Final Exam with Notes review.docx

General concepts: Drug calculations Life threatening or potential debilitating side effects of pharmacologic interventions we administer/discussed in class, e.g. tissues necrosis from D50% & pressors, iatrogenic acute heart failure from fluids, EPS and how to treat, fluid bolus before pressor ad...

General concepts: Drug calculations Life threatening or potential debilitating side effects of pharmacologic interventions we administer/discussed in class, e.g. tissues necrosis from D50% & pressors, iatrogenic acute heart failure from fluids, EPS and how to treat, fluid bolus before pressor administration, problems with paralytics, etc How to recognize, treat or reverse untoward effects of pharmacologic interventions we administer and for commonly prescribed medications with known safety issues: organophosphates, digoxin, EPS on phenothiazines & "typical" antipsychotics, K+ relative to furosemide & dialysis pts, TCA overdose, statins and rhabdo, insulin, opioids, benzos, MAOIs, etc Organophosphates Atropine opioids Naloxone Benzos Flumazenil Furosemide Could cause hypokalemia in patients with renal failure or on dialysis TCA overdose Extrapyramidal symptoms (spasms, etc…) Treat with sodium bicarbonate Statins and Rhabdo Increased use of statins can cause rhabdomyolysis This is where the muscle cells break down and release proteins and electrolytes into the blood stream Could be fatal Insulin For insulin overdose solution is IV with d50 Parameters/S&S that we use when making pharmacologic intervention choice/selection, e.g. why/when you would use pressor X vs Y, Pressors Dopamine Sympathetic agonist Dopamine is a naturally occurring catecholamine. It acts on α, β1, and dopaminergic adrenergic receptors. Its effect on α-receptors is dose- dependent, higher dose = more vasoconstriction Dopamine increases both the systolic blood pressure and the pulse pressure (the difference between the systolic and diastolic blood pressures), but, as a rule, there is usually less effect on the diastolic pressure Used in cardiogenic shock Norepinephrine Sympathetic agonist Naturally occurring catecholamine. Acts on both α- and β-adrenergic receptors. Action on α-receptors is more profound. Reserved for emergencies in which dopamine may not be effective Increases myocardial oxygen demand Dobutamine It acts primarily on β1-receptors but is a less potent β-agonist than isoproterenol. Increases the force of the systolic contraction (positive inotropic effect) with little chronotropic activity. Useful in the management of CHF when an increase in heart rate is not desired. what's the appropriate route and concentration for Epi during allergic reactions, 0.3-0.5 mg IM for anaphylaxis double adenosine when pt's on aminophylline, Adenosine's effects are concentration-dependent. Adenosine's receptors are competitively antagonized by methylxanthines such as aminophylline. Aminophylline competitively antagonizes the cardiac actions of adenosine at the cell surface receptors. Thus, it increases heart rate and contractility BP relationship with NTG, Generally not good to administer if systolic is <90. Will bottom patient out burns and succs use, etc A major concern with burn patients is the upregulation of acetylcholine receptors subsequent to a burn resulting in life-threatening hyperkalemia after using succinylcholine Pharm terms/concepts: ADME, PK, PD, indication, contraindication, placebo effect, summation, potentiate, tolerance, untoward effect, trade name, USP name, diffusion, osmosis, first pass effect, affinity, ionotropic, chronotropic, etc How to safely prepare and deliver the tools/methods we have at our disposal: IV, IM, SQ, IVPB, IO, NEB... drug names drug sources reference materials Physicians Desk Reference components of a drug profile Class Mechanism Indications Contra Precautions Interactions Side effects Etc… legal regulations schedule classification – know the names of examples in schedule 1 Definitions: assay – A test to find and measure the amount of a specific substance bioequivalence - the property of two dosage forms or active ingredients with similar blood concentration levels that produce the same effect at the site of physiologic activity. Bioassay - an analytical method to determine the concentration or potency of a substance by its effect on living animals or plants (in vivo), or on living cells or tissues teratogenic - the ability of a drug to cause fetal abnormalities or deformities. therapeutic index- a ratio of the therapeutic dose to the toxic dose lethal dose - an amount of a drug or other agent that will kill a human or animal if administered effective dose - a dose or concentration of a drug that produces a biological response. second messenger - small molecules and ions that relay signals received by