Cne Pharm Test 1

Front 1

ADME

Back 1

A = absorption
D = distribution
M = metabolism (or biotransformation)
E = excretion/elimination

Front 2

list drug characteristics that affect pharmacokinetic movement (how drug moves through body)

Back 2

1. *Lipid solubility
2. *Degree of ionization (Pka) & relative solubility of ionized and non-ionized forms
3. *Protein binding
4. Molecular size
5. Structural features

Front 3

How does lipid solubility affect pharmacokinetic movement of a drug?

Back 3

Lipid solubility = a measure of how readily a drug can dissolve in water vs lipid.
It affects the entire process of ADME --> drugs that are highly lipid soluble very easily cross plasma membranes (absorption through diffusion is very rapid, distribution can also be very rapid, lipid-soluble drugs often require liver transformation in order to eliminate).
*It's easy to GET lipid-soluble drugs into the bloodstream, but rather difficult to clear them.

Front 4

How does degree of ionization affect pharmacokinetic movement of a drug?

Back 4

Degree of ionization refers to drugs that are weak acids or bases (many drugs are). Weak acid or base drugs can be present in ionized or non-ionized form.
When a drug is non-ionized form (not charged) --> non-polar/lipid-soluble --> can more readily cross plasma membranes/be absorbed.
Therefore the ionization of weak acids & bases affect the rate and location of absorption.

**Acidic drugs that are in acidic solutions are non-ionized and therefore more readily absorbed (think ASA in stomach).

Front 5

How does protein binding affect pharmacokinetic movement of a drug?

Back 5

(this includes binding to plasma proteins & tissue proteins)
The extent to which a drug binds to a plasma distribution affects distribution, rate of metabolism, and rate of excretion.
This is important for issues of toxicity (how tightly in binds to tissue proteins) and for the rate at which a drug is cleared by the body.

Front 6

first pass effect

Back 6

When drugs are first taken into the body (the "first pass"), there is a significant % of removal/deactivation by metabolism before it can get into bloodstream & to site of action.
- Has to do w/ the effect of liver on drugs taken orally --> these drugs must pass through liver before getting into circulation to the rest of body. For some, this means a significant amount of deactivation by the liver & overall low bioavailability.
- Ex: opiates have a high first pass effect

Front 7

List both common & less common routes of administration

Back 7

Common:
1. Oral
2. Intravenous (IV)
3. Subcutaneous
4. Intramuscular

Less common:
5. Transdermal
6. Rectal
7. Intra-arterial
8. Intrathecal
9. Inhaled drugs
10. Topical application

Front 8

Oral administration of drugs

Back 8

Drug absorption: can be variable/erratic and depends on many factors.

Advantages: most common, convenient, economical, and usually safest.
Disadvantages: need patient compliance (can be unpredictable), drug absorption can be variable and depend on many factors, bioavailability can be erratic.

Front 9

IV administration of drugs

Back 9

Drug absorption: bypasses absorption & goes directly into circulation (rapid)

Advantages: Immediate action/good for emergency situations, permits titration (good for when therapeutic index is narrow), good for administering large volumes over time, good for potentially irritating substances.
Disadvantages: Increased risk of serious adverse reactions.

Front 10

Subcutaneous administration of drugs

Back 10

Drug absorption: Can be fast or slow depending on drug prep, can be affected by changes in blood flow to tissue.

Advantages: Good for self-administration
Disadvantages: Not suitable for large volumes, possible pain or necrosis at site.

Front 11

Intramuscular administration of drugs

Back 11

Drug absorption: Can be fast or slow depending on drug prep, can be affected by changes in blood flow to tissue.

Advantages: Good for self-administration
Disadvantages: Contraindicated for use with anticoagulants.

