Pharmacotherapy Exam 1 September 27: Lecture 3 - Sympathomimetic Drugs, ETC

Which drugs select α₁ receptors and indicate whether agonistically or antagonistically.

• Epinephrine

• Norepinephrine

• Phenylephrine

• Oxymetazoline

• Clonidine

• Isoproterenol

• Dobutamine

• Albuterol

• Salmetertol

• Agonistically

• Antagonistically

Ephedrine and Pseudo-Ephedrine are called mixed acting drugs for what reason?

Clonidine uniquely stimulates α₂ receptors, yet affects the heart rate which is normally affected by beta receptors.  Why can this drug affect the heart rate by affecting alpha instead of beta receptors?

Some drugs with names ending in -stigmine are acetylcholinesterase inhibitors.  Two diseases we discussed could be treated in their beginning stages with these drugs.  One was Alzheimer's.  the other, in which nicotinic receptors get destroyed by autoimmune process,  is:

Random questions not having time to make them into quiz questions: What is pharmokinetics? how the body handles drug absoption, distribution metabolism and excretion. What is pharmacodynamics? a study of the vast majority of drugs exert their effects by interacting with target cells What is a receptor? Most drugs produce their efects by interacting w/ specific proteins that are usually located on a cells outer membrane.  Named according to the type of drug that it interacts with. What is the ED-50? Effective dose 50%: a dose that produces one half the maximal response What is the LD-50? The dose that kills 50% of the animals given the drug. What are adverse effects? effects of the drug that are not intentional or expected What is the therapeutic index? a rough indicator of the drugs margin of saftey, where the ratio of the LD50 and the ED50 are compared (margin of safety) Why is it important to understand the relationship between dose and response from a drug?   What is a dose response curve? a curve that shows the relationship between the drug response and the amount (dose) of a drug given What are the 3 routes that a drug can take into the cell? passage thru the membrane (most common), passage thru channels or pores, or passage with the aid of the transport system What is the combination of excretion and metabolism called? elimination Why arent more drugs made to travel thru the pores of a cell? b/c the pores are very small and made for only certain substances What does it take to make a drug able to penetrate the cell membrane? they have to be lipid soluble (lipophilic) What are the 2 routes of administration? enteral (via the GI tract), or parenteral which means by either IV, IM or Sub Q What is chemical equivelence? drug preparations are considered chemically equivelant if the have the EXACT same chemical compound What is bioavailability? if the drugs are absorbed at the same rate and in the same context What are the 6 possible consequences of drug metabolism? accelerated renal excretion, drug inactivation, increased theraputic action, increased toxicity, decreased toxicity What kind of things can cause variation in drug effects? body weight/composition, age, pathophysiology, tolerance, placebo affect, variability in absorption, gender, race, diet, drug interactions, failure to take meds as prescribed What are the four ways the body processes a drug? Absorption, excretion, distribution and liver metabolism Discuss the oral (PO) route of administration and name a drug given this way. variable abdsorption, best for self admin. but requires good compliance,  ibuprofen. Discuss the IM route of administration and name a drug given this way. rapid if aqueous solution.  Requires admin. by nursing staff, only suitable for small volumes, painful, may cause muscle damage, penicillin G. Discuss the IV route of administration and name a drug given this way. absorption is immediate, ideal for emergency, adverse affects appear rapidly, effects may be short duration: epinephrine Discuss the sub Q route of administration and name a drug given this way. same as IM. rapid if aqueous solution.  Requires admin. by nursing staff, only suitable for small volumes, painful, may cause muscle damage: insulin Discuss the Inhalation route of administration and name a drug given this way. rapid absorption unless specifically designed for resp. tract., common route for bronchiodiltors or any gaseous liquid drug that cant be given any other way like anesthesias.  