cell-surface receptors to effector proteins pharmacodynamis -study of the biochemical and physiologic effects of drugs pharmacokinetics -activity of drugs in the body over a period of time, including the processes by which drugs are absorbed, distributed in the body, localized in the tissues, and excreted. diffusion -the drug molecule moves according to the concentration gradient from a higher drug concentration to a lower concentration until equilibrium is reached osmosis -process by which molecules of a solvent pass through a semipermeable membrane from a less concentrated solution into a more concentrated one, thus equalizing the concentrations on each side of the membrane filtration – Movement of water out of the plasma across the capillary membrane into the interstitial space bioavailability – The amount of the drug that is active when it hits the target tissue blood-brain barrier – Serves as a filter. Controlling which molecules can pass from the blood into the brain. Lipid soluble molecules are easily passed. placental barrier – Membrane that limits what is exchanged between mother and fetus metabolism – biotransformation biotransformation a metabolic process that takes place mainly in the liver and helps to facilitate the excretion of both exogenous and endogenous substances first-pass effect - phenomenon in which a drug gets metabolized at a specific location in the body that results in a reduced concentration of the active drug upon reaching its site of action or the systemic circulation receptor affinity – how well a drug binds to the receptor efficacy – The ability to produce the desired result agonist – initiates a physiological response when binded to a receptor antagonist – inhibits the reactions of others by binding to receptors agonist-antagonist (partial agonist)- a molecule or chemical compound that can bind to a receptor and weakly activates the receptor know an example onset of action duration of action biologic half-life medication concentration isotonic solutions – know examples Central veins vs peripheral veins Administration sets types of catheters IV insertion complications Six rights of medication administration Patient Route Dose Time Documentation drug Drug routes –enteral and parenteral Enteral Oral, buccal, rectal, sublingual Parenteral IV, ET, IO, IM Bypasses the digestion system Drug forms, drug storage and factors affecting medication elimination Medication names – chemical, trade etc... Generic (Diazepam) Brand (Valium) Chemical (chemical structure breakdown) Pharmacokinetics Absorption Distribution Excretion Pharmacodynamics How a drug effects the physiology Cross tolerance Tolerance to one drug impacts the effectiveness or tolerance to another drug in the same class Potentiation – intensified effect Membrane transport mechanisms – osmosis, diffusion, active transport and facilitated transport. Facilitated diffusion – passive transport guided by a “helper” IV problems – what do you do for infiltration, clot obstruction? Intra-osseous route – when would you use it? Would not use it for pneumonia (as was on the test) Any time you cannot establish IV access Parenteral delivery – benefits. Bypass the GI Track Rapid absorption CNS medications: Treatment of grand mal seizures Diazepam Morphine Sulfate – actions, treatment of OD, side effects. Actions – Narcotic Analgesia, Binds to the mu opiate receptor Treatment of OD – Narcan Side effects – hypotension, depressed respiratory rate Extra Pyramidal Symptoms - signs and symptoms and treatment. an inability to sit still, involuntary muscle contraction, tremors, stiff muscles, and involuntary facial movements Caused by antipsychotics Like haloperidol Antidepressants whose side effects cause seizures. Tricyclic antidepressants (amitriptyline and clomipramine) MAOI’s action and food to avoid Avoid foods high in Tyramine Medications called monoamine oxidase inhibitors (MAOIs) block monoamine oxidase, which is an enzyme that breaks down excess tyramine in the body. Blocking this enzyme helps relieve depression. TCA overdose – the drug and it’s mechanism of action. block the reuptake of serotonin and norepinephrine in presynaptic terminals, which leads to increased concentration of these neurotransmitters in the synaptic cleft Could Cause seizures Xanax, what type of drug is it and know the antagonist. Benzodiazepine Flumazenil is the antagonist Used to treat seizures/anxiety Autonomic Nervous System: Main actions of alpha 1, beta 1, beta 2 and nicotinic receptors. Know both stimulation and inhibition. A1 Vasoconstriction Increased peripheral resistance (blood flow) Increased blood pressure Mydriasis Increased closure bladder Sphincters B1 Increased heart rate Increased lipolysis Increased myocardial contractility Increased renin B2 Vasodilation Decreased peripheral resistance