Pharmacology-Pharmacokinetics 2024 PDF

MODULE 4: Pharmacology-Pharmacokinetics Pharm8 [PHARMACOLOGY] 2024 PHARMACOKINETICS Pharmacokinetics refers to the movement...

MODULE 4: Pharmacology-Pharmacokinetics Pharm8 [PHARMACOLOGY] 2024 PHARMACOKINETICS Pharmacokinetics refers to the movement of drug into, through, and out of the body. PHARMACOKINETIC PROCESSES DRUG ABSORPTION ABSORPTION Absorption is the transfer of a drug from the site of WHICH IS ABSORBABLE? administration to the bloodstream. ACIDIC vs BASIC LIPOPHILIC + NONPOLAR 𝐻𝐴 𝐻𝐵 UNIONIZED pH is less than pKa, protonated form predominates. → Route of Administration affects absorption. − 𝐴 𝐵 pH is greater than pKa, deprotonated form predominates. ________________________________________________ Example: Stomach → pH = 1.5 less Acidic drug absorbs in stomach. Basic drug absorbs in intestine. pKa Aspirin: 3.5 IONIZATION Propranolol: 9.45 The process in which an atom/molecule acquires a positive/negative charge by losing or gaining electrons. ________________________________________________ IONIZED DRUGS → Water soluble → Polar UNIONIZED DRUGS → Lipid soluble → Nonpolar Drugs should be unionized. Example: Jejunum pH & IONIZATION → pH = 9.5 PROTONATION → the adding of a proton (𝐻 ) + more pKa Aspirin: 3.5 Propranolol: 9 ________________________________________________ NOTE: DEPROTONATION UNIONIZED DRUGS ARE ABSORBABLE LIPOPHILIC DRUGS ARE ABSORBABLE PHARMACY 4A 100% RPh 2024-2025  MODULE 4: Pharmacology-Pharmacokinetics | PHARMACOLOGY FACTORS AFFECTING DRUG ABSORPTION PROTEIN BINDING RATE OF DISSOLUTION SURFACE AREA BLOOD FLOW → Decreases / inhibits LIPID SOLUBILITY distribution, metabolism, and pH PARTITIONING excretion. FIRST PASS EFFECT – Metabolism before systemic absorption. LIPOPHILICITY BIOAVAILABILITY LIPOPHILIC DRUGS – How much and how fast the drug enters the blood. → Readily cross membranes → Blood flow affects its DISTRIBUTION distribution The process by which a drug passes from the bloodstream to body tissues and organs. HYDROPHILIC DRUGS → Do not readily penetrate membrane HIGHLY VASCULARIZED ORGANS → Must pass through slit junctions → Brain → Heart ↑ 𝑏𝑙𝑜𝑜𝑑 𝑣𝑒𝑠𝑠𝑒𝑙𝑠 = ↑ 𝑑𝑖𝑠𝑡𝑟𝑖𝑏𝑢𝑡𝑖𝑜𝑛 → Lungs → Liver 𝑚𝑢𝑠𝑐𝑙𝑒𝑠 & 𝑓𝑎𝑡𝑠 = ↓ 𝑏𝑙𝑜𝑜𝑑 𝑣𝑒𝑠𝑠𝑒𝑙 = ↓ 𝑑𝑖𝑠𝑡𝑟𝑖𝑏𝑢𝑡𝑖𝑜𝑛 Lipophilic drugs easily distributed (including brain). Hydrophilic drugs need active transport or pores. VOLUME OF DISTRIBUTION 𝐴𝑚𝑜𝑢𝑛𝑡 𝑜𝑓 𝑑𝑟𝑢𝑔 𝑖𝑛 𝑡ℎ𝑒 𝑏𝑜𝑑𝑦 FACTORS AFFECTING DISTRIBUTION 𝑉𝑑 = 𝑃𝑙𝑎𝑠𝑚𝑎 𝑐𝑜𝑛𝑐𝑒𝑛𝑡𝑟𝑎𝑡𝑖𝑜𝑛 CAPILLARY PERMEABILITY 𝐻𝑖𝑔ℎ 𝑉𝑑 = 𝑙𝑜𝑤 𝑝𝑙𝑎𝑠𝑚𝑎 𝑐𝑜𝑛𝑐. → Drug concentrate in tissues → Increase Vd = more conc. in tissue 𝐿𝑜𝑤 𝑉𝑑 = ℎ𝑖𝑔ℎ 𝑝𝑙𝑎𝑠𝑚𝑎 𝑐𝑜𝑛𝑐. → Drug concentrate in blood/plasma EFFECT OF Vd ON DRUG HALF LIFE ↓ 𝑉𝑑 = ↑ ℎ𝑎𝑙𝑓 𝑙𝑖𝑓𝑒 METABOLISM The metabolic breakdown of drugs. Elimination; Drug Clearance through → LIVER Metabolism → Large fenestrations Goal allow drugs to move ○ To degrade between blood and ○ Water solubility interstitium in the liver. DRUG + Enzyme CYP450 = DEGRADATION DRUGS → should be LIVER → main metabolizing organ. small enough to pass. PHASES OF METABOLISM PHASE 1 “FUNCTIONALIZATION” Oxidation Reduction Hydrolysis BRAIN PHASE 2 → Lipophilic “CONJUGATION” → Carrier-mediated transport Glucuronidation Glycine conjugation Glutathione conjugation Methylation Acetylation Sulfation PHARMACY 4A 100% RPh 2024-2025  MODULE 4: Pharmacology-Pharmacokinetics | PHARMACOLOGY DRUG AFFECTING ENZYME ACTIVITIES → Drugs should be free. → Drugs should be small enough to be filtered in the ENZYME INDUCERS glomerulus. → Drugs should be ionized. Active secretion of ionized drugs KIDNEY → major route for drug elimination. WHICH IS EXCRETABLE? + 𝐻𝐴 𝐻𝐵 Increase CYP 450 activity − Makes drug clearance FASTER 𝐴 𝐵 DECREASE drug effect ↑ 𝑑𝑒𝑔𝑟𝑎𝑑𝑎𝑡𝑖𝑜𝑛 ENZYME INHIBITORS Decrease CYP 450 activity Makes drug clearance SLOWER INCREASE drug effect ↓ 𝑜𝑟 𝑛𝑜 𝑑𝑒𝑔𝑟𝑎𝑑𝑎𝑡𝑖𝑜𝑛 ________________________________________________ Drug A + Rifampicin ○ Metabolism to excretion: (drug A) ↑ ○ Therapeutic effect: (drug A) ↓ NOTE: Drug A + Isoniazid Medication excretion can also occur in lactating women ○ Metabolism to excretion: (drug A) ↓ through their breast milk, exhalation through the lungs, ○ Therapeutic effect: (drug A) ↑ release into bile, and elimination through saliva and sweat. ________________________________________________ ASSESSMENT Another goal: To activate 1. General absorption of basic drugs are in? PRODRUG + ENZYME = ACTIVATION a. Stomach b. Intestine Prodrug + Carbamazepine c. Lungs ○ Therapeutic effect: (prodrug) ↑ d. Kidney Prodrug + Metronidazole 2. General absorption of acidic drugs are in? a. Stomach ○ Therapeutic effect: (prodrug) ↓ | × b. Intestine c. Lungs ZERO ORDER KINETICS d. Kidney A constant fraction of drug is metabolized per unit of time. 3. Absorbable form of acidic drugs? IV admin a. Protonated b. Deprotonated FIRST ORDER KINETICS c. Ionized A constant amount of drug is metabolized per unit of time. d. Both B and C Oral admin 4. Absorbable form of basic drugs a. Protonated EXCRETION b. Deprotonated Drug Clearance through: Kidney Excretion c. Ionized Elimination route: d. Both B and C 5. High Vd means the drug concentrates in the blood Hepatic - Biliary 6. Enzyme inducers decreases drug concentration in the Urinary body Renal (Drug Excretion Process) - ○ Glomerular Filtration ○ Active Tubular Secretion ○ Passive Tubular Reabsorption Unionized drugs are reabsorbed back to the circulatory system. ○ Excretion PHARMACY 4A 100% RPh 2024-2025  MODULE 4: Pharmacology-Pharmacokinetics | PHARMACOLOGY PHARMACODYNAMICS EFFECTOR MOLECULES Pharmacodynamics describes the actions of a drug on the body and the influence of drug concentrations on the magnitude of the response. cAMP CAMP IP3 DRUG Cyclic adenosine Diacylglycerol Inositol → act as signals monophosphate triphosphate RECEPTOR → act as signal detectors 𝐺𝑠 𝐴𝑐𝑡𝑖𝑣𝑎𝑡𝑖𝑜𝑛 → responsible for selectivity of drug action → The α subunit of the stimulatory G protein-coupled → mediate the actions of pharmacologic agonists and receptor. When a stimulatory ligand binds to this receptor, antagonists. the α subunit is activated, finally resulting in gene ______________________________________________________________ transcription, protein secretion, and cell proliferation. AGONIST → mimics ______________________________________________________________ 𝐺𝑞 𝐴𝑐𝑡𝑖𝑣𝑎𝑡𝑖𝑜𝑛 INVERSE AGONIST → G protein activate beta isoforms of phospholipase C that → A drug that binds to the same receptor as an agonist but hydrolyzes phosphatidylinositol phosphate to diacylglycerol induces a pharmacological response opposite to that of the and inositol trisphosphate, leading to the protein kinase C agonist. activation and intracellular Ca(2+) mobilization, respectively. Stimulates negative response ○ CNS Depression ○ Example: GABA receptor Depressant action FULL AGONIST → Has high efficacy → Producing a full response while occupying a relatively low proportion of receptors. PARTIAL AGONIST → ​Also binds to a receptor but only partially activates it. → Has lower efficacy than a full agonist. ______________________________________________________________ ANTAGONIST → inhibits ______________________________________________________________ COMPETITIVE INHIBITION ❖ Substrate molecule is prevented from binding to the active site of an enzyme by a molecule that is very similar in structure to the substrate. ALLOSTERIC INHIBITION (NONCOMPETITIVE) ACTIONS OF EFFECTOR MOLECULES ❖ An inhibitor binds to an allosteric site; the substrate INTERPLAY AMONG SIGNALING MECHANISMS can still bind to the enzyme, but the enzyme is no → Dual Role or cAMP longer in optimal position to catalyze the reaction. ______________________________________________________________ SIGNALING MECHANISM & DRUG ACTION cAMP → smooth muscle contraction Transmembrane ligand-gated ion channels Transmembrane G protein–coupled receptors Enzyme-linked receptors Intracellular receptors TRANSMEMBRANE SIGNALING → The recognition and binding of an extracellular signal by an integral membrane receptor protein and the generation of intracellular signals by one or more effector proteins. SECOND MESSENGER SYSTEMS G Proteins 𝐺𝑠 𝐺𝑖 𝐺𝑞 activates Adenylyl inhibits Adenylyl activates cyclase cyclase Phospholipase C ↑ 𝑐𝐴𝑀𝑃 ↓ 𝑐𝐴𝑀𝑃 ↑ 𝐼𝑃3, 𝐷𝐴𝐺, & 𝐶𝑎𝑙𝑐𝑖𝑢𝑚 PHARMACY 4A 100% RPh 2024-2025  MODULE 4: Pharmacology-Pharmacokinetics | PHARMACOLOGY EFFICACY → Efficacy is the magnitude of response a drug causes when it interacts with a receptor. Efficacy is dependent on the number of drug–receptor complexes formed and the intrinsic activity of the drug INTRINSIC ACTIVITY → Ability to activate the receptor and cause a cellular response. cAMP & IP3 INSULIN RELEASE ASSESSMENT 1. What is the effect of nitric oxide in the smooth muscle? 2. What do you call those receptors whose ligands are presently unknown? 3. The channel is usually closed until the receptor is activated by an agonist, which opens the channel briefly for a few milliseconds a. Transmembrane ligand-gated ion channels b. Transmembrane G protein–coupled receptors c. Enzyme-linked receptors d. Intracellular receptors 4. Gq protein activates what enzyme? 