Basic Pharmacology

What is a drug? - any chemical agent which effects any biological process What is pharmacology ? - the study of how drugs effect biological systems

Introduction A. Physical Nature of Drugs  Solid drugs -> oral route aspirin or atropine  Liquid drugs -> oral route, IM, SC nicotine or ethanol  Gaseous drugs -> inhalation nitrous oxide, halothane, amylnitrite Many drugs are weak acids or bases pH differences in the body may alter the degree of ionization of drug

What is Pharmacology ? Pharmacology Pharmacokinetics Pharmacodynamics What the body does to drug What the drug does to body Pharmacotherapeutics Pharmacocognosy The study of the use of drugs Identifying crude materials as drugs Toxicology

Pharmacokinetics What the body does to the drug - Absorption - Distribution - Metabolism (Biotransformation) - Excretion Half-life (t1/2) - the time required for the plasma concentration of a drug to be reduced by 50 %

Pharmacodynamics What the drug does to the body - Drug receptors - Effects of drug - Responses to drugs - Toxicity and adverse effects of drugs

Sources of Drugs Pharmacocognosy Animals Plants Minerals Synthetic Microbes

Many of these old sources are still in use today Foxglove plant Meadow flower Colchicum autumnale Beef or pork pancreas Digitalis comes from the foxglove plant and is used in the treatment of CHF Colchicine is the drug of choice for treatment of gout Insulin is used today to treat diabetes and is derived from the pancreas of beef or pork or may be synthetically produced as well.

Drugs Derived from Plants Ephedrine is present in the leaves of a bushy shrub (species name Ephedra), which, when burned were used by the ancient Chinese to treat respiratory ailments. Today, it is a bronchodilator. Many estrogen hormone replacement therapy drugs are derived from yams. The belladonna plant – source of atropine, which is still used to dilate the pupils.

DRUG CLASSIFICATION - Based on the chemical structure - Based on the main effect (e.g. analgesics). - Based on the therapeutic use (e.g. antipsychotic). - Based on mechanism of action (e.g. serotonin agonist).

Drug Nomenclature - Chemical name - *Generic name - Trade name Chemical Name: 2-(4-isobutylphenyl)-propionic acid Generic Name: ibuprofen Trade Names: Advil, Aches-N-Pain, Brufen, Emodin, Haltran, Medipren, Midol 200, Motrin, Nuprin, Rufen, Trendar, Wal-Profen * preclinical nomenclature = company abbrev (e.g. WAY , MK-869)

Routes of Administration Critical to efficacy  Rapidity of onset  Duration of effects  Magnitude of effects Systemic administration  Drug into circulatory system via... Enteral routes Parenteral routes  Drug effects throughout body ~

Routes of Drug Administration  Enteral  within or by way of the GI tract  Oral (PO), rectal, sublingual  Parenteral  Not within the alimentary canal  Inhalation, IM, SC, IP, topical  Central  Into the brain or spinal cord  Intrathecal, ICV

Routes of Drug Administration common abbreviations… PO = per os = oral IV = intravenous = into the vein IM = intramuscular = into the muscle SC = subcutaneous = between the skin and muscle IP = intraperitoneal = within the peritoneal cavity icv = intracerebroventricular = directly into the ventricle of the brain

Oral Per Os (PO) by mouth  absorption across membrane in GI  most common  most variable  1 st pass metabolism Cooperation required Can recall ~

Oral Sublingual  Absorption: mucous membrane salivary glands  e.g., nitroglycerin, buprenorphine Chewing  absorbed across lining of mouth ~

Injection Intravenous (iv)  directly into vein  rapid onset of effects Fastest ~ Intramuscular (im) Location important  Deltoid - rapid  Thigh - moderate  Buttocks - slowest  Difference in blood supply & distance

Routes of Drug Administration and Absorption. Injecting (Intravenous):  Puts drugs directly into a vein  Put drugs into muscles or under skin

Injection Subcutaneous (sc)  under skin  slow, steady absorption Disadvantages  Variable absorption  limited volume  skin irritations ~

Injection Intrathecal  under sheath of nerve fibers, spinal cord, or brain Mostly as local anesthesia  little importance for most psychoactive drugs ~

Inhalation Smoking Lungs  gases or vapors  densely lined with capillaries  large surface area Fast absorption  Similar to iv ~

Routes of Drug Administration and Absorption. Inhaling:  Allows the vaporized drug to enter the lungs, the heart and then the brain in about 7-10 seconds (Most rapid) (Pictures) Marijuana inhaling tent used by the Scythians, c. 500 B.C. Man in India smokes ganja (marijuana) in a “chillum” pipe.

Other routes Transdermal patches  absorbed by skin  slow continuous release also liposomes: via injection Suppositories - rectal or vaginal  absorption incomplete & unpredictable Pellets - Norplant Microcatheter & pump ~

Routes of Drug Administration and Absorption Contact or Transdermal Absorption Absorption through the skin is the slowest method of drug use. It often takes 1–2 days for effects to begin and the absorption can continue for about 7 days. Nicotine, fentanyl, and heart medications can also be absorbed this way Skin creams & ointments absorbed through skin

Toxicity Toxicity is the ability of a chemical to damage an organ system, to disrupt a biochemical process, or to disturb an enzyme system.

Drug Formulation Dosage = the amount of drug to be administered usually based on weight Example: mg/kg Concentration = how the drug is formulated Example: mg/ml Injection Volume = a liquid measurement based on weight Example: ml/kg

Factors Affecting Response to Drugs Dosage Route of Administration IV IH subling IM, SC IP PO topical Rate of Absorption Rate of Elimination Physiochemical properties of the drug age, sex, species, metabolism, etc…

Drug-Receptor Interactions Agonists activates or enhances cellular activity. triggers a series of biochemical events alteration in function second messengers: biochemicals that initiate these changes Antagonists do not initiate a change in cellular function. prevent the binding and the action of agonists “blockers”

Drug-Receptor Interactions Factors Governing Drug Action 1. Affinity: measure of the tightness that a drug binds to the receptor 2. Intrinsic activity: measure of the ability of a drug to generate an effect, producing a change in cellular activity

Binding of a drug drug must interact with complementary surfaces on the receptor.

Antagonist exhibit affinity for the receptor do not have intrinsic activity at the receptor competitive antagonist: binds to the receptor in a reversible mass-action manner -agonists given in high concentrations  can displace the antagonist from the receptor -agonist can then produce its effect