Front 12

sublingual administration

Back 12

absorbed via oral mucosa, bypasses liver

Front 13

transdermal administration

Back 13

absorbed through intact skin (but ONLY good for intact skin), good for drugs that are highly lipid-soluble, bypasses liver

Front 14

rectal administration

Back 14

50% of rectally administered drugs bypass the liver but absorption can be irregular

Front 15

intra-arterial administration

Back 15

administration requires GREAT CARE, but good for localizing drug effect & it bypasses the liver

Front 16

intrathecal administration

Back 16

drugs administered directly into CSF (into ventricles of brain or spinal subarachnoid space), can bypass BBB

Front 17

inhaled drug administration

Back 17

Absorbed through pulmonary epithelium & mucous membranes of respiratory tract --> VERY RAPID. Mostly used for gases and aerosolized droplets.
Bypasses liver, good for local application where lung is target

Front 18

topical application administration of drug

Back 18

to mucous membranes (i.e., nasopharynx, oropharynx, vagina, colon, urethra, bladder, eye) - goal is only to have local effect, rarely systematically absorbed

Front 19

What factors is drug distribution dependent upon?

Back 19

1. Physiological factors - cardiac output, regional blood flow (blood flow of organ), capillary permeability (how easily drug gets out of capillaries), tissue volume
2. Physiochemical properties of drug - lipid solubility, pH partitioning, drug binding to plasma protein and/or tissue molecules
3. Other important factors - Fat as drug reservoir (sequestration), bone sequestration, redistribution
*Special considerations* - distribution to CNS & CSF, placental transfer of drug

Front 20

sequestration

Back 20

sequestration = accumulation of a drug into a particular organ (and its possibility of release back into blood stream slowly over a long period of time --> how rapidly this happens depends on how tightly the drug is sequestered).

*Sometimes this is therapeutic, but often it's not.

Front 21

opiate prototype & agonists

Back 21

*remember: huge first-pass effect with opiates
PROTOTYPE: morphine
AGONISTS:
- demerol
- codeine
-dilaudid

Front 22

opiate agonist/antagonist drugs

Back 22

Agonist/antagonist drugs were created to battle abuse of opiates (esp. oxycontin) --> these drugs act as agonists when used properly and antagonist when used improperly (i.e., crushed up to be snorted).
PROTOTYPE: pentazocine (talwin)
- stadol
- nubain

Front 23

opiate antagonists

Back 23

PROTOTYPE: narcan
**For addicts, this can cause immediate withdrawal.

Front 24

therapeutic & adverse effects of opiates

Back 24

THERAPEUTIC: interferes with pain impulses, has some amount of vasodilating effect
ADVERSE:
- depresses CNS (depresses respiration, sedation, dizziness)
- depresses GI tract (N&V, constipiation)
- alters psychological responses to pain (decreases anxiety)
- produces euphoria --> high risk for addiction/abuse

Front 25

clinical uses for opiates

Back 25

- relief of moderate-severe pain
- pre-op sedation
- L&D
- invasive diagnostic tests
- acute pulmonary edema (has a bit of a vasodilating effect)
- severe non-productive cough (CNS depression = decreased reflexes, including cough reflex) --> codeine

Front 26

contraindications & risks for opiates

Back 26

CONTRAINDICATIONS:
- chronic lung infections
- kidney/liver disease
- increased intracranial pressure
- patients that already have a depressed respiratory rate (ALWAYS hold opiate drugs if respirations are below 8/min)
- hx of addiction
RISKS:
- increased fall risk

Front 27

symptoms of opiate overdose & treatment drugs

Back 27

SYMPTOMS: pinpoint pupils, slurred speech, erratic gait, constipation, slow HR & resp. rate

TREATMENT (therapeutic withdrawal meds):
- methadone
- buprenorphine (suboxone)

Front 28

3 categories of pain relievers

Back 28

1. opiates/opioids (narcotics)
2. nonopiates (acetaminophen, ASA, NSAIDs)
3. adjuvant analgesics --> do not actually reduce pain but address issues associated with pain (i.e., benzodiazopines for anxiety, TCA, corticosteroids)

