Pharm Exam 1

Graded dose-response curve

a graph of increasing response to increasing drug concentration or dose

- 1 patient

potency

the strength of a drug

- more potent = less dosage

- determined by affinity for its receptor and/or ability of the drug to reach its site of action

efficacy

the ability to produce a desired or intended result

determined by:

- type of interaction with the receptor (agonist vs antagonist)

- limitations on amount that can be administered

POTENCY DOES NOT EQUAL MAXIMUM EFFICACY

Emax

Maximum effect achievable by a drug

quantal dose response curve

represents dose response relationships in POPULATIONS

- Y-axis with end in "ing"

- represents variations in drug responses

hyporeactive

the intensity of a given dose of a drug is less than anticipated.

hyperreactive

intensity of a given dose of drug is greater than anticipated

tolerance

Time-related loss of response to a drug

- within weeks to months of being on a drug

idiosyncratic drug response

infrequently observed drug effect

tachyphylaxis

rapid decrease in response to a drug

- within minutes to hours of being on a drug

hypersensitivity

allergic reaction to a drug

therapeutic index

TD50/ED50 = TI

- indicator of a drug's safety

- greater the value of TI, the safer the drug is considered to be

- larger the TI, the larger the dose to evoke a toxic response

when the benefits outweigh the risks (cancer)

When is it acceptable to take a drug with a low TI?

Pharmacokinetics

Study of drug absorption, distribution, metabolism, and excretion.

bioavailability

The extent to which the drug reaches systemic circulation

- Through IV = 100%

- Orally, first pass effect

volume of distribution

body space into which a drug can diffuse

clearance

amount of blood from which all of a drug is removed per unit of time

half life

predicts how long it takes the dosing regimen to achieve steady-state concentrations

- 4-5 half lives

pharmacodynamics

study of a drug at the site of action and the EFFECT ON THE BODY

affinity

refers to the attraction between a receptor and a ligand (drug)

efficacy

____ refers to the ability of a ligand to bind to the receptor, activate it, and lead to some physiological response

agonist

a drug that binds to the receptor and causes some type of response

- has both affinity and efficacy

antagonist

a drug that binds to the receptor without resulting in any response

- only has affinity

selectivity

Drug elicits only the response for which it is given

- no such thing because of side effects

first pass effect

a phenomenon in which drugs given orally are carried directly to the liver after absorption, where they may be largely inactivated by liver enzymes before they can enter the general circulation; oral drugs frequently are given in higher doses than drugs given by other routes because of this early breakdown

- 50% is active

ED50

median effective dose:

- dose at which 50% of population responds in specified manner

TD50

median toxic dose

- dose at which 50% of the population exhibits adverse effect

no (high abuse: LSD, heroin)

are schedule I drugs used medically?

IV

Schedule II-___ drugs are used medically but also have the potential for abuse

aspirin uses

- analgesic

- antipyretic

- anti-inflammatory

- anti-platelet

blood thinner

the advantage of aspirin having antiplatelet qualities is that it can act as a ____ ____ and reduce the risk of heart attack, however, it increases the risk of hemorrhage

aspirin

Irreversible inhibitor of COX

- effects persist until new COX generated

doan's

Magnesium Salicylate (NSAID)

- relieve's musculoskeletal pain and inflammation

ben-gay

topical salicylate

- external use for pain and inflammation

- think icy hot

inhibition of COX

these drugs all have a MOA of _____ ___ ____

- ibuprofen

- naproxen

- fenoprofen

- piroxicam

- indomethacin

ibuprofen

shorter duration of action than naproxen

- anti-inflammatory

- anti-pyretic

- analgesic

- safe to use with anticoagulants

naproxen

has a long half life so administered less frequently

- anti-inflammatory

- antipyretic

- analgesic

- decreases renal blood flow

- shows an increase in liver toxicity in marathon runners

fenoprofen

less intense GI side effects than those occurring with aspirin

- reversible inhibitor of COX

- anti-inflammatory

- antipyretic

- analgesic

- good for mild/moderate pain (cramps, dental pain, headaches)

- good for OA and RA

piroxicam

once a day dosing (half life= 50-60 hours)

- used for OA and RA- 9.5x higher risk for peptic ulcer and bleeding compared to other NSAIDS

