Pharm 1 Quiz

Graded Dose Response Curve (Def, EC50, Emax)

• The more the dose the more effective it will be

• EC50 is dose in a patient that is half the max effect

• Greatest response a drug can produce

Potency

Dose required to produce a response

The more potent the less needed

Depends on receptor affinity and ability to reach the site

Efficacy

Ability of a drug to produce an effect

Quantal Dose Response Curve

Shows the dose response relationship in a population rather than an individual

Hyper-reactive

Respond at a lower dose

Hypo-reactive

Responds at a higher dose

Tolerance

Loss of response to a drug

May need to increase dosage to get same effect

Idiosyncratic Drug Response

Unusual drug effect

Tachyphylaxis

Tolerance that develops quickly (within mins to hrs)

Hypersensitivity

An allergic reaction to a drug

Therapeutic Index

Indicator of drug safety

Larger the index the safer the drug

Therapeutic Index Equation

TI = TD50 / ED50

Pharmacokinetics

Drug movement across membrane

Bioavailability

Drug reaches systemic circulation

Volume of Distribution

How a drug can be diffuse

Whether a drug is absorbed into the blood or into tissue

Clearance

Amount of blood from which all drug is removed per unit of time

Half Life

Predicts how long a dosing regimen takes to reach steady state (4-5 half lives)

Absorption is affected by

Route

Formulation

Gastric emptying

Disease

Interactions

First past effect

pH

Distribution

Movement of drug from blood to tissue

Influenced by:

Lipid solubility

Molecular size

Ionization

Protein binding

Blood flow

Barriers

Metabolism (Def, Phase 1 and 2)

Chemical alteration of drug

Phase 1 → Make drug more hydrophilic

Phase 2 → Make drug more polar for elimination

Elimination

Removal of drug from body through filtration, active/passive transport

Pharmacodynamics

Study of drug at the site of action and how it effects the body

Receptors

Proteins with unique binding sites located on cell surface and inside cell

What do Receptors do?

Interact with endogenous and exogenous compounds

Middle man between drug and inside of cell

Interpret a signal from the drug and turn it into a physiological effect

Signal transduction

Drug binds with a receptor and produces a cellular effect

Second Messanger

Converts an external stimulus to a cellular response

Selectivity

Drugs influence to a certain tissue/receptor and produce a specific response

Agonist

Drug that binds to a receptor and causes a response (Has both affinity and efficacy)

Antagonist

Drug binds to a receptor without resulting in a response (Only has affinity)

Toxicology

Study of harmful effects of drugs

OTC

Does not require a doctors note

First Pass Effect

Liver metabolizes much of oral drug (Put 50 mg in, only 25 mg actually active)

Affinity

Attraction between receptor and ligand/drug

Prostaglandins

Local mediators derived from arachidonic acid

Help regulate cell function and contributes to inflammation, pain, fever, dysmenorrhea, and thrombus formation

NSAIDS

Drug that inhibits prostaglandin synthesis by blocking COX

Major effect of NSAIDS

Anti-inflammatory

Analgesic

Antipyretic

Glucocorticoids

Steroid with powerful anti-inflammatory effect

Inhibits inflammatory cytokines and increase annexing 1 → inhibits phospholipase A2 → reduces arachidonic acid/prostaglandin synthesis

Asprin

Salicylate and irreversible COX inhibitor with analgesic, antipyretic, anti-inflammatory, and antiplatelet effects

Doan’s

Contains magnesium salicylate for musculoskeletal pain/inflammation.

Ben-Gay

Topical salicylate product for external use

Ibuprofen

NSAID that inhibits COX

Used for inflammation, rheumatoid arthritis, moderate pain, fever, and dysmenorrhea

Naproxen

NSAID that inhibits COX

longer acting than ibuprofen

Used for all as ibuprofen + bursitis/tendonitis

Indomethacin

NSAID/COX inhibitor

Used for arthritis, bursitis, tendonitis, gouty arthritis, and closure of the ductus arteriosus in premature infants

Has antiplatelet effect and high incidence of dose related side effects

Fenoprofen

Reversible COX inhibiting NSAID with anti-inflammatory, antipyretic, and analgesic effects

Used for mild-moderate pain and osteoarthritis/rheumatoid arthritis

Piroxicam

COX-inhibiting NSAID used for rheumatoid and osteoarthritis

Has a 50-60 hour half life

High risk of peptic ulcer/bleeding

Celecoxib

Selective COX-2 inhibitor used for osteoarthritis and rheumatoid arthritis

Provides anti-inflammatory, antipyretic, and analgesic effects without platelet aggression

Causes fewer GI ulcers

Acetaminophen

Weak COX inhibitor that mainly inhibits prostaglandins in the CNS

Analgesic and antipyretic but NOT anti inflammatory

Major liver injury if taken in high doses

COX-1

Housekeeping cyclooxygenase that is active and functions in platelets, stomach. and kidney

COX-2

Cyclooxygenase associated with the anti-inflammatory process, rapidly induced during inflammation

DMARDS

Drugs for rheumatoid arthritis that can slow disease/joint deterioration

Effects can take weeks to monthsM

Methotrexate

Rapid acting DMARD

Chemotherapy drug

Often used first

Side effects: liver fibrosis and bone marrow suppression

Contraindicated: pregnancy

Sulfasalazine

Conventional DMARD

Treats inflammatory bowel disease and retards progression of joint deterioration

Side effects: GI problems, rash, serious hypersensitivity, and blood dyscarasias

Leflunomide

Conventional DMARD

Suppresses immune cell proliferation/lymphocyte activation, reduces inflammation , and slowing of bone erosion

Side effects: GI distress, rash, and liver effect

Biologics

Drugs made from living organisms or their products.

