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NU578 Unit 1 Study Guide
1. Difference between adverse effects, side effects and toxicity Adverse drug reaction - ADR (adverse drug reaction)- any noxious, unintended, and undesired effect that occurs at normal drug doses - Adverse reactions can range in intensity from mildly annoying to life threatening - When drugs are used properly, many ADRs can be avoided, or at least minimized. - 3 possible outcomes of when drugs interact ▪ One drug may intensify effects of other (potentiative interaction) ▪ One drug may reduce the effects of the other (inhibitory interaction) ▪ Combination may produce a new response not seen with either drug alone - Anticipating ADRs can help minimize them - Nurses and patients should know the major ADRs that a drug can produce - In severe illness increased risk of ADR - Adverse events are most common in older adults and the very young. (Patients older than 65 years account for more than 50% of all ADR cases.) Side effect - A nearly unavoidable secondary drug effect produced at therapeutic doses - Ex: drowsiness caused by traditional antihistamines, gastric irritation caused by aspirin - Generally predictable, intensity is dose dependent. - May develop soon after drug use starts or may not appear until a drug has been taken for weeks or months - There is no such thing as a wholly selective drug: all drugs can cause side effects - Can be disturbing if they occur without warning. Ex: rifampin (tuberculosis) imparts a harmless red-orange color to urine, sweat, saliva, and tears. Your patient will appreciate knowing about this in advance. Toxicity - The degree of detrimental physiologic effects caused by excessive drug dosing - Ex: Overdose of morphine coma, overdose of insulin severe hypoglycemia - Know early signs and procedure - Toxicity has come to mean any severe ADR, regardless of the dose that caused it o Anticancer drug in therapeutic doses neutropenia high risk of infection 2. Controlled substances—what are the schedules and how are they set? For instance, is a CS2 drug more or less addicting than a CS3 drug? Controlled substances - CSA- principal federal legislation addressing drug abuse - Schedule I, II, III, IV, or V
o Schedule I: high potential for abuse and no approved medical use in the United States o Schedules II through V all have approved applications, based on abuse potential and potential for causing physical or psychologic dependence o Of the drugs that have medical applications, those in Schedule II have the highest potential for abuse and dependence ▪ Drugs in the remaining schedules have decreasing abuse and dependence liabilities
- CS2 is more addicting than a CS 3. How do drugs cross membranes? What things influence this—what do polarity and charge (ionization) have to do with drugs crossing membranes (or not crossing them)? - drugs must cross membranes to leave the vascular system and reach their sites of action - drugs must cross membranes to undergo metabolism and excretion Three Ways to Cross a Cell Membrane
- Passage through channels or pores
- Very few drugs, channels are extremely small and specific for certain molecules
- Passage with the aid of a transport system
- Transport systems are carriers that can move drugs from one side of the cell membrane to the other
- All transport systems are selective: They will not carry just any drug.
- P glycoprotein or multidrug transporter protein- transmembrane protein that transports a wide variety of drugs out of cells. In the liver, kidney, placenta, intestine, brain capillaries
- Direct penetration of the membrane itself (most common)
- Most drugs are too large to pass through channels and lack transport systems to help them across the membrane
- Like dissolves like- membranes are composed of lipids, drugs that are lipid soluble can directly penetrate membranes
- Some molecules are not lipid soluble and cannot penetrate membranes- this group is made up of polar molecules and ions o Polar molecules- uneven distribution of electrical charge- positive and negative charges within the molecule tend to congregate separately from one another ▪ Ex: gentamycin, water o Equal protons (positive) and electrons (negative) which make them have no net charge o Polar molecules will dissolve in polar solvents (ex: water), not in nonpolar solvents (ex: oil) o Ions: molecules that have a net electrical charge (positive or negative) and except for very small molecules are unable to cross membranes
disease states affecting other organs, and pathways involved in the way the drug distributes through the body, such as first-pass metabolism.
