Sanders: Mosby's Paramedic Textbook, Revised 3 rd Edition PowerPoint Lecture Notes Chapter 17: Pharmacology

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1 Sanders: Mosby's Paramedic Textbook, Revised 3 rd Edition PowerPoint Lecture Notes Chapter 17: Pharmacology Chapter 17 Pharmacology Explain what a drug is Objectives Identify four types of drug names Outline drug standards and legislation Describe the paramedic s s responsibilities in drug administration Distinguish among drug forms Objectives Outline autonomic nervous system functions that may be changed with drug therapy Discuss factors that influence drug absorption, distribution, elimination Describe how drugs react with receptors to produce their desired effects 1

2 Objectives List variables that can influence drug interactions Identify considerations for drug administration to pregnant, pediatric, and older patients Outline drug actions for patient who is given drugs that affect body systems Explain meaning of drug terms used in drug references Scenario An 80-year year-old woman has fallen and is experiencing severe pain. You observe obvious deformity of the hip. Her husband hands you a sack that contains her pill bottles, but he is too upset to tell you what she is being treated for. Discussion Why is it important to understand the general actions of her home medications? What additional information will you need to obtain prior to treating her pain? How will the age of this patient affect your drug administration? 2

3 Ancient Health Care Pharmacology dates to 10,000 to 7,000 B.C. Medicinal herbs Medications mentioned in Bible Plant-derived drugs used in Middle Ages Historical Trends in Pharmacology Chemical medicine born in 17 th century Studies of drug dosage in 19 th century Led to development of manufacturing plants to produce drugs Modern Health Care Expansion of consumer health education Increased research Incentives to develop orphan drugs for treatment of rare, chronic diseases 3

4 Drugs Defined as: Any substance taken by mouth; injected into a muscle, blood vessel, or cavity of the body; inhaled; or applied topically to treat or prevent a disease or condition Sources of Drugs Five major sources Plants (alkaloids, glycosides, gums, and oils) Animals and humans Minerals or mineral products Microorganisms Chemical substances made in laboratory Chemical name Generic name Nonproprietary name Drug Names Trade name Brand or proprietary name Official name 4

5 Drug References American Medical Association (AMA) Drug Evaluation American Hospital Formulary Service (AHFS) Medication package inserts Mosby s s Drug Consult Physician's Desk Reference (PDR) Nursing Drug Reference (NDR) Electronic data bases FDA web page Medline PharmInfoNet web page Toxline Drug Standards and Legislation Before 1906: Little control Pure Food and Drug Act, 1906 Shirley Amendment, 1912 Harrison Narcotic Act, 1914 Federal Food, Drug, and Cosmetic Act, 1938 Durham-Humphrey Amendment, 1952 Kefauver-Harris Amendment, 1962 Comprehensive Drug Abuse Prevention and Control Act, 1970 Also called the Controlled Substances Act (CSA) Superseded Harrison Narcotic Act of 1914 Classified drugs into five categories (schedules) based on: Potential for abuse and physical and psychological dependence Defined terms drug dependency and drug addiction Established education and treatment programs for drug abuse 5

6 Drug Schedules Schedule I High abuse potential No accepted medical use Schedule II High abuse potential Accepted medical uses Schedule III Less abuse potential than drugs in schedules I and II Accepted medical uses; may lead to some physical dependence or high psychological dependence Drug Schedules Schedule IV Lower abuse potential than schedule III drugs Accepted medical uses; may lead to limited physical or psychological dependence Schedule V Low abuse potential compared to schedule IV drugs Accepted medical uses; may lead to limited physical or psychological dependence Drug Regulatory Agencies In 1973 the Drug Enforcement Agency (DEA) became the sole drug enforcement organization in the U.S. Other regulatory bodies or services Food and Drug Administration Public Health Service Federal Trade Commission Canadian drug control International drug control 6

7 General Properties of Drugs Therapeutic effects Desirable drug actions Side effects Undesirable or harmful drug actions Drug interaction with other drugs Can produce unpredictable effects Drug actions are biochemical interaction between drug and tissue components Pharmaceutical Phase Pharmaceutics Science of dispensing drugs Dissolution Rate at which a solid drug goes into solution after ingestion More rapid rate of dissolution = more quickly drug is absorbed Pharmacokinetic Phase Pharmacokinetics How the body handles a drug over a period of time Absorption Distribution Biotransformation Excretion 7

8 Drug Absorption Movement of drug molecules from site of entry to general circulation Variables affecting drug absorption Absorbing surface Blood flow to the administration site Drug solubility ph Drug concentration Dosage form Routes of Medication Administration Mode affects the rate of onset of action May affect the therapeutic response Drugs are given for local or systemic effects Routes of Medication Administration Topical Enteral Pulmonary Parenteral 8

9 Enteral Route Drugs administered along GI tract Oral Rectal Nasogastric Safe, convenient, economical Least reliable and slowest route Food contents Emotional state Physical activity Oral Absorption Rich blood supply, little absorption in mouth Nitroglycerin and some hormones administered by sublingual or buccal routes Rapidly dissolve in salivary secretions Gastric Absorption Length of time a drug remains in the stomach varies depending on: ph of the environment Gastric motility 9