Targets specific immune proteins/cells

Given by injection or IV

Etanercept

Biologic anti-TNF drug given by subcutaneous injections weekly

Targeting TNF reduces cytokine-driven inflammation

Adalimumab

Biologic anti-TNF alpha drug similar to etanercept

Tofacitinib

Targeted synthetic DMARD and janus kinase inhibitor

Blocks cytokine-mediated signaling involved in joint inflammation

TB can occur

Steroids

Very potent anti-inflammatory for chronic inflammatory disease, asthma, and acute flare-ups of joint disease.

Long term use discouraged

Prednisone

Glucocorticoid steroid used for inflammatory conditions including arthritis flare ups and serious asthma

Gout

Metabolic disease caused by urate deposits/crystals in joint and cartilage, producing recurrent acute arthritis

Colchicine

Used to prevent gout

Binds Tubulin and prevents microtubule formation, inhibiting leukocyte migration and phagocytosis

Adverse effect: Diarrhea

Probenecid

Uricosuric drug that decreases renal tubular reabsorption of uric acid. increasing its elimination

Allopurinol

Xanthine oxidase inhibitor that prevents uric acid production

Long term use to lower uric acid and gout attacks

Osteoarthritis

Joint disease involving an intrinsic defect/degeneration of cartilage

Opioids

Analgesic drugs that bind opioid receptors involved in neurotransmission

Agonists can produce analgesia, euphoria, sedation, constipation, cough suppression, respiratory depression, nausea, and pupil constriction

Mu

Opioid receptor associated with enkephalins/endorphins

Produces analgesia and is strongly associated with physical defense

Kappa

Opioid receptor associated with dynorphins

Delta

Opioid receptor associated with enkephalins

Morphine

Mu agonist

Relieves severe pain and lasts 4-5 hours

Adverse effects: Respiratory depression, constipation, orthostatic hypotension, nausea, urinary retention, tolerance, and physical dependence

Hydromorphone

Mu agonist that is more lipid soluble than morphine

Crosses BBB rapidly

Used for severe pain when both medicine are inadequate or not tolerated

Codeine

Opioid for mild to moderate pain with lower maximal efficacy than morphine

Often combined with aspirin or acetaminophen and also used for cough suppression

Oxycodone

Schedule II opioid used for pain

High abuse/addiction potentional

Methadone

Mu agonist with morphine like potency but longer duration

Used in opioid-use treatment because withdrawal symptoms are milder and it can be tapered

Fentanyl

Very potent synthetic mu agonist

100x more potent than morphine

Tramadol

Weak Mu agonist used for mild-moderate pain and chronic neuropathic pain

Could cause seizures and is listed as a schedule IV drug

Naloxone

Mu opioid antagonist used to treat opioid overdose

Opioid agonist-antagonist

Drug that acts as an agonist at kappa receptors and an antagonist at Mu receptor

Physical dependence

Body functions abnormally when the drug is stopped

Opioid withdrawal can cause restlessness, sweating, yawning, irritability, tremor, vomiting, tachycardia, dehydration, and other symptoms

Histamine

Mediator involved in allergy/inflammatory response

H1 blocker

Used for allergy related symptoms

H2 blocker

Reduces gastric acid secretion

Cromolyn Sodium

Mast-cell stabilizer that prevents release of mast-cells contents/histamine

Takes about 2-3 weeks to become effective

Available as a nasal spray

Diphenhydramine

First get H1 blocker (Benadryl) used for allergies

Causes substantial sedation, is antiemetic and is available OTC

Dimenhydrinate

First gen H1 blocker (dramamine) used for motion sickness

Blocked brain signals involved in motion related nausea/dizziness

Can cause weakness and drowiness

Fexofenadine

2nd gen H1 blocker (Allegra) for allergies

Causes less drowsiness and is the active metabolite of terfenadine

Loratadine

2nd gen H1 blocker (Claritin) for allergies

Less sating and available in once daily extended release formulations

Cimetidine

H2 blocker that reduces gastric acid

Can cause headaches, impotence, and gynecomastia

Famotidine

H2 blocker (Pepcid) used for heartburn/gastric acid relief and Zollinger-Ellison syndrome

Hormones

Chemical messengers produced and released to act on target tissues.A

Anabolic steroids

Synthetic derivatives of testosterone

Exogenous testosterone may be used as a PED

Corticosteriods

Steroid hormones produced in the adrenal cortex

Hypothalamus

Releases regulatory factors such as corticotropin-releasing hormones (CRH) which controls anterior pituitary ACTH secretion

Anterior Pituitary

Releases ACTH into systemic circulation

ACTH travels to the adrenal gland and stimulates corticosteroid production

Mineralocorticoid

Adrenocortical steroid class that regulates salt and water balance and real handling of sodium, potassium, and hydrogen

Aldosterone

Most important endogenous mineralocorticoid

Promotes sodium and water reabsorption and potassium/hydrogen excretion

Glucocorticoid

Adrenocortical steroid class that increases glucose availability

Participates in the stress response

Immunosuppressive/anti inflammatory effects

Cortisol

Major endogenous glucocorticoid

Supports glucose availability and stress response

Cortisone

Used for glucocorticoid replacement in adrenal insufficiency

Hydrocortisone

Similar to cortisol and also has mineralocorticoid activiity

Used for replacement therapy and, at higher doses, allerfic reactions, inflammation, and cancer

Fludriocortisone

Mineralocorticoid used for replacement therapy

Used in Addisons disease, hypoaldosteronism, and confentiral adrenal hyperplasia