Bronchodilation Increased glycogenolysis Increased glucagon release Relaxes uterine smooth muscle Epinephrine – effects Epinephrine acts on both alpha- and beta-adrenergic receptors and is used in several routes including intravenously (IV), subcutaneously, intramuscularly, and via inhalation. Epinephrine decreases vasodilation and increases vascular permeability through its alpha-adrenergic receptor action, which can lead to loss of intravascular fluid volume and hypotension. Through its action on beta-adrenergic receptors, epinephrine causes bronchial smooth muscle relaxation and helps alleviate bronchospasm, wheezing, and dyspnea that may occur during anaphylaxis Bronchodilation Atropine - effects Anti-cholinergic Atropine is a muscarinic antagonist Anticholinergic agents oppose parasympathetic nervous system. – Muscarinic cholinergic antagonists: block effects of acetylcholine at muscarinic receptors (anticholinergics or parasympatholytics). – Prototype anticholinergic drug: Inidications: Bradycardia Antidote for organophosphate poisoning Premedication for RSI All ANS terminology, example - cholinergic, adrenergic, sypathomimetic, sympatholytic, parasympathomimetic, parasympatholytic Cholinergic - act upon the neurotransmitter acetylcholine, the primary neurotransmitter within the parasympathetic nervous system (PNS) Adrenergic - The part of your body that uses epinephrine and norepinephrine as biochemical messengers Sympathomimetic – mimics the SNS. SNS Agonist Sympatholytic – inhibits the SNS Parasympathomimetic – mimics the PNS Parasympatholytic – inhibits the PNS Define: Action potential - Propagate – To reduce, to generate Depolarization - loss of polarization. especially : loss of the difference in charge between the inside and outside of the plasma membrane of a muscle or nerve cell due to a change in permeability and migration of sodium ions to the interior Repolarization - a stage of an action potential in which the cell experiences a decrease of voltage due to the efflux of potassium (K+) ions along its electrochemical gradient Synthesis - Putting together different entities to make a whole which is new and different Transmission Endogenous - originating within the body Pre-synaptic - of, occurring in, or being a neuron by which a nerve impulse is conveyed to a synapse a presynaptic membrane a presynaptic neuron Post-synaptic - After release into the synaptic cleft, neurotransmitters interact with receptor proteins on the membrane of the postsynaptic cell, causing ionic channels on the membrane to either open or close. When these channels open, depolarization occurs, resulting in the initiation of another action potential. Synapse - The space between the junction of two neurons in a neural pathway, where the termination of the axon of one neuron comes into proximity with the cell body or dendrites of another Axon - portion of a nerve cell (neuron) that carries nerve impulses away from the cell body Dendrite - any of the usually branching protoplasmic processes that conduct impulses toward the body of a nerve cell. Neurotransmitters acetylcholine and norepinephrine Acetylcholine (PNS) Nicotinic Found at the neuromuscular junction of skeletal (only) muscles Found on postganglionic parasympathetic nerves Found on many neurons in the brain Nicotine is an agonist Curare is an antagonist Muscarinic Found at the neuromuscular junction of smooth and cardiac muscle Found on postganglionic sympathetic nerves Muscarine is an agonist Atropine is an antagonist Norepinephrine (SNS) A1 and b1 agonist. Ions involved in action potentials. Na in to depolarize, K Organophosphate poisoning – S.L.U.D.G.E. + BRADYCARDIA Treatment of Organophosphate poisoning – Atropine. Autonomic Nervous System: Pre and post ganglionic neurotransmitters. Adrenergic/sympathetic/sympatholytic Cholinergic/parasympathetic/parasympatholytic Cardiology Inotrope - Inotropic agents, or inotropes, are medicines that change the force of your heart's contractions. There are 2 kinds of inotropes: positive inotropes and negative inotropes. Positive inotropes strengthen the force of the heartbeat. Negative inotropes weaken the force of the heartbeat. Dromotrope - A dromotropic agent is one which affects the conduction speed in the AV node, and subsequently the rate of electrical impulses in the heart Chronotrope - influencing the rate especially of the heartbeat The effect of Nitroglycerine on pre load and stroke volume. Preload – Decrease Stroke Volume - Decrease Primary ions involved in action potential synthesis. Phase 0 – Sodium Summit in Sodium depolarization Phase 1 – potassium Plummet potassium out Phase 2 – calcium Continue calcium in contraction Phase 3 – potassium Repolarization, plummet potassium out Phase 4 – resting phase The effect of calcium channel blockers