Pharmacology Flashcards
What’s pharmacokinetics?
Body does to the drug
Pharmacokinetics processes
Absorption
Distribution
Metabolism
Excretion
Routes of drug admin
Enteral
Parenteral
Inhalation
topical
Transdermal - patch, onset 15min. I.e: Fentanyl patch
Types of enteral admin
Buccal/ sublingual
Oral - slowest. Absorbed best in duodenum
Rectal
Types of parental admin
IV - fastest. Only one 100% bioavailability
IM - Deepest. 5min. Site: upper lateral quadrant of the gluteal muscle
SC - 15min
What’s bioavailability
Amount of drug that reaches site of action
Lipophilic & acidic drugs are easier to absorb. TRUE/FALSE
True.
What’s “hepatic 1st pass effect”?
Drug gets metabolized in the liver - through the Hepatic portal syst- an amount will become inactive
Only PO and rectal will pass this pathway. I.e: Pen G- completely inactive if PO - best route: IV/IM
> H < bioavailability
What are the absorption mechanisms?
Passive transfer -no energy
Active transport
Types of passive transfer
Simple passive diffusion - gradient. Hydrophobic/Lipophilic/non-ionized
Filtration - Hydrophilic/Lipophobic/ionized
Facilitated diffusion - carrier-based
Types of active transport
Needs ATP
Against gradient
I.e: Glucose
Needs carrier
Osmosis
Similar to filtration
lipid-soluble compounds get through BBB? T/F
True
Non-ionized drugs have higher lipid solubility
I.e: Thiopental, ultra-short barbiturate
Factors affecting distribution
Rate of blood flow
Protein binding - albumin (plasma protein) highest ability to bind to drugs - < distribution
Permeability - leaky capillary >distribution. In BBB <distribution
Gastric emptying time
> blood flow >concentration of a drug?
T/F
True.
Most important factor
I.e: brain, kidneys, liver
What’s bio transformation of a drug?
Lipophilic to lipophobic
Active to inactive
It gets easily excreted by kidneys
Types of biotransformation
Inactivation
Formation of active metabolite from active drug. I.e: Digitoxin - Digoxin
Activation of inactive drug - Prodrugs. I.e: Levodopa (inactive) - Dopamine (active)
Where does Phase I rx occurs and kind of rx?
Liver - Hepatocytes - CYP450 (Cytochromes) system
Oxidation, reduction, hydrolysis
Which cytochrome causes genetic polymorphism
CYP2D6
Rapