Routes of Drug Administration

By Bobby Elliott,2015-01-07 10:23
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Routes of Drug Administrationdrug,Drug,DRUG


     Topical (Percutaneous)

    Routes of Drug Administration Rectal or Vaginal



     Pills (single dose)


     Coated Tablets (shell)

    Types of Orally Administered Drugs Matrix Tablets (carrier meshwork)

    Capsules (gelatin shell)



     Ointment + Lipophilic cream



    Percutaneous Drug Administration Gels

    Can be single or multilayer, or

    contained in a reservoir

     Eye Drops

     Nose Drops

    Other Topicals Pulmonary Formulations




     Cartridge Ampules

    Parenteral Drug Administration Infusions

    Advantage: 100% Absorption,

    enters circulation without hepatic

    elim, better bioavailability of

    hydrophilic drugs

     External Absorption Barriers:

     (epithelial layer on skin, lung,

    Types of Barriers for Drug intestineLipophilic barrier)

    Distribution/Absorption Internal Blood-Tissue Barriers:

    Cardiac muscle, endocrine glands,

    gut, liver, CNS

     Passive Diffusion

     Active Transport

    Drug Distribution Receptor-mediated Endocytosis




     The AUC of the administered drug

     divided by the AUC of the

    Bioavailability intraveneously administered drug


     Vd=Amt of drug in the mody/[drug]

     R of E: Via kidney (filtration) or

    Volume of Distribution liver (metabolism)

    Rate of Elimination Usually first order kinetics

    3 drugs have zero-order kinetics

     Rate of Elim/[Drug]

     Rate of Elim= k*Cp*Vd

    Clearance K= ln2/T ?

    CL= K*Vd

     Convert parent compound into more

    Phase I Reactions polar metabolite

     Add/unmask functional group:

    OH, SH, NH2, COOH, etc

    Oxidation, Reduction, hydrolytic

    cleavage, Alkylation, Dealkylation,


     Conjugation with endogenous

     substrate (increase aq solubility)

    Phase II Reactions Conjugation with gucoronide,

    sulfate, acetate, amino acid

     Require reducing agent and

     molecular oxygen

     Two enzymes: 1) Flavoprotein,

    MFO NADPH-cytochrome c reductase

    Mixed Function Oxidases 2) Cytochrome P450 (electron

    acceptor); CYP

     PPAR ligands, CYP1, CYP2E,


    P450 Enzymes Polymorphisms cause changes in

     drug metab: CYP2C19, CYP2B,


    Induction of P450

    enzymes=metabolize drug



    Conjugation Reactions Acetylation

    Amino acid Conj

    Glutathione Conj

    Fatty acid Conj

    Condensation Reaction

     Catalyze oxidative deamination of

     endogenous catecholamines


    Monoamine Oxidases (MAO) Lacated in never terminals and

     peripheral tissues

    Many drug/food interactions!

    (cheese, wine)

    Inhib by MAO inhib

     Maximum non-toxic dose/Min

     effective dose

    Therapeutic Index Doesn’t take into account variability

     btw indivs


     Can be drugs or endogenous ligands

     for the receptor

     Increasing [agonist] will produce Agonist increase in biological response

    Full:evokes 100% max possible effect

    Partial: not 100%

     Block or reverse effect of agonist

     No effect on their own

    Antagonist Competitive, Non-competitive,

     inverse agonist (triggers neg



    Four major drug targets Enzyme

    Ion Channel


     Regulates many cellular and phys.


     Gradient btw extracellular and

    Ca++ as a Second Messenger intracellular (high:low) creates many

     opportunities for regulation

    Stored in ER and other

     Voltage mediated: L, N, T

     Ligand gated

     Store operated

    Ca Channels Sesnsors: Annexins, EF-hand

    proteins, Calmodulin, ProponinC

    Target of many drugs!

     GPCR: transmembrane

     Bind GTP and GDP

     GAPS, GEFS, RGSs important in

    G-Protein-coupled Receptors this regulation

    Main Targets: Phospholipase C,

    Adenylate cyclase

     G-Proteins: Guanine nucleotide

     binding proteins

     2 groups:

    G-Proteins Small GTP binding

    Heterotrimeric G proteins

     Target of cAMP

     Four subunits (2 reg, 2 catalytic)

    PKA Phosphorylates transcription factors

    ex: CREB

     Heterologous desensitization

     (Incoming signal from different

    Regulation of Receptors receptor)

    Homologous desensitization (only

    occurs on receptor which has already

    been stimulated)

     Lipid soluble ligands that penetrate

     cell membrane, Receptors contain Nuclear Receptors DNA-binding domains

    GC, Mineralcorticoids, Retinoids (transcriptional

    PPARs activators/suppressors)