on the heart. Used for chronic hypertension preventing calcium from entering the cells of the heart and arteries. Calcium causes the heart and arteries to squeeze (contract) more strongly. By blocking calcium, calcium channel blockers allow blood vessels to relax and open The action of Aspirin on platelets. ASA Prevents the coagulation of platelets in the blood TPA is a clotbuster The mechanism by which thrombolytics act. Dissolving/busting a major clot quickly The effect of Lidocaine on ventricular repolarization, potassium and sodium channels blocks a fraction of the activated sodium channels that do not inactivate during the plateau of the action potential, and thereby reduce action potential duration. blocks sodium ions across nerve membrane, therefore blocking nerve conductivity QRS complex and automaticity. Anticoagulants that block the effects of vitamin K. warfarin (coumadin) Treatment of a heparin overdose. Protamine (?verify) Pre-hospital first line treatment of HTN. *** Beta blockers (labetalol, the other -lol’s) (hypertensive emergencies) Have an immediate effect Calcium channel blockers for chronic HTN Understand the role of HDL and LDL in coronary artery disease. HDL (good cholesterol) helps rid your body of excess cholesterol so it's less likely to end up in your arteries LDL is called “bad cholesterol” because it takes cholesterol to your arteries, where it can collect in your artery walls Mechanism and effects of furosemide administration. Available in oral or IV Used for hypertension and edema Also known as Lasix increase the excretion of Na+ and water by the kidneys by inhibiting their reabsorption Factors affecting BP Cardiac output CO (HR x SV) x PVR = BP Respiratory Treatment regimens for asthma – be able to prioritize the drugs, first-line, second-line etc. Management of Asthma Correct hypoxia Reverse Bronchospasm Treat inflammatory Changes First line Treatment – Bronchodilators (epinephrine) Second line – Beta2 Agonists (albuterol) Anticholinergics can be used also (atropine) Rate the following drugs in terms of beta 2 agonism: Racemic epinephrine Slightly different chemically from the other epinephrine compounds. Compounds that differ only in chemical arrangement are called isomers. This particular form frequently used in children to treat croup Stimulates both α- and β-adrenergic receptors. Has a slight preference for β2- adrenergic receptors and causes bronchodilation. Also has some effect in relieving the subglottic edema associated with croup. Aminophylline= Methylxanthines Specific beta2 agonist bronchodilator that sometimes proves effective in cases where sympathomimetics have not been effective Achieves its bronchodilation effects via a different mechanism than the sympathomimetics. Relaxes bronchial smooth muscle with no adrenergic effect. Also stimulates the respiratory center in the brain. Has mild diuretic properties; increases the heart rate and cardiac output. Terbutaline A synthetic sympathomimetic that is selective for β2-adrenergic receptors Causes immediate bronchodilation with limited cardiac effects Onset of action similar to epinephrine Endocrine Type II diabetes medications. Type II More common than Type I Adult Onset Pancreas is less responsive to stimulation from increased Blood glucose levels More prone to HHC and less likely to develop DKA Insulin Effects of Glucagon - understand glycogenolysis and gluconeogenesis. Indications for D50 and Glucagon Gluconeogenesis metabolic pathway that results in the generation of glucose from certain non-carbohydrate carbon substrates Glycogenolysis process by which glycogen, the primary carbohydrate stored in the liver and muscle cells of animals, is broken down into glucose to provide immediate energy and to maintain blood glucose levels during fasting D50 Drug of choice in the management of insulin-induced hypoglycemia is D50W glucagon Hormone and antihypoglycemic Contraindication is Cachexia (according to professor, not in notes or book) Protein secreted by the Alpha cells Used to raise BGL in cases where IV cannot be immediately established Only effective if there are sufficient stores of glycogen within the liver Miscellaneous Pharmacokinetics/dynamics – terminology used in these processes. CHF and pulmonary edema. Know presentation and treatment Treatment of nausea and vomiting in a chemotherapy patient. CHF increasing oxygenation through supplemental oxygen, increasing airway pressures, and decreasing pre-load Rx: furosemide PE Suspected PE patients should be placed on high-flow oxygen both to relieve the patient's hypoxia and reduce the patient's anxiety EPS – signs, symptoms and treatment. Overdose on TCA Antidepressants. Involuntary spasms/movement/ Sodium bicarbonate is treatment CCB effects on cardiovascular system. Used for chronic hypertension