged, direct sunlight. • Open vials: Can be stored at room temperature. Check storage guidelines specific to the insulin formulation. This is usually in the product package. (ie. Levamir = 42 days, Lantus =28 days Insulin Administration • SC injections in upper arms, thighs, and abdomen. Rotate injection sites. • Vial + Syringe and needle: Syringe and needles are available in different sizes for individual needs • Pen injectors: Pre-filled device with disposable needle • Portable Insulin Pump: computerized device delivers a basal rate with mealtime boluses by pressing a button. Patients must be highly motivated & be able to comprehend the education required for safe care & maintenance of insulin pumps. • Continuous insulin infusion: for emergency blood glucose reduction in hospital setting Types of Insulin Insulin Type Ultra Short / Fast Acting Lispro Insulin (Humalog) Aspart Insulin (Novolog) Glulisine Insulin (Apidra) Short / Fast Acting Regular Insulin (Humulin R) (Novolin R) Intermediate Acting NPH [Isophane] Insulin (Humulin N) (Novolin N) Long /Slow Acting Insulin Detemir (Levemir) Glargine insulin (Lantus) Premixed Insulin Mixtures NPH / Regular Mixture (Humulin 70/30 & Novolin 70/30) NPH / Regular Mixture (Humulin 50/50) NPL / Aspart (Novolog Mix 70/30) NPL / Lispro (Humalog Mix 75/25) Onset Duration Misc Information 10 - 30 min 3 – 5 hrs Clear. Rx only, can be taken with meals or right after eating, IV, pumps, sq 30 – 60 min 6 – 10 hrs Clear. Can be given IV, pumps, sq 60–120 min 16-24 hrs Cloudy. Mix or swirl. Don’t shake. ?? 12h: 0.2 u/kg 20h: 0.4 u/kg 70 min > 24 hrs 30 – 60 min 16-24 hrs 30 – 60 min 16-24 hrs 15 – 20 min 16-24 hrs 15 – 20 min 16-24 hrs Clear. Duration is dose dependent; Peak = 6-8 hours; Cannot mix with other insulins. Clear. Flat plasma insulin levels; Little peak effect; Cannot mix with other insulins. Cloudy. 70% NPH / 30% Reg “A little for now, a lot for later.” Cloudy. 50% NPH / 50% Reg Cloudy. 70% NPL / 30% Aspart NPL insulin clinically identical to NPH. NPH is incompatible with Aspart. Cloudy. 75% NPL / 25% Lispro NPL insulin clinically identical to NPH. NPH is incompatible with lispro. 46 Oral Hypoglycemics Biguanides *Metformin (Glucophage) (metFORmin) Therapeutic Uses • Type 2 diabetes(considered drug of choice for initial therapy); prevention of Type 2 diabetes in high risk patients; gestational diabetes; polycystic ovary syndrome Mechanism of Action • Primary: Decreases glucose production in the liver (gluconeogenesis) Adverse Effects • Decreased appetite, nausea, diarrhea, weight loss (average 7 to 8 lbs – may be an added benefit of this drug), decreased absorption of vitamin B12 & folic acid. Rarely lactic acidosis. Administration • Taken orally with a meal to avoid GI related adverse effects Contraindications/Precautions • Renal. Manufacturer guidelines state that this agent is contraindicated in patients with poor renal function. Avoid in patients > 85 years old due to impaired renal function. Avoid in clinical situations predisposing to renal dysfunction: certain surgeries or 48 hours after administration of iodinated radiocontrast dye. Sulfonylureas *glipizide (Glucotrol & Glucotrol XL) glimepiride (Amaryl) glyburide (Diaβeta, Glynase, Micronase) (GLIPizide) (GLYEmepyeride) (GLYEbyooride) Therapeutic Uses • Type 2 diabetes Mechanism of Action • Primary: Stimulate the pancreatic β-cells to release insulin. • Secondary: Enhances the cellular sensitivity to the insulin (makes the insulin work better) Adverse Effects • Can cause hypoglycemia; weight gain Administration • Taken orally typically with a meal Meglitinides (Glinides) *repaglinide (Prandin) (repaGLInide) nateglinide (Starlix) (nateGLYEnide) Therapeutic Uses • Type 2 diabetes Mechanism of Action • Primary: Stimulate the pancreatic β-cells to release insulin. • Similar chemical structure and mechanism of action to sulfonylureas. Considered alternatives to sulfonylureas. Do not give WITH sulfonylureas – they are too similar. Adverse Effects • Can cause hypoglycemia; weight gain. Administration • Taken orally 15 – 30 minutes before or with a meal 47 Thiazolidinediones (Glitazones) *pioglitazone (Actos) rosiglitazone (Avandia) (THIGHahZOlideenDYEown) (pyeohGLItazone) (rohsiGLItazone) Therapeutic Uses • Type 2 diabetes Mechanism of Action • Primary: Decreases insulin resistance: “Insulin sensitizers” • Activates the peroxisome proliferators-activated receptor gamma (PPAR-gamma) receptors. Basically it turns on insulin-responsive genes that help regulate carbohydrate and lipid metabolism; increasing insulin sensitivity. This takes several weeks for benefits to be seen. Adverse Effects • Can cause fluid retention, edema (precaution against use in mild CHF & contraindicated in severe CHF). May cause resumption of ovulation in pts taking oral contraceptives. Raises HDL and lowers triglycerides, which are good, but may also raise LDL. Probably NOT hepatotoxic but liver function tests may still be monitored. Administration • Taken orally with food to enhance bioavailability. α-Glucosidase Inhibitors *acarbose (Precose) miglitol (Glyset) (AYcarbose) (MIGlitol) Therapeutic Uses: Type 2 diabetes. Mechanism of Action • Inhibit the enzyme α-glucosidase in the small intestine. This enzyme normally turns dietary starch & sucrose into an absorbable form. Cause delayed glucose absorption. Decreased post-prandial blood glucose levels. Adverse Effects • Oral absorption is minimal, so adverse effects are mostly GI related; fermentation (50%) leads to flatulence, cramps, abdominal distention, borborygmus (rumbling bowel sounds), & diarrhea. Liver dysfunction may be a concern with long-term, high dose therapy. Administration • Taken orally with the first bite of a meal (TID with meals). • IMPORTANT: If hypoglycemia occurs, only glucose increases blood sugar levels. Cane sugar is sucrose & will not be effective…Use the oral glucose tablets or gel to reverse hypoglycemia. Gliptins (DPP-4 inhbitors) *Sitagliptin (Januvia) Saxagliptin (Onglyza®) • • • • (SI (SAX·a·glip·tin) Linagliptin (Tradjenta®) Alogliptin (Nesina®) (LINA·a·glip·tin) (AL o glip tin Therapeutic Uses: Type 2 diabetes Mechanism of Action: Inhibits peptidyl peptidase, blocking breakdown of incretin hormones such as glucagon-like peptide-1 (GLP-1). Normally GLP-1 stimulates insulin release from the pancreas and inhibits the liver’s production of glucose, therefore by inhibiting the breakdown of GLP-1 increases GLP-1 levels resulting in increased insulin release and reduced production of glucose by the liver. Adverse Effects: mild stomach discomfort, diarrhea Administration: Taken orally once daily 48 Sodium-Glucose Co-Transporter 2 (SGLT-2) Inhibitors *Canagliflozin (Invokana®) Dapagliflozin (Farxiga®) Therapeutic Uses: Type 2 Diabetes Mechanism of Action: Glucose is filtered in the kidneys and then reabsorbed back into the blood. Sodium-glucose transporter 2 (SGLT-2) is primarily the transporter (or pump) that is responsible for reabsorbing the glucose back in to the blood. By blocking SGLT-2 less glucose is reabsorbed and is excreted in the urine thereby reducing blood glucose. Adverse Effects: genital yeast infections, urinary tract infections, increased urination Administration: Taken orally once daily Amylin mimetics pramlintide (Symlin) (PRAMlintide) inj Therapeutic Uses • Type 1 or Type 2 diabetes Mechanism of Action • Synthetic version of a human neuroendocrine hormone called amylin. Amylin is normally produced in the pancreas to assist in postprandial glucose control (after a meal) by slowing stomach emptying, inhibiting the release of glucagon after meals, and by reducing appetite. Adverse Effects • Hypoglycemia, nausea (20 – 40%), loss of appetite (9 – 17%). Insulin doses should be reduced by 50% when starting pramlintide to avoid hypoglycemia. Injection site reactions. Administration • Taken subcutaneously (SQ). Incretin mimetics *Exenatide (Byetta) Liraglutide (Victosa®) Albiglutide (Tanzeum®) (exENatide) inj (LIR·a·GLOO·tide) inj (al bi GLOO tide) inj Therapeutic Uses • Type 2 diabetes Mechanism of Action • Synthetic version of glucagon-like peptide-1 (GLP-1); normally, GLP-1 is released from cells in the GI tract after a meal. GLP-1 increases insulin release and reduces production of glucose by the liver as well as slows gastric emptying and suppresses appetite. Adverse Effects Hypoglycemia (14 – 35%), nausea (45%), diarrhea (13%), feeling jittery (9%). Reduce dose of oral medications when starting to avoid hypoglycemia. Administration • Exenatide-Administered SQ twice daily before the morning and evening meals. • Liraglutide-Administered SQ once daily before a meal • Albiglutide—Administered SQ once weekly 49 Antidepressants Overview of Clinical Depression • Depression is extremely common. An estimated that 30% of the population will develop depression serious enough to warrant treatment at some point in their life. At any given time, about 5% of the population is clinically depressed. Incidence in women is twice that in men. Only about 1/3 of depressed people seek help. • There are both hereditary and situational factors involved in the risk of developing depression. Etiology & Treatment of Clinical Depression • Etiology of depression is still unknown and thought to be very complex. Current theories all involve the CNS monoamines norepinephrine, dopamine, and/or serotonin. • 40% of patients with depression that are treated with an antidepressant will achieve remission. Another 20-30% achieve a 50% reduction in symptom severity. • All antidepressants have nearly equal efficacy. • Drug selection is initially based on the drugs’ side effects, cost and the patient’s past medical history, past response to antidepressants, family members’ responses to antidepressants, and, ultimately, trial and error. Some patients, for unknown reasons, respond better to different drugs. • First-line antidepressants include: SSRIs, SNRIs, bupropion, and mirtazapine • The onset of action is slow (4-5 weeks for full effects). • IMPORTANT: the term “CNS depressant” does NOT mean that the drug causes clinical depression. “CNS depressant” means that the drug causes sedation, drowsiness, slowed thought processes, etc. Symptoms Common to Depression Clinical depression is diagnosed when at least 5 of these symptoms are present daily for > 2 weeks • Mood of sadness, despair, emptiness • Loss of interest or pleasure in most/all activities • Significant weight loss or gain without dieting • Insomnia or hypersomnia • Psychomotor agitation or retardation • Fatigue or loss of energy • Feelings of worthlessness or inappropriate guilt • Diminished ability to concentrate/indecisiveness • Suicidal ideas: Clinical depression should be taken seriously. There is a risk of death associated with depression just as with many other disease states. For example, patients with CHF are often fatigued & tired. We do not tell these patients to “snap out of it.” We attempt to treat the underlying disease. Depression should be no exception. Key Points to tell any patient on an antidepressant • • • • Symptoms resolve slowly. Initial response generally takes 1 – 3 weeks. Maximal benefits may not be seen for up to 5 weeks. Therapeutic trial should not be considered a failure until drug has been taken for at least a month. Patients usually see improved energy, sleep patterns, and control of emotions first. Antidepressants are not addictive. Antidepressants only affect depressed people. They do not provide mood elevation in non-depressed people. Therefore, drug abuse is not a problem and should not concern the patient. It is usually recommended to continue therapy for at least 4 – 9 months after symptoms subside, before trying to stop the medication. Some patients will require life-long therapy; this varies from person to person. 