Drugs must be admin. properly for proper effect (requires manual dexterity): albuterol Discuss the transdermal route of administration and name a drug given this way. incomplete/erradic unless drug spec. designed for local effects. Offer concenience for and acceptance by many pt's., limited volume: scopolopine Discuss the rectal route of administration and name a drug given this way. absorption may be erratic, useful for small children or unconscious pt. (local; or systemic drugs), uncomfortable, require time to dissolve: colace Discuss the sublingual (buccal) route of admimnistration and name a drug given this way. Absorption is usually rapid (complete), preffered route for drugs that are inactivated by first pass metabolism.  Efficacay, speed, duration of effects depend on keeping tablet at admin. site: nitroglycerin Discuss the topical route of admimnistration and name a drug given this way. Generally incomplete absorption, useful to treat derm problems, prolonged use may cause allergic rxns, rashes.  Precise dose hard to achieve: lubraderm How can kidney failure or liver disease alter the the drug levels? if the kidneys aremnt functioning properly, then the drug can stay in the system much longer causing toxicity What is glomerular filtration? filtration moves drug from the blood to the urine, but drugs bound to proteins will not be filtered What is  tubular secretion? depends on proximal parts of of kidney tubules which contain pumps or transport system  to secrete drugs.  Elimination will be impaired by drugs that compete for the same transport system=>increase the tixicities of these drugs What can hamper tubular secretions and etherfore limit the amount of the drug that leaves the body? tubular sreabsorption: high lipid solubility and non ionized molecules will be readily absorbed and not be eliminated How are drugs removed from the body? the two major processes are glomerular filtration and tubular secretion What is drug tolerance? a decrease in responsiveness to a drug due to repeat exposure to the drug What are the 3 categories of drug tolerance? pharmacodynamic tolerance, metabolic tolerance and tachyphylaxis (occurs quickly) What is the placebo effect? that copmponent of a drug response that is caused by psycholgical factors and not the physiological properties of the drug What are the FDA pregnancy risk categories? ABCDX, X is the one that drugs are KNOWN to do harm to the fetus What are the functions of the thyroid hormone? stimulation of energy use, stimulation of the heart and promotion of growth and development, regulates fetal development, metabolic rate, cardiac rate, peripheral vasodilation, hepatic metabolic enzymes, bone turnover How do thyroid hormones produce their effects? by modulating the activity of certain genes What are some indications for hypothyroidism? decreased metabolic rate, lethargy, weight gain, decraesed CO, BP and HR What are some indications for hyperthyropidism? warmth, sweating, increased CO, BP, HR, nervous, irritable or insomnia,increased metabolic rate, goiter, weight loss, hyperglycemia How does the release of thyroid hormone happen? the hypothalamus secretes thyrotropin-releasing hormone (TRH) which acts on the pituitary gland to secrete thyrotropin (TSH).  The TSH then acts on the thyroid to stimulate all aspects thyroid function, which release the thyroid hormones T3 and T4 until blood levels go up What are the 2 forms of hyperthyroidism? Graves disease and toxic nodular goiter (Plummers disease) What is the class of drugs that are antithyroid drugs? thionamides What 2 active hormones does the thyroid produce? triiodothyronine (T3) and tertraiodothyronine What are the 4 steps of thyroid hormone synthesis by the thyroid? uptake of iodide by thyroid, conversion of iodide to iodine, linking of iodine to tyrosine and coupling of 2 iodinated tyrosines to form T3 or T4. Whats the difference between glucocorticoids and mineralcorticoids? mineral corticoids such as aldosterone influence renal procssing of Na, K and H, but the main function of glucocorticoids is to influence the carbohydrate metabolism (cortisol) Whats the advantage to an alternate day regimen schedule? reduced adrenal suppresion, reduced risk of growth retardation, reduced toxicity overall Whats the difference between high and low doses of glucocorticosteroids? the low dose has a physiological effect by modulating glucose metabolism.  A pharmacological effect is given by high doses for inflammatory disorders What is the recommended method for corticosterioid withdrawl? should be done slowly, tap[er the dosage to physiological range within 7 days, switch from multiple daily doses to single doses in the morning, taper to 50% of physiological values over next month, and monitor for endogenous cortisol, when basal levels return to normal cease routine steroid admin. What nursing interventions should be done for glucocorticoid use? measure baseline  data and monitor changes with therapy.  