to lower blood pressure Phases of New Drug Application Acid-Base balance. Drug used to treat postpartum hemorrhage. Oxytocin Know the action of the following drugs: Racemic epinephrine non-selective α- and β-adrenergic receptor agonist temporary relief of symptoms associated with bronchial asthma (e.g., shortness of breath, chest tightening, wheezing) and to treat croup in children. Aminophylline Bronchodilator, relief of bronchospasm associated with asthma and in chronic obstructive pulmonary disease Methylxanthines – this is a class of drug, know the indication. COPD & Asthma. termination of acute bronchospasm secondary to asthma or COPD exacerbation Terbutaline Beta Agonist To prevent and treat bronchospasm (narrowing of airways) associated with asthma, bronchitis, and emphysema Methylprednisolone corticosteroid Reduces airway inflammation, or swelling Norepinehrine Sympathomimetic blood pressure control in certain acute hypotensive states Solumedrol Glucocorticosteroid, indicated in COPD and Asthma Albuterol. to prevent and treat difficulty breathing, wheezing, shortness of breath, coughing, and chest tightness caused by lung diseases such as asthma and chronic obstructive pulmonary disease Retrovir – know the indication. is indicated for the prevention of maternal-fetal HIV-1 transmission Drug Receptor Selectivity Clinical Use Comments Epinephrine β1 = β2 > α1* = α2* Anaphylactic shock; cardiogenic shock; cardiac arrest Low doses produce cardiac stimulation and vasodilation, which turns to vasoconstriction at high doses. *At high plasma concentrations, α = β selectivity. Norepinephrine β1 = α1 > β2 = α2 Severe hypotension; septic shock Reflex bradycardia masks direct stimulatory effects on sinoatrial node. Dopamine β1 = β2 > α1* Acute heart failure, cardiogenic shock and acute renal failure Biosynthetic precursor of norepinephrine; stimulates norepinephrine release. *At low doses, it stimulates the heart and decreases systemic vascular resistance; at high doses, vasodilation becomes vasoconstriction as lower affinity α-receptors bind to the dopamine; also binds to D1 receptors in kidney, producing vasodilation. Dobutamine β1 > β2 > α1 Acute heart failure; cardiogenic shock; refractory heart failure Net effect is cardiac stimulation with modest vasodilation. Beta-Agonists Cardiac effects Increase contractility (positive inotropy) Increase relaxation rate (positive lusitropy) Increase heart rate (positive chronotropy) Increase conduction velocity (positive dromotropy) Vascular effects Smooth muscle relaxation (vasodilation) Other actions Bronchodilation Hepatic glycogenolysis Pancreatic release of glucagon Renin release by kidneys Arterial pressure (AKA BLOOD PRESSURE) can be raised by 1) increasing cardiac output and by 2) constricting the systemic vasculature. Most pressor drugs are sympathomimetic agents that mimic the effects of sympathetic adrenergic activation on the heart (cardiostimulatory drugs) and blood vessels (vasoconstrictor drugs). Some of these drugs increase heart rate and cardiac contractility by stimulating cardiac beta1-adrenoceptors (beta-agonists). Other sympathomimetic drugs increase systemic vascular resistance by stimulating vascular alpha-adrenoceptors (alpha-agonists). Finally, there are nonsympathomimetic, vasoconstrictor drugs, such as vasopressin analogs, that have proven to be effective pressor agents. https://www.cvpharmacology.com/pressor/pressor Norepinephrine Heart Rate - Decreases due to reflex increase in vagal tone on SA and AV nodes. Contractile Force - Increases due to effects on beta1-ARs on myocardial cells MILD Total Peripheral Vascular Resistance - Increases due to activation of alpha1-ARs on vascular smooth muscle cells MAJOR Blood Pressure - Increases due to effects on total peripheral vascular resistance Dopamine has a complex pharmacology. It can activate at least 4 different receptors: the beta1, dopamine1 (DA1), alpha1 and alpha2. Activation of the beta1 receptor increases the force of myocardial contraction. Dopamine has a very unusual action on the heart in that it selectively increases the force of myocardial contraction without a significant effect on heart rate. However, high doses of dopamine, like all catecholamines which activate the beta1 system, can induce rhythm disturbances. The beneficial effects of dopamine are due to stimulated DA1 and beta1 - receptors. Activation of the alpha1 receptor will produce increases in vascular resistance which is counterproductive to the effects on the heart and kidney. The increase in peripheral resistance would increase the pressure the heart has to work against and hence act to decrease cardiac output. Dopamine can be used to treat congestive heart failure and cardiogenic shock… AND THUS NOT A GOOD CHOICE WITH DISTRIBUTIVE SHOCKS! K.I.S.S-