10 Absorption in the Small Intestine Rich blood supply and large absorption area Most drug absorption occurs in the upper portion of the small intestine Rectal Absorption Effective for some medications Vascular surface area capable of drug absorption Erratic absorption may occur from: Rectal contents Local drug irritation Uncertainty of drug retention No hepatic alteration on first pass through body Parenteral Administration Subcutaneous Intramuscular Intravenous Intradermal Intraosseous Endotracheal 10

11 Subcutaneous Administration An injection beneath skin into connective tissue or fat beneath dermis Used for small volumes of drugs (<0.5( ml) that do not irritate tissue Absorption rate is slow Can provide sustained effect Intramuscular Administration Injection given into skeletal muscle Absorption occurs more rapidly than SC injection Greater tissue blood flow Intravenous Administration An injection given directly into the bloodstream Bypasses absorption process Almost immediate effect Most IV drugs are administered slowly to help prevent adverse reactions 11

12 Intradermal Administration Injection just below the epidermis Primarily used for allergy testing and to administer local anesthetics Intraosseous Administration An injection directly into the bone marrow cavity through an IO infusion system Agents circulate via bone s s medullary cavity Time from injection to onset of action similar to venous route Endotracheal Administration Generally through an ET tube Drug delivery into the pulmonary alveoli Systemic absorption via lung capillaries Absorption almost as rapid as IV route Usually reserved for situations in which an IV line cannot be established 12

13 Endotracheal Administration Adult ET medications include: Lidocaine (Xylocaine) Epinephrine (Adrenalin) Atropine Naloxone (Narcan) Pulmonary Route Drugs given by gas or fine mist (aerosol) Absorption in blood is rapid due to: Large surface area Rich alveolar capillary network Produces primarily local effects Occasionally unwanted systemic effects Topical Route Drugs applied topically to skin and mucous membranes Usually rapidly absorbed to produce a local effect Only intact skin surfaces used to prevent systemic effects Massaging skin promotes drug absorption 13

14 Drug Distribution Transport of a drug through the bloodstream to body tissues and site of action Distribution rate depends on capillary permeability to drug Cardiac output and regional blood flow affect rate and extent of distribution Drug Reservoirs Drugs accumulate at storage sites, form reservoirs by binding to specific tissues Two types of drug reservoirs: Plasma protein binding Tissue binding Blood-Brain Brain Barrier Single layer of capillary endothelial cells Line blood vessels entering the CNS Permits only lipid-soluble drugs to be distributed into brain and CSF e.g., general anesthetics and barbiturates Drugs poorly soluble in fat have trouble passing this barrier Cannot enter the brain e.g., many antibiotics 14

15 Placental Barrier Membrane layers separate blood vessels of mother and fetus Not permeable to many lipid-insoluble insoluble drugs Provides some protection to the fetus Allows passage of certain non-lipid lipid-soluble drugs Steroids, narcotics, anesthetics, and some antibiotics Can affect developing embryo or neonate if given to pregnant mother Biotransformation Process by which the drug is chemically converted to a metabolite Purpose is to "detoxify" a drug and render it less active Liver is primary site of drug metabolism If drug metabolism is delayed, drug accumulation and cumulative drug effects may occur Excretion Elimination of toxic or inactive metabolites Organs of excretion Kidneys Intestine Lungs Sweat and salivary glands Mammary glands 15

16 Excretion by Kidneys Can be excreted in urine unchanged or as metabolite of its previous form Renal excretion Passive glomerular filtration Partial reabsorption Active tubular secretion Hemodialysis Substances completely or almost completely excreted by the normal kidney can be removed by this artificial process Not effective for highly tissue- or protein- bound drugs Limited benefit with rapidly acting toxins Excretion by the Intestine Drugs eliminated by biliary excretion After liver metabolism, metabolites are carried in bile, passed into duodenum, and eliminated with feces Some drugs are reabsorbed by the bloodstream, returned to the liver, and later excreted by the kidneys 16

17 Excretion by the Lungs Drugs that can be excreted by the lungs include General anesthetics Volatile alcohols Inhaled bronchodilators Factors that can alter elimination via the lungs are Rate and depth of respiration Cardiac output Secretion through Sweat and Salivary Glands Sweat is unimportant means of drug excretion Drugs excreted in saliva are usually swallowed and eliminated in the same manner as other orally administered drugs Excretion through Mammary Glands Many drugs or their metabolites cross the epithelium of the mammary glands Are excreted in breast milk Breast milk is acidic (ph 6.5) Nursing mothers are cautioned against medication use 17

18 Factors that Influence Actions of Drugs Age Body mass Gender Environment Time of administration Pathological state Genetic factors Psychological factors Pharmacokinetic Phase of Drug Action Pharmacodynamics Study of how a drug acts on a living organism Pharmacologic response relative to the concentration of a drug at an active site in the organism 18

19 Pharmacodynamics Most drugs produce effects by: Drug-receptor receptor interaction Agonists Antagonists Affinity Efficacy Types of receptors Drug-enzyme interaction Nonspecific drug interaction Drug-Receptor Interaction Drug-Receptor Interaction Agonists Drugs that bind to a receptor and cause a physiological response Antagonists Drugs that bind to a receptor and whose presence prevents a physiological response or other drugs from binding 19

20 Drug Response Assessment Assess by observing the physiological parameters e.g., BP, pain Effects of some drugs cannot be monitored solely by the patient's response Plasma Level Profiles Relationship between plasma concentration and level of therapeutic effectiveness over time Depend on: Rate of absorption Distribution Biotransformation Excretion Plasma Level Profiles Therapeutic range Concentration (dose) that provides highest probability of response Least risk of toxicity Some patients fail to respond to therapeutic doses Others may develop toxicity 20

21 Plasma Level Profiles Biological Half-Life Time needed to metabolize or eliminate half of total amount of drug in body A drug is considered gone from the body after five half-lives lives have passed Affected by renal and hepatic function Therapeutic Index Measures relative safety of a drug Ratio between: Lethal dose 50 (LD 50) Dose of a drug lethal in 50% of laboratory animals tested Effectiveness dose (ED 50) Dose that produces a therapeutic effect in 50% of a similar population TI = LD 50/ED 50 The closer the ratio to 1, the greater the danger in administering the drug to humans 21

22 Drug-Receptor Interaction Most drug actions Chemical interaction between drug and various receptors in body Most common form of drug action is the drug- receptor interaction Most drugs are thought to bind to drug receptors to produce their desired effect Drug Interactions Variables influencing drug interaction: Intestinal absorption Competition for plasma protein binding Drug metabolism or biotransformation Action at the receptor site Renal excretion Alteration of electrolyte balance Drug-Drug Interactions Some drug-drug interactions are dangerous Drugs associated with significant interactions: Blood thinners Tricyclic antidepressants Monoamine oxidase (MAO) inhibitors Amphetamines Digitalis glycosides Diuretics Antihypertensives 22

23 Drug Interactions Other factors influencing drug interactions: Drug-induced malabsorption of foods and nutrients Food-induced malabsorption of drugs Enzyme alterations that affect the metabolism of foods or drugs Alcohol consumption Cigarette smoking Food-initiated alteration of drug excretion Drug Storage Refer to local protocol Drug potency can be affected by: Temperature Light Moisture Shelf life Controlled medications security Paramedic Responsibilities Use correct medications and techniques Observe and document the effects of drugs Keep current on changes in pharmacology trends Maintain professional relationships with health care team 23

24 Paramedic Responsibilities Understand pharmacodynamics of drugs being administered Carefully evaluate patients for drug indications and contraindications Take a thorough patient medication history Consult with medical direction as needed Components of a Drug Profile Drug names Classification Indications Pharmacokinetics Side/adverse effects Components of a Drug Profile Dosages Routes of administration Contraindications Special considerations Storage requirements 24

25 Special Considerations Pregnant patients Pediatric patients Geriatric patients Pregnancy Ratings for Drugs Category A Risk of fetal harm remote Category B Inconclusive risk in first trimester, no risk in later trimesters Category C Give only if potential benefit outweighs risk to fetus Category D Evidence of fetal risk; may be acceptable if life-threatening situation Category X Risk outweighs any benefit Pediatrics Effects unpredictable in infants Drug doses weight related Higher doses of water-soluble drugs may be needed Less effective blood-brain brain barrier in infants Slow drug clearance, excretion Longer half-life life 25

26 Elderly Patient Causes of noncompliance and medication errors: Expense Forgetfulness or confusion Symptoms disappear Errors in taking medications Noncompliance may be deliberate Drugs that Affect the Nervous System Autonomic Nervous System Effects of many drugs depend on: Which branch of ANS they act on Whether the ANS branch is stimulated or inhibited by drug therapy 26

27 Autonomic Nervous System CNS Brain Spinal cord PNS Cranial and spinal nerves and their branches Connects all parts of body to CNS Types of Nerve Fibers Visceral afferent (sensory) Convey impulses from internal organs to CNS Visceral efferent (motor) Convey impulses from CNS to internal organs, glands, and smooth and cardiac muscle Somatic afferent (sensory) Convey impulses from head, body wall, and extremities to CNS Somatic efferent (motor) Convey impulses from CNS to striated muscles Autonomic Nervous System Peripheral nervous system provides a double set of nerve fibers: Sympathetic (adrenergic) Exit from thoracic and lumbar regions Parasympathetic (cholinergic) Exit from cranial and sacral portions 27

28 Autonomic Nervous System Sympathetic nerve stimulation Excitatory effects in some organs Inhibits effects in others Parasympathetic stimulation Excitation in some organs Inhibition in others Autonomic Nervous System Both systems function continuously Occasionally react in reciprocal fashion Most organs are dominantly controlled by one system Overview of Nervous System 28

29 Pre- and Postganglionic Neurons A two-neuron chain exists in a series between the CNS and effector organs Preganglionic neuron located in the CNS Passes between CNS and ganglia Postganglionic neuron located in the periphery Passes between ganglia and effector organ Synapse Junction between two neurons Autonomic Conduction Pathways Acetylcholine (ACh) Neurotransmitter At junction between preganglionic fiber and synapse At junction between postganglionic fiber and effector cell Fibers that release ACh are known as cholinergic fibers All preganglionic fibers of autonomic division All postganglionic fibers of parasympathetic division 29