    Takes longer to actrequires

    penetration and protein synth first

     Common fatty acid chain+glycerol


     PLA2 (reg through Ca++ and phos), Phospholipids PLC (Beta: Reg through GPCR, Phospholipases Gamma: EGFR or TCR, activated

    through tyrosine phosphorylation

     DAG: membrane bound, acts as a Phospholipases… substrate for PLA2

     IP3: Ca++ regulated

     Eicosanoids: derivative of

     arachadonice acid

     Rapidly metab by COX into PG and

    Arachidonic Acid Metabolism LTs

    st1 reaction: cyclic ring structure

    nd(COX), 2 reaction: oxidation


     Vascular tone (relaxation,


    Function of PGs Platelet agg (Inc and Dec)

    Uterus tone (Inc)

    Bronchial Muscle (Contriction,


    Gastric secretion (Inib), temp/pain

     LTC4, D4 and E4 mediate allergic

     rxn (SRS-A)

    Leukotrienes Mediate anaphylactic shock, 10,000

     more postent than histamine

    Constricts bronchi, dilates bv

    LTB4 strong chemattractant for


     Divided into CNS and PNS

     PNS div into Somatic and Nervous System Autonomous

     Auto: Sypmathetic and


     Muscarinic Receptors:

     Heterotrimeric G protein coupled,

    Cholinergic Receptors CNS, gastric mucosa M1

     Cardiac=M2, Glandular=M3

    Nicotinic Receptors: Ion channel

    coupled Muscle type, Ganglion type,

    CNS type

     Direct Parasympathomimetics:

     Affinity for M or N receptors (mimic


    Cholinomimetics= Inderect Parasympathometics:

    Parasympathomimetics Inhibit activity of Achesterase (Ach


     1. Mimic Input

     2. Block Input

    To affect Paraympathetic…

    To Treat associated diseases…. 3. Promote Parasymp

    4. Block Symp

    Pilocarpine Muscarinic Parasymp, does not

     activate N rec, treates glaucoma

     (local! Eyedrops)

    Muscarine Muscarine has no therapeutic


     Achestease Inhibitors, raise Ach

    Carbamate Physiostigmine (topical only)


    Quaternary Alcohols Edrophonium (diagnose Myasthenia


     AcCh-ase inhib

     Acts as AcCh-ase inhib but active

     ingredient unkown

    Horny Goat Weed Indirect stimulation of M3 receptor

    (vascular), triggers NO


    Action similar to Viagra (dangerous)

Ogranophosphates AcCh-ase inhibitors (irreversible)

     No medical application

    Nerve Gasses

     Muscarinic Parasympathomimetic

     Atropine (antagonist of cholinergic Atropine system): CNS stimulant, before

     anesth. Prevent hypersecretion of Hyoscine bronchial mucus, treats bradycardy..

    Hyoscine=CNS depressant,


     Competitive Antagonists: Compete

     with AcCh for N rec, prevent

     depolarization, reversible

    Nicotinic Parasympatholytics Agonists: Depolarizing blockers,

    AcCh mimetics not hydrolyzed by

    AcCh-ase, trigger a sustained

    depolarization, irreversible

     Dimeric AcCh, Acts as agonist like

     AcCh, not hydrolyzed by AcCh-ase

    Succinocholine/Suxamethonium (only plasma esterase)

     Depolarization triggers muscle

     twitching initially,

    Used for brief procedures

     AcCh: Preganglionic, parasyathetic

     post ganglionic neurons

    Transmitters in the Autonomic Norepinephrine: Most symp. Post

    Nervous System ganglionic neurons (except sweat

     glands and renal arteries)

    Epinephrine (adrenalin): Adrenal

    medulla--symp impulses (no gang)

     Reuptake into presynaptic nerve

    Termination of (Nor)epinephrine ending

    action Catechol-O-methyltransferase


    Presynaptic alpha 2 receptors

     Alpha1 (vasc smooth muscle)

     Alpha 2 (presynaptic)

    Adrenergic Receptors Beta 1 (Heart)

    Beta 2 (repiratory, uterine SM cells)

    Beta 3 (Adipocytes)


     Indirect Sympathicomimetics

     Inhib of MAO causes increase in free Tranylcypromine Nor-Ep, in CNS NAO metab Moclobemide dopamine and serotonin

    (inhib=increase in happy hormones)

     Indirect Sympathicomimetics

     Displace nor-E in storage

    Ephedrine vesicles=forced release of NorE

    Dietary Supplements

     Indirect Sympathomimetics

    Amphetamines Displace norE in storage vesicles, Methylphenidate forced release, inhib NorE re-uptake

    Fenfluramine and deg by MAO (TRIPPLE Metamphetamine ACTION), Meth=ADD,

     Fen=Appetite suppressant,

     Meta=more lipophilic, depletes NorE

     Non-selective Agonists

    Epinephrine Sympathomimetics

     Ep: Activates alpha and beta rec

    Norepinephrine Blood pressure increase, dilates

    bronchii, vasopressor, Treat

    anaphylactic shock

    NorE: alph receptors, increase BP,

    potent vasopressor

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