8. What are characteristics of agonists and antagonists? Partial agonists? Chapter 5 Page 49- Agonists are molecules that activate receptors. Exposure to an agonist wound cause the cell to become less responsive or desensitized. Drugs that mimic the body’s own regulatory molecules are agonist. Antagonists produce their effects by preventing receptor activation by endogenous regulatory molecules and drugs. The body does not produce antagonists as a response to a medication. Partial agonists are an agonist that has only moderate intrinsic activity. As a result, the maximal effect that a partial agonist can produce is lower than that of a full agonist. Partial agonist is interesting in that they can act as antagonists as well as agonists. 9. What is the advantage of a drug with a high therapeutic index? Chapter 5 page 53 High therapeutic index (large or wide) indicates that a drug is relatively safe. Conversely, a small (low or narrow) therapeutic index indicates that a drug is relatively unsafe. A patient would have to take a much higher dose of such a drug to reach the toxic threshold than the dose taken to elicit the therapeutic effect. A ratio that compares the blood concentration at which a drug becomes toxic and the concentration at which the drug is effective. The larger the therapeutic index (TI), the safer the drug is. 10. What is P-glycoprotein and how can it influence drug-drug interactions? P.26& 34 (10th^ edition) P-Glycoprotein (PGP) is a transmembrane protein that transports a wide variety of drugs OUT of the cells. This transporter is present in many sites, including the liver, kidney, placenta, intestine, and capillaries of the brain. Like P450 isoenzymes, PGP is subject to induction and inhibition by drugs. In fact, most of the drugs that induce or inhibit P450 have the same effect on PGP. Drugs that induce PGP can have the following effects on other drugs:
- Reduced absorption—by increasing drug export from cells of the intestinal epithelium into the intestinal lumen
- Reduced fetal drug exposure—by increasing drug export from placental cells into the maternal blood
- Reduced brain drug exposure—by increasing drug export from cells of brain capillaries into the blood
- Increased drug elimination—by increasing drug export from liver into the bile and from renal tubular cells into the urine Drugs that inhibit PGP will have opposite effects. 11. How does grapefruit juice consumption interfere with drug metabolism? Grapefruit juice can inhibit the metabolism of certain drugs, thereby raising their blood levels. Grapefruit juice raises drug levels mainly by inhibiting CYP3A4 metabolism. CYP3A4 is an isoenzyme of cytochrome P450 found in the liver and the intestinal wall. Inhibition of the intestinal isoenzyme is much greater than inhibition of the liver isoenzyme. By inhibiting CYP3A4, grapefruit juice decreases the intestinal metabolism of many drugs and thereby increases the amount available for absorption. As a result, blood levels of these drugs rise, causing peak effects to be more intense. Because inhibition of CYP3A4 in the liver is minimal, grapefruit juice does not usually affect metabolism of drugs after they have been absorbed. Importantly, grapefruit juice has little or no effect on drugs administered intravenously. Because, with IV administration, intestinal metabolism is not involved. Inhibition of CYP3A4 is dose dependent; the more grapefruit juice the patient drinks, the greater the inhibition. 12. Explain the interaction of food with drugs and the “empty stomach” rule Decreased Absorption Food frequently decreases the rate of drug absorption and occasionally decreases the extent of absorption. Reducing the rate of absorption merely delays the onset of effects; peak effects are not lowered. In contrast, reducing the extent of absorption reduces the intensity of peak responses. Increased Absorption With some drugs, food increases the extent of absorption. When this occurs, peak effects are heightened. Administration of drugs at the appropriate time with respect to meals is an important part of drug therapy. As discussed, the absorption of some drugs can be significantly decreased by food, and hence these drugs should be administered on an empty stomach (i.e., at least 1 hour before or 2 hours after a meal). 13. Know the terms idiosyncratic, iatrogenic, teratogenic, allergic reaction.
- Idiosyncratic: An uncommon drug response resulting from a genetic predisposition. Ex: people with G6PD deficiency who take sulfonamides or aspirin develop varying degrees of red blood cell hemolysis, which may be life threatening.
- Iatrogenic: A disease that occurs as the result of medical care or treatment such as DRUGS. EX: patients who take certain antipsychotic drugs develop a syndrome with symptoms that closely resemble those of Parkinson Disease.
- Teratogenic effect: a drug induced birth defect- medicines and other chemicals capable of causing birth defects are teratogens
- Allergic Reaction: an immune response that requires prior sensitization of the immune system, after which reexposure to the drug can trigger an allergic response. Can range from mild itching to anaphylaxis. Estimated less than 10% of adverse drug reactions are caused by this. Intensity is determined by the degree of sensitization, not drug dosage so reactions are independent of dosage and can vary between patients.
- Inadequate patient education: develop strong collaborative partnerships with patients and caretakers and consider their perspectives and preferences when making treatment decisions; verify understanding by repeating instructions or demonstrating procedures; provide handouts to reinforce teaching (written at 5 th^ grade or at most 8 th grade level) 16. What is pharmacodynamics tolerance? Metabolic tolerance? Tachyphylaxis?
- Pharmacodynamic Tolerance: type of tolerance associated with long-term administration of drugs like morphine and heroin- result of chronic receptor occupation. Requires increased drug levels to produce effect, raising the minimum effective concentration abnormally high.
- Metabolic Tolerance: tolerance resulting from accelerated drug metabolism. Brought about by the ability of certain drugs to induce synthesis of hepatic drug-metabolizing enzymes (barbiturates), causing rates of drug metabolism to increase. This then causes dosage to be increased to maintain therapeutic levels, but does not affect minimum effective concentration
- Tachyphylaxis: a reduction in drug responsiveness brought on by repeated dosing over a short time, unlike metabolic and pharmacodynamic tolerance which take time to develop. EX: Transdermal nitroglycerin effect is less than 24 hour if patch is left in place around the clock, results from depletion of cofactor for nitro to work. When given on an intermittent schedule, rather than continually, cofactor can replenish between doses, and no loss of effect occurs
- How can genetics affect drug metabolism? Pharmacogenomics is the study of how genetic variations can affect individual responses to drugs. The most common way that genetics can affect drug response is by altering drug metabolism. Variants in genes that code enzymes can increase/decrease metabolism of many drugs. Important for drugs with narrow therapeutic index. Genetic variants causing decreased drug benefits: a. Cytochrome P450-2D6 (CYP2D6) converts tamoxifen to its active form endoxifen (a drug used to prevent breast cancer recurrence). Genetic deficiency in CYP2D6 causes the drug to have little benefit b. CYP2C19 catalyzes clopidogrel (Plavix) into active form. 25% of people have variant CYP2C19*2 which causes a weak antiplatelet response. c. 52% of Americans with European heritage metabolize isoniazid (tuberculosis drug) slowly and 48 metabolize it rapidly because of 2 different forms of N-acetyltransferase- (enzyme that metabolized isoniazid) - treatment failure or toxicity if dose not adjusted. d. 1 in 14 people of European heritage have a form of CYP2D6 that is unable to convert codeine into morphine Genetic variants that cause increase in drug toxicity:
a. CYP2C9 variants increase toxicity (bleeding) from warfarin (variant CYP2D metabolize warfarin too slowly allowing it to accumulate in the body) i. FDA recommends testing for variant, but can also just monitor INR (cheaper) b. Thiopurine methyltransferase (TPMT) activity can be decreased by variant gene codes, causing delayed metabolic deactivation of 2 thiopurine anticancer drugs (thioguanine and mercaptopurine [Purinethol]. Increased levels can fatally damage bone marrow. i. FDA recommends testing for TPMT variant and give reduced dose c. 1 % of US population produces a form of dihydropyrimidine dehydrogenase that poorly metabolizes fluorouracil (treats cancer). Toxic levels can cause death from CNS injury. Genetic variants that alter DRUG TARGETS: Alter STRUCTURE of drug receptors and other target molecules Affected targets on normal cells: a. Beta1-adrenergic receptor (ADRB1) that are hyperresponsive to activation i. Activation – exaggerated increase in hypertension ii. Blockade – exaggerated decrease in blood pressure iii. Usually European ancestry- beta blockers work better for light skinned b. Warfarin works by inhibiting vitamin K epoxide reductase complex 1 (VKORC1) i. Variant VKORC1 can be easily inhibited (anticoagulation is achieved at lower levels of warfarin) Normal doses can cause excessive bleeding. ii. FDA recommends testing for variant VKORC Affected targets on cancer cells and viruses: a. Human epidermal growth factor receptor type 2 (HER2) protein is a receptor for hormones that stimulate tumor growth. It is over expressed in 25% of breast cancer patients and indicates poor prognosis but also better response from trastuzmab (Herceptin) – works only against tumors that overexpress HER i. FDA requires + test for HER2 overexpression b. Cetuximab (Erbitux) for metastatic colorectal cancer works only against tumors that express the epidermal growth factor receptor (EGHR) i. FDA requires evidence of EGFR expression to use drug c. Maraviroc (Selzentry) for HIV infection works by binding with viral surface protein chemokine receptor 5 (CCR5). CCR5 binds to strains of HIV that are CCR5 tropic to enter immune cells. Maraviroc only works on CCR5 tropic strains of HIV. i. FDA requires testing to confirm CCR5 tropic HIV infection Genetic variants that alter IMMUNE RESPONSE to drugs: Increases risk of severe hypersensitivity reactions a. Carbamazepine (Tegretol, Carbatrol) for epilepsy and bipolar disorder
- can cause life threatening skin reactions i. usually Asians that carry gene code for unusual human leukocyte antigen (HLA) called HLA-B*
makes the precise effect of absorption unpredictable. Additionally, gastric acidity is very low 24 hours after birth and doesn’t reach adult values for 2 years making absorption of acid-labile drugs increased. ▪ Intramuscular Administration: in neonates absorption after IM injection is slow and erratic due to low blood flow through muscle during first days of life. By early infancy IM drugs absorption is more rapid than neonates and adults ▪ Transdermal Absorption: drug absorption through the skin is more rapid and complete in infants than older children and adults. The stratum corneum of infants is thinner, and blood flow to the skin is greater, because of enhanced absorption infants are at increased risk of toxicity. o Protein binding of drugs: limited in infants because (1) serum albumin is low and (2) endogenous compounds (fatty acids, bilirubin) compete for binding sites. Thus, drugs that undergo protein binding in adults undergo less in infants resulting in higher levels of free drug in infants intensifying effects. To reduce this dosage should be reduced; protein-binding capacity reaches adult values within 10-12 months. o Exclusion of drugs from the central nervous system by the blood-brain barrier: the blood-brain barrier is not fully developed at birth, so drugs and other chemicals have easy access to the CNS, making infants sensitive to drugs that affect CNS function. All medicines used for CNS effects (morphine, phenobarbital) should be given in reduced dosage. If a drug is capable of producing CNS toxicity its’ dosage should also be reduced o Hepatic drug metabolism: The drug-metabolizing capacity of newborns is low, making them sensitive to drugs that are eliminated by hepatic metabolism. Reduce the dosage when using, the capacity of the liver to metabolize many drugs reaches complete maturation at 1 year o Renal excretion: renal drug excretion is significantly reduced at birth because renal blood flow, glomerular filtration, and active tubular secretion are all low durin infancy. If a drug is primary eliminated from the kidneys, dosage should be reduced or have longer dosing intervals or both. Adult levels of renal function are achieved by year 1
- Children older than 1: by age 1 pharmacokinetic parameters in children are similar to those of adults, so drug sensitivity in children older than 1 year is more like that of adults than that of the very young. There is one important difference: they metabolize drugs faster than adults until the age of 2 and then this gradually declines (sharply during puberty when adult values are reached. This may cause a need for an increase in dosage or reduction in dosing interval for drugs eliminated by hepatic metabolism. 21. What is polypharmacy? Polypharmacy is the concurrent use of multiple medications by a patient; most commonly affects elderly. It can be described as being on five or more medications.
22. Make sure you know the basics of the receptor types and subtypes in the peripheral nervous system (alpha 1 and 2, beta 1 and 2, dopamine, cholingergic). Chapter 13 (Physiology of the Peripheral Nervous System) p 109-117 (10th^ edition book) There are 2 basic categories of receptors located with the PNS: cholinergic and adrenergic. Cholinergic mediate responses to acetylcholine. Adrenergic mediate responses to epinephrine and norepinephrine. Cholinergic receptors have 3 subtypes: nicotinic N, nicotinic M, and muscarinic. Adrenergic receptors have 4 subtypes: alpha 1, alpha 2, beta 1, and beta 2. Dopamine receptors are classified as adrenergic, these receptors do not respond to epinephrine or norepinephrine; they only respond to dopamine, a neurotransmitter found primarily in the CNS. Cholinergic receptor subtypes : Activation of nicotinic N (neuronal) receptors promote ganglionic transmission at all ganglia of the sympathetic and parasympathetic nervous systems. These receptors release epinephrine from the adrenal medulla. Activation of nicotinic M (muscle) receptors cause contraction of skeletal muscle. Activation of muscarinic receptors (located in target organs of parasympathetic nervous system) elicits an appropriate response from the organ involved. Causing increased glandular secretions, contraction of smooth muscle in the bronchi and GI tract, slowing heart rate, contraction of the sphincter muscle of the iris causing miosis, contraction of the ciliary muscle of the eye causing the lens to focus for near vision, dilation of blood vessels, and voiding of the urinary bladder. Muscarinic cholinergic receptors are not associated with the nervous system in any way. It is not clear how they active physiologically; drugs are able to active these receptors and cause vasodilation which can cause blood pressure to fall. Adrenergic receptor subtypes: Alpha 1 receptors are located in the eyes, blood vessels, male sex organs, prostatic capsule, and bladder. Ocular alpha 1 receptors activation leads to mydriasis (dilation of the pupil). Activation of alpha 1 receptors in the blood vessels produces vasoconstriction. Activation of alpha 1 receptors in the sexual apparatus of males causes ejaculation. Activation in the bladder causes contraction. Alpha 2 receptors are located on nerve terminals. These receptors are referred to as presynaptic or prejunctional. The function of these is to regulate transmitter release. Alpha 2 receptors are also present in the CNS. Beta 1 receptors are located in the heart and kidney. Activation of these causes increases in heart rate, force of contraction, and velocity of impulse conduction through the atrioventricular node. Activation in the kidney causes release of renin into the blood; this helps elevate blood pressure. Beta 2 receptors in the lung leads to bronchial dilation. Activation in the uterus causes relaxation of uterine smooth muscle. Activation in the arterioles of the heart, lungs, and skeletal
impairment of CNS function. Multiple doses of the medication may be needed due to the short half-life. This drug is approved only for overactive bladder. (p 125-127 10 th^ edition) Scopolamine is an anticholinergic drug with actions like atropine. Exceptions are: therapeutic doses of scopolamine cause sedation, also, scopolamine suppresses emesis and motion sickness where atropine does not. Principal uses for scopolamine are motion sickness, production of cycloplegia and mydriasis for ophthalmic procedures, and production of preanesthetic sedation and obstetric amnesia. Watch for antimuscarinic poisoning: dry mouth, blurred vision, photophobia, hyperthermia, hallucinations/delirium, respiratory depression, death. (p 128 10th^ edition)
24. WHAT ARE THE DIFFERENCES IN THE CHOLINESTERASE INHIBITORS? Lehne 10th edition CH. 15 PG. 131- Cholinesterase inhibitors are drugs that prevent the degradation of acetylcholine. Cholinesterase inhibitor are divided into two categories: reversible and irreversible. Reversible inhibitors produce effects of moderate duration (BRIEF) and irreversible inhibitors produce effects of long duration (LAST LONG). Reversible inhibitors Neostigmine (Bloxiverz)- serves as the prototype for the group. -has a role in the management of myasthenia gravis. -contains a quaternary nitrogen atom and always carries a positive charge. Because of the positive charge it cannot readily cross membranes, including those of the GI tract, blood- brain barrier, and placenta. Neostigmine is absorbed poorly following oral administration and has minimal effects on the brain and fetus. -decreases breakdown of acetylcholine, which makes acetylcholine more available and can intensify transmission at all junctions where acetylcholine is the transmitter. In sufficient doses, cholinesterase inhibitors can produce skeletal muscle stimulation, ganglionic stimulation, activation of cholinergic receptors, and activation of peripheral muscarinic receptors, and activation of cholinergic receptors in the CNS. Physostigmine-main inhibitor used for myasthenia gravis. Also, drug of choice for treating poisoning by atropine and other drugs that cause muscarinic blockade. -readily crosses membranes unlike neostigmine. Lacking a charge so it is able to cross the blood brain barrier to reverse muscarinic blockade in the CNS. IRREVERSIBLE CHOLINESTERASE INHIBITORS pg. 133- They are highly toxic and are employed primarily as insecticides. The only clinical indication is for glaucoma. - all irreversible inhibitors contain an atom of phosphorous and almost all are highly lipid soluble. As a result, these drugs are readily absorbed from all routes of administration. Once absorbed they have ready access to all tissues and organs, including the CNS. -The irreversible inhibitor binds to the active center of cholinesterase, preventing the enzyme from hydrolyzing acetylcholine. Although these drugs can be spilt from cholinesterase, the splitting is extremely slow, hence, why their binding to cholinesterase can considered irreversible. 25. How and why are neuromuscular blockers used? What must the patient be monitored for? (Lehne pg. 140)