- antiplatelet: more similar to aspirin

indomethacin

used for arthritis, bursitis, gouty arthritis, close DA in premies

- reduces pain and fever but not used for these effects

- antiplatelet effects

- high incidence of dose-related side effects (25-50%)

- INITIAL TREATMENT OF GOUT AND MOST OFTEN USED TODAY FOR GOUT

celecoxib

used for OA and RA

- NO platelet aggregation

- anti-inflammatory

- antipyretic

- analgesic

- works on COX-2 and not on COX-1, so leaves protective prostaglandins in stomach

- fewer GI ulcers than other NSAIDS

- may increase risk for serious CV events (MI/stroke)

acetaminophen

only inhibits prostaglandins in CNS

- weak inhibition of COX

- analgesic

- antipyretic

- NOT an anti-inflammatory agent

- categorized as an analgesic

-used in fever reduction in children

-liver toxicity is most serious side effect

methotrexate

- rapid acting DMARD (3-6 weeks)

- this is the drug given initially to treat, other agents if not working

sulfasalazine

treats IBD

- retards progression of joint deterioration

- GI problems and rash

- may produce serious hypersensitivity and blood dyscrasias

leflunomide

suppresses immune cell proliferation (reduces inflammation)

- slows formation of bone erosion

- well tolerated, benefits in 1 month

- side effects: GI distress, rash, liver function

etanercept

anti tumor necrosis factor (TNF) drug

- biologic

- injection under the skin weekly

- increased risk of infection especially if used with other immunosuppressants

- prevents release of cytokines (role in immune response and inflammation)

adalimumab

- biologic

- anti TNF alpha drug

- injection under the skin weekly or bi-weekly

- increased risk of infection especially if used with other immunosuppressants

Tofacitinib

- janus kinase inhibitor (which play a role in joint inflammation)

- possibly inhibits progression of structural damage

colchicine

- prophylaxis of recurrent episodes of gouty arthritis

- troublesome diarrhea

- grapefruit can elevate levels

probenecid

- decreases net reabsorption of uric acid by affecting transport sites

- large urine volume recommended to minimize possibility of kidney stones

allopurinol

- xanthine oxidase inhibitor

- long-term treatment to prevent gout attacks

- not used to treat acute gout attacks

morphine

- mu agonist

- does not reach the brain quickly, lasts 4-5 hours

- relieves pain

- side effects: orthostatic hypotension, constipation, pupil constriction, respiratory depression

Hydromorphone

- mu agonist

- more lipid soluble, able to cross BBB more rapidly, faster acting

- relieves severe pain, extended release capsules exist

- constipation and dizziness can occur

codeine

- mild to moderate pain reliever (never achieves morphine-like efficacy)

- often used in combination with aspirin or acetaminophen

oxycodone

- never achieves morphine-like efficacy

- schedule II drug (VERY addictive)

- Purdue Pharma scandal

methadone

- mu agonist

- equipotent with morphine

- longer duration of action

- used in treatment of opioid abuse (milder withdrawal symptoms, helps taper them off)

fentanyl

- mu agonist

- most widely used of synthetic opioids (legally and illegally)

- 100x more potent than morphine

- short acting (1-1.5 hours)

tramadol

- weak mu agonist

- mild to moderate pain

- may cause seizures (never give to epileptics)

- useful in chronic neuropathic pain

naloxone

- aka narcan

- mu antagonist

- used to treat opioid overdoses

naltrexone

- useful in treatment of alcoholism (blocks endogenous opioids that give feeling of euphoria)

cromolyn sodium

- stabilizes mast cells and prevents release of contents

- takes 2-3 weeks to be effective

- aerosol and nasal spray

- side effects: burning, itching, sneezing, coughing

H1 blockers

- classical type

- allergies

- first generation (drowsiness)

- second generation (non-sedating)