Front 29

Cox 1

Back 29

PROTECTIVE/PHYSIOLOGIC prostaglandins:
- decreased gastric acid & increased mucous --> protects GI tract
- protects renal system
- regulates smooth muscle tone in vasculature
- bronchodilation
- regulates blood clotting

Front 30

Cox 2

Back 30

PATHOLOGIC prostaglandins:
- inflammation
- edema
- cause release of cytokines (cause vasodilation & pain)
- leukocytosis (rush of white blood cells to area)

Front 31

cascade of events involved in physiology of pain

Back 31

1. injury to cell
2. these cells release arachidonic acid & bradykinins
3. arachidonic acid leads to release of cox 1 & 2
4. cox 1 & 2 release prostaglandins

Front 32

ASA

Back 32

PROTOTYPE: aspirin
- analgesic (mild pain)
- anti-inflammatory (non-selective COX blocker)
- antipyretic (fever reducing)
- anti-thrombotic/anti-coagulent (prevents clotting)

Front 33

Clinical uses for ASA

Back 33

- pts with headaches often treated with ASA
- pts with temperatures greater than 101
- rheumatoid arthritis
- to prevent clotting/stroke/heart attack (1/day)
**Always instruct pts to take with full glass of water

Front 34

adverse effects of ASA

Back 34

- increased bleeding: bruising, nose bleeds, hematuria, bleeding gums, hematemosis (throwing up blood)
- tinnitus
- Reye's syndrome (brain & liver function damage) in children who have been given ASA for viral infection
- GI bleeding, N&V, ulceration
- too much can cause acidosis
- pregnancy --> prolonged gestation & labor, risk of hemorrhaging, transmission through breastfeeding
- ASA-sensitive asthma

Front 35

contraindications for ASA

Back 35

- children under 12
- history of GI ulcers/bleeding
- ASA-sensitive asthma
- liver/kidney problems
- pregnancy/breastfeeding
- 1 week before surgery

Front 36

Signs & treatment of a pt overdosing on ASA (has acidosis)?

Back 36

SIGNS:
- drowsiness, confusion, stupor/coma, thirstiness (vasodilation), increased sweating

TREATMENT:
- tell them to hyperventilate to blow of CO2
- IV bicarbonate

Front 37

NSAID

Back 37

NSAID (non-steroidal anti-inflammatory drugs)
PROTOTYPE: ibuprofen (advil)
- analgesic (mild pain)
***These drugs are good for musculoskeletal pain relief
- anti-inflammatory (non-specific COX blocker)
- antipyretic
- anti-thrombotic (only binds with platelets WHILE it's in your system --> reversible binding --> short-lived effects) ***This drug is not effective for treating high-risk heart attack/stroke pts because they would have to take a dose every 4 hours

Front 38

adverse effects of NSAID

Back 38

- GI ulcers & bleeding
- effects on pregnancy and lactation
- tinnitus
- slightly CNS depressant (may cause some drowsiness)
- rarely can cause kidney necrosis (very serious)
- LOTS of drug interactions

Front 39

drug interactions of NSAID

Back 39

- increases action of steroids (high risk for bleeding & ulcers)
- oral anti-coagulants (high risk for bleeding)
- can increase toxicity of lithium
- oral hypoglycemics (taken by diabetes pts)
- increased GI irritation with alcohol
- heparin (also increases bleeding)

Front 40

contraindications for NSAID

Back 40

- pregnancy/lactation
- on lithium, oral anti-coagulants, heparin, steroids, or oral hypoglycemics
- 1 week before surgery

Front 41

acetaminophen

Back 41

PROTOTYPE: acetaminophen (tylenol)
- analgesic (mild pain)
- antipyretic
*NO ANTI-INFLAMMATORY EFFECTS --> does not bind with platelets
also: no GI effects & less adverse side effects than ASA or ibuprofen

Front 42

adverse effects of acetaminophen

Back 42

**less than ASA & ibuprofen**
- in large doses (around 30 or more) OR in combination with alcohol --> can cause liver necrosis or hepatotoxicity
- contraindicated for liver/kidney failure
- rash
- urticaria (hives)
- nausea