· (Nondepolarizing) Pancuronium · (Depolarizing) Succinylcholine · Administered IV..works by blocking the effects of acetylcholine at nicotinicm receptors at the neuromuscular junction causing muscle relaxation. Commonly used with general anesthesia to aid in intubation and to maintain skeletal muscle relaxation during surgical procedures. · Monitor: perception of pain (patient can be fully alert, but unable to communicate, respiratory arrest (monitor vitals until muscle function fully recovers- keep artificial ventilation available for immediate use), hypotension (due to significant amounts of histamine release), Electrolyte disturbance (low potassium enhances paralysis---high potassium reduces paralysis), Malignant hyperthermia (elevated body temp high as 43degrees C, cardiac dysrthythmias, unstable blood pressure, metabolic acidosis, muscle rigidity)
26. How is anaphylaxis treated (Lehne pg. 152 & 845) · The drug of choice to treat anaphylaxis is Epinephrine (catecholamine) · Epinephrine can be given IV or IM, subQ, intraspinal, inhalation, topical. Injections available solutions 0.1mg/mL and 1mg/mL · Works by activating alpha1 (increase cardiac output-increase blood pressure, promotes vasoconstriction, beta1, and beta2 (counteract bronchoconstriction) · Adverse Effects : hypertensive crisis, dysrhythmias, angina pectoris, necrosis, hyperglycemia · Adrenergic Agonists : Epinephrine, adrenalin · Bete-Delective Adrenergic Agonists -Isoproterenol (Isuprel) Anaphylactic shock is a syndrome characterized by bronchoconstriction, hypotension, and edema of the glottis. Histamine plays a minor role in anaphylaxis, and are of little help as treatment options. · H1 antagonists (classic antihistamines) treat allergic disorders, motion sickness, insomnia…first generation (highly sedating) examples: Diphenhydramine, Promethazine, Hydroxyzine (see table 70.1 pg. 847 Lehne) second generation examples: Certirizine, Loratadine.
- Know your alpha blockers and their adverse effects—what is the difference between selective and nonselective? Make sure you have pages marked (or learn!) some of the properties of the individual agents)
Alpha-Adrenergic Antagonists: Pharmacokinetic Properties Drug Route^ Peak^ Half-Life Metabolisma Excretion Uses NONSELECTIVE AGENTS Phenoxybenzamine PO, IV PO: 4–6 hr PO: unknown IV: 24 hr Urine (primary), bile Pheochromocytoma only Phentolamine IM, IV, local infiltration IM: 30–45 min IV: 1–2 min IM: unknown IV: 20 min Hepatic, urine -diagnosis and treatment of pheochromocytoma -prevention of tissue necrosis after extravasation -reversal of soft tissue anesthesia ALPHA 1 -SELECTIVE AGENTS Alfuzosin PO 8 hr 10 hrb^ Hepatic, feces BPH only Doxazosin PO 2–3 hr 22 hrc^ Hepatic, bile HTN and BPH. Extended release: BPH only Prazosin PO 1–3 hr 2–3 hr Hepatic, bile HTN and BPH Silodosin PO 3–6 hr 13–24 hrc^ Hepatic, feces (primary), urine BPH only
Alpha-Adrenergic Antagonists: Pharmacokinetic Properties Drug Route^ Peak^ Half-Life Metabolisma Excretion Uses Tamsulosin PO 4–5 hr (with food) 6–7 hr (without food) 9–15^ hr c (^) Hepatic, urine(primary) and feces BPH only Terazosin PO 1–2 hr 9–12 hrc^ Hepatic, bile (primary) and urine HTN and BPH Tables of Drugs are on pages 161 & 162
- Beta blockers are huge—make sure you know the difference between selective (B1), nonselective (B1 and B2) and those with alpha 1 blocking activity. How are these used and what are the adverse effects? You will see these again in Unit 3, so you might as well get a good handle on them now! Page 164- Therapeutic applications: -angina pectoris, hypertension, cardiac dysrhythmias, myocardial infarction, reduction of perioperative mortality, heart failure, hyperthyroidism, migraine prophylaxis, stage fright, pheochromocytoma, glaucoma. Adverse effects of Beta1 blockade: -bradycardia, reduced cardiac output, precipitation of heart failure, AV heart block, and rebound cardiac excitation. Adverse effects of Beta2 blockade: -bronchoconstriction. Drugs that block beta 2 receptors contraindicated in pts with asthma
- hypoglycemia from glycogenolysis. Contraindicated in pt with diabetes. Bet1 should be given. -can cause bradycardia, respiratory distress, and hypoglycemia in neonates First generation (nonselective) eg porpanalol- block beta1 and beta2 receptors. Propranolol (pg 166) Second generation (cardioselective) eg metoprolol- selective blockage of beta1 receptors metoprolol (pg168) Third generation ( vasodilating) eg carvedilol- act on blood vessels to cause dilation, but may produce nonselective or cardioselective beta blockade.
Beta-Adrenergic Antagonists: Pharmacokinetics and Pharmacologic Properties Generic Name ISA Lipid Solubility Peak Half-Life (Adults) Metabolism Excretion Labetalol 0 Low IV: 5–15 min PO: 2–4 min 6–8 hr Hepatic Urine (primary), feces Nebivolol 0 High 1.5–4 hr 12–19 hr Hepatic Urine (primary), feces
- Indirect-acting alpha blockers—what are they used for? You will see them here and in the next unit, so learn the uses and the (many) adverse effects and the monitoring that must be done! Centrally acting Alpha2 Agonists- used for HTN eg Clonidine: used for HTN, pain, and ADHD. Adverse effects: drowsiness, xerostomia (dry mouth), rebound hypertension, do not use in pregnancy, substance abuse. Methyldopa and methyldopate: oral hypertensive. Drug of choice for HTN during pregnancy. Adverse effects: + coombs test- blood counts should be obtained. Hemolytic anemia could occur. Hepatotoxicity. Adrenergic neuron blocking agents- Reserpine- only one available. Primary indication is hypertension. Greatest adverse effect is severe depression. Drug Preparation Dosage Administration CENTRALLY ACTING ALPHA 2 AGONISTS Clonidine [Catapres, Catapres- TTS-1, Catapres-TTS-2, Catapres-TTS-3, Kapvay, Dixarit ] Tablets IR: 0.1, 0.2, 0.3 mg Tablets ER: 0.1, 0.2 mg Transdermal patch: 2.5-mg patch delivers 0.1 mg/24 hr 5-mg patch delivers 0.2 mg/24 hr 7.5-mg patch delivers IR: 0.1 mg twice a day; typical maintenance dose 0.1–0.8 mg/day in divided doses ER: 0.1–0.4 mg/day Patches: 1 every 7 days May be taken with or without food. When immediate-release (twice- daily) dosing is used, taking the majority of the daily dose at bedtime can minimize daytime sedation. Patches should be applied to hairless, intact skin on the upper arm or torso.
Drug Preparation Dosage Administration 0.3 mg/24 hr Guanfacine [Tenex, Intuniv XRa] Tablets IR: 1, 2 mg Tablets ER: 1, 2, 3, 4 mg Usual dose:^1 mg/day Take IR tablets at bedtime to minimize daytime sedation. Do not administer with grapefruit juice. Methyldopa Tablets: 250, 500 mg Initial dose: 250 mg 2– times/day Maintenance dose: 0.5– Gm in 2–4 divided doses May be taken without regard to meals. If dosage is increased, scheduling the increase at bedtime can decrease daytime drowsiness. ADRENERGIC NEURON-BLOCKING AGENTS Reserpine Tablets: 0.1, 0.25 mg 0.5 mg/day for 1–2 weeks then increase as needed Maintenance dose: 0.1– 0.25 mg daily May be administered with food if GI upset occurs. aExtended-release guanfacine (Intuniv XR) is approved only for treatment of ADHD. Page 174-