30 Norepinephrine Neurotransmitter between sympathetic postganglionic fiber and effector cell Adrenergic fibers Release norepinephrine Most postganglionic neurons of the sympathetic division are adrenergic Nerve Impulse Transmission Acetylcholine combines with cholinergic receptors Nicotinic Excitatory response Muscarinic Excites or inhibits Nerve Impulse Transmission Norepinephrine combines with alpha and beta receptors in effector organs Binds to and activates both types of receptor molecules More affinity for alpha receptors 30

31 Nerve Impulse Transmission Epinephrine is an adrenergic substance: Produced by adrenal medulla Nearly equal affinity for both receptors In tissues containing alpha- and beta-receptor cells, one type is more abundant Has a dominating effect Nerve Impulse Transmission Drugs that Affect the ANS 31

32 Classifications Cholinergic (parasympathomimetic) Cholinergic blocking (parasympatholytic) Adrenergic (sympathomimetic) Adrenergic blocking (sympatholytic) Narcotic Analgesics and Antagonists Narcotic analgesics relieve pain Narcotic antagonists reverse the narcotic effects of some narcotic analgesics Pain Components Sensation of pain Involves the nerve pathways and the brain Emotional response to pain Anxiety level Previous pain experience Age Gender Culture 32

33 Narcotics Contain or abstracted from opium Morphine: Chief alkaloid of opium Bind with opioid receptors in brain and other body organs Alters pain perception and emotional response to pain Narcotics Undesirable effects Nausea and vomiting Constipation Urinary retention Cough reflex suppression Orthostatic hypotension CNS depression Opioid Analgesics Morphine (morphine sulfate) Codeine (methylmorphine) Hydromorphone (Dilaudid, Dilaudid-HP) Meperidine (Demerol) Methadone (Dolophine, Methadose) Oxycodone (Percodan, Tylox, Percocet) Hydrocodone (Lortab) Propoxyphene (Darvon, Dolene) 33

34 Opioid Antagonists Block opioid analgesics Displace analgesics from receptor sites Examples: Naloxone (Narcan) Naltrexone (Trexan) Nalmefene (Revex) Opioid Agonist-Antagonists Antagonists Analgesic and antagonist effects Pharmacokinetic and adverse effects similar to morphine Lower dependency risk than opioids Less severe withdrawal symptoms May cause withdrawal symptoms in addicts Nonnarcotic Analgesics Peripheral mechanism Interferes with local mediators released when tissue is damaged Mediators stimulate nerve endings Cause pain Nonnarcotic analgesics decrease nerve ending stimulation 34

35 CNS depressants Anesthetics Reversible action on nervous tissue Major categories of anesthesia: General Regional Local Antianxiety Agents and Alcohol Antianxiety agents Reduce feelings of apprehension Nervousness Worry Fearfulness Sedative-Hypnotic Agents Depress CNS Calming effect Sedatives and hypnotics differ by degree of CNS depression Agent may be sedative and hypnotic Depends on dose used 35

36 CNS depressant Alcohol Can produce sedation, sleep, and anesthesia Enhances sedative-hypnotic effects of other drugs Blood alcohol measured (mg/dl) Behavioral effects based on blood alcohol levels Benzodiazepines Bind to receptors in cerebral cortex and limbic system Actions Anxiety reducing Sedative-hypnotic Muscle relaxing Anticonvulsant Schedule IV drugs Benzodiazepines Commonly prescribed benzodiazepines Alprazolam (Xanax) Chlordiazepoxide (Librium) Clorazepate (Tranxene) Diazepam (Valium) Flurazepam (Dalmane) Prazepam (Centrax) Midazolam (Versed) Lorazepam (Ativan) Triazolam (Halcion) 36

37 Duration of action Ultra-short acting Short acting Intermediate acting Long acting Barbiturates Miscellaneous Sedative-Hypnotic Drugs Not benzodiazepines or barbiturates More like barbiturates than benzodiazepines Examples Chloral hydrate (Noctec) Ethchlorvynol (Placidyl) Meprobamate (Equanil, Meprospan) Some antihistamines have sedative effects Hydroxyzine hydrochloride (Vistaril, Atarax) Anticonvulsants Treat seizure disorders Mode of action not understood Choice of drug depends on: Type of seizure disorder Patient's drug tolerance Medication noncompliance common 37

38 CNS Stimulants Classified by site of action Cerebrum Medulla and brainstem Hypothalamic limbic regions Common CNS stimulant drugs Anorexiants Amphetamines Psychotherapeutic Drugs Psychotherapeutic drugs include Antipsychotic agents Antidepressants Lithium Treat psychoses and affective disorders Schizophrenia, depression, and mania Psychotherapeutic Drugs Neurotransmitters in CNS affecting emotion: Acetylcholine Norepinephrine Dopamine Serotonin Monoamine oxidase 38

39 CNS and Emotions Alterations in neurotransmitter levels associated with changes in mood and behavior Drug therapy alleviates symptoms Temporarily modifies unwanted behavior Antipsychotic Agents Schizophrenia (primary use) Tourette syndrome Senile dementia associated with Alzheimer disease Antipsychotic (neuroleptic) drugs block CNS dopamine receptors Antipsychotic Agents Classifications Phenothiazine derivatives Butyrophenone derivatives Dihydroindolone derivatives Dibenzoxapine derivatives Thienbenzodiazepine derivatives Atypical agents 39

