Pharmacology Basics

Pharmacology

• Pharmacology is the science of drugs
• A drug is a chemical agent that modifies functions within a biological system

Drug Sources

• Drugs can be sourced naturally or synthetically.
• Natural sources include plants (e.g., atropine), animals (e.g., insulin), microorganisms (e.g., penicillins), and minerals (e.g., iron, zinc)
• Most drugs are synthetic

Drug Names

• Every drug has three names: chemical group name, generic name (uniform worldwide), and trade name
• Example: Acetyl salicylic acid (chemical name), Aspirin (generic name), Juspirin/Ezacard/Dispirin/Bayer's aspirin (trade names)

Drug Action Types

• Local/topical drugs act at the application site (e.g., eye drops)
• Systemic/general drugs act on different systems
• Reflex action drugs act on one site and elicit a response at another (e.g., reflex tachycardia from vasodilators)

Drug Administration Routes

• Drugs can be administered locally or systemically.
• Local administration is possible if the action site is on the body surface or easily reached (e.g., via injection)
• Local administration routes include: epidermal, subcutaneous, conjunctival, intranasal, buccal, intrathecal, intrapleural, intrauterine, intracardiac, intravaginal, intraarticula

Systemic Drug Administration

• Systemic administration involves four main routes:
• Enteral
• Parenteral
• Inhalation
• Transdermal.

Enteral Route of Administration

• Drugs are given to the GI tract and absorbed there
• Three enteral routes: oral, sublingual, and rectal

Oral Route

• Advantages: easy, safe, painless, and requires no equipment
• Disadvantages: slow action, variable absorption, unsuitable for emergencies/unconscious patients/vomiting, subject to first-pass metabolism

First Pass Metabolism

• First-pass metabolism occurs mainly in the liver, but can also occur in the stomach via HCL, intestinal enzymes and within the portal vein

Intravenous Route

• Advantages: rapid onset, accurate dose adjustment, suitable for emergencies/vomiting/diarrhea, allows large fluid volumes, bypasses first-pass metabolism
• Disadvantages: risk of infection, difficult to reverse overdose, requires trained professionals, unsuitable for oily substances or depot forms

Transdermal Route

• Advantages: easy, painless, sustained release, bypasses the GI Tract
• Disadvantages: patch can fall off, suitable for a limited drug number, potential toxicity for children, may cause local allergy

Intramuscular Route

• Advantages: suitable for aqueous/oily solutions and insoluble suspensions
  • Aqueous solutions are absorbed rapidly
  • Absorption is retarded by adding a vasoconstrictor
• Disadvantages: not suitable for large volumes

Subcutaneous Route

• Advantages: suitable for non-irritant drugs in aqueous solutions or fine suspensions
  • Absorption is retarded by adding a vasoconstrictor
• Disadvantages: not suitable for irritant drugs or large volumes

Sublingual Route

• The drug is inserted beneath the tongue and should be palatable, soluble, and effective in a small dose.
• Advantages: rapid absorption, protection from first-pass effects and GI enzymes/pH, suitable when vomiting/unconsciousness is present, and for those lacking cooperation
• Disadvantages: not suitable for diarrhea or drugs causing sublingual vasoconstriction

Inhalation Route

• Absorption from the alveolar membrane is rapid
• Drugs are administered as gas (e.g., oxygen, nitrous oxide), volatile liquid (e.g., halothane), solution via nebulizer, or finely micronized powder via inhaler.

Dosage Forms of Drugs

Oral Dosage Forms: Tablets

• Tablets are solid dosage forms of varying weight, size, and shape
• Simple tablets are compressed with inert substances
• Sugar-coated tablets and enteric-coated tablets exist
  • Enteric coating resists stomach acid but dissolves in the alkaline intestine to protect the gastric mucosa

Tablet Coating

• Enteric coating material reduces gastric bleeding from aspirin
• Sustained release tablets provide prolonged action with less frequent dosing
• Effervescent tablets offer improved palatability
• Sublingual tablets are placed under the tongue

Capsules

• Gelatin shells containing individual doses of the drug: hard capsules with powdered drugs, soft capsules with liquid drugs

Liquids

• Mixture: drug dissolved in water
• Emulsion: fats/oils dispersed in liquid with an emulsifier
• Suspension: solid particles suspended in liquid
• Syrup: sugar solution with flavoring and therapeutically active substances
• Elixir: aromatic, sweetened alcohol and water solution
• Tincture: alcoholic extracts of plants or vegetable substances

Rectal Dosage Forms

• Suppositories: medicinal substances in a firm base (e.g., cocoa butter) for rectal insertion, melting at body temperature
• Enema: fluid preparations for rectal administration

Parenteral Preparations

• Sterile liquids in ampoules or powdered form in sealed vials, dissolved in sterile water before injection
• Ampules are sealed glass containers for liquid medication
• Vials are glass containers with rubber stoppers for liquid/powdered medication
• Cartridges/Tubex are single-dose units with a specific injecting device
• Glass/plastic bottles are used for fluid infusions with or without drugs.