5. Which is more potent? COMMON EFFECTS OF PHOSPHORYLATIONS AMPLIFICATION PHOSPHORYLATION DE-PHOSPHORYLATION powerfully amplifies the initial erases the memory, taking a regulatory signal by recording longer time to do so than is Log D (Drug Concentration) a molecular memory that the required for dissociation of an 6. What is the enzyme that catalyze the formation of cGMP? pathway has been activated allosteric ligand 7. The receptor is entirely intracellular, and therefore, the ligand must diffuse into the cell to interact with the DOSE RESPONSE RELATIONS receptor. GRADED DOSE–RESPONSE RELATIONS a. Transmembrane ligand-gated ion channels b. Transmembrane G protein–coupled receptors POTENCY c. Enzyme-linked receptors → A measure of the amount of drug necessary to d. Intracellular receptors produce an effect of a given magnitude. 8. What second messenger is/are responsible for releasing ______________________________________________________________ intracellular calcium? EC50 9. The extracellular domain of this receptor contains the ligand-binding area, and the intracellular domain interacts The concentration of drug (when activated) with an effector molecule. producing 50% of the a. Transmembrane ligand-gated ion channels maximum effect (EC50) is b. Transmembrane G protein–coupled receptors usually used to determine c. Enzyme-linked receptors potency. d. Intracellular receptors 10. What is the enzyme activated by Gs protein? 11. What are the second messengers of Gq? 12. What kind of antagonist binds covalently to the active site of the receptor, thereby reducing the number of receptors available to the agonist? a. Competitive antagonists b. Irreversible antagonists c. Allosteric antagonists d. Functional antagonism PHARMACY 4A 100% RPh 2024-2025  MODULE 4: Pharmacology-Pharmacokinetics | PHARMACOLOGY AUTACOIDS HISTAMINE RECEPTORS ARE A physiologically active substance that is produced by the G-COUPLED RECEPTORS body and typically has a localized effect of brief duration. ❖ Undesirable peripheral effects H1 HISTAMINE STIMULATION ❖ No clinical application → Responsible for Reddening of skin Pain Difficulty of breathing MAST CELLS → skin’s first responders to detected threat ○ Allergies ○ Bug bites ○ Stress Releases histamine → swelling, itchiness ○ If it happens too often → hive → Examples: H2 HISTAMINE STIMULATION Histamine (neurotransmitter) Serotonin Endogenous Peptides Prostaglandins Leukotrienes HISTAMINE _______________________________________________________________________________________ Allergic reaction HISTAMINE PHARMACODYNAMICS Inflammatory response Gastric acid secretion H1 H2 HISTAMINE LOCATION Gq Gs → Lungs → Blood vessels → activates → activates Adenylyl → Skin → Mast cells Phospholipase C cyclase → Gastrointestinal → Basophils ↑ 𝐼𝑃3, 𝐷𝐴𝐺, & 𝐶𝑎𝑙𝑐𝑖𝑢𝑚 ↑ 𝑐𝐴𝑀𝑃 _______________________________________________________________________________________ HISTAMINE SUMMARY OF EFFECT HISTAMINE SYNTHESIS HISTAMINE RELEASE HISTAMINE MECHANISM OF ACTION → Destruction of cells as a result of cold, toxins from organisms, venoms from insects and spiders, and trauma. H1 Receptors ______________________________________________________________ EXOCRINE EXCRETION IMMUNOLOGIC ○ ↑ 𝑝𝑟𝑜𝑑𝑢𝑐𝑡𝑖𝑜𝑛 𝑜𝑓 𝑛𝑎𝑠𝑎𝑙 𝑎𝑛𝑑 𝑏𝑟𝑜𝑛𝑐ℎ𝑖𝑎𝑙 𝑚𝑢𝑐𝑢𝑠 CHEMICAL or MECHANICAL 𝑟𝑒𝑠𝑝𝑖𝑟𝑎𝑡𝑜𝑟𝑦 𝑠𝑦𝑚𝑝𝑡𝑜𝑚𝑠 ______________________________________________________________ BRONCHIAL SMOOTH MUSCLE → Histamine release due to trauma. ○ 𝐶𝑜𝑛𝑠𝑡𝑟𝑖𝑐𝑡𝑖𝑜𝑛 𝑜𝑓 𝑏𝑟𝑜𝑛𝑐ℎ𝑖𝑜𝑙𝑒𝑠 𝑠𝑦𝑚𝑝𝑡𝑜𝑚𝑠 𝑜𝑓 𝑎𝑠𝑡ℎ𝑚𝑎 ↓ 𝑙𝑢𝑛𝑔 𝑐𝑎𝑝𝑎𝑐𝑖𝑡𝑦 INTESTINAL SMOOTH MUSCLE ○ 𝐶𝑜𝑛𝑠𝑡𝑟𝑖𝑐𝑡𝑖𝑜𝑛 𝑖𝑛𝑡𝑒𝑠𝑡𝑖𝑛𝑎𝑙 𝑐𝑟𝑎𝑚𝑝𝑠 𝑑𝑖𝑎𝑟𝑟ℎ𝑒𝑎 SENSORY NERVE ENDINGS ○ 𝑖𝑡𝑐ℎ𝑖𝑛𝑔 ○ 𝑝𝑎𝑖𝑛 PHARMACY 4A 100% RPh 2024-2025  MODULE 4: Pharmacology-Pharmacokinetics | PHARMACOLOGY H1 and H2 Receptors H1 Antihistamine: 2nd Gen CARDIOVASCULAR SYSTEM Specific for peripheral H1 receptors ○ 𝑙𝑜𝑤𝑒𝑟𝑠 𝑠𝑦𝑠𝑡𝑒𝑚𝑖𝑐 𝑏𝑙𝑜𝑜𝑑 𝑝𝑟𝑒𝑠𝑠𝑢𝑟𝑒 𝑏𝑦 𝑟𝑒𝑑𝑢𝑐𝑖𝑛𝑔 ○ Less CNS depression 𝑝𝑒𝑟𝑖𝑝ℎ𝑒𝑟𝑎𝑙 𝑟𝑒𝑠𝑖𝑠𝑡𝑎𝑛𝑐𝑒 Some contain hydrophilic groups ○ 𝑝𝑜𝑠𝑖𝑡𝑖𝑣𝑒 𝑐ℎ𝑟𝑜𝑛𝑜𝑡𝑟𝑜𝑝𝑖𝑠𝑚 ○ More affinity to P-glycoprotein 𝑚𝑒𝑑𝑖𝑎𝑡𝑒𝑑 𝑏𝑦 𝐻2 𝑟𝑒𝑐𝑒𝑝𝑡𝑜𝑟𝑠 ○ 𝑝𝑜𝑠𝑖𝑡𝑖𝑣𝑒 𝑖𝑛𝑜𝑡𝑟𝑜𝑝𝑖𝑠𝑚 𝑚𝑒𝑑𝑖𝑎𝑡𝑒𝑑 𝑏𝑦 𝑏𝑜𝑡ℎ 𝐻1 & 𝐻2 𝑟𝑒𝑐𝑒𝑝𝑡𝑜𝑟𝑠 SKIN ○ 𝑑𝑖𝑙𝑎𝑡𝑖𝑜𝑛 & ↑ 𝑝𝑒𝑟𝑚𝑒𝑎𝑏𝑖𝑙𝑖𝑡𝑦 𝑜𝑓 𝑡ℎ𝑒 𝑐𝑎𝑝𝑖𝑙𝑙𝑎𝑟𝑖𝑒𝑠 H1 ANTIHISTAMINES: THERAPEUTIC USE 𝑙𝑒𝑎𝑘𝑎𝑔𝑒 𝑜𝑓 𝑝𝑟𝑜𝑡𝑒𝑖𝑛𝑠 𝑓𝑙𝑢𝑖𝑑 𝑖𝑛𝑡𝑜 𝑡ℎ𝑒 𝑡𝑖𝑠𝑠𝑢𝑒𝑠 → Allergic and Inflammatory conditions → 𝑐𝑙𝑎𝑠𝑠𝑖𝑐 "𝑡𝑟𝑖𝑝𝑙𝑒 𝑟𝑒𝑠𝑝𝑜𝑛𝑠𝑒": → Motion sickness and nausea ○ 𝑤ℎ𝑒𝑎𝑙 𝑓𝑜𝑟𝑚𝑎𝑡𝑖𝑜𝑛 → Somnifacients ○ 𝑟𝑒𝑑𝑑𝑒𝑛𝑖𝑛𝑔 𝑑𝑢𝑒 𝑡𝑜 H1 ANTIHISTAMINES: PHARMACOKINETICS 𝑙𝑜𝑐𝑎𝑙 𝑣𝑎𝑠𝑜𝑑𝑖𝑙𝑎𝑡𝑖𝑜𝑛 ○ 𝑓𝑙𝑎𝑟𝑒 ("ℎ𝑎𝑙𝑜") Absorption: 1-2 hrs H2 Receptors Metabolism: CYP450 STOMACH ○ T1/2: 4-6 hrs ○ 𝑠𝑡𝑖𝑚𝑢𝑙𝑎𝑡𝑖𝑜𝑛 𝑜𝑓 𝑔𝑎𝑠𝑡𝑟𝑖𝑐 ℎ𝑦𝑑𝑟𝑜𝑐ℎ𝑙𝑜𝑟𝑖𝑐 𝑎𝑐𝑖𝑑 Distribution: distributed in all tissues, including the 𝑠𝑒𝑐𝑟𝑒𝑡𝑖𝑜𝑛 CNS Excretion: HOW ALLERGIC REACTION