40 Antidepressants Treatment of affective disorders (mood disturbances) Depression Mania Elation Tricyclic antidepressants and MAO inhibitors are prescribed for depression Lithium is preferred treatment for mania Antidepressants Newer classes of antidepressants (second- generation drugs) have been developed Examples Bupropion (Wellbutrin) Fluoxetine (Prozac) Trazodone (Desyrel) Sertraline (Zoloft) Paroxetine (Paxil) Tricyclic Antidepressants Increase levels (block reuptake) of norepinephrine and serotonin Examples Imipramine (Tofranil) Amitriptyline (Elavil) 40

41 MAO Inhibitors Central-acting acting monoamines, especially norepinephrine and serotonin are thought to cause depression and mania Monoamine oxidase is responsible for metabolizing norepinephrine within nerve MAO inhibitors block this enzyme, leading to increased norepinephrine levels Lithium Alters sodium transport in nerve and muscle cells Affects norepinephrine and serotonin Antimanic effects are thought to result from: Increased norepinephrine uptake Increased serotonin receptor sensitivity Drugs for Specific CNS-Peripheral Dysfunction Parkinson disease Muscle rigidity Tremors Suspected cause: Low dopamine levels Huntington disease Progressive dementia Involuntary muscle twitching Dopamine, acetylcholine imbalance 41

42 Drugs with Central Anticholinergic Activity Inhibit or block acetylcholine Anticholinergic Restore brain s s dopamine-acetylcholine acetylcholine balance Examples Benztropine (tablets and injections) Ethopropazine hydrochloride Drugs Affecting Brain Dopamine Three classifications Those that release dopamine Those that increase brain levels of dopamine Dopaminergic agonists Skeletal Muscle Relaxants Central acting Baclofen (lioresal) Cyclobenzaprine (flexeril) Diazepam (valium) Direct acting Dantrolene (Dantrium) Neuromuscular blockers Can cause paralysis Pancuronium (Pavulon), vecuronium (Norcuron) Succinylcholine (Anectine) 42

43 Drugs Affecting the ANS Autonomic drugs Mimic or block effects of sympathetic and parasympathetic divisions of autonomic nervous system Autonomic Drugs Cholinergic drugs Parasympathomimetic Mimic parasympathetic nervous system Cholinergic-blocking drugs Parasympatholytic Block parasympathetic nervous system Autonomic Drugs Adrenergic drugs Sympathomimetic Mimic sympathetic nervous system (adrenal medulla) Adrenergic-blocking drugs Sympatholytic Block actions of sympathetic nervous system (adrenal medulla) 43

44 Receptors Catecholamines act on alpha and beta receptors Alpha 1 Alpha 2 Beta 1 Beta 2 Norepinephrine Acts mainly on alpha receptors Epinephrine Acts on alpha and beta receptors Alpha and Beta Activities Alpha activities Vasoconstriction Arterioles in the skin and splanchnic area Pupil dilation Relaxation of the gut Beta activities Cardiac acceleration and increased contractility Vasodilation of skeletal muscle arterioles Bronchial relaxation Uterine relaxation Alpha-Blocking Drugs Block the vasoconstricting effect of catecholamines Used in certain cases of hypertension Prevent necrosis after norepinephrine (Levophed) or dopamine (Intropin) extravasation into tissues Limited use in prehospital setting 44

45 Beta-Blocking Blocking Agents Block beta receptors Selective beta 1 blockers Metoprolol, atenolol Treatment of hypertension, angina Nonselective beta blockers Nadolol, propranolol, labetalol Antianginal, antihypertensives Cardiac Drug Terminology Chronotropic drugs Affect heart rate Dromotropic drugs Affect conduction velocity through the conducting tissues of the heart Inotropic drugs Affect force of contraction Cardiac Glycosides Positive inotropic effect Increase contractility Negative chronotropic effect Slow heart rate Negative dromotropic effect Slow conduction velocity Digoxin (Lanoxin) Small therapeutic index Side effects common 45

46 Antidysrhythmics Treat and prevent disorders of cardiac rhythm Work by: Direct action on the cardiac cell membrane (lidocaine) Indirect action that affects the cell (propranolol) Both Antidysrhythmics Classifications Based on mode of action on cardiac muscle Drugs that belong to the same class do not produce identical actions All antidysrhythmics can suppress automaticity Class I Sodium Channel Blockers Class I-AI Decrease conduction velocity Prolong electrical potential of cardiac tissue Procainamide (Pronestyl) Class I-BI Decrease or have no effect on conduction velocity Lidocaine (Xylocaine) Class I-CI Profoundly slow conduction Control life-threatening ventricular dysrhythmias Flecainide (Tambocor) 46

47 Class II Beta-blocking agents Reduce adrenergic stimulation of the heart Negative chronotrope Propranolol (Inderal) Class III Potassium channel blockers Increase contractility Do not suppress automaticity Have no effect on conduction velocity Terminate dysrhythmias that result from reentry of blocked impulses Amiodarone (Cordarone) Class IV Calcium channel blockers Block inflow of calcium through cell membranes of cardiac and smooth muscle cells Depresses the myocardial and smooth muscle contraction Decreases automaticity and in some cases decreases conduction velocity Diltiazem (Cardizem) 47

48 Diuretics Antihypertensives Sympathetic blocking agents (sympatholytic drugs) Vasodilators Angiotensin-converting enzyme (ACE) inhibitors Calcium channel blockers Angiotensin II receptor antagonists Diuretics Renal excretion of excess salt and water Thiazide diuretics Moderately effective in lowering blood pressure Hydrochlorothiazide (HCTZ) Loop diuretics Short-acting agents that inhibit sodium and chloride reabsorption in loop of Henle Furosemide (Lasix) Potassium-sparing sparing diuretics Less potassium loss than other diuretics Spironolactone (Aldactone) Sympathetic Blocking Agents Beta-blocking agents and adrenergic- inhibiting agents Beta-blocking agents Treatment of suspected myocardial infarction, high-risk unstable angina, and hypertension Atenolol (Tenormin), metoprolol (Lopressor) Labetalol (Normodyne, trandate), nadolol (Corgard) 48

49 Adrenergic Inhibiting Agents Centrally acting adrenergic inhibitors Clonidine hydrochloride (Catapres) Peripheral adrenergic inhibitors Doxazosin (Cardura) Mechanism by which many of these agents work is unknown Vasodilator Drugs Act directly on the smooth muscle walls of arterioles, veins, or both Lower peripheral resistance and blood pressure Arteriolar dilator drugs Hydralazine (Apresoline) Arteriolar and venous dilator drugs Nitroglycerin sublingual tablet (Nitrostat) Angiotensin-Converting Enzyme (ACE) Inhibitors Angiotensin II is a powerful vasoconstrictor: Raises blood pressure Causes the release of aldosterone Contributes to sodium and water retention Inhibits conversion of angiotensin I to angiotensin II (brought about through ACE) Renin-angiotensin angiotensin-aldosterone aldosterone system is suppressed Blood pressure is lowered Captopril (Capoten) 49

50 Calcium Channel Blockers Inhibit contractility of vascular smooth muscle Reduce peripheral vascular resistance Dilate coronary vessels Verapamil (Isoptin) Diltiazem (Cardizem) Angiotensin II Receptor Antagonists Selectively inhibit angiotensin II receptors Lower systolic and diastolic BP Candesartan (Atacand) Irbesartan (Avapro) Losartan (Cozaar, Hyzaar) Monoamine Oxidase (MAO) Inhibitors Block release of norepinephrine at the sympathetic junction Interfere with vasoconstriction Reduce peripheral vascular resistance Decrease blood pressure Not widely used to treat hypertension 50

51 Antihemorrheological Agents Used to treat peripheral vascular disorders caused by pathological or physiological obstruction Antihemophilic Agents Hemophilia Hemophilia A (classic hemophilia) is caused by a deficiency of factor VIII Hemophilia B (the Christmas disease ) ) results from a deficiency in factor IX complex Replacement therapy of the missing clotting factor can be effective in the management of hemophilia Factor VIII (Factorate) Factor IX (Konyne) Antiinhibitor coagulant complex (Autoplex) Drugs that Affect the Blood Drugs that affect blood coagulation may be classified as: Antiplatelet agents Anticoagulant agents Fibrinolytic agents 51

52 Antiplatelet Agents Interfere with platelet aggregation Prevention of clots, MI, stroke Treatment of valvular disease, shunts Include: Aspirin Dipyridamole (Persantin) Abciximab (ReoPro) Anticoagulants Used to prevent intravascular thrombosis Decreases blood coagulability Examples Heparin (Liquaemin) Coumadin (Warfarin) Fibrinolytic Agents Used to dissolve clots after formation Used for some acute myocardial infarcts Used in some stroke patients Examples Streptokinase Tissue plasminogen activator (t-pa) Reteplase (Retavase) Alteplase (Activase) Tenecteplase (TNKase) 52

53 Hemostatic Agents Hasten clot formation to reduce bleeding Systemic hemostatic agents Control rapid blood loss after surgery by inhibiting fibrinolysis Topical hemostatic agents Control capillary bleeding during surgical and dental procedures Blood and Blood Components Replacement therapies Whole blood (rarely used) Packed red blood cells Fresh-frozen plasma Plasma expanders (Dextran) Platelets Coagulation factors Fibrinogen Albumin Gamma globulins Antihyperlipidemic Drugs Hyperlipidemia: Excess lipids in plasma Used in conjunction with diet and exercise to control serum lipid levels Examples Atorvastatin (Lipitor) Cholestyramine (Questran) Niacin (Nicobid) Pravastatin (Pravachol) Lovastatin (Mevacor) Simvastatin (Zocor) 53