Advise pt of problems with NA and water retention, hyperglycemia  and glycosuria What is the principle effect of low dose glucocorticoids? the elevation of  blood glucose How are glucocorticoids different from other drugs? 1)they have the receptors on the inside of the cell, 2) they modulate the production of regulatory proteins, rather than the actiity of signal pathways How are glucocorticoids produced and regulated? a stimuli from the CNS or stress activate the hypothalamus to producecorticotropin-releasing hormone (CRH) which goes to the anterior pituitary gland which then produces adrenocorticotropic hormone.  This acts on the adrenal cortex to produce glucocorticoids until the blood levels of them shut off the production of both ACTH and CRH. What are some adverse reactions of glucocorticoids? adrenal insufficiency, osteoporosis, increased vulnerability to infection, muscle wasting, thinning skin, fluid and electrolyte imbalance, glucose intolerance and peptic ulcer disease. What are some special barriers to drug entry? blood-brain barrier, placental barrier What are some specialized sites for drug uptake and storage? fat, bone and teeth, kidneys What drugs are best absorbed? non-ionized and lipophillic How are some drugs stored? by being bound to the protein Albumin in our blood, then these drugs get distributed to the body via the capillaries What does the liver do for drug metabolism? hepatocytes conain microsomal enzymes that metabolize the drugs What happens to drugs in the liver? many drugs get broken down and metabolized, but sometimes nothing happens What are the factors that effect plasma concentration of a drug over time? age, nutritional status, gentic makeup, liver disease and hormones What is the onset of action? the time needed for the drug to reach minimum levels What is the therapeutic range? a range from MEC to toxic levels in which there is enough drug to produce therapteutic effects but not enough to produce toxicity What is the duration of action? the time during which blood concentrations of the drug are above the minimum effetive concentration What is drug half-life? the time required for the amount of drug in  the body to reduce by 50% What are the 4 main areas of distribution for drugs? cells, capillaries, liver and kidneys What are the ways that drugs get into the cell? passive diffusion (only if uncharged), active transport (minor), pinocytosis (minor), filtration through pores (minor) What is the oral route of administration? variable, depends on composition of drug and gut pH, What does the liver do for drug metabolism? hepatocytes conain microsomal enzymes that metabolize the drugs What is the IM route of  administration? rapid if aquueous solutions used, slow and prolonged if oily or other depot preparation What is the IV route of administration? absoprbtion is immediate into blood What is the Sub Q route of administration? much like IM What is the inhalation route of administration? rapid absorption unless drug is specifically formulated for local effects What is the transdermal route of administration>? incomplete, irratic unless drug specifically formulated for this route. What is the rectal route of administration? absorption may be erratic Ewhat is the sublingual,buccal route of administration? absorbtion is usually rapid, complete What is the topical route of administration? generally incomplete, erratic What is the proper drug solubility in water and lipids? rate and amount of drug absorbed from admin site depends on  chemical nature of drug.  Need to be soluble in water and lipids What happens to proteins and hormones in the stomach? the are  destroyed by the stomach acid How is the destruction of hormones/proteins prevented? enteric coating or time release capsules to get into the small intestine What are some other fcators for drug absorbtion in GI tract? motility (diarhea and vomiting), drugs which irritate the stomach can be taken with food, some foods can inhibit absorption(milk binds to tetra cycling) What is local blood flow? flow affects the amount of blood reaching organs Which drugs are able to absorb into the blood? only those drugs that are NOT bound to plasma proteins are able to produce a pharmocological effect, be metbolized, excreted or be accumulated What arte the metabolic fates of a drug? excretion w/o metabolism, inactivated drug, less activated drug, more active drug What is the first pass effect? when the drug is taken via the gi tract the active drug is then in a higher concentration in hepatic portal vein than in the arteries or venous circ. So drug effects are minimal.  