NCM 106 Pharmacology Lecture 5 PDF

NCM 106: Pharmacology Lecture 5: DRUGS ACTING ON THE IMMUNE SYSTEM, CNS, AND PNS Compiled by: Villanueva, Bea Denise PART 1: DRUGS ACTING ON THE IMMUNE SYSTEM Immune system - responsible for recognizing and disposing of foreign material, such as bacteria, viruses, fungi,...

NCM 106: Pharmacology Lecture 5: DRUGS ACTING ON THE IMMUNE SYSTEM, CNS, AND PNS Compiled by: Villanueva, Bea Denise PART 1: DRUGS ACTING ON THE IMMUNE SYSTEM Immune system - responsible for recognizing and disposing of foreign material, such as bacteria, viruses, fungi, protozoa, worms, drugs or even transplanted organs that enter the body. Immunity - could be natural, (inborn & permanent) and acquired. Both of this immunity involves cellular and chemical components of the body. Injury – causes damage to tissues or cells Tumor (swelling) - body reacts by sending extra fluid to the injured area to protect and heal it Rubor - blood vessels around the injury get wider to let more blood flow to the area Calor (heat) - increased blood flow also brings warmth to the area Dolor - injury and swelling can irritate nerves, which send pain signals to the brain CELLULAR COMPONENTS Mast cells: Large tissue cells that release chemical substances that promote inflammation by increasing the permeability of the blood vessels. Polymorphonuclear leukocytes (PMN): another cellular component which is considered to be scavenger white blood cells that have granules with powerful antibacterial enzymes. Macrophages: Large tissue cells that remove damage cells, bacteria, and other debris from the body. Lysosome: an enzyme released by macrophages which attack the cell wall of the bacteria. Interferon & Interleukins: low molecular weight proteins that regulate the extent and duration of the immune and inflammatory response. INFLAMMATION - a normal reaction of living tissue to injury and is usually considered as a useful and part of body defenses. DRUGS USED TO TREAT INFLAMMATION ARE GENERALLY CLASSIFIED AS: 1. Steroidal - chemically related to cortisone, a hormone secreted by the adrenal cortex. 2. Nonsteroidal - synthetic compound not chemically related to substances produced in the body. NONSTEROIDAL ANTI-INFLAMMATORY AGENTS (NSAIDs) are considered to be the most important treatment for rheumatoid arthritis and related inflammatory disorders. VILLANUEVA | 1 NCM 106: Pharmacology Lecture 5: DRUGS ACTING ON THE IMMUNE SYSTEM, CNS, AND PNS Compiled by: Villanueva, Bea Denise are believed to exhibit varying degree of analgesic and antipyretic effects and exert anti-inflammatory effects by inhibiting the release of prostaglandins may be classified as Salicylates and Non-salicylate NSAIDS MEDICATIONS A. Salicylates - are drugs chemically related to salicylic acid. Example: Aspirin - (ASA) inhibitor of prostaglandin and produces adverse effects like gastric intolerance and bleeding. - Hypersensitivity may also develop. - It is also a good anti platelet aggregation making it useful in preventing heart attacks. B. Non-Salicylates NSAID - treatment of most forms of arthritis. This includes agents that inhibit both cyclooxygenase, (COX-1) and (COX-2) prostaglandins - able to control pain and inflammation but they also have adverse effects like gastric irritation and risk for gastric bleeding especially when used for chronic conditions. Example of Non-Salicylates NSAIDs: 1. Celecoxib (Celebrex) - not recommended during the 3rd trimester of pregnancy. 2. Diclofenac (Voltaren, Cataflam) - do not crush enteric coated tablets and avoid taking this drug with milk, antacids and alkaline foods. 3. Etodolac (Lodine) - indicated for acute and long-term mgt. of pain and symptoms of osteoarthritis. 4. Ibuprofen (Advil) - may develop visual changes. 5. Indomethacin (Indocin) - may impair alertness, avoid use with aspirin, and observe from s/s of Gl bleeding such as black, tarry stool. - May produce visual & hearing changes, and sodium retention. - not recommended for children below 14 y/o. 6. Ketoprofen (Oruvail) - available in a 200 mg sustained release capsule. 7. Ketorolac (Toradol) - protects this drug from light and should be used only for a brief period (less than 1 week). - Should be given round the clock for best effect. 8. Naproxen (Naprosyn) - may prolong bleeding time. Use cautiously to the patient who is 9. Piroxicam (Feldene) - given OD and therapeutic effect is not evident for the first 2 weeks of therapy. PATIENT TEACHING TIPS 1. Patients should understand that NSAIDs are for the treatment of pain, an injury, or a disease process by decreasing the inflammation that leads to pain 2. Patients should know the various and most common side effects of NSAIDS 3. Because these agents can cause Gl upset, it must be taken with food, milk, or antacid 4. Patients should monitor their stools for bleeding 5. Drug interactions information must be given to patients for each NSAIDs medications. NURSING CONSIDERATION 1. Many contraindications to the use of NSAIDs such as GI tract lesions, peptic ulcers, allergies to them, and bleeding disorders. 