OCCURS ○ Cetirizine & Levocetirizine → excreted _______________________________________________________________________________________ largely unchanged in urine ANAPHYLACTIC SHOCK ○ Fexofenadine → excreted largely Too much release of histamine unchanged in feces ○ Dilated blood vessel Onset of action: 1–3 hrs ○ Low blood pressure Duration of action: 24 hrs ○ Swelling H1 ANTIHISTAMINES: ADVERSE DRUG REACTIONS Closes the airway ○ Bronchoconstriction → Drowsiness → Vertigo Closes the airway → Urinary retention → Dry mouth → EPINEPHRINE → Tachycardia → Increased appetite Vasoconstrict blood vessel → Low BP _______________________________________________________________________________________ Bronchodilate _______________________________________________________________________________________ H2 ANTIHISTAMINES ANTIHISTAMINES → Inhibitors of gastric acid secretion to treat ulcers and H1 Blocker heartburn. H2 Blocker HOW? H1 ANTIHISTAMINES Gastric Acid Secretion _______________________________________________________________________________________ + H1 Antihistamine: 1st Gen 𝐶𝑂2 + 𝐻2𝑂 → 𝐻2𝐶𝑂3 → 𝐻 + 𝐻𝐶𝑂3 Nonpolar Penetrate the CNS GASTRIC ACID FORMATION & SECRETION ○ Causing sedation Interact with other receptors ○ Producing a variety of unwanted adverse effects PHARMACY 4A 100% RPh 2024-2025  MODULE 4: Pharmacology-Pharmacokinetics | PHARMACOLOGY SEROTONIN SEROTONIN PHARMACODYNAMICS → Mood → Sleep → Appetite → Pain tolerance SEROTONIN RECEPTORS → Blood pressure → Vomiting → Depression → Anxiety → Migraine RECEPTOR POSTRECEPTOR DISTRIBUTION SUBTYPE MECHANISM SEROTONIN SYNTHESIS & LOCATION 5 − 𝐻𝑇1𝐴 Raphe nuclei, 𝐺𝑖 , ↓ 𝑐𝐴𝑀𝑃 hippocampus 5 − 𝐻𝑇1𝐵 Substantia nigra, globus 𝐺𝑖 , ↓ 𝑐𝐴𝑀𝑃 pallidus, basal ganglia 5 − 𝐻𝑇1𝐷 Brain 𝐺𝑖 , ↓ 𝑐𝐴𝑀𝑃 5 − 𝐻𝑇1𝐸 Cortex, putamen 𝐺𝑖 , ↓ 𝑐𝐴𝑀𝑃 5 − 𝐻𝑇1𝐹 Cortex, hippocampus 𝐺𝑖 , ↓ 𝑐𝐴𝑀𝑃 5 − 𝐻𝑇1𝑃 Enteric nervous system 𝐺𝑜 , 𝑠𝑙𝑜𝑤 𝐸𝑃𝑆𝑃 5 − 𝐻𝑇2𝐴 Platelets, smooth 𝐺𝑞 , ↑ 𝐼𝑃3 muscle, cerebral cortex 5 − 𝐻𝑇2𝐵 Stomach fundus 𝐺𝑞 , ↑ 𝐼𝑃3 Choroid, hippocampus, 5 − 𝐻𝑇2𝐶 substantia nigra 𝐺𝑞 , ↑ 𝐼𝑃3 + Area postrema, sensory 𝑅𝑒𝑐𝑒𝑝𝑡𝑜𝑟 𝑖𝑠 𝑁𝑎 / 5 − 𝐻𝑇3 and enteric nerves + 𝐾 𝑖𝑜𝑛 𝑐ℎ𝑎𝑛𝑛𝑒𝑙 _______________________________________________________________________________________ 5 − 𝐻𝑇4 CNS and myenteric neurons, smooth muscle 𝐺𝑠 , ↑ 𝑐𝐴𝑀𝑃 SEROTONIN IN: PINEAL GLAND → Serotonin as precursor for melatonin 5 − 𝐻𝑇5𝐴,𝐵 Brain ↓ 𝑐𝐴𝑀𝑃 5 − 𝐻𝑇6,7 Brain 𝐺𝑠 , ↑ 𝑐𝐴𝑀𝑃 _______________________________________________________________________________________ Activation of 5-HT2A → Hallucination Blocking Reuptake _______________________________________________________________________________________ (Fluoxetine - Serotonin Reuptake Inhibitor) SEROTONIN IN: GIT → Antidepressant Activation of 5-HT1A → Anxiolytic Activation of 5-HT1D → Antimigraine Activation of 5-HT3 → Emesis Blocking of 5-HT3 (Ondansetron - inhibit 5-HT3) _______________________________________________________________________________________ → Antiemesis SEROTONIN IN: PLATELETS 5-HT2 → Vasoconstriction → Platelets release serotonin (Heart & Skeletal muscle) 5-HT2B → Vasodilation during thrombus formation & acute inflammation. PHARMACY 4A 100% RPh 2024-2025  MODULE 4: Pharmacology-Pharmacokinetics | PHARMACOLOGY 5-HT2 (Smooth muscle, Platelets) ○ Ketanserin 5-HT2 Blocker Hypotensive action probably involves 𝛼-1 adrenoceptor blockade more than 5-HT2 receptor blockade SEROTONIN ANTAGONIST: ADVERSE DRUG REACTIONS Ondansetron, Granisetron SEROTONIN DISEASES ○ Diarrhea ○ Headache Dolasetron ○ Contraindicated with HTN EICOSANOIDS SEROTONIN AGONIST 5-HT2C ○ Dexfenfluramine An appetite suppressant Cardiac Toxicity 5-HT1D/1B _______________________________________________________________________________________ ○ Sumatriptan Antimigraine CYCLOOXYGENASE 5-HT4 → COX 1 ○ Cisapride Regulates normal cellular processes Treatment of motility disorders → COX 2 ○ Tegaserod Increase prostaglandins at site of inflammation and For irritable bowel syndrome with disease constipation _______________________________________________________________________________________ 5-HT1A PROSTAGLANDINS ○ Buspirone Effective nonbenzodiazepine TXA2 anxiolytic THROMBOXANE ○ Vasoconstriction ○ Platelet aggregation PGE2 PROSTAGLANDIN E2 ○ Vasodilation ○ Hyperalgesia ○ Fever ○ Diuresis ○ Immunomodulation ○ GI protection SEROTONIN ANTAGONIST Mucus production ○ Inflammation PGE F2a PROSTAGLANDIN F2a ○ Vasoconstriction ○ Bronchoconstriction ○ Mucus production PGD2 PROSTAGLANDIN D2 ○ Vasoconstriction 5-HT2 ○ Induces sleep ○ Phenoxybenzamine ○ Inhibit platelet aggregation ○ Ritanserin PGI2 ○ Cyproheptadine PROSTACYCLINE Has antimuscarinic effect ○ Vasodilation → sedation ○ Inhibit platelet aggregation PHARMACY 4A 100% RPh 2024-2025  MODULE 4: Pharmacology-Pharmacokinetics | PHARMACOLOGY _______________________________________________________________________________________ PROSTAGLANDINS RECEPTORS: LIPOOXYGENASE G-COUPLED PROTEINS LEUKOTRIENES PGE1 ○ Keep ductus arteriosus open ○ Vasodilation → ALPROSTADIL ❖ For congenital heart conditions ❖ Erectile dysfunction ○ Stimulates Cl-channel opening PGE1 – opens chloride channel → Na is transported out; water follows ↑ 𝐼𝑛𝑡𝑒𝑠𝑡𝑖𝑛𝑎𝑙 𝑓𝑙𝑢𝑖𝑑𝑠 → LUBIPROSTONE ❖ Chronic idiopathic constipation ❖ Opioid-induced constipation ❖ IBS ○ Increase mucus, increase bicarbonate ○ Decrease acid production ALTERNATIVE ANTI-ASTHMA TREATMENT ○ Uterine contraction LEUKOTRIENE MODIFIERS → MISOPROSTOL ❖ Decrease NSAIDs induced ulcer ❖ Abortifacient 🚫 Phospholipase ○ CORTICOSTEROID PGF2a ○ Increase uveoscleral outflow → reducing 🚫 Lipooxygenase ○ ZILEUTON intraocular pressure → LANTOPROST, TAFLUPROST, 🚫 CysLT1 Receptor ○ MONTELUKAST TRAVOPROST ○ ZAFIRLUKAST ❖ Open angle glaucoma 1. Drainage canal blocked; build-up of fluid 2. Increased pressure damages blood vessels & optic nerve a. Iris pushed forward b. Intraocular pressure build-up ○ Increase eyelash prominence, length, and darkness → BIMATOPROST ❖ Hypotrichosis PGI2 ○ Pulmonary vasodilators → EPOPROSTENOL, ILOPROST, TREPROSTINIL ❖ Tx of pulmonary hypertension PHARMACY 4A 100% RPh 2024-2025  MODULE 4: Pharmacology-Pharmacokinetics | PHARMACOLOGY AUTONOMICS SYMPATHETIC: SYSTEM EFFECTS ASSESSMENT Mydriasis 1. Which of the ff systems originates from craniosacral? ○ Dilation of pupils – contraction of iris radial a. Sympathetic c. Enteric muscle b. Parasympathetic d. Somatic Bronchodilation 2. Which of the ff systems originates from thoracolumbar? a. Sympathetic c. Enteric ○ Dilation of lungs b. Parasympathetic d. Somatic ↑ Heart rate contractility 3. What is the main neurotransmitter of cholinergic system? No urination a. Acetylcholine c. Serotonin ○ Relaxation of detrusor b. Norepinephrine d. Histamine ○ Contraction of trigone and sphincter 4. What is the main neurotransmitter of adrenergic system? ↓ Motility a. Acetylcholine c. Serotonin Dry eyes b. Norepinephrine d. Histamine 5. What is the main receptor of cholinergic system? (Saliva) Thick & viscous a. Muscarinic c. Beta receptor Adrenal Medulla b. Alpha receptor d. H1 receptor ○ Secretion of epinephrine and 6. Which has a long preganglionic neuron? norepinephrine a. Sympathetic c. Enteric (Female genitalia) Relaxation of uterus b. Parasympathetic d. Somatic (Male genitalia) Stimulation of ejaculation 7. What is the receptor at the ganglia? _______________________________________________________________________________________ a. Muscarinic c. Beta receptor b. H2 receptor d. Nicotinic receptor PARASYMPATHETIC 8. Pupil constriction: → Rest & digest a. Miosis c. Optic Origin: Craniosacral b. Mydriasis d. Vasoconstriction 9. Pupil dilation: → Pre-ganglia a. Miosis c. Optic Nicotinic receptor b. Mydriasis d. Vasoconstriction → Post-ganglia _______________________________________________________________________________________ Muscarinic receptor Neurotransmitter → Pre-ganglia Acetylcholine (ACh) → Post-ganglia Acetylcholine (ACh) _______________________________________________________________________________________ PARASYMPATHETIC: SYSTEM EFFECTS AUTONOMIC Miosis → Ganglia ○ Constriction of pupils – contraction of Sympathetic sphincter muscle Parasympathetic ○ Contraction of ciliary muscle – lens for Enteric accommodation of near visions Urination SYMPATHETIC ○ Contraction of detrusor → Fight/flight ○ Relaxation of trigone & sphincter Origin: Thoracolumbar (T1-L2) ↑ Motility Stimulation of tears → Pre-ganglia (Saliva) Copious, watery secretion Nicotinic receptor (Male genitalia) Stimulation of erection _______________________________________________________________________________________ → Post-ganglia Adrenergic receptor ROLE OF THE CNS IN THE CONTROL OF AUTONOMIC FUNCTIONS → BARORECEPTOR REFLEX Neurotransmitter Baroreceptor (sends signals via nerves; → Pre-ganglia glossopharyngeal & vagus) Acetylcholine (ACh) ○ Acetylcholine – released to ↓ BP ○ CATECHOLAMINES ○ Norepinephrine – released to ↑ BP Epinephrine _______________________________________________________________________________________ Norepinephrine Dopamine Serotonin → Post-ganglia Norepinephrine (NE) _______________________________________________________________________________________ SYMPATHETIC Stimulates ADRENAL MEDULLA ○ To release EPINEPHRINE (surge of energy) PHARMACY 4A 100% RPh 2024-2025  MODULE 4: Pharmacology-Pharmacokinetics | PHARMACOLOGY CHEMICAL SIGNALING ENDOCRINE DIRECT CONTACT SYNAPTIC SIGNALING SIGNALING HORMONES LOCAL MEDIATORS NEUROTRANSMITTERS Endocrine cells Act locally on cells in Communicate secrete hormones into the immediate between nerve cells the blood environment and effector organs They do not enter the blood ACh needs to be stored in a vesicle Insulin Histamine Acetylcholine to prevent degradation Oxytocin Prostaglandin Norepinephrine Epinephrine Dopamine Serotonin GABA SIGNAL TRANSDUCTION IN THE EFFECTOR CELL Vesamicol inhibits storage of ACh CHEMICAL SIGNALING ​ CHOLINERGIC → “PARASYMPATHETIC SYSTEM” ASSESSMENT 1. What is the antidote for organophosphate poisoning? a. Echothiophate c. Pralidoxime b. Edrophonium d. Botulinum toxin 2. Which of the ff drugs is irreversible indirect cholinergic agonist? a. Carbachol c. Bethanechol b. Echothiophate d. Rivastigmine 3. Which of the ff drugs is reversible indirect cholinergic agonist? a. Carbachol c. Bethanechol b. Echothiophate d. Rivastigmine 4. Which of the ff drugs binds covalently at the active site? a. Carbachol c. Bethanechol b. Echothiophate d. Rivastigmine 5. Which of the ff drugs inhibit synthesis of acetylcholine? a. Reserpine c. Botulinum toxin b. Hemicholinium d. Amphetamine 6. Which of the ff drugs inhibit storage of acetylcholine? a. Reserpine c. Botulinum toxin b. Hemicholinium d. Amphetamine ACh binds to 7. Which of the directly stimulate muscarinic receptors? muscarinic receptors a. Tabun c. Pilocarpine for cholinergic b. Edrophonium d. Botulinum toxin effects ACh binds presynaptic receptors PHARMACY 4A 100% RPh 2024-2025  MODULE 4: Pharmacology-Pharmacokinetics | PHARMACOLOGY INDIRECT ACTING: REVERSIBLE CHOLINERGIC AGONIST Degradation of ACh by AChE Choline transported back to the neuron INDIRECT ACTING: IRREVERSIBLE CHOLINERGIC AGONIST CHOLINERGIC RECEPTORS Muscarinic receptors Gq coupled receptors IP3 and DAG formation CHOLINERGIC: ANTAGONIST → Similarity of muscarinic to nicotinic receptors CHOLINERGIC DRUGS CHOLINERGIC: AGONIST TYPES OF CHOLINERGIC AGONIST _______________________________________________________________________________________ DIRECT ACTING Ganglionic Blockers Muscarinic Blockers Stimulate receptor Neuromuscular Blockers ABC2 NP ANTIMUSCARINIC → I STAB _______________________________________________________________________________________ INDIRECT ACTING Block metabolism AChE degrades ACh → Choline & Acetate _______________________________________________________________________________________ ○ BLOCK AChE ↑ ACh concentration in the ATROPINE synapse Mydriasis/Cycloplegic More ACh binding to receptors → ○ Cycloplegia, or paralysis of the muscles more ACh activity that are responsible for accommodation to focus on nearby objects. Antispasmodic Treatment of bradycardia Antidote for cholinergic agonist IPRATROPIUM & TIOTROPIUM Bronchodilators for maintenance treatment of bronchospasm associated with COPD CHRONIC OBSTRUCTIVE PULMONARY DISEASE PRALIDOXIME → reactivates AChE Emphysema ○ Antidote for organophosphate Chronic bronchitis poisoning SCOPOLAMINE Indirect Acting cholinergic drugs Anti-motion sickness Reversible Irreversible BENZTROPINE & TRIHEXYPHENIDYL ○ Covalent bonding Treatment of Parkinson’s Disease PHARMACY 4A 100% RPh 2024-2025  MODULE 4: Pharmacology-Pharmacokinetics | PHARMACOLOGY ANTIMUSCARINIC: ADVERSE DRUG REACTIONS ADRENERGIC Mydriasis → “SYMPATHETIC AGONIST” Urinary retention ADRENERGIC SYSTEM constipation NOREPINEPHRINE GANGLIONIC BLOCKERS (Neurotransmitter) → NICOTINE → MECAMYLAMINE _______________________________________________________________________________________ NICOTINE Synthesis of Dopamine/ – Depolarizes autonomic ganglia, resulting first in Norepinephrine stimulation and then in paralysis of all ganglia. _______________________________________________________________________________________ NEUROMUSCULAR BLtpOCKERS DOPA = dihydroxyphenylalanine → Used as a skeletal muscle relaxant. VMAT storage of NE/Dopamine MUSCLE CONTRACTION – influx of sodium contracts the → to prevent degradation muscle NONDEPOLARIZING ANTAGONIST DEPOLARIZING AGONIST NEUROMUSCULAR BLOCKERS: NONDEPOLARIZING → Prevent the binding of ACh → No sodium = no contraction ↓ DOSE → can be reversed by AChE inhibitors NEUROMUSCULAR BLOCKERS: Metyrosine – inhibit synthesis of NE/Dopamine CHOLINESTERASE INHIBITORS Reserpine – inhibit storage of NE/Dopamine Bretylium, Guanethidine – inhibit release of NE/Dopamine