Pharmacodynamics, Pharmacokinetics, and Neurotransmitters

PHARMACOLOGY PHARMACODYNAMICS PHARMACOKINETIC  ACTION OF THE DRUG TO THE BODY Body (Cells) drug binds into: • Receptors Replace a missing substance (Insulin, Cortisol, T3 & T4) Increase cellular activities (Epinephrine) Depress cellular activities (Beta-Blockers, CCB) Interfere the growth of a foreign body (Antibiotics) Drug Action through: 1. Receptors 2. Enzymes 3. Pumps 4. Chemical Interaction 5. Alternating Metabolic Process • • •  L A C. Non-Competitive Antagonist • Blocks the receptor site • Reduces action of agonist e.g. Cephalosporin reduced by PPI Drug-Enzyme Interactions e.g. Cholinesterase Inhibitors Breakdown Ach(“stigmines”) Chemical Interaction • Antacid Interrupting Metabolic Processes • Insulin Liberation • Release of active ingredients Absorption • Bloodstream • Oral Slowest absorption • IV Most rapid absorption time • SUBQ & IM Depends on blood perfusion at injection site D Distribution • Bring to target tissue • Transportation of the medication by bodily fluids to where it needs to go M Metabolism • If oral Liver detoxification (makes the drug less active) • The breakdown of the medication • FIRST-PASS EFFECT: The effect of the drug is reduced as only part of the drug is reduced as only part of the drug reaches systemic circulation, they are LESS POWERFUL & will not produce a full therapeutic effect. • Drug-Receptor Interactions A. Agonist Stimulates a receptor site e.g. Opioid agonist (Morphine) binds to the receptor. B. Competitive Antagonist Blocks the receptor site Blocks the action of the antagonist e.g. Opioid Antagonist (Naloxone) Flumazenil (Benzodiazepine Overdose Acetylcysteine (Acetaminophen Overdose) RESPONSE OF THE BODY TO THE DRUG “LADME” E Excretion • The removal of the unmetabolized medication from the body. • Most commonly done by kidneys (urine) • GIT (poops) & Skin (sweat) NEUROTRANSMITTERS The body’s chemical “messengers” Produced by nerves Acetylcholine (Ach) • Muscle contraction • Memory • LACK: Alzheimer’s Disease • EXCESS: Bipolar/Mania • NERVES: Cholinergic Nerves Norepinephrine/ Epinephrine (NE/Epi) • Adrenaline • Released during SNS stimulation • LACK: Depression • EXCESS: Mania • NERVES: Adrenergic Nerves Dopamine (Dopa) • Motor • Behavior • LACK: Parkinson’s • EXCESS: Schizophrenia Treatment for Schizophrenia: Antipsychotic/Neuroleptics: Typical: blocks dopa receptor Atypical: blocks dopa & 5Ht receptor Serotonin 5-hydroxytryptamine (5-HT) • Arousal, Sleep & Motivation • Behavior • EXCESS: Schizophrenia • NERVES: Serotonergic nerves Gamma-aminobutyric acid (GABA) • Inhibitory neurotransmitter • Used in seizure • NERVES: Gabaminergic nerves AUTONOMIC NERVOUS SYSTEM SYMPATHETIC NERVOUS SYSTEM PARASYMPATHETIC NERVOUS SYSTEM ADRENERGIC NERVOUS SYSTEM Neurotransmitter: Preganglionic: Acetylcholine (Ach) Postganglionic: Norepinephrine General Response Origin Preganglionic Neurotransmitter Postganglionic Neurotransmitter Termination of Impulse CHOLINERGIC NERVOUS SYSTEM Neurotransmitter: Preganglionic: Acetylcholine (Ach) Postganglionic: Acetylcholine (Ach) FIGHT or FLIGHT Thoracolumbar Short