H2 blockers

inhibits gastric acid secretion

- relieves symptoms of ulcers

diphenhydramine

- first generation

- H1 blocker

- for allergies

- sedation in 50% of patients

dimenhydrinate

- aka dramamine

- H1 blocker

- 1st generation

- causes muscular weakness/drowsiness

fexofenadine

- 2nd generation

- H1 blocker

- for allergies

- causes less drowsiness

loratadine

- 2nd generation

- H1 blocker

- for allergies, less sedating

- once a day extended release formulas

cimetidine

- H2 blocker

- inhibits cytochrome p450 metabolism of other drugs

- causes headaches, breast tissue in males

famotidine

- H2 blocker

- heart burn and gastric acid relief

glucocorticoids

- influence carbohydrate metabolism

mineralcorticoids

- modulate salt and water balance

cortisol

____ is the most important endogenous glucocorticoid

ACTH

the synthesis of glucocorticoids is controlled by ____

aldosterone

____ is the most important endogenous mineralcorticoid

RAAS (renin-angiotensin-aldosterone system)

mineralcorticoids are regulated by the ____

hydrocortisone

- similar to cortisol

- also has mineralcorticoid properties

- replacement therapy

- also to treat allergic reactions, inflammation, cancer

- at low doses, generally safe

fludrocortisone

- mineralcorticoid available for replacement therapy

- also glucocorticoid activity

- treats Addison's disease, hypoaldosteronism, and congenital adrenal hyperplasia

- if dose is too high, salt and water retention= weight gain, HTN, hypokalemia, and edema

withdraw

you should never _____ someone abruptly from a corticosteroid as it is life-threatening

- may need to taper from 2 months-1 year

- need to allow recovery of normal pituitary-adrenal response to endogenous corticosteroids

false

T/F: corticosteroids decrease blood glucose levels

cortisone

- an inactive form of cortisol, or a synthetic, anti-inflammatory medication used in medical treatments

PSNS

Housekeeping (GI, bladder, eye)

- slows HR

- increased gastric secretion

- emptying of bladder

- emptying of bowel

- focusing of the eye for near vision

- constriction of pupil

- contraction of bronchial smooth muscle

SNS

Fight or flight

- increased HR and BP

- shunting of blood away from skin to muscles

- dilation of bronchi

- dilation of pupils

- mobilization of stored energy

Ach

what NT is binds to cholinergic receptors?

- Nicotinic N/M and muscarinic

NE and Epi

What NTs bind to adrenergic receptors

- Alpha 1/2, Beta 1/2/3, and dopamine

heart

Beta1 is dominate in the ____

lung

beta2 is dominate in the ____

life cycle of Ach

choline + acetylcoenzyme A

- stored

- destroyed by AchE

- uptake of choline

life cycle of NE

- precursors

- stored in vesicles

- reuptake

- converted to Epi

bethanechol

- muscarinic agonist

- relieves urinary retention

atropine

- muscarinic antagonist

- used for muscarinic poisoning

physostigmine

- inhibitor of AchE

- given for antimuscarinic poisoning (atropine poisoning)

neostigmine

- reversible cholinesterase inhibitor

- used for myasthenia gravis

- binds to cholinesterase preventing it from catalyzing breakdown of Ach

tubocurarine

- neuromuscular blocking agent (non-depolarizing)

- competes with Ach to bind to nicotinicM receptors

- Uses: muscle relaxation during surgery, mechanical ventilation, endotracheal intubation, and electroconvulsive therapy

succinylcholine

- neuromuscular blocking agent (depolarizing)

- binds to nicotinicM receptors and remains bound resulting in constant depolarization

- uses: endotracheal intubation, electroconvulsive therapy, endoscopy

epinephrine

- catecholamine (adrenergic agonist)

- alpha1, alpha2, beta1, beta2

- anaphylactic shock, delay absorption of anesthetics, hemostasis, reduce nasal congestion, overcome AV heart block, pupil dilation, asthma

norepinephrine

- catecholamine (adrenergic agonist)

- alpha1, alpha2, beta1

- used for hypotension and cardiac arrest

isoproterenol

- catecholamine (adrenergic agonist)

- beta1, beta2

- uses: AV heart block, asthma, bronchospasm

dopamine

- catecholamine (adrenergic agonist)

- dopamine, beta1, alpha1

- uses: shock, heart failure, acute renal failure

terbutaline

- noncatecholamine

- beta2

- uses: asthma and preterm labor

ephedrine

- noncatecholamine

- alpha1, alpha2, beta1, beta2

- uses: nasal congestion and narcolepsy