Pharmacology

Therapeutic equivalence: A drug can be substituted with a new additional brand of an existing drug (generic drug) & still equal effects

-> Aspirin exists in different formations but same amount of active ingredient, efficacy, side effects

Physio.: Norepinephrine reuptake from synapse

Pharm.: Target of cocaine and some tricyclic antidepressants

Physio.: Serotonin reuptake from synapse

Pharm.: Target of selective serotonin reuptake inhibitors and some tricyclic antidepressants

Physio.: Transport of dopamine and norepinephrine into adrenergic vesicles in nerve endings

Pharm.: Target of reserpine and tetrabenazine

Physio.: Transport of many xenobiotics out of cells

Pharm.: Increased expression confers resistance to certain anticancer drugs; inhibition increases blood levels of digoxin

Physio.: Leukotriene secretion

Pharm.: Confers resistance to certain anticancer and antifungal drugs

PK -> Pharmacokinetics

“What does the body do to the drug”

PD -> Pharmacodynamics

“What does the drug do to the body”

ADME

absorption

distribution

metabolism

excretion

Covalent bond -> irreversible bond

weak base in blood & acidic urine -> drug through nephron cells into urine -> ionization of drug -> trapped in urine & excreted

same happens with milk of mother -> dangerous for child

Aspirin (weak acid) overdose -> mixed respiratory alkalosis and metabolic acidosis

prolonged effect due to serum & urinary acidosis (no ionic trap but reabsorption of exreted drug & entry into tissue)

Sodium bicarbonate (weak base) "-> alkalosis -> drug clearance

• Passive (simple) diffusion

  • water soluble drugs

  • mol. weight below 1000

• Active transport

  • transport maximum -> rate of active transport depends on drug concentration in enviroment

  • also important for resistence

• Facilitated diffusion

  • diffusion but with carrier proteins

  • saturable

• Pinocytosis

caffeine

ascorbic acid

acetylsalicylic acid

nicotinamide

• mol./particle size

  • small size -> increased absorption rate

• Lipid solubility

  • high sol. -> incr. abs.

• Degree of ionization

  • ionized -> decreased abs.

• Dosage form

  • liquid solution form of drug mol -> faster abs.

• Chem. nature

  • salt forms of weak acid & base incr. abs

• Complex form.

  • solubility increased -> incr. abs.

  • incr size -> decr abs

• Pharmacological effect

  • transition time in GI tract

  • effect on blood flow

• Drug conc

  • high conc -> high abs

Epinephrine -> vasoconstriction

-> decr. blood flow -> decr. absorption -> longer duration

-> decr. blood flow -> reduced bleeding

-> higher conc at injection site (local)

• Local administration

  • Epidermal, Intracutaneous, Conjunctival, Buccal…

• Systemic administration

  • Enteral route

  • Parenteral route

  • Inhalation

  • Transdermal route

• Enteral -> via GI tract

  • Oral

    • Disintegration, dissolution & absorption of what’s left

      • absorbed from duodenum, jejunum and upper ileum

    • bioavailability affected by various factors

  • Sublingual

    • high lipophilic drugs (Cardiac nitrates, Ca+ channel blockers like nifedipine and steroids)

    • quick effect & high bioavailability

  • Rectal

    • enema (liquid), suppositories (solid)

    • immediate effect

    • esp. gastric mucosa irritating drugs, bad taste

• liver metabolizes drug to inactive form

• Bioavailability: In which extent the body benefits from the drug/how much unchanged drug reaches circulation after escaping liver (~10%)

• differences in first-pass metabolism

• diff. in general metabolism (pharmacogenomics)

• diseases affecting GI motility (diarrhea affects absorption)

• body weight (lipophilic drug distribution, needs to be calculated on lipid content normally)

• drug-drug/drug-food interactions

• stomach emptying time

• full/empty stomach

Empty -> faster absorption maybe gastric side effect

Full -> slower absorption & maybe interaction with food (Paracetamol never with protein)

• into veins (100% bioavailability), muscle (80% b., max. 5ml inj.), subcutaneous (60% b., max. 2ml inj.)

Highly lipophylic f.e. nicotine, morphine, steroids