50 Selective Serotonin Reuptake Inhibitors (SSRIs) *fluoxetine (Prozac, Sarafem) (flooOKSeteen) *citalopram (Celexa) (syeTALohpram) *sertraline (Zoloft) (SERtraleen) *paroxetine (Paxil) (paROKSeteen) *escitalopram (Lexapro)  Mechanism of Action • SSRIs inhibit reuptake of serotonin into CNS nerve terminals. Thus SSRIs initially increase concentrations of serotonin in the CNS. • SSRIs are Selective: they have little effect on norepinephrine and low affinity for histaminic, cholinergic, or α-receptors. Other Therapeutic Uses of SSRIs • Generalized anxiety disorder; social phobia; panic disorder, PTSD, obsessive-compulsive disorder, (OCD); premenstrual dysphoric disorder (PMDD); bulimia; Adverse Effects • Nausea (~20%), headache (~20%), insomnia & nervousness (~15%), akathisia • Generally dosed once daily in the AM, to avoid insomnia. • Sexual dysfunction is common in both genders (nearly 70% of patients). May be erectile dysfunction, retrograde ejaculation, or dysorgasmia. If you don’t ask, the patient may not tell you!! • Less likely than TCAs to cause orthostatic hypotension, sedation, & anticholinergic side effects. • Serotonin Syndrome: Symptoms of serotonin syndrome can occur without warning & include: hypotension or hypertension, agitation, muscle tightness & twitching, hyperthermia, shivering, tachycardia & other arrhythmias, seizures, coma, and death. • Discontinuation Syndrome: Abrupt discontinuation can cause dizziness, headache, nausea, sensory disturbances, tremor, anxiety, dysphoria and flu-like symptoms. Taper over several weeks to avoid withdrawal reaction. • Use late in pregnancy can cause neonatal issues Drug Interactions • Using MAO-Is or TCAs with an SSRI increases risk of serotonin syndrome. • Fluoxetine is highly protein bound….. Serotonin/Norepinephrine Reuptake Inhibitors (S/NRIs) *duloxetine (Cymbalta ) *venlafaxine (Effexor  desvenlafaxine (Pristiq) levomilnacipran (Fetzima®) (dooLOXateen) (VENlafakseen)  (lee voe mil NA sip ran) Mechanism of Action • SNRI’s inhibit the reuptake of serotonin and norepinephrine into CNS nerve terminals causing an increase in serotonin and norepinephrine concentrations in the CNS. Other Therapeutic uses of S/NRI’s • Generalized anxiety disorder, social anxiety disorder, and panic disorder • Duloxetine also FDA approved for fibromyalgia, diabetic peripheral neuropathic pain, chronic musculoskeletal pain Adverse Effects: insomnia, nervousness, dry mouth, anorexia, mild CV effects, sexual dysfunction, sweating, HTN Drug Interactions: • Using MOA-I’s or TCA’s with an SNRI increases the risk of serotonin syndrome • Contraindicated with MOAI’s 51 Miscellaneous Antidepressants *Bupropion (Wellbutrin , Zyban  ) (byoo PROE pee on) • Inhibits reuptake of norepinephrine & dopamine. FDA approved for smoking cessation • ADRs: similar to SNRIs, plus weight loss, HTN, & seizure • Does not cause problems with sedation or sexual dysfunction *Mirtazepine (Remeron  ) (mir TAZ a peen) • Mechanism of action unclear: presynaptic α2-adrenergic blocker, increases CNS norepinephrine & serotonin. Also has serotonin & histamine blocking properties. Also, mild muscarinic and α1 blocking properties • ADRs: similar to SSRIs & SNRIs, weight gain, sedation, HTN, paresthesias (fairly common) Trazodone (Desyrel ) (oral) (TRAZ oh done) • Combined serotonin reuptake inhibitor and serotonin antagonist • ADRs: sedation, EPSE, less CV effects than other antidepressants Tricyclic Antidepressants (TCAs) *amitriptyline (Elavil) clomipramine (Anafranil) doxepin (Sinequan) desipramine (Norpramine) (a imipramine (Tofranil)  nortriptyline (Pamelor)  protriptyline (Vivactil)  trimipramine (Surmontil)     Mechanism of Action • TCAs inhibit reuptake of norepinephrine and serotonin into CNS nerve terminals. • Thus, TCAs initially increase concentrations of these neurotransmitters in the CNS. • These drugs are not selective for the CNS receptors only; therefore, they can cause side effects throughout the body. This lack of selectivity = increased adverse effects. Other Therapeutic Uses of TCAs • Generalized anxiety disorder; phobic disorders; obsessive-compulsive disorder (OCD), bipolar disorder • Neuropathic pain: diabetic peripheral neuropathy pain; post-herpetic neuralgia (shingles pain); migraine prophylaxis • Attention deficit hyperactivity disorder (ADHD) Adverse Effects • TCAs have a narrow therapeutic window — overdoses can be fatal. • Weight gain, sexual dysfunction • Anticholinergic side effects: Blockade of acetylcholine at the muscarinic receptors can cause dry mouth, blurred vision, urinary retention, constipation, tachycardia, and confusion. • Cardiovascular: increased adrenergic activity (they increase norepinephrine levels) can result in cardiac overstimulation, which can be life threatening in an overdose situation. • Antihistamine side effects: Blockade of histamine at the H1-receptors in the CNS can cause sedation & drowsiness (Some tolerance may develop to this side effect.) • α1-blockade: orthostatic hypotension  increased risk of falls in the elderly. • Seizures: Lowers seizure threshold. • To minimize side effects, initiate therapy with a low bedtime dose & gradually increase every 3 – 4 days until the patient demonstrates significant improvement OR the patient is receiving the usual therapeutic dose, OR side effects become excessive. 52 Drug Interactions • MAO-Is: Severe hypertension from excessive adrenergic stimulation • Adrenergic agonists (sympathomimetics) such as epinephrine & oral decongestants (pseudoephedrine, phenylepherine) will have additive cardiovascular side effects • Anticholinergics such as antihistamines, drugs to treat overactive bladder, etc will have additive anticholinergic side effects. • CNS depressants will have additive sedation effects. This includes alcohol, sedating antihistamines, opioid pain medications, benzodiazepines, etc. Monoamine Oxidase Inhibitors (MAO-Inhibitors) phenelzine (Nardil) (FENelzeen) isocarboxazid (Marplan) tranylcypromine (Parnate) (tranilSIProemeen) selegiline (Emsam) patch Mechanism of Action • Inhibit both of the enzymes, monoamine-oxidase-A (MAO-A) & monoamine-oxidase-B (MAO-B). • The monoamine-oxidase enzymes are present in the liver, intestines, and in some nerve terminals. • MAO-A metabolizes (inactivates) the monoamines like norepinephrine, serotonin, & tyramine. • MAO-B metabolizes (inactivates) dopamine. • Thus, blocking this enzyme leads to elevated concentrations of these neurotransmitters in the CNS. • Generally not the drugs of choice to treat depression because of their adverse effects. Adverse Effects • Orthostatic hypotension, dizziness, sexual dysfunction, sleep disturbance. Food Interactions with MOA-Is • Hypertensive Crisis from Tyramine containing foods: cheese, liver, aged or smoked meats, soy sauce, figs, bananas, some imported wines and beers. WHY? Tyramine promotes the release of norepinephrine. Tyramine is normally broken down in the intestines & during 1st pass metabolism by MAO-A. (See complete list of foods in text.) • Hypertensive Crisis from foods containing vasopressors: chocolate, ginseng, caffeine. Drug Interactions • Hypertensive Crisis can occur with amphetamines, cocaine, TCAs & SSRIs. • Serotonin Syndrome can occur with SSRIs & perhaps TCAs. Symptoms of serotonin syndrome can occur without warning & include: hypotension or hypertension, agitation, muscle tightness & twitching, hyperthermia, shivering, tachycardia & other arrhythmias, seizures, coma, and death. To avoid this interaction, wait at least 2 – 3 weeks (5 half-lives) after discontinuing an SSRI or TCA before starting therapy with a MAO-Inhibitor. • Hyperpyrexia (excessive body temperature) can occur with meperidine (Demerol) Electroconvulsive Therapy (ECT) • • • • • Effective Rapid onset Usually requires three treatments for 2 to 4 weeks Adjunct medications make procedure much less traumatic Major adverse effect is short-term memory loss 53