54 Bronchodilators Primary treatment for obstructive pulmonary disease Asthma, chronic bronchitis, and emphysema Classified as: Sympathomimetic drugs Xanthine derivatives Many agents are administered by inhalation via a nebulizer or pressure cartridge Sympathomimetic Drugs Nonselective adrenergic drugs Have alpha, beta-1 1 (cardiac), and beta-2 2 (respiratory) activities Epinephrine (Adrenalin, Asmolin) Nonselective beta-adrenergic adrenergic drugs Have both beta-1 1 and beta-2 2 effects Isoproterenol inhalation aerosol (Isuprel) Selective beta-2 2 receptor drugs Act primarily on beta-2 2 receptors in the lungs Albuterol (Proventil, Ventolin) Xanthine Derivatives Xanthine drugs include caffeine, theophylline, and theobromine Actions Relax smooth muscle (particularly bronchial smooth muscle) Stimulate cardiac muscle and CNS Increase diaphragmatic contractility Promote diuresis through increased renal perfusion 54

55 Other Respiratory Drugs Prophylactic asthmatic agents Cromolyn sodium (Intal) Aerosol corticosteroid agents Beclomethasone dipropionate (Vanceril inhaler, Beclovent) Muscarinic antagonists Ipratropium (Atrovent) Antileukotrienes Montelukast (Singulair) Mucokinetic Drugs Move respiratory secretions and sputum along tracheobronchial tree Alter consistency of secretions so that they can more easily be removed from the body Diluents (water, saline) Expectorants (Mucomyst) Oxygen Treatment of hypoxia and hypoxemia Colorless, odorless, and tasteless gas essential for sustaining life 55

56 Respiratory Stimulants Direct stimulants (analeptics) Act on medullary center of brain Increase rate and depth of respirations Reflex respiratory stimulants Spirits of ammonia only inhalation drug given as a reflex respiratory stimulant Administered during cases of fainting Respiratory Depressants Includes opium and barbiturate groups Respiratory depression is a common side effect Seldom given to intentionally inhibit rate and depth of respiration Cough Suppressants Cough is a protective reflex to expel harmful irritants It may be: Productive (removes airway secretions) Nonproductive (dry and irritating) Antitussive agents Narcotic agents (codeine) Nonnarcotic agents Benzonatate (Tessalon) 56

57 Antihistamines Chemical mediator in most body tissues Highest in the skin, lungs, and GI tract Body releases histamine if exposed to antigen Antihistamines compete with histamine for receptor sites Prevent action of histamine Antihistamines H 1 receptors Act primarily on blood vessels and bronchioles H 2 receptors Act mainly on GI tract Anticholinergic or atropine-like action Antihistamines Primary clinical use is for allergic reactions Also for motion sickness, sedative, antiemetic Examples Dimenhydrinate (Dramamine) Diphenhydramine (Benadryl) Promethazine (Phenergan) 57

58 Serotonin Naturally occurring vasoconstrictor In platelets and in cells of brain and intestine Serotonin is not administered as a drug Has a major influence on other drugs and some disease states Helpful in repairing damaged blood vessels Stimulates smooth muscle contraction Acts as a neurotransmitter in the CNS Antiserotonins Antiserotonins (serotonin antagonists) work to inhibit responses to serotonin and its influence on other drugs and disease states Vascular headache, allergic disorder treatment Cyproheptadine (Periactin) Methysergide maleate (Sansert) Drugs Affecting the GI System Antacids (Alka-Seltzer) Antiflatulents (Mylicon) Digestants (Pancrease) Emetics (syrup of ipecac) 58

59 Drugs Affecting the GI System Antiemetics Compazine, Phenergan Cytoprotective agents Protect cells from damage Cytotec, Carafate Drugs Affecting the GI System H2 receptor antagonists Reduce volume and acidity of gastric acid Zantac, Tagamet, Pepcid Proton pump inhibitors Treat symptomatic gastroesophageal reflux disease, esophagitis Nexium, Prevacid, Prilosec, Aciphex Drugs Affecting the Lower GI Tract Laxatives Constipation causes: Neurological disease, pregnancy, rectal disorders, surgery, drug poisoning Epsom salt, Dulcolax, Colace Antidiarrheals Adsorbents (Pepto-Bismol) Anticholinergics (Donnatal) Opiates (paregoric) Other (Lomotil, Imodium) 59

60 Drugs Affecting the Eye Antiglaucoma agents Pilocarpine, acetazolamide Mydriatic and cycloplegic agents Treat inflammation, relieve pain Atropine, homatropine opthalmic solution Drugs Affecting the Eye Antiinfective/antiinflammatory agents Treat conjunctivitis, sty, keratitis Topical anesthetic agents Prevent pain, rapid onset Proparacaine HCl, tetracaine HCl Drugs Affecting the Ear Antibiotics for infection Chloramphenicol Steroid/antibiotic combinations Superficial bacterial infections Cortisporin Otic Miscellaneous preparations Treat ear wax, fungal infections, inflammation 60

61 Drugs Affecting the Endocrine System Endocrine system works to control and integrate body functions Natural chemicals (hormones) are produced by endocrine glands Drugs Affecting the Pituitary Anterior and posterior pituitary gland hormones regulate secretion of other hormones Anterior pituitary drugs Treat growth failure in children caused by growth hormone deficiency Posterior pituitary drugs Treat symptoms of diabetes insipidus due to antidiuretic hormone deficiency Drugs Affecting the Thyroid Thyroid hormone controls rate of metabolic processes Required for normal growth and development Parathyroid hormone regulates level of ionized calcium in blood through: Release of calcium from bone Absorption of calcium from the intestine Rate of excretion of calcium by the kidneys 61

62 Thyroid Gland Disorders Goiter Enlargement of thyroid Hypothyroidism Thyroid hormone deficiency Hyperthyroidism Thyroid hormone excess Drugs to treat hypothyroidism and prevent goiters Thyroid (Synthroid) Iodine products Levothyroxine Parathyroid Disorders Hypoparathyroidism and hyperparathyroidism Drugs to treat hyperparathyroidism Vitamin D Calcium supplements Drugs Affecting the Adrenal Cortex Adrenal cortex secretes steroid hormones Glucocorticoids (cortisol) Raise blood glucose Deplete tissue proteins Suppress the inflammatory reaction Mineralocorticoids (primarily aldosterone) Regulate electrolyte and water balance Sex hormones Little physiological effect under normal circumstances 62

63 Drugs Affecting the Pancreas Hormones of the pancreas Insulin Primary hormone that regulates glucose metabolism Glucagon Stimulates liver to break down glycogen so that glucose is released into the blood Also inhibits uptake of glucose by muscle and fat cells Drugs Affecting the Pancreas Insulin Preparations Rapid acting Insulin lispro Insulum aspart Short acting Regular Intermediate acting Lente Insulin NPH Insulin Long acting Ultralente Insulin glargine Oral Hypoglycemic Agents Amaryl Glucophage Glucotrol Micronase Oral Combination Agents Glucovance Metaglip Avandamet Drugs Affecting the Pancreas Hyperglycemic Agents Glucagon Diazoxide (Proglycem) Dextrose Oral glucose (Glutose, Insta-Glucose) 63

64 Drugs Affecting the Reproductive System Includes synthetic and natural substances Hormones Female Male Female Sex Hormones Two hormones secreted by ovary: Estrogen Progesterone Supplemental estrogen indicated for: Estrogen deficiency or replacement Treatment of breast cancer Prophylaxis for osteoporosis in postmenopausal women Progesterone (and synthetic progestins) used to: Treat hormonal imbalance Treat endometriosis Treat specific cancers Prevent pregnancy when properly used Oral Contraceptives Oral contraception most effective form of birth control Commonly known as the pill Combination of estrogen and progesterone that results in suppression of ovulation Available in several different forms 64

65 Ovulatory Stimulants and Infertility Drugs Absence of ovulation (anovulation) may be a pathological condition in women with abnormal bleeding or infertility Sometimes treated with: Gonadotropins Thyroid preparations Estrogen Synthetic agents Drugs Affecting the Male Reproductive System Testosterone therapy Indicated for treatment of: Hormone deficiency (e.g., testicular failure) Impotence Delayed puberty Female breast cancer Anemia Drugs Affecting Sexual Behavior Drugs that impair libido and sexual gratification Includes some antihypertensives, antihistamines, antispasmodics, sedatives, tranquilizers Drugs that enhance libido and sexual gratification Levodopa (L-dopa) Sildenafil (Viagra) 65

66 Drugs Used in Neoplastic Diseases Antineoplastic agents Used in cancer chemotherapy to prevent proliferation of malignant cells Do not directly kill tumor cells Interfere with cell reproduction or replication Examples Adrucil Mustargen Amethopterin Antibiotics Treat local or systemic infection Kill or suppress growth of microorganisms Disrupt bacterial cell wall Disturb functions of cell membrane Interfere with cell s s metabolic functions Includes: Penicillins Cephalosporins and related products Macrolide antibiotics Tetracyclines Miscellaneous antibiotic agents Antifungal Drugs Some fungi are always present in body Mouth, skin, intestines, and vagina Prevented from multiplying through competition from bacteria and from actions of the immune system Infection occurs when person becomes immunocompromised Tinactin, Diflucan, Mycostatin 66

67 Antiviral Drugs Few effective drugs to treat minor viral infections Viral infections range from harmless (e.g., warts) to serious diseases Often have toxic effects Acyclovir (Zovirax) Zidovudine (Retrovir) Lamivudine; zidovudine (Combivir) Protease Inhibitors Complete mechanism of action not clear Appear to inhibit replication of retroviruses (e.g., HIV) in acute and chronically infected cells Side effects and adverse reactions Indinavir (Crixivan) Ritonavir (Norvir) Analgesic-Antipyretic Antipyretic Drugs Antipyretics reduce fever Analgesic-antipyretic antipyretic drugs work by reversing the effect of the pyrogen on the hypothalamus Analgesics act on peripheral pain receptors to block activation Acetaminophen Aspirin 67

68 Nonsteroidal Antiinflammatory Drugs Aspirin is the prototype of the NSAIDs Inhibit enzymes so that prostaglandins (substances that promote inflammation and pain) are not formed Aspirin Ibuprofen Naproxen Ketorolac Celecoxib Drugs Affecting the Immunological System Immunosuppressants Antirejection, anticancer, corticosteroid drugs Immunomodulating agents Serums Vaccines Conclusion To ensure maximum effectiveness and reduce the potential for harm, the paramedic must have a thorough understanding of drugs and their actions before they are administered. 68

69 Questions? 69

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