Large initial doses can overcome this What is responsible for breaking down the drugs in the liver? P450 enzymes, hepatocytes contaoin microsomial enzymes that metabolize drugs What is a prodrug? a drug that is initially inactive but is activated by the liver metabolism (L-dopa) What organs are involved in metabolism of drugs? primarily in the liver and to a lesser extent the lungs, GI mucosa, kidneys and blood, sweat and saliva Why is nitroglycerine given sublingually? to get it directly in the blood stream and bypass the first pass effect What is inhibition? competition of one drug with another for microsomial enzymes.  Hepatic substances such as large amounts of alcohol or monamine oxidase inhibitors What is stimulation? some drugs such as birbiturate sedative phenobarbital and anticonvulsant drugs phenytoin and small amounts of alcohol will stimulate the livers ability to metabolize other drugs by increasing the amounts of drug metabolizing enzymes How are drugs eliminated? glomerlar filtration and tubular secretion What is plasma half life? the time needed for the plasma concentration of a drug to fall to 50% of its previous concentration What is the plateau principle? it takes about 4-5 half lives for average blood concentration and the related intensity of response to reach steady level What are second messengers? the binding of a drug molecule to its receptor is the first step leading to a response. Is a chemical synthesized that links the drug binding response (cAMP) What is an agonist? drugs that bind to a receptor and then after some biologica funtion to produce an effect, or response What are the two properties of an agonist? affinity and efficacy What is affinity and efficacy? affinity: the ability to interact with or bind to or occupy a specific receptor site in a reversible manner. Efficacy: a measure of the abiolity of the agonist to cause a response What is an antagonist?` drugs which can interact with the cell recpetors but do not cause a response Why are there so many different receptor subtypes? the sligfhtly different shapes allow more selective or specific interactions with either antagonist or agonists. What is a dose response curve? shows the relationship between drug response and the amount of drug given What is the effective dose? ED50 a dose that produces on half the maximum response What is potency? the dose of drug needed to produce a response, compared with the dose of another drug needed to cause the same response What is the difference between efficacy and potency? efficacy provides info about intensity of the response. Potency can ofetn be misleading and in general effciacy is more important than potency What is the lethal dose? a dose that kills 50% of the animals its given to What is a therapeutic index? a rough indicator of the drugs margin of saftey, where the ratio of the LD50 and the ED50 are compared What are the 2 hormones that the thyroid gland synthesizes? T3, triodothyronine: T4 Thyroxine (converted in body to T3) What are the drugs to treat hypothyropidism? levothyroxine (T4)preferred, liothyronine (T3), liotrix (T4 and T3, 4:1) What are the mechansims of action for thyroid meds? supplement of bodys supply of thyroid hormone What are the 3 classes of steroid hormones are there? gucocorticoids, mineralocorticoids, androgens What are the physiological effects of of glucocorticoids? carb metabolism, protein metabolism, fat ,etabolism, maintains integrity of vascular system, support striated muscle function, enhances CNS excutablitily, cause increase secretions of glucocorticoids and epi to maintain BP and glucose, debvelopment of respiratory system of full term fetus Cholineric Neurotransmission Cholineric Neurotransmission What is the difference between afferent and efferent? afferent are sensory nerves that transmit to the brain, efferent nerves transmit out of the brain to peripheral organs and tissues What do somatic nerves do? inervate the skeletal muscles (voluntary movement).  1 neuron system travel directly to inervate skeletal muscle. Neurotransmitter is acetylcholine for ALL somatic nerves What does the autonomic nervous system do? inervate (control or contact) smooth muscle, cardiac muscle, and certain glands What are the effectors of the autonomic nervous system? smooth muscle, cardia muscle and glands What is the neuro muscular junction? the contact between the nerve and the skeletal muscle What does the autonomic nervous system do for us? it maintains the involuntary functions of the body..It is a 2 nerve system.  The preganglionic nerves are before the ganglia.  