2. Most NSAIDs are better tolerated orally if taken with food to minimize Gl upset. 3. Patients should be closely monitored for the occurrence of bleeding such as blood in the stool or emesis. 4. Therapeutic effects in patients with arthritis usually occur within 3-4 weeks. VILLANUEVA | 2 NCM 106: Pharmacology Lecture 5: DRUGS ACTING ON THE IMMUNE SYSTEM, CNS, AND PNS Compiled by: Villanueva, Bea Denise CORTICOSTEROIDS are steroidal agents that are used for systemic & local inflammatory disorders. have the capacity to prevent or suppress the development of inflammatory symptoms but the underlying cause of the symptoms may remain and the disease may continue to progress. It may also suppress symptoms that can be used in diagnosing a disease and evaluating the effectiveness of treatment These drugs are used for systemic conditions like bronchial, asthma, neoplastic disease and other endocrine disorders It is safer if used locally such as in joint or single skin lesions. These are used widely as topical treatment for dermatological disorders, like dermatitis and psoriasis. Systemic use may be associated with gastric ulceration, hypertension, changes in fat deposits and suppression of the hypothalamic pituitary adrenal system. CORTICOSTEROID MEDICATIONS A. Naturally occurring steroids compounds - are produced in the adrenal cortex which have anti-inflammatory and salt retaining properties. Ex: Glucocorticoids & Mineralocorticoids. B. Synthetic Steroids - Most of these agents alter CHO, CHON, and lipid metabolism by changing the ways in which these nutrients are metabolized and distributed. Ex: Prednisone and Prednisolone have the same effects to that of the 2 natural steroids Systemic steroids - A corticosteroid taken by mouth or given by intramuscular injection these are synthetic derivatives of the natural steroid, cortisol, produced by the adrenal glands, and have profound anti-inflammatory effects. Example: 1. Betamethasone 2. Triamcinolone 3. Dexamethasone 4. Prednisolone 5. Hydrocortisone 6. Methylprednisolone C. Mineralocorticoids - act on the distal tubules of the kidney to enhance reabsorption of Na from the tubular fluid to the plasma. - These agents are also capable of increasing excretion of K and hydrogen ions and alters fluid and electrolyte balance Adverse Effects 1. Fluid retention 2. Altered glucose level 3. Altered fat deposition (moon face, buffalo bump) 4. Muscle wasting in extremities & delayed growth in children PATIENT TEACHING TIPS 1. Emphasize importance of not discontinuing medications and take exactly as ordered 2. Report unpleasant side effects like fever, weakness or lethargy, and sore throat 3. Encourage adequate rest, exercise, and nutrition 4. Topical corticosteroid must be applied as recommended and oral agents are to be taken with meal or food. VILLANUEVA | 3 NCM 106: Pharmacology Lecture 5: DRUGS ACTING ON THE IMMUNE SYSTEM, CNS, AND PNS Compiled by: Villanueva, Bea Denise 5. Keep medications out of reach of children. NURSING CONSIDERATION 1. Administer medication as ordered and keep in mind all special instructions prior to administration. 2. Adverse effects to monitor includes weight gain, blood pressure, pulse, mental and nutritional status, electrolyte imbalance, and fluid volume excess 3. Patients should not be taken off these agents abruptly 4. Monitor patients carefully for other side effects like jaundice, rash, fever, or skin lesions AGENTS THAT PROVIDE ACTIVE & PASSIVE IMMUNITY (VACCINES) The normal immune system is capable of defending the body from invasion of organisms by natural resistance and stimulation of the body's defenses. In cases where the natural and adaptive immune responses are inadequate or may not be effective, there's a need to stimulate the immune system through immunization. A. Passive Immunization - involves administering preformed antibodies that will act rapidly but has a shorter duration of action. I. Immune Serums 1. (CMV) Cytomegalovirus (IV) - to prevent CMV during kidney transplant Immune globulin 2. Hepatitis B immune Globulin (IM) - contraindicated to patient who is allergic to gamma globulin and to those with anti- immunoglobulin A antibodies (IM) 3. Immune globulin (IV) - for patients with immunodeficiency syndrome. (HIV/AIDS) - Do not use a solution that has been frozen & turbidity exists 4. Immune globulin (IM) - for prevention of Hepa A, and rubella in the high-risk group. - use of the muscles of the buttocks is preferred. 