Subcutaneous Implants

• Drugs are implanted under the skin in solid pellet form, absorbed over weeks or months (e.g., some hormones).

Topical Preparations

• Liniments: liquid suspensions for lubrication, applied by rubbing
• Lotions: liquid suspensions that can be protective, cooling, or cleansing
• Ointments: semisolid medicine in base for local protective or transdermal application (e.g., nitroglycerin)
• Pastes: thick ointment primarily used for skin protection
• Creams: emulsions with aqueous and oily bases
• Drops: aqueous solutions (with/without a gelling agent) to increase retention time in the eye

Transdermal Patches

• Patches containing medication are absorbed through the skin, providing days or weeks of medication at a steady state (e.g., nitroglycerin, scopolamine)

Topical Administration

• Eye: eye drops, ointments, and lotions
• Ear: ear drops
• Vagina: vaginal tablets and pessaries
• Nose: nasal drops, sprays, and inhalers
• Mouth: mouthwash, gargle, and lozenges
• Skin: ointment, cream, lotion, and dusting powder

Inhalation Dosage Forms

Metered Dose Inhaler

• Delivers a specific amount of aerosolized medicine for inhalation
• Take off cap and shake inhaler hard
• Breathe out all the way
• Hold inhaler 1-2 inches from mouth
• Start breathing slowly in through your mouth and press down on the inhaler one time.
• Count slowly to 10 while holding your breath
• Rinse mouth to reduce side effects.

Spacers

• Spacers make aerosol inhalers easier to use and more effective
• Help deliver more medicine to the lungs and are convenient and compact
• Reduce side effects from higher doses of preventer medicines

Nebulizers

• Convert drug solution into an aerosol mist for inhalation and delivers higher doses of drug to airways than standard inhalers.
• Attach nebulizer hose to an air compressor
• Most nebulizers need 6-8 liters/min gas flow, can be driven by piped air or oxygen

Nebulizer Use

• Place drug in small cup, air from compressor converts drug into aerosol mist inhaled through mouthpiece or mask
• The patient takes slow, deep breaths and relax for 5-30 minutes

Pharmacokinetics

• Pharmacokinetics involves how the body affects the drug, including absorption, distribution, metabolism, and elimination

Drug Absorption

• Absorption is the movement of a drug across biological membranes.
• Mechanisms of drug absorption: passive/simple diffusion, active transport, pinocytosis, and facilitated diffusion

Bioavailability

• Bioavailability is the fraction of unchanged drug reaching systemic circulation after administration by any route
  • E.g., 70% bioavailability if 70mg of a 100mg oral dose are absorbed unchanged

Drug Distribution

• Distribution is the process where a drug moves freely between body compartments.

Drug Half-Life

• Half-life is the time for the plasma concentration to decrease by half

Biotransformation

• Biotransformation involves chemical changes to drugs inside the body, aiming to reduce lipid solubility

Drug Elimination

• Drugs are mainly eliminated via the kidney (in urine), liver (in feces), and lungs (for volatile gases)

Side Effects of Drugs

• Type A (predictable): extension of pharmacological effects (e.g., hypoglycemia from insulin)
• Type B (non-predictable): allergy e.g. allergy to penicillin

Autonomic Nervous System (ANS)

• The Autonomic Nervous System distributed throughout the body regulates autonomic functions without conscious control
• Contains sympathetic and parasympathetic nervous systems

Sympathetic Nervous System

• Neurotransmitters: adrenaline and noradrenaline

Sympathetic Receptors

• Alpha receptors: α1 (postsynaptic) and α2 (presynaptic and postsynaptic)
• α1 stimulation results in vasoconstriction
• α2 stimulation inhibits noradrenaline release
• Beta receptors:
  • β1 (mainly in heart and kidneys)
  • β2 (mainly in blood vessels, bronchi, and uterine smooth muscles)
  • β3 (mainly in adipose tissue)

Organ Responses

• Eye: Radial muscle-Mydriasis (α1) and Circular muscle Miosis.
• Heart: Increase rate, Increase contractility, and Increase conductivity (β1).
• Blood vessels: Constriction skin and mucosa(α1) and dialation of skeletal muscle(β2).
• Bronchi: Relaxation (β2).
• GIT: Decrease motility and Contraction (α&β α1) and increases relaxation.
• Urinary Bladder: Relaxation of wall and contraction of sphincter (β2 α1).

