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Ad Random : Ad Aa Aa Ad Ad BASIC PRINCIPLES pharmacology-study of drugs 3 AREAS : BRANCHES what a 1....

Ad Random : Ad Aa Aa Ad Ad BASIC PRINCIPLES pharmacology-study of drugs 3 AREAS : BRANCHES what a 1. Effects of drugs (MOA) Pharmacomicsand do. Fate & 2 Disposition (ADME) Pharmacokinetics. 3 Clinical Uses/Rational Drug Use Pharmacotherapeutics CLASSES OF DRUGS : · Dobutamine (B , selective agonist) 1. Functional Modifiers - ( + ) inotropy (Force : lakas ( - alter biochemical & physiologic activities - (+) chronotropy (HR : bilis)a of the cell - (t) dromotropy (conduction velocity - MAJORITY 4. Chemotherapeutic Agents -must be absent (bacteria viruses, , cancer cells 2. Replenishers #natural/self made - kill/inhibit growth of Foreign cells Fungie which EX ANTI-bacterial , viruses , etc can supplement endogenous cmpds -. are insufficient - Ex. Hypothyroidism : T & To ↳ Tz (Triiodothyronine) - ex more potent us Ta ↳ [p (Tetraiodothyronine/Thyroxine ( ix : Thyroxine -undergoes isomerism "Levo : preparation of choice 4% of levo's activity Dextro : ! Also : Type IDM : binsulin iX : Insulin DI (Diabetes Insipidus) : Avasopressin/ Antidiuretic hormone TX : Vasopressin. 3 Diagnostic Agents For diagnosis - drug alt : - EX : Dobutamine a measure of cardiac ↑ efficiency vs "stress " mechanical. For Pharmacologic Stress Test ↳ (treadmill) (Drug) PHARMACODYNAMICS - effects of drugs (MOA) 2. Regulatory Proteins ? EX (4) drug-body - - :. a. VGICs (Voltage Gated (on Channels) Molecular MOA electrical 1 conduct changes in signals -. ① : Excitatory 11 Interactions. Doug Receptor III. Dose Response Relationships 0 : Inhibitory - CRITERION EXCITATORY INHIBITORY I MOLECULAR MOA.. Cell charge (t) ( ) - key concepts : State Depolarization Hyperpolarization now ? Drug = moA * Effects VGICs that open Nat & Ca+ channels C1- & K + channels Response stimulation &Els Relaxation ↓ CHON X CHON contraction Depression VCHON Protein MON A. : Target Dilation D that BLOCK XGICs > - p Drugs : P = effect Nat channel Blockers i. A X - - Depolarization : RELAXANT structural Regulatory · cell framework/ · maintain cell EX. Class 1 Antiarrhythmics cytoskeleton Functions some Anticonvulsants (Phenytoin Carbamazepine , 1. Structural Protein Local Anesthetics (- caine - Ex Microtubules esters(11) : Procaine (BN). amide (2i) : Lidocaine Xylocaine , a. Biosynthesis Microtubules - ii. K "Channel Blockers polymeri From Tubulins tion ↳ native (functional) miodarone hyperpolarization STIMULANTS Sta - - : ↳ nascent (non-functional) · Mitosis · cell movement EX : Class 11) Antiarrhythmics (EX. Diseases & Insulin Pinsulin release b Drugs secretagogues =. ↓ b sulfonylureas (Climepiride) ↳ I. CA vinca alkaloids (vincristine ( Taxanes (Paclitaxel) Colchicine 1st line acute dougs b Carrier Molecules 2. Inflammation > :. Fungal infection Griseofulvin energy requiring -. 3 - EX : Nat-k Pump (NAP) +. i - ATPase For Caltion extrusion - 2 : - 2 : For Caltion extrusion c. Enzymes ↓ ↳ "lumalabas" - biological catalysts (fastern) For contraction - EX : MAO (Monoamine Oxidase) : ↳ metabolism s of biogenic amines (b) Nat Nat NE , Epi , Dopamine 5 HT- MAOB N N Nat , MAO A ↳ Diseases : · major depression : bNE & 5- HT kt Nat Parkinsonism · : ↓ dopamine Drug : Digoxin Ginotropy - inh NAP = O NCX ↳ Drugs : MAOIs : "Conc. PCa(i) M O PO - For.. For.. X Moclobemide MAO A sel. Phenelzine - ii. Kt-H + -ATPase Pump (Proton Pump socarboxazid I ranylcypromine # on-sel. - parietal cells (stomach) V Selegiline MAOp sel. = HC production (acidic d Receptors Comediators ↑ drugs. ACh Histamine Gastrin interacts via lock & - specific proteins where a ligand key Active site A ①Erg signal transduction - Effect 10 Depolarization/ Hyper 11 20 proton messengers · / pump 1.IIo Phosphorylation Ht No Gene expression gastric Cl- TYPES : lumen # 11 C1- R 1. Type 1 : Conotropic (GICs (Ligand-GICs) Drugs : Proton Pump Inhibitors (PPIs) - cell membrane · - prazole drugs EXCEPT ARPRIPRAZOLE - milliseconds Cantipsychotic effective against hyperacidity Channel ldepolaria > glon · Most on -  " ? Ex : "anong channel angkasama EX : most abundant - · ① GABAA : Cl-channels 1 Adrenoceptors (Sympathetic) : a , B ↳ hyperpolarization : INHIBITORY a , O- B , B2 Ga Drugs Conists (supports) Gi Gs Gs ↳ : - > CNS Depressants EX : a, (- Losin) Blockers · Benzodiazepines (- colam , - zepam) ) arteriolar vasodilation ↳ ↑ · Cl-channel Frequency of opening O Barbiturates (-barbital ↳ BP opDuration ② Muscarinic R : Nat channels M , M2 Ms ② Nicotinic R : Ga Gi Ga ↳ depolarization : EXCITATORY EX : -tropium (Ipratropium ↳ Drugs : O Blockers ↳ Ng blocker · Neuromuscular Blockers ↳ Bronchodilator for BA , COPD /Tubocurarine (relaxants skeletal muscles (Kinase-linked 4) ↓ targets. 3 Type III - cell membrane * Type 11 (7-transmembrane/Serpentine/GPCRs/ - min. Metabotropic - EX. Insulin Receptors - cell membrane Growth Factor Rec. - seconds L Epidermal p latelet-derived 0 j /Gene Transcription Linked R/Nuclear / he IV 4. Type - Intracellular R) - nucleus. metabolism Product : ↳ C - his Messenger 4 effects Ligands Lipophilic : - MAJOR EX : a. Steroidal hormones · Mineralocorticoids " Aldosterone - metabolism : Enzymes - · Glucocorticoids - cortisol - o sex hormones Estradiol Adenyly1 Estrogen Phospholipase - C cyclase (AC) (PLC) Progesting Progesterone = 20 msgr : cAMP = 20 msgrs : IPg , DAG Androgens Testosterone # Ca (intral (t) AC (-) AC Gs G; = contraction. b Thyroid Hormones is , is Ga. c Vit D & Vit D derivatives P cAMP ↓ CAMP... B CHON Protein MOA X : Non-Target MECHANISMS (3) : 1. Physical Interactions EX Mannitol. Colligative Mechanism - - Osmotic Diuretic # ↳ Purine excretion (H-0) Osmosis - solvent (H = 0) [fromI solute conc. to P solute conc ]. "pupunta and tubig sa mas matapang na lugar" Urine Kidney tubule blood 00 H,0 mannitol (1) (k) = Aquaresis ↑ S/E Dehydration: Hypovolemia Nat (blood) - conc. = Hypernatremia 2. Chemical Interactions -chemruns a. Neutralization/Acid-Base RX ↳ Antacids (bases) vs. Hyperacidity ↳ Protamine 50p (B) vs. Heparin. Chelation Reaction b ↳ Chelating agents vs Heavy Metals. 3 Counterfeit Mechanism aka drug incorporation - - interfere DNA intermediary metabolism 1 block DNA synthesis Guanine - EX : Antimetabolites A ~ PUrC-Adenine Purine Antagonist Mercaptopurine Thioguanine : , Pyrimidine Antagonist 5-flurouracil Cytarabine : , PyCUT cytosine uracil Thymine # DRUG RECEPTOR INTERACTIONS ② Receptor/Pharmacologic A. Features/Characteristics (Ligand) - eligands same targets opp effects. 1. Affinity ability - to bind - EX : NE vs Propranolol 2. Intrinsic Activity (1A)-ability to activate (+ B, 29)4 B, (-) = Tachycardia : Bradycardia B Classes. (Ligand) 1. Agonist affinity : + 1A Chemical ③ - aka Inactivation Full Partial Inverse - chemryn : RECALL CHEM INT. IA : 1 1A : 30 " IA :< O Heparin (Neutralization , - Ex. Protamine SOp vs · Partial Agonist Deferoxamine vs Fe (Chelation mixed agonist & antagonist effect - COMBINED W/ administered. DOl b (Duration of Interaction ALONE Full Agonist - - EX : key concept : Nalbuphine + Morphine Canalgesic) Y Canalgesic - Partial Agonist - Full Agonist Antago R = howlong ? Whapons - enz : NAT (N-Acetyltransferase ( EX Penicillin vs Probenecid. = reabsorption of Peni (43) - substrates : Hydralazine - saturable Isonian a ide = Michaelis - Mente/zero order) Sulfa drugs. Biliary B. Misc.: 3 sulfation - dominant in neonates - via bile acids > - stool Methylation (COMT) - for high MW dougs ; HIP ex.OralContrast Glycine & Glutamate Conjugation - Limitation : Drug reabsorption via B R.. concept : Whatever happens to bile acids,. ENZYME ALTERATIONS D DRUG FOLLOWS ! D 10 % Excretion : Stool enz Drug - Metabolite. BA 90 % via Biliary Recycling/ Induction Inhibition Reabsorption : · ↑ enz. ↓enz ·. Enterohepatic Recirculation · P met. · ↓ met. C Miscellaneous. Induction Inhibition expired air Drug 1. Lungs - Prodrugs ↑ Active = PE Active = E. 2 Mammary Gland- Milk IA A+ Most common Ex : Tetracyclines PA Toxicity ↑ IA bE C/1 (mottling of teeth) = A IA = : children lactation. 3 Sweat glands - > sweat EX. Rifampicin (red-orange D/C Of sweat  AUTONOMIC DRUGS murian Process 2 a. Impulse a Depolarization · I ANATOMY & PHYSIOLOGY (ANS) b Exocytosis.. # Autonomic NS Binding Pr Division : neurons - subdivision of the efferent peripheral NS , · aka Motor Neurons · carry responses (Brain "Effector). d Exocytosis Brain ganglion Effector Post Preganglion -a d · BindingtoPosts ↳ involuntary a ↑ e ganglion · cardiac muscles. (exclusive · smooth muscles CNS · exocrine glands * ANS : 2 motor neurons - salivary O - lacrimal synaptic transmission W/ ganglion - sweat involuntary effectors. subdivisions C (ANS) · Enteric B. Synaptic Neurotransmission · sympathetic 1 parts of Synapse · Parasympathetic sending cell receiving cell - - - YS PARASYMPATHETIC SYMPATHETIC ↓ Anatomy Functions sending Pre-synapse : synthesis storage release S · , , OF NT (vesicle) via Exocytosis (Ca2 + ) A Anatomy (5) Enzymes : Metabolism (ANT) Origin of · 1. Neurons · Autoreceptors : effect is inhibitory S : T , - Ti2 Thoracolumbar NS Cleft - - Enzymes 11 - 15 ~& O - CN 3 , 7 , 9 10 ps : , Craniosacral NS Sz S4 · - receiving : ·S Post-synapse majorityofreceptors - coul e enter 2. Length of Neurons S: - · Enzymes : Metabolism (ANT) short long PS : < E long short 3. Location of Ganglion S : Near the SPINAL CORD PS : Near the EFFECTOR  4. Neurotransmitters II SYMPATHETIC DRUGS. i in catecholamines pre-ganglion Post-ganglion A. Endogenous NE Adrenergic EX. Epi , NE , Dopamine ACh Cholinergic BS Storage "Release Termination True Love Does Not Exist 1. Biosynthesis Receptors (post-synapse Formation of L-DOPA. 5 a. I I Ganglion Effector Enz : Tyrosine hydroxylase (RL enzyme Adrenoceptors (a B) Nicotinis , Cholinoceptors /M N) , Tyrosine L-DOPA (precursor ↑Inhibitor Metyrosine : B. Functional. Formation of DA b 1. General Enz : L-DOPA decarboxylase I Dopamine (1st * Sympha PM L- DOPA cat. ) · NiAdrenergi N stress. Formation c of NE - Fight/Flight - Rest & Digest - inside the vesicle - Enz : Dopamine B-hydroxylase. 2 Specific : Functional Antagonists DA - NE EFFECTOR S PS d. Formation of Epi Heart Tachycardia Bradycardia - adrenal medulla (inner layer) Eyes Mydriasis MiOSIS - En2 : Phenylethanolamine N-methyltransferase (PENMT( Smooth sel Bronchi Bronchodilation Bronchoconstriction muscle 1 GIT lleus/constipation BM/Diarrhea NE Epi Urinary Bladder Urine Retention Urination / Mictuition / (Relaxation - Enuresis (contraction ( (Apocrine /"Ecrine sweating sweating sweat glands : Palms , soles : Generalize : (For Thermoregulation (  2. storage : VESICIES · Reuptake D major M - NET DA :: via : NE Transporter/Uptake 1 Transporter - - enz ↑ Drugs : Reuptake Inhibitors - YMAT : · PNE binding Agonists = Vesicular Monoamine Transporter Ex Cocaine. Atomoxetine Purpose : To prevent premature Sibutramine metabolism of Dopamine 4 Metabolism. Reserpine : -UMAT 2 inh Enz MAO storage of DA : - · DA catechol-o-methyltransferase (COMT) o · Antagonist - NE , Epi : 3-methoxy-p-hydroxymandelic acid. Release 3 : EXOCYTOSIS laka : Vanilylmandelic acid) Dopa : Homovanillic acid - Enhancers Inhibitors Drugs : - (Agonists (Antagonists). MAOls a : 4 NE binding (Agonists Tyramine i nane the dine Ephedrine Kanadrel EX : MPITS Angio- Amphetamine tensin / , retylium Methamphetamine. COMT Inhibitors b EX : -capone (Entacapone Tolcapone) , 4. Termination - cleft = to remove NE - binding B. ADRENOCEPTORS (a B) , & esynapse Alpha : 1. a : smooth muscles = Contraction Panglalaki - Blood vessels : vasoconstriction = PBP Urine Reuptake - Bladder Trigone & sphincter : Closure = Retention & - Prostate Gland = contraction = Passive abolism - inactive - Radial SM (Iris of the Eyes = contraction Diffusion & = Iris is small ; pupil is big : MYDRIASIS - Pilomotor SM : Piloerection = Goose bumps X Post-synapse systemirelation - Pre-synaptic 2. Az Post-synaptic. a Pre-synaptic : Inhibitory - Autoregulation : inh. NE release I NE binding · · Antisympathetic  Sedation Central : " Depression · Exocytosis : Vasodilation DBP Reuptake Inhibition Peripheral : = · : b. Post-synaptic : Excitatory (Gq). 3 Mixed-Acting : DA + 1A (1 Exocytosis) - Blood vessels (Eyes) Vasoconstriction = D) IRECT-ACTING a & B Beta Non-selective sel : MT 1 general type of adrenoceptors I. B, selective : ONLY 1 gen type Heart : Inno] cardiac stimulation one a or B Kidneys (Juxtaglomerular Apparatus : 1. NON-SELECTIVE ↳ renin release Angiotensin I EX. Endogenous Catecholamines (PBP) Epi NE Dopa - , , smooth 2. B2 skeletal pang babae 1 Properties (3) : BB B. 9 Smooth Muscles : Relaxation a. Polar X brain · Bronchi : Bronchodilation - no CNS effects · Uterus : Tocolysis (stay baby !) b. Rapidly inactivated by MAO , CONT · Blood vessels (skeletal Muscles ( - short DOA vasodilation no oral prep IROA : I , SQ inh) = - ,