5. RHO (D) Immune globulin (RhoGAM) (IM, IV) - used for suppression of the Immune response of non- sensitized RHO (D) negative persons who receive RHO (D) positive blood. 6. Tetanus immune globulin (IM) - used to prevent tetanus infection. 7. Varicella-zoster immune globulin (IM) - used for persons exposed to varicella. (Chicken pox) - obtain weight of the patient prior to injection. II. Antivenins and Antitoxins 1. Antivenin polyvalent (IV, IM) - for protection against the venoms of the rattlesnakes, cotton mouths, copperheads and moccasins. It should be given as soon as possible after bite. 2. Black widow spider species antivenin (IM, IV) - used for the treatment of bites of black widow spider. IV route is preferred for children. 3. Diphtheria Antitoxin (IM, IV) - use to prevent diphtheria. Be alert for s/s of anaphylaxis. 4. Tetanus Antitoxin (IM, SC, IV) - given if tetanus immune globulin is not available. - given at the same time with tetanus toxoid. B. Active Immunization - involves administering antigen (vaccine) that is diluted, weakened or killed to make it sure that this will not harm the body. I. Bacterial vaccine 1. BCG vaccine (ID) - prevents TB. It is not given to patient who is positive to tuberculin test. - a live vaccine so proper handling is needed. 2. Haemophilus B vaccine (IM) - used against Haemophilus influenza B. It should not be given if fever and active infection exist. 3. Meningococcal vaccine (SC) - prophylaxis for meningitis. 4. Pneumococcal vaccine (SC, IM) - prevention for most common types of pneumococci. 5. Typhoid vaccine (PO, SC, ID) - used for protection against typhoid. VILLANUEVA | 4 NCM 106: Pharmacology Lecture 5: DRUGS ACTING ON THE IMMUNE SYSTEM, CNS, AND PNS Compiled by: Villanueva, Bea Denise II. Viral vaccine 1. Hepatitis A vaccine (IM) - immunization against Hépa A virus. 2. Hepatitis B vaccine (IM) - immunization against hep B virus. 3. Influenza Virus vaccine (IM) - protection against strains of influenza viruses. 4. Japanese encephalitis virus vaccine (IM) - active immunization against Japanese encephalitis virus 5. Measles, mumps, rubella live vaccine MMR (IM) - simultaneous vaccine against measles, mumps, and rubella 6. Measles (rubeola) vaccine (IM) - given to children 15 months and older. 7. Mumps virus vaccine (IM) - for children 12 months 8. Poliovirus vaccine (IM, PO) - immunization against poliomyelitis. 9. Varicella vaccine (IM) - effective against chickenpox and shingles. III. Toxoids 1. DPT vaccine (IM) - only well children 2 months and above not more than 7 y/o should be given. 2. Tetanus toxoid (IM) - recommended for adults and children who are frequently exposed to injuries RA 10152 - an act providing for mandatory basic immunization services for infants and children, repealing for the purpose presidential decree no. 996 Department of Health - Expanded Program on Immunization Recommended Adult Immunization Schedule for ages 19 years or older by Center for Disease Control and Prevention (CDC) VILLANUEVA | 5 NCM 106: Pharmacology Lecture 5: DRUGS ACTING ON THE IMMUNE SYSTEM, CNS, AND PNS Compiled by: Villanueva, Bea Denise AGENTS USED IN THE PROPHYLAXIS OF RABIES Rabies - infection that affects humans usually transmitted by a bite or scratch of an infected animal. VACCINES 1. Rabies immune globulin, human - a passive protection against rabies after exposure. Injection site may develop soreness and slight fever may occur. 2. Rabies vaccine human, human diploid cell culture (ID, IM) - pre-exposure treatment of persons at risk for contact with rabid animal. IMMUNOSUPPRESSANT AGENTS agents that suppress the immunological system of the body They are used to prevent organ rejection in kidney, liver, heart and other organ transplants. They are used in combination with corticosteroids to improve efficacy IMMUNOSUPPRESSANT AGENTS 1. Azathioprine - a derivative of 6-mercaptopurine, an antimetabolite used in the treatment of other forms of Cancer. - some of its adverse effects are bone marrow depression, nausea and vomiting, and carcinogenicity. 2. Cyclosporine - considered to be one of the most effective immunosuppressant agents. - believed to be responsible for the dramatic advances made in the transplant surgery. - it is nephrotoxic and may cause tremor, hirsutism, hypertension and gum hyperplasia. 3. Tacrolimusan - an immunosuppressant agent that prolongs the survival of the host and transplanted grafts in clients who had organ transplants. 4. Basiliximab - one of the newer agents that prevents acute rejection in adults and children 2 years and older after kidney transplant. 