Acetylcholine (Ach) Long Norepinephrine Monoamine oxidase (MAO) Catechol-O-methyltransferase (COMT) BODY’S RESPONSE Heart HR Contractility Bronchus Bronchodilation Pupils Dilate (MYDRIASIS) GIT Constipation Urinary Bladder Retention of Urine Sphincter Contract Detrusor Muscle Relax Blood Vessels Vasoconstriction SYMPATHETIC NERVOUS SYSTEM ADRENERGIC NERVOUS SYSTEM Agonist = stimulate/activate Mimetic = mimic, copy REST and DIGEST Craniosacral Long Acetylcholine (Ach) Short Acetylcholine (Ach) Cholinesterase HR Contractility Bronchoconstriction Constrict (MIOSIS) Diarrhea Emptying of Urine Relax Contract Vasodilation PARASYMPATHETIC NERVOUS SYSTEM CHOLINERGIC NERVOUS SYSTEM Antagonist = block Lytic = block, destroy, dissolve AUTONOMIC NERVOUS SYSTEM DRUGS ADRENERGIC AGONIST | SYMPATHOMIMETIC Alpha Adrenergic Alpha-2 Beta-1 Adrenergic Agonist Adrenergic Agonist Agonist a. Epinephrine a. Midodrine a. Clonidine a. Dobutamine b. Dobutamine (Catapres) c. Dopamine b. Methyldopa d. Norepinephrine (Aldomet) ADRENERGIC ANTAGONIST | SYMPATHOLYTIC Alpha and Beta Alpha Adrenergic Alpha-1 Adrenergic Beta-Adrenergic Adrenergic Antagonist Antagonist Antagonist Antagonist a. Carvediol a. Phentolamine b. Prazosin a. Propranolol b. Labetalol c. Doxazosin b. Timolol d. Terazosin e. Alfuzosin f. Tamsulosin Adrenergic Agonist Beta-2 Adrenergic Agonist a. b. c. d. Albuterol/Salbutamol Terbutaline Formoterol Salmeterol Beta-1 Specific Adrenergic Antagonist a. b. c. d. e. f. Betaxolol Esmolol Atenolol Metoprolol Bisoprostol Acebutolol ATROPINE SULFATE • • • Drug Class: Anticholinergic Drug used in pre-operative and patients with bradycardia Action: SNS Effect decreases secretions decrease risk of aspirations Diagnosis: SCHIZOPHRENIA Treatment: Antipsychotic/Neuroleptics Side Effects: Tardive Dyskinesia, Pseudoparkinsonism, Neuroleptic Malignant Syndrome (NMS), Akathisia, Dystonia, and Anticholinergic Side Effects: Constipation, Retention of Urine, Dryness of Mouth, Decrease Urine Output SYMPATHETIC NERVOUS SYSTEM | ADRENERGIC Alpha 2 Beta 1 Alpha 1 Blood Vessels Vasoconstriction Urinary Bladder Retention of Urine Iris Dilation: Mydriasis CNS Nerve Membrane Decrease NE release Weakens SNS PSNS Response Pancreas Decrease Insulin release Hyperglycemia Alpha-1 Adrenergic Agonist ACTIONS: Decongestant Blood Vessels Cells Shrink Albuterol/ Salbutamol (Ventolin) • Used in bronchoconstriction (asthma) • Used in hyperkalemia • A.K.A. Short Acting Beta Agonist (SABA) Used for emergency rescue inhaler • Side Effects: palpitation & tremors SNS Effect Vasoconstriction TPR BP Methyldopa • Used in Hypertension • Side Effect: Hypotension Terbutaline (Bricanyl) • Used in asthma & COPD • Tocolytic: blocks muscle contraction: used in premature labor: uterine muscle Vasopressor Vasoconstriction TPR BP Alpha Adrenergic Agonist Midodrine • Used in chronic orthostatic hypotension Formoterol (Salmeterol) • LABA • Used in preventing future attacks of asthma. SNS Effect: Vasoconstriction – Inc HR, TPR, and BP Alpha 1 Adrenergic Antagonist Alpha Adrenergic Antagonist Prazosin Used in Hypertension Vasodilation TPR BP Phentolamine • Pharmacodynamics: Vasodilation TPR BP • Used in Hypertensive Crisis due to: Pheochromocytoma (Tumor in Adrenal Medulla) Secretes NE SNS BP • MAOIs Increase NE BP Doxazosin Used in Hypertension Emptying of the bladder for BPH Terazosin Used in Hypertension Emptying of the bladder for BPH Alfuzosin & Tamsulosin Emptying of the bladder for BPH Lungs Bronchodilation Uterus Relaxation Blood Vessels Vasodilation Liver Glycogenolysis Hyperglycemia Beta-2 Adrenergic Agonist Clonidine (Catapres) Crosses BBB BP HR Vasoconstriction Blood Flow Heart Increase HR Increase Contractility Kidney Increase Renin release Alpha-2 Adrenergic Agonist Phenylephrine • SNS response • No effect on HR • Used in hypertension • Used in an eye exam Beta 2 Beta-Adrenergic Blockers Propranolol • for tachycardia in hyperthyroidism • for stage fright • prophylaxis in migraine Timolol • For Open-Angle Glaucoma, by decreasing the production of aqueous fluid dec IOP • Prophylaxis for migraine (eye drops) Nadolol DOC for Angina + Hypertension Side Effects Bradycardia Hypotension Hypoglycemia Bronchoconstriction Erectile Dysfunction Contraindications/ NC Hold if HR < 60bpm Hold if BP <90/60mmHg Caution in DM, may mask Avoid in Asthma & COPD MYASTHENIA GRAVIS Causes: • Women, 20-40 years old • Idiopathic • Autoimmune Treatment: Anticholinesterase • Blocks the cholinesterase • Cholinergic drug as it protects the Ach by blocking the cholinesterase Antibody destroys the Ach receptor Ach cannot bind to receptor Pyridostigmine • 1st line drug of Myasthenia Gravis • DOC for Atropine Sulfate Toxicity (Anticholinergic Drug) muscle relax Ptosis • Weakness of the upper eyelid (initial sign) • There is a damaged receptor Paralysis Neostigmine (Prostigmine) • Long-term • Increase Ach-receptor binding No receptor (late sign) Descending Muscle Weakness (it starts with the eyelid) Nursing Priorities: 1. Airway 2. Aspiration 3. Mobility Goal: • Increase tone of muscle contraction Ach binds to the receptor Block the cholinesterase Side Effects: • Bradycardia • Diarrhea • Emptying of the bladder • Hypotension dec HR, dec BP • Hypersalivation • Peripheral NS Effects Corticosteroids Immunosuppressant effect Decadron (Dexamethasone) Edrophonium (Tensilon Test) For diagnostic only (5-10mins) S/SX Cause Treatment How do we differentiate? MYASTHENIC CRISIS Weakness and paralysis Underdose of cholinergic drug Cholinergic drugs “stigmines” Improvement or Relief of the Paralysis Slow IV Administration CHOLINERGIC CRISIS Weakness and paralysis Overdose of cholinergic drug Anticholinergic drug Atropine Sulfate Worsening of the Paralysis to avoid severe cholinergic effects CHOLINERGIC ANTAGONIST Atropine Sulfate • Antidote to cholinergic crisis • Drug used in pre-operative and patients with bradycardia • Action: SNS Effect decreases secretions decreases risk of aspirations Side Effects: • Dryness of mouth • Retention of Urine • Mydriasis in cataracts • Constipation • Bradycardia Dicyclomine • Antispasmodic, Antimuscarinic • Hyperactive Bowel in adults Scopolamine (Hyoscine) • Motion sickness • Decrease secretions • Pupil Dilation • Post-Operative: Nausea and Vomiting