Front 43

signs & treatment of liver necrosis/hepatotoxicity (due to acetaminophen overdose)

Back 43

SIGNS:
- flu-like symptoms in first 24 hours, then:
- decreased urine output
- pain in upper right quadrant (location of liver)
- jaundice
- can lead to complete renal failure
TREATMENT:
- acetylcysteine

Front 44

Cox 2-specific inhibitors

Back 44

ONLY block pathologic effects of Cox 2
PROTOTYPE: celecoxib (celebrex)
- analgesic
- great anti-inflammatory

Front 45

adverse effects of Cox 2-specific inhibitors

Back 45

- increased platelet activity --> HIGH risk for clotting

* Absolutely contraindicated for pts at high risk for heart attack and stroke - has black box warning for this.

Front 46

cholinergic & adrenergic receptors

Back 46

CHOLINERGIC
- muscarinic: internal organs & glands (secretions)
- nicotinic: motor nerves & muscles

ADRENERGIC
- alpha 1: peripheral vasoconstriction --> takes blood toward central organs and skeletal muscles; fast blood coagulation (could be positive or negative); dilates pupils (mydriasis); causes pallor & increases sweating
- beta 1: effects heart --> chronotropic (increases HR), inotropic (increases contractility); gluconeogenesis; increased tension/anxiety
- beta 2: bronchodilation, increases respiration rate & O2 consumption, increases blood sugar (can cause diabetes), increases fatty acid concentration in blood

Front 47

define half-life

Back 47

time it takes for the serum concentration of a drug to decrease by 50%

Front 48

inducers vs inhibitors

Back 48

inducer = if a drug INCREASES the rate of activity of an enzyme

inhibitor = if a drug REDUCES the rate of activity of an enzyme

Front 49

2 mechanisms of tolerance

Back 49

a) Expression of enzymes that metabolize drug is enhanced/increases activity
--> less likely to lose tolerance over time with this mechanism

b) Target cell reduces its expression for the receptor of the drug (decreased sensitivity to drug)

Front 50

4 parameters that dictate the plasma concentration of a drug in your blood (which is directly proportional to the drug's effect)

Back 50

1. bioavailability
2. clearance (how fast)
3. volume distribution (how much blood you have)
4. half life of drug in body

Front 51

steady state plasma concentration of a drug (define and average time it takes to get to this point)

Back 51

DEFINITION: when the average concentration at any point is stable & within therapeutic range; the goal is to reach this point.

TIMING: we usually reach steady state within 4 half-lives of the drug (administering it 4-5 times)

Front 52

drug dosing regimen

Back 52

1. Loading dose (initial large dose to reach therapeutic range, usually for emergency situations)
2. Maintenance dose (to keep within therapeutic range)
3. Dose interval (interval of time between doses)
4. Individualized dose (catering the dose to an individual
--> titrating dose until it becomes stable and steady state for that individual; must be checked regularly)

Front 53

6 general effects a medication can have?

Back 53

- Palliative (ex: morphine)
- Curative (ex: antibiotics)
- Supportive (ex: blood pressure medication)
- Substitutive (ex: insulin for diabetics)
- Chemotherapeutic (to treat cancer)
- Restorative (i.e., iron for anemia)

Front 54

drug fever

Back 54

low grade or spiking fevers while on a medication - especially antibiotics; usually goes away within 48 hours

Front 55

definition of hematological (adverse drug effects)

Back 55

causing bleeding; could also cause bone marrow depression, anemia, leukopenia

Front 56

How are teratogenic drugs rated?

Back 56

Category A = studies done on pregnant women - no effects

Category B = studies done on animals - no effect

Category C = animal studies showed some potential risks to fetus --> this is where you start considering whether or not benefits outweigh risks

Category D = evidence of human fetal risk

Category X = risk outweighs any potential benefits & absolutely should not be used with pregnancy