5. Mycophenolate Mofetil HCL - a prophylactic agent but is not recommended for children. - used in combination with other immunosuppressant agents and corticosteroids. Below are some of the newest agents used as immunosuppressant are: 1. Sirolimus 2. Lymphocyte Immune globulin 3. Mycophenolic acid 4. Cytomegalovirus Immune Globulin PATIENT TEACHING TIPS 1. Patient should avoid crowds to minimize infection 2. It may take a few months for a therapeutic response to be experienced by the patient. 3. For women, they must use contraception during treatment and up to 12 weeks after the end of therapy 4. Watch out carefully for any side or adverse effects and report to provider immediately 5. Patients should be made aware that lifelong therapy is indicated with organ transplantation. VILLANUEVA | 6 NCM 106: Pharmacology Lecture 5: DRUGS ACTING ON THE IMMUNE SYSTEM, CNS, AND PNS Compiled by: Villanueva, Bea Denise NURSING CONSIDERATION 1. Lab studies like blood work ups should be performed and recorded before, during, and after the therapy. 2. If taken orally, it should be taken with food to minimize Gl upset. 3. Oral forms of the drugs should be used whenever possible to decrease the risk infection associated with IM injections 4. Patients should report any fever, sore throat, chills, joint pain, or fatigue, which may indicate severe infection. PART 2: Drugs Acting on the CNS (brain & spinal nerve) and PNS Our nervous system is divided in two components: 1. Central nervous system (CNS), which includes the brain and spinal cord 2. Peripheral nervous system (PNS), which encompasses nerves outside the brain and spinal cord. PHYSIOLOGICAL FUNCTIONS OF THE MAIN CNS NEUROTRANSMITTERS 1. Noradrenaline - control of mood (functional deficiency resulting depression), controlling wakefulness, and alertness. 2. Dopamine - is important in motor control (Parkinsonism is due to dopamine deficiency), has behavioral effects (excessive dopamine activity is implicated in schizophrenia), important in hormone release (prolactin, GH) and dopamine in chemoreceptor trigger zone causes nausea and vomiting. 3. 5-HT (Serotonin)- Physiological functions includes; feeding behavior, behavioral response (hallucinatory behavior), control of mood and emotion, control of body temperature and vomiting. 4. Acetylcholine (Ach) - has effects on arousal, on learning, and on short-term memory. Dementia and parkinsonism are associated with abnormalities in cholinergic pathways. 5. GABA (gamma-aminobutyric acid)- is an inhibitory neurotransmitter in CNS. 6. Glycine- acts on GABA like receptor in the spinal cord. GENERAL ANESTHETICS General anesthesia involves the physiological changes: Reversible loss of response to painful stimuli, loss, of consciousness and loss of motor and autonomic reflexes. General anesthetics are classified into two based on their route of administration as inhalation and intravenous anesthetics. INHALATION ANESTHETICS 1. Halothane - Is the most widely used agent, highly lipid soluble, potent. 2. Nitrous Oxide - Odorless and colorless gas. It is rapid in action and an effective analgesic agent. 3. Enflurane - Halogenated ether that is less toxic than halothane 4. Ether - Has analgesic and muscle relaxant properties. INTRAVENOUS ANESTHETICS 1. Thiopentone - a barbiturate with very high lipid solubility 2. Etomidate - suppresses the adrenal cortex 3. Ketamine - known as dissociative anesthesia 4. Benzodiazepines - useful in anesthesia as premedication and intraoperative sedation 5. Opioid Analgesic - can be used for general anesthesia 6. Preanesthetic medication - making anesthesia safer and agreeable to the patient SEDATIVE AND HYPNOTIC DRUGS Anxiolytic drugs - treat the symptoms of anxiety, whereas hypnotic drugs used to treat insomnia. The same drugs are used for both purposes. VILLANUEVA | 7 NCM 106: Pharmacology Lecture 5: DRUGS ACTING ON THE IMMUNE SYSTEM, CNS, AND PNS Compiled by: Villanueva, Bea Denise 1. Benzodiazepines- are the most important group, used as sedative and hypnotic agents. 2. 5-HT1A receptor agonist (e.g. buspirone) - is recently introduced anxiolytic. 3. Barbiturates (phenobarbitone) - are nowadays less commonly used as sedative hypnotics. 4. B -adrenoceptor antagonists (Propranolol) - are used to treat some forms of anxiety, where physical symptoms (sweating, tremor, and tachycardia), are troublesome. They are not used as hypnotics. 