Cocaine, Tricyclic Antidepressants – inhibit reuptake of NE/Dopamine ○ Amitriptyline ○ Amoxapine CHOLINESTERASE INHIBITORS: DRUG INTERACTION ○ Desipramine (Norpramin) ○ Doxepin ○ Imipramine (Tofranil) ○ Nortriptyline (Pamelor) Amphetamine – promote release of NE/Dopamine ADRENERGIC RECEPTOR → All are G-coupled proteins ALPHA RECEPTORS 𝛼1 – Gq NEUROMUSCULAR BLOCKERS: DEPOLARIZING Gq coupled receptors IP3 and DAG formation → Mimics ACh Post-synaptic Transient contraction Muscle relaxation 𝛼2 – Gi Gi coupled receptors NEUROMUSCULAR BLOCKERS: SUCCINYLCHOLINE Inhibit cAMP formation – Useful when rapid endotracheal intubation is required Pre-synaptic during the induction of anesthesia ○ Inhibit release of Neurotransmitters BETA RECEPTORS SUCCINYLCHOLINE: ADVERSE DRUG REACTIONS β1 Hyperthermia β2 Apnea Gs coupled receptors Hyperkalemia cAMP formation POTENCIES ON THE RECEPTOR PHARMACY 4A 100% RPh 2024-2025  MODULE 4: Pharmacology-Pharmacokinetics | PHARMACOLOGY Ephedrine Longer duration of action Penetrates CNS ADRENERGIC AGONIST CLASSIFICATION DIRECT INDIRECT MIXED Epinephrine Cocaine Ephedrine Norepinephrine Amphetamine Pseudoephedrine Phenylephrine Isoproterenol PHENYLEPHRINE → Decongestant Receptor: 𝛼1 OXYMETAZOLINE → Decongestant COMT → ← MAO Receptor: 𝛼1 EPHEDRINE → Decongestant Receptor: alpha, beta CLONIDINE → Treatment of hypertension Receptor: 𝛼2 SALBUTAMOL ADRENERGIC RECEPTORS EFFECTS → Bronchodilator Receptor: β2 𝛼1 Vasoconstriction EPINEPHRINE ↑ peripheral resistance → Anaphylactic shock ↑ BP Receptor: all adrenergic receptors ↑ closure of internal sphincter of bladder DOPAMINE Mydriasis → Treatment of congestive heart failure 𝛼2 Receptor: 𝛼1, β2, and dopamine receptors Inhibit release of: DOBUTAMINE ○ Norepinephrine → Treatment of acute heart failure ○ Acetylcholine Receptor: β1 ○ Insulin AMPHETAMINE β1 → ADHD, Narcolepsy Tachycardia ↑ myocardial contractility ADRENERGIC AGONIST ADVERSE DRUG REACTION ↑ release of renin Arrhythmia ↑ lipolysis Headache β2 Hyperactivity Bronchodilation Insomnia Vasodilation Nausea ↓ peripheral resistance Tremors ↑ muscle & liver glycogenesis ↑ release of glucagon Relaxation of uterine smooth muscle ADRENERGIC AGONIST CATECHOLAMINES Epinephrine Norepinephrine Dopamine Isoproterenol High potency Rapid inactivation Poor penetration into the CNS NON-CATECHOLAMINES Phenylephrine Longer duration of action PHARMACY 4A 100% RPh 2024-2025  MODULE 4: Pharmacology-Pharmacokinetics | PHARMACOLOGY ADRENERGIC Adverse Drug Reactions → “SYMPATHETIC ANTAGONIST” Fatigue Bronchoconstriction ADRENERGIC ANTAGONIST CLASSIFICATION Arrhythmias ○ Upon abrupt withdrawal Sexual dysfunction BETA BLOCKERS: DRUG INTERACTIONS ALPHA BLOCKERS PHENOXYBENZAMINE Covalent interaction (alpha receptors) Use: Pheochromocytoma ○ Type of neuroendocrine tumor that grows from cells called chromaffin cells Raynaud’s Disease/Frostbite ○ Blood vessels go into a temporary spasm, which blocks the flow of blood PRAZOSIN, TERAZOSIN (“zosin”) Competitive inhibitor of alpha 1 (𝛼1) Use: ○ Treatment of hypertension YOHIMBINE Selective competitive alpha 2 (𝛼2) blocker Use: ○ Treatment of erectile dysfunction Contraindicated in: ○ Cardiovascular disease, psychiatric conditions, and renal dysfunction ALPHA BLOCKERS: ADVERSE DRUG REACTIONS Orthostatic hypotension Tachycardia Dizziness Sexual dysfunction BETA BLOCKERS → Competitive antagonist of beta receptors → Do not induce postural hypotension → Treatment of hypertension, angina, cardiac arrhythmias, myocardial infarction, heart failure, hyperthyroidism, & glaucoma → Used for prophylaxis of migraine headaches BETA BLOCKERS: CLASSIFICATION METOPROLOL, PROPRANOLOL Reduce cardiac output and renin secretion TIMOLOL Glaucoma → reduce intraocular pressure PROPRANOLOL Migraine prophylaxis PHARMACY 4A 100% RPh 2024-2025  MODULE 4: Pharmacology-Pharmacokinetics | PHARMACOLOGY ANESTHESIA Benzodiazepines – cause oral clefts; cause temporary hypotonia and altered thermoregulation Anesthesia is the use of medicines to prevent pain during in the newborn surgery and other procedures. EXCITATORY PATHWAYS PREANESTHETIC AGENTS Antacids ○ Famotidine, Ranitidine To reduce gastric acidity Anticholinergics ○ Glycopyrrolate To prevent bradycardia and secretion of fluids into the respiratory tract Antiemetics ○ Ondansetron To prevent nausea Antihistamines INHIBITORY PATHWAYS ○ Diphenhydramine To prevent allergic reactions Benzodiazepines ○ Midazolam, Diazepam To allay anxiety and facilitate amnesia Opioids ○ Fentanyl For analgesia STAGES OF ANESTHESIA _______________________________________________________________________________________ INDUCTION ○ The time from administration to HOW TO PREVENT PAIN? development of anesthesia Inhibit excitatory pathway MAINTENANCE Stimulate inhibitory ○ Provide sustained anesthesia RECOVERY WHAT TO CONSIDER WHEN GIVING AN ANESTHESIA? ○ The time from discontinuation of anesthetic PATIENT FACTORS IN SELECTION OF ANESTHESIA until consciousness and protective reflexes return Brain Respiratory INDUCTION OF ANESTHESIA Cardiovascular Liver & Kidney PROPOFOL Pregnancy ○ Route of Administration: IV ○ Produce unconsciousness in 30-40 CARDIOVASCULAR CONSIDERATIONS seconds → Anesthetics suppress cardiovascular functions ROCURONIUM, VECURONIUM, Treatment: Vasoactive agents SUCCINYLCHOLINE ○ Route of Administration: IV Caution with: coronary artery disease, heart failure, ○ Neuromuscular blockers dysrhythmias, valvular disease ○ To facilitate tracheal intubation and muscle relaxation RESPIRATORY CONSIDERATIONS SEVOFLURANE → INHALED ANESTHETICS ○ For children without IV access Depressed respiration ○ Inhaled to induce general anesthesia → IV ANESTHETICS Suppress respiration DEPTH OF ANESTHESIA LEVEL 1 Caution with: asthma, ventilation or perfusion abnormalities ○ Loss of pain LIVER & KIDNEY CONSIDERATIONS LEVEL 2 ○ Excitement/combative behavior → Anesthetics damage the liver and kidney Rapid acting IV agents should be Release of fluoride, bromide, and other metabolites of given before inhalation halogenated hydrocarbons. anesthesia LEVEL 3 PREGNANCY CONSIDERATIONS ○ Surgical Anesthesia Nitrous oxide – cause aplastic anemia in the fetus Loss of muscle tone and reflexes Monitor is necessary to prevent stage 4 PHARMACY 4A 100% RPh 2024-2025  MODULE 4: Pharmacology-Pharmacokinetics | PHARMACOLOGY LEVEL 4 LOCAL ANESTHESIA ○ Medullary Paralysis LOCAL ANESTHESIA: MECHANISM OF ACTION Severe depression of the respiratory and vasomotor → Sodium Channel Blockers centers occurs NO SODIUM IN = NO PAIN CLASSIFICATION OF ANESTHESIA GENERAL ANESTHESIA LOCAL ANESTHESIA: AMIDES GENERAL ANESTHESIA: MECHANISM OF ACTION → General anesthetics have been in clinical use for more than 160 years but their mechanism of action remains unknown. 🚫 Inhibit excitatory pathway LOCAL ANESTHESIA: ESTER ○ ○ ○ 🚫 🚫 Nicotinic Receptor Muscarinic Receptor NMDA Receptor ○ ✅ GABA Receptor Stimulate inhibitory pathway ○ ✅ Glycine Receptor ○ ✅ Potassium Channels GENERAL ANESTHESIA: CLASSIFICATION INHALATIONAL ANESTHESIA DESFLURANE ○ Must be delivered using a special vaporizer ○ Anesthetic for outpatient procedures ○ Not used for inhalation induction HALOTHANE ○ Reduces BP ○ Arrhythmias ○ Hepatic toxicity ○ Sensitize myocardium to catecholamines SEVOFLURANE ○ Potential renal toxicity ○ Good for patients with asthma ○ Rapid onset / recovery ○ Not irritating / useful in children ISOFLURANE NITROUS OXIDE INTRAVENOUS ANESTHESIA THIOPENTAL ○ Poor analgesia ○ Potent anesthesia ○ Little muscle relaxation ○ Causes significant nausea ○ Laryngospasm KETAMINE, FENTANYL ○ Causes dissociative amnesia ○ Dissociated state in which the patient is unconscious (but may appear to be awake) and does not feel pain PROPOFOL DEXMEDETOMIDINE PHARMACY 4A 100% RPh 2024-2025  MODULE 4: Pharmacology-Pharmacokinetics | PHARMACOLOGY ANTI-PARKINSONS HOW? Parkinson’s Disease (Parkinsonism) is a progressive neurological disorder of muscle movement, characterized by tremors, muscular rigidity, bradykinesia, and postural and gait abnormalities. PROBLEM IN PARKINSON’S DISEASE ↓ Dopamine ↓ Dopaminergic neurons DOPAMINE PATHWAY IN PARKINSON’S ANTI-PARKINSON’S: LEVODOPA → Dopamine precursor for synthesis PROBLEM WITH LEVODOPA Degraded before reaching the brain CARBIDOPA → Prevent degradation of levodopa before reaching the brain. ANTI-PARKINSON’S: COMT INHIBITORS → Inhibit dopamine degradation Entacapone Tolcapone ANTI-PARKINSON’S: MAOIs → Inhibit dopamine degradation Selegiline Rasagiline ANTI-PARKINSON’S: DOPAMINE RECEPTOR AGONIST Bromocriptine Apomorphine Pramipexole Ropinirole Rotigotine ANTI-PARKINSON’S: ANTIMUSCARINIC AGENTS Dopamine activates go signal Benztropine Dopamine deactivates stop signal Trihexyphenidyl Procyclidine Biperiden NO DOPAMINE → No inhibition → More ACh production Solution? → Increase Dopamine PHARMACY 4A 100% RPh 2024-2025  MODULE 4: Pharmacology-Pharmacokinetics | PHARMACOLOGY ALZHEIMER’S DISEASE ANTIPSYCHOTICS Alzheimer’s Disease is a specific type of dementia PSYCHOSIS characterized by progressive memory loss and cognitive → When people lose some contact with reality. decline. → During an episode of psychosis, a person’s though