Catecholamines and Sympathomimetics

• Drugs producing effects similar to sympathetic postganglionic nerve stimulation are called sympathomimetics
• They are inactivated by MAO and COMT and poorly penetrate into CNS
• Catecholamines (epinephrine, norepinephrine, dopamine, isoproterenol, and dobutamine) and Non-catecholamines have longer half-lives and better CNS penetration

Natural Acting Catecholamines

Adrenaline (Epinephrine)

• Actions:
• Potent stimulant of both α and β adrenergic receptors.
• Major component of adrenal medullary secretions (80%).
• Cardiovascular effects:
  • Powerful cardiac stimulant via Beta 1 receptor.
  • Increases systolic blood pressure.
  • Dilates skeletal muscle Beta 2 receptor, and decreases peripheral resistance.
• Catabolic effect
• Actions on muscles:
  • potent bronchodilator via Beta 2, and inhibition of antigen-induced mediators from mast cells.

Norepinephrine

• Actions:
• released by postganglionic adrenergic nerves. (α1, α 2, β1).
• HR, contractility, increase stroke volume, increase increase Cardiac output and Systolic, diastolic pressure and mean arterial pressure and vasoconstriction.

Dopamine

• Actions:
• Acts as an agonist at D1,α, β1 Responses.
• In low dose acts mainly on D1 receptors (vasodilatation of the renal and mesenteric arteries with increase in GFR & renal blood flow).
• In moderate dosages acting directly on the beta-1 and increase.
• Myocardial contractility and stroke volume.

Shock

• Shock: a state of peripheral circulatory failure with hypotension and impaired tissue perfusion

Shock Type

• Hypovolemic
• Anaphylactic
• Septic

Hypovolemic Shock

• Etiology: Blood loss (hemorrhage), Plasma loss (burns, peritonitis), Fluid loss (dehydration, diarrhea) Clinical picture:
• Rapid weak pulse.
• Hypotension and low pulse pressure.
• Subnormal temperature.
• Increased Rate & depth of respiration.

Anaphylactic Shock

• Etiology: Administration of an antibiotic, anesthisia, etc
• Pathophysiological: Capillary paralysis --> histamine release.
• Clinical Picture: Hypotension, airway obstruction (Laryngeal edema) and bronchospams.

Septic Shock

• Due to infection treated by empirical anti- biotics.

Antimicrobials

• Classification: antibacterials, antivirals, antifungals, anthelminthics, and antiprotozoals

Antibacterial Classification Based on Mechanism of Action:

• Folic acid synthesis inhibitors ex: Sulfonamides, trimethoprim
• Bacterial cell wall synthesis inhibitors Penicillins, cephalosporins, vancomycin
• Bacterial protein synthesis inhibitors ex: Aminoglycosides, chloramphenicol, macrolides, tetracyclines
• Nucleic acid synthesis inhibitors Fluoroquinolones, rifampin

Inhibitors of Cell Wall Synthesis

• All bactericidal and divided into Beta-Lactam (Penicillins, cephalosporins) and Non-Beta-Lactam (Vancomycin) groups
• Penicillin spectrum is active against gram positive bacteria
• Types of penicillin: Natural, Anti-staph, and Broad spectrum

Cephalosporins

• Mechanism of action simillar to penicillin.
• First general examples of Drugs: cefadroxil/cefazolin/Cephalexin.
• Second Generation: cefaclor/cefprozil/cefuroxime.
• Third generation: cefotaxime/cefoperazone, ceftazidime ceftriaxone/cefpodoxime/cefixime.
• Fourth Generation: Cefepime/cefpirome.

Nucleic Acid Inhibitors:Flouroquinolones

• Inhibit DNA synthesis
• Used for Pneumonia and soft tissue damages.
• Examples are Levo/Gati/Gemifloxacin.

Protein Synthesis Inhibitors

• Ex: Tetracyclines, aminoglycosides, chloramphenicol, and macrolides
• All are bacteriostatic, except aminoglycosides

I- Tetracyclines

• Broad spectrum against positive and negative bacteria
• Short, Intermidiate, Long and Very long acting.
• Should not be given to growing child, as it impairs bone and teeth.

Aminoglycosides

• Active against aerobic gram-negative bacteria for tuberculosis
• Examples: gentamicin, tobramycin, amikacin, streptomycin, and neomycin
• Poorly absorbed orally and poorly penetrate CNS, therefore, used for serious systemic infections.
• May cause ototoxicity, leading to hearing loss or balance issues

Chloramphenicol

• Possesses a broad spectrum of antimicrobial activity
• Used to treat only life, threating infections.
• Major side effect is hemotological/bone marrow impairment.

Marcrolides

• Active against gram positive with examples Erythromycin, Azithromycin
• Erythromycin causes stomach upset and liver upset.
• Clarithomycin Causes liver and stomach upsed.
• Aythromycin has lower drug interactions.

Tuberculosis drugs

• First and second-line TB drugs exist, with use depending on resistance and toxicity.