5. Miscellaneous drugs (Chloral Hydrate, Paraldehyde, and Diphenhydramine) - are not commonly recommended for anxiety or insomnia. ANTIEPILEPTIC DRUGS Seizure - is associated with the episodic high frequency discharge of impulses by a group of neurons in the brain. - It may be partial or generalized depending on the location and the spread of the abnormal neuronal discharge. The attack mainly involves motor, sensory or behavioral phenomena. Partial seizures - are often associated with damage to the brain, whereas generalized seizure occurs without obvious cause. - Two common forms of generalized seizures are grand mal and petit mal. ANTICONVULSANT DRUGS 1. Phenytoin - commonly used antiepileptic drug. It is effective against different forms of partial and generalized seizures; however, it is not effective in absence seizures. 2. Carbamazepine - derived from tricyclic antidepressant. it is chiefly effective in the treatment of partial seizure. It is also used in the treatment of trigeminal neuralgia and manic-depressive illness. 3. Valproate - is chemically unrelated to the other antiepileptic drugs. It is used in grand mal, partial, petit mal and myoclonic seizure. 4. Ethosuximide - Has fewer side effects and used in the treatment of absence seizures. 5. Phenobarbitone - the clinical use is nearly the same as that of phenytoin Grand mal seizure (tonic-clonic seizure) - loses consciousness, their muscles stiffen (tonic phase), and then they experience shaking or jerking movements (clonic phase). Petit mal seizure (absence seizure) – milder, zone out ANTIPARKINSON AGENTS Parkinsonism - is characterized by a combination of rigidity, bradykinesia, tremor, and postural instability. - It is due to the imbalance between the cholinergic and dopaminergic influences on the basal ganglia. AIM OF THE TREATMENT: either to increase dopaminergic activity (by dopamine agonist) or to decrease cholinergic (antimuscarinic drugs) influence on the basal ganglia. 1. Levodopa - the immediate metabolic precursor of dopamine, does penetrate the blood brain barrier, where it is decarboxylated to dopamine. 2. Dopamine agonists - drugs acting directly on dopamine receptors like Bromocryptine. 3 Mongamine Oxidase Inhibitors a. Selegiline (Deprenyl) - a selective inhibitor of monoamine oxidase B that hinders the breakdown of dopamine b. Amantadine - an antiviral agent that may potentiate dopaminergic function by influencing the synthesis, release, or reuptake of dopamine. 4. Acetylcholine Blocking Drugs - a centrally acting antimuscarinic preparations. Antimuscarinic drugs may improve the tremor and rigidity of Parkinsonism but have little effect on bradykinesia. Examples: Benztropine and Trihexyphenidyl VILLANUEVA | 8 NCM 106: Pharmacology Lecture 5: DRUGS ACTING ON THE IMMUNE SYSTEM, CNS, AND PNS Compiled by: Villanueva, Bea Denise ANTIPSYCHOTIC DRUGS Psychotic illness - characterized by delusion, hallucinations, thought disorder, social withdrawal and flattering of emotional response. Antipsychotics are a group of drugs used mainly for treating schizophrenia. 1. Typical neuroleptics (Chlorpromazine, Thioridazine, Haloperidol, Flupenthixol). The Phenothiazine antipsychotic drugs, with chlorpromazine as the prototype, have a wide variety of central nervous system, autonomic, and endocrine effects. It blocks receptors including; dopamine and alpha-adrenoceptor, muscarinic, H1 histaminic, and serotonin (5-HT2) receptors. 2. Atypical neuroleptics (Clozapine, Sulpiride) Clinical uses Schizophrenia Mania Vomiting Adverse Reactions Extrapyramidal reactions Seizures Autonomic nervous system effects (antimuscarinic effects, orthostatic hypotension) Metabolic and Endocrine Effects (weight gain, hyperprolactinemia, infertility, loss of libido and impotence) ANTIDEPRESSANT AGENTS Depression is one of the most common psychic disorders. Antidepressants are the drugs which are mainly used in the management of depression. 1. Tricyclic antidepressants (TCAS)- TCAs block the uptake of amines (noradrenaline and 5-HT) by nerve terminals by competition for the carrier transport system like Imipramine and Amitriptyline 2. Monoamine oxidase inhibitors (MAOI)- MAOI causes a rapid and sustained increase in the 5-HT (serotonin), noradrenaline and dopamine like Tranylcypromine which inhibits MAO-A 3. 5-HT uptake inhibitors - like Fluoxetine and Fluvoxamine lack antimuscarinic and cardiovascular effects. 