And a post-ganglionic nerve which inervate the effectors What is the difference between pre and post ganglionic nerves? pre ganlionic are mylenated and faster…But acetylcholine is always the neuro transmitter in the ganglia for both Where do parasympathetic nerves pathways originate from? cranial or sacral areas of the spinal cord What is the function of the parasympathetic nervous system? conserve energy, rest and digest nervous system. What are features of the parasympathetic NS? the neurotransmitter is acteylcholine, the pre ganglionic nerve is longer Where do sympathetic NS nerves originate? thoracic or lumbar What are the features of the sympathetic NS? short pre ganglionic nerve, ALL POST ganlionic sympathetic neurotransmitter is NOREPINEpHRINE What is the function of the sympathetic NS? helps body deal with stress, fight or flight NS,   What is the sympathoadrenal branch? acteylcholine is used in the adrenal medulla, which contact chromaffin cells to release epi and norepi to stimulate cardiac muscle smooth muscle and glands What is the neuroeffector junction? the contact between a nerve and its effector What are the sites for acetylcholine  is the neurotransmitter? neuromucular junction, parasymapathetic neuroeffector junction, parasympathetic ganglia, sympathetic ganglia, adrenal medulla Where is Norepinephrine the neurotransmitter? sympathetic neuroeffector junction What are cholinoceptors? stimulated by acetylcholine What are adrenergic receptors? all receptors stimulated by epinephrine, alpha and beta What are the drugs that ineract with alpha receptors? Phentolamine   α1 – Phenylephrine, α2 – Clonidine What are the drugs that interact with beta receptors? Isoproterenal   β1 – Dobutamine β2 – Albuterol  Where are alpha and beta receptors? only on effectors Where are the Nicotinic receptors? parasympathetic ganglia, sympathetic ganglia, skeletal muscle,  Where are the muscarinic receptors? parasympathetic effectors Where are alpha and beta receptors? effectors inervated by sympathetic nerves What is the only body part that ONLY has parasympathetic NS? blood vessels What are muscarinic receptors stimulated by? methacholine What is Alzheimers caused by and what drugs treat it? Degeneration of nerves in the brain including many cholinergic nerves. Many drugs approved to treat Alzheimer’s are cholinesterase inhibitors like:Donepezil (Aricept) Rivastigmine(Exelon), Galantamine(Razadyne)  What are the adverse effects of cholinesterase inhibitors? Similar to direct acting muscarinic receptor agonists: Ocular: miosis, loss of accommodation of the lens for far vision. Respiratory: bronchoconstriction, increased secretions. Cardiovascular: bradycardia. GI: diarrhea, nausea, vomiting, sialorrhea.GU: urination What are the adverse effects that are UNIQUE to cholinesterase inhibitors? Medium dose -Muscle fasciculation, tremor. High dose -Desensitization, flaccid paralysis, respiratory collapse. What is the overdose treatment for cholinesterase inhibitors? Intermediate-acting cholinesterase drugs:  give atropine to block muscrinic receptors and respiratory support. Long acting irreversible organophosphate inhibitors:  atropine and slow infusion of pralidoxime (within 6 hours of exposure) Pralidoxime reactivates the cholinesterase enzyme What are Muscarinic Receptor Antagonists also called? antimuscarinics What is the mechanism of action for antimuscarinics? Competitive antagonism of muscarinic receptors. Pharmacological effects: Blockade of parasympathetic nerve signals, Tissue sensitivity = glands > heart > eye > GU > GI > lung > stomach.  CNS actions  What are the Ocular Effects and Uses of Antimuscarinics ? Effect: Iris muscle relaxation: mydriasis.  Effect: Cycloplegia-lens is fixed to focus for far vision. Therapeutic use:  pupillary dilatation (tropicamide) What are the CV uses of antimuscarinics? Effect: Tachycardia, Therapeutic use to treat:  bradycardia, cardiac arrest,  Atropine  What are the effects on and therapeutic uses for antimuscarinics in the respiratory system? Effect: Bronchodilation, Inhibition of respiratory secretions, Some reduced ciliary clearance of mucous Therapeutic use: Tiotropium and ipratropium in COPD.  What are the GI effects and use for antimuscarinics? Gastrointestinal effects:  Xerostomia, reduced GI motility, reduced gastric acid secretion • Therapeutic uses: antimotility, antidiarrheal – dicyclomine  What are the GU effects and use for antimuscarics? Genitourinary effects: Block detrusorcontraction, block relaxation of sphincters Therapeutic use: incontinence, overactive bladder - tolterodine(Detrol), Solifenacin(Vesicare) etc. How are antimuscarinics used for respiratory system?   Effect: Bronchodilation, Inhibition of respiratory secretions, Some reduced ciliary clearance of mucous. Thera