4. Atypical antidepressants - have no common mechanisms of action, some are monoamine uptake blockers, but others act by unknown mechanisms. Clinical Indications: The major indication of TCAs is endogenous depression, panic attacks, phobic and obsessional states (clomipramine) and bed-wetting in children. MAOIs are used in severe depression refractory to other treatment and phobias. Adverse Effects: Postural hypotension, dry mouth, blurred vision, constipation, urine retention, sedation, are the most important side effects of TCAS. MAOI causes postural hypotension, atropine-like effects, weight gain, and CNS stimulation causing restlessness, tremor, and insomnia. OPIOD ANALGESICS Opioid is any substance that can produce morphine-like effects. - are used in severe, constant pain, acute pulmonary edema (pulmonary edema associated with left ventricular failure), cough suppression, diarrhea, and pre- anaesthetic medication. Opium is an extract of the juice of the poppy Papaver Somniferum that contains many alkaloids related to morphine. VILLANUEVA | 9 NCM 106: Pharmacology Lecture 5: DRUGS ACTING ON THE IMMUNE SYSTEM, CNS, AND PNS Compiled by: Villanueva, Bea Denise 1. Morphine analogues. Compounds closely related in structure to morphine. They may be agonist (Codeine and Heroin), partial agonists (Nalorphine) or antagonists (Naloxone). 2. Synthetic derivatives. Pethidine, Fentanyl, Methadone, and Pentazocine are examples of synthetic derivatives. EFFECTS OF MORPHINE AND ITS SYNTHETIC DERIVATIVES 1. Central nervous system effects - The principal effects of the opioid analgesics with affinity for mu receptors are on the central nervous system; the more important ones include analgesia, euphoria, sedation, and respiratory depression. With repeated use, a high degree of tolerance occurs to all of these effects except respiratory depression. They also cause addiction and dependence. 2. Peripheral nervous system effects a. Cardiovascular system: Hypotension effects b. Gastrointestinal tract: Constipation c. Biliary tract: Biliary colic d. Genitourinary tract: Depressed renal function e. Uterus: May prolong labor f. Neuroendocrine: Inhibit the release of luteinizing hormone CNS STIMULANTS Central Nervous System (CNS) stimulants stimulate the central nervous system are therapeutically not so useful as they lack selectivity of action. 1. Convulsants and Respiratory Stimulants - can be used in respiratory failure eg. Srychnine Picrotoxin, Nikethaimide 2. Psychomotor Stimulants - can cause increased motor activity, euphoria, excitement and anorexia due to release of noradrerline and dopamine eg. Amphetamine, cocaine, caffeine 3. Psychotomimetic Drug - can cause sensory changes, hallucinations and delusions eg. Lysergic and Diethylamide (LSD), Psilocybin, Phencyclidine. LOCAL ANESTHETICS Local anesthetics - it blocks the initiation of action potentials by preventing the voltage- dependant increase in Na+ conductance - used in minor surgery, dentistry, abdominal surgery and painless childbirth - are either Esters (Procaine, Dibucaine, Benzocaine, etc) which contain compounds are usually inactivated in the plasma and tissues by non-specific esterases or Amides (Lidocaine, Prilocaine, Bupivacaine, etc). THE METHODS OF ADMINISTRATION AND CLINICAL USES OF LOCAL ANESTHESIA VILLANUEVA | 10  NCM 106: Pharmacology Lecture 5: DRUGS ACTING ON THE IMMUNE SYSTEM, CNS, AND PNS Compiled by: Villanueva, Bea Denise PATIENT TEACHING TIPS 1. Take medication as prescribed 2. Avoid abrupt withdrawal 3. Do not take OTC meds without checking with your physician 4. Keep medications out of reach of children 5. Avoid consuming alcohol 6. Report any untoward reactions immediately 7. Keep all appointments and follow up visits with your physician 8. It may take a few weeks to notice the therapeutic effects of the drug. PART 3: DRUGS ACTING ON THE ANS ANS or the Autonomic Nervous System is the part of the PNS that controls involuntary functions in the body, like circulation, respiration, digestion and the maintenance of body temperature. It is subdivided into two major sub-divisions: 1. sympathetic (thoracolumbar) 2. parasympathetic (craniosacral) 2 IMPORTANT NEUROTRANSMITTERS 1. Acetylcholine - a neurotransmitter which is released after stimulation of the parasympathetic nervous system to act on effector organs (cells) to elicit their response, but it also acts as a neurotransmitter (Cholinergic Activity) 2. Noradrenaline- neurotransmitter released by post ganglionic sympathetic nerves to elicit its effect on effector cells. (Adrenergic Activity) AUTONOMIC DRUGS 1. Drugs acting on the sympathetic nervous system a) Sympathomimetics or adrenergic drugs are drugs that mimic the effects of sympathetic nerve stimulation. b) Sympatholytic are drugs that inhibit the activity of sympathetic nerve or that of sympathomimetics. 2. Drugs acting on the parasympathetic nervous system a) Parasympathomimetic or cholinergic drugs are drugs which mimic acetylcholine or the effects of parasympathetic nerve stimulation. b) Parasympatholytic are drugs that inhibit parasympathetic nervous system activity or that of cholinergic drugs. CHOLINERGIC DRUGS 1. Direct-acting - bind to and activate muscarinic or nicotinic receptors (mostly both) and include the following subgroups: a. Esters of choline: Methacholine, Carbachol, Betanechol b. Cholinergic alkaloids: Pilocarpine, Muscarine, Arecoline, Nicotine 1. Acetylcholine is the prototypical cholinergic agent. It functions as a neurotransmitter at all cholinergic sites in the body (Esters of Choline) Actions of Acetylcholine 1. Nicotinic actions- those produced by stimulation of all autonomic ganglia and the neuromuscular junction 2. Muscarinic actions- those produced at postganglionic cholinergic nerve endings VILLANUEVA | 11 NCM 106: Pharmacology Lecture 5: DRUGS ACTING ON THE IMMUNE SYSTEM, CNS, AND PNS Compiled by: Villanueva, Bea Denise 2. Carbachol are synthetic derivatives of choline that is completely absorbed from the gastrointestinal tract and is stable towards hydrolysis by cholinesterase enzyme; therefore, it can be given both orally and parenterally (Synthetic Choline Esters) Indications Glaucoma Retention of urine (postoperative) Paralytic ileus Pilocarpine - drug directly stimulates the muscarinic receptors to bring about all the muscarinic effects of Acetylcholine. (Cholinergic Alkaloids) Indications Glaucoma 2. Indirect-acting - inhibit the action of acetylcholinesterase enzyme (Anticholinesterase Drugs) a. Reversible: Neostigmine, Physostigmine, Edrophonium b. Irreversible: Organophosphate compounds; Echothiophate The commonly used cholinesterase inhibitors fall into three chemical groups: 1. Simple alcohols bearing quaternary amines, e.g., Edrophonium 2. Carbamate and related quaternary or tertiary amines, e.g., Neostigmine, Physostigmine 3. Organic derivatives of phosphates, e.g., Isofluorophate, Echothiophate CARBAMATE 1. PHYSOSTIGMINE - It increases and prolongs the effect of endogenous acetylcholine at the different sites. 2. NEOSTIGMINE - it inhibits cholinesterase enzyme, and it has a direct nicotinic action on skeletal muscles ANTICHOLINERGICS Anticholinergics - block the effects of acetylcholine and other cholinergic drugs at cholinergic receptors of effector cells. 1. Antinicotinics which include ganglion blockers such as Hexamethonium, Trimethaphan, etc., and neuromuscular blockers such as Gallamine, Tubocurarine, Pancuronium, etc. 2. Antimuscarinics include tertiary amines such as Atropine, Scopolamine, Tropicamide, etc, and quaternary amines such as Propantheline, Ipratropium, Benztropine, etc. ATROPINE is found in the plant Atropa belladonna and it is the prototype of muscarinic antagonists. It antagonizes the effect of acetylcholine by competing for the muscarinic receptors peripherally and in the CNS Clinical Indications - Pre anesthetic medication to reduce the amount of secretion and to prevent excessive vagal tone due to anesthesia. - As antispasmodic in cases of intestinal, biliary, and renal colic - Heart block - Hyperhidrosis - Organophosphate poisonings VILLANUEVA | 12 NCM 106: Pharmacology Lecture 5: DRUGS ACTING ON THE IMMUNE SYSTEM, CNS, AND PNS Compiled by: Villanueva, Bea Denise SYNTHETIC ATROPINE DERIVATIVES 1. Mydriatic atropine substitutes - this group of drugs have shorter duration of action than atropine and are used locally in the eye Ex Homatropine. Eucotropine etc. 2. Antisecretory antispasmodic atropine substitutes -effective more localized to the Gl. Ex Propantheline and Hyoscine 3. Mydriatic atropine substitutes - the group of drugs have a shorter duration of action than atropine and are used Incally in the eve Ex. Nosmatrupine, Ecotropine etc 4. Antiparkinsonianatropine substitute - drugs like Benztropine, Trihexyphenidyl 5. Atropine substitute - decrease urinary bladder activity like Oxybutynin 6. Atropine substitute - used in bronchial asthma drugs like Ipratropium HYOSCINE - drug has the same effect as atropine except for some differences like it has shorter duration of action and is more depressant to the CNS. Clinical Indications -Better for preanesthetic medication because of strong antisecretory and antiemetic action and also brings about amnesia -Can be used for short-travel motion sickness Adrenergic Drugs - these drugs resemble sympathetic nerve stimulation in their effects Groups based on Chemical Structure 1. Catecholamines - have a catechol nucleus with direct action on sympathetic effectors cells through interactions with receptor sites on the cell membrane. These includes Adrenaline, Noradrenaline, Dopamine, Isoprenaline, and Dobutamine. 2. Non-catecholamines - lack the catechol nucleus. They may directly act on the receptors or may indirectly release the physiologic catecholamines. eg. Ephedrine, Phenylephrine, Amphetamine Groups based on Mode of Action a. Direct mode of action: directly interact with and activate adrenoreceptors, e.g., Adrenaline and Noradrenaline b. Indirect mode of action: their actions are dependent on the release of endogenous catecholamines. This may be: i. Displacement of stored catecholamies from the adrenergic nerve endings, e.g., Amphetamine, Tyramine ii. Inhibition of reuptake of catecholamines already released, e.g. Cocaine, Tricyclic Antidepressants DRUGS ACTING ON THE ADRENERGIC RECEPTOR SUBTYPES Adrenaline - is the prototype of adrenergic drugs and is produced in the body by the cells of the Adrenal medulla and by chromaffin tissues. - directly stimulates all the adrenergic receptors both and brings about effects of sympathetic nerve stimulation. VILLANUEVA | 13 NCM 106: Pharmacology Lecture 5: DRUGS ACTING ON THE IMMUNE SYSTEM, CNS, AND PNS Compiled by: Villanueva, Bea Denise Indications 1. Acute bronchial asthma 2. Anaphylaxis 3. Local hemostatic to stop bleeding in epistaxis 4. With local anesthesia to prolong the action 5. Cardiac arrest Nor-adrenaline - is the neurochemical mediator released by nerve impulses and various drugs from the postganglionic adrenergic nerves. - is a predominantly a receptor agonist with relatively less ẞ agonist action when compared to adrenaline. Indications 1. Nor adrenalines are used as hypertensive agents in hypotensive states E.g. During spinal anesthesia or after sympathectomy. ISOPRENALINE, DOPAMINE, DOBUTAMINE - are the other catecholamines which have similar properties to adrenaline and noradrenaline. - These drugs have advantage because they are more selective in their action and have fewer side effects than adrenaline and noradrenaline. Dopamine is naturally occurring and is a precursor of noradrenaline. Isoprenaline and Dobutamine- are synthetic. Dopamine and Dobutamine are very useful drugs for the treatment of shock. ADRENERGIC BLOCKERS -These drugs prevent the response of effectors organs to adrenaline, noradrenaline and other sympathomimetic amines whether released in the body or injected. - The drugs act by competing with the catecholamines for a or ẞ receptors on the effector's organs. They don't alter the production or release of the substances. 1. a- Adrenergic blockers may be reversible or irreversible. a. Reversible antagonists dissociate from the receptors e.g. Phentolamine, Tolazoline, Prazosin, Yohimbine, etc. b. Irreversible antagonists tightly bind to the receptor so that their effects may persist long after the drug has been cleared from the plasma e.g. Phenoxybenzamine Prazosin - effective drug for the management of hypertension by lowering blood pressure, reducing venous return and. cardiac output and it also reduces the tone of the Internal sphincter of the urinary bladder. - leads to relaxation of both arterial and venous smooth muscles due to the blockage of alpha1 receptors Indications 1. Essential hypertension - Raynaud's syndrome 2. Benign prostatic hyperplasia 2. B- Adrenergic blockers use may be classified by their selectivity for receptors in different tissues. a. Drugs blocking all the ẞ receptor effects of adrenaline (non-selective beta blockers) VILLANUEVA | 14 NCM 106: Pharmacology Lecture 5: DRUGS ACTING ON THE IMMUNE SYSTEM, CNS, AND PNS Compiled by: Villanueva, Bea Denise e.g. Propanalol, Pinadolol, Timolol etc b. Drugs blocking mainly the ẞ1 effects those on the heart with less effect on the bronchi and blood vessels (beta 1- selective blockers), e.g. Atenolol, Practalol, Acebutalol, etc Propranolol - is a non-selective ẞ adrenergic blocker and it also has other actions like membrane stabilization. Indications Cardiac arrhythmias Hypertension Prophylaxis against angina Myocardial infarction Thyrotoxicosis Anxiety states (suppression of the physical manifestations of situational anxiety) Prophylaxis against migraine attacks Glaucoma PATIENT TEACHING TIPS 1. Patients should always take medication as ordered 2. Avoid abrupt withdrawal 3. Do not take OTC meds without your physician's approval 4. It is often more effective to space the doses of medications evenly apart 5. Report any untoward reactions immediately 6. Keep all appointments and follow up visits with your physician NURSING CONSIDERATION 1. Medication should be given as directed and educate patients properly 2. Observe and monitor patient carefully for any untoward reactions and report 3. Encourage patient taking cholinergic to change positions slowly 4. Patients should avoid any OTC because of possible drug interaction Apply pressure to inner canthus after ophthalmic use 5. Check antidote for any drug overuse “Nurse: just another word to describe a person strong enough to tolerate anything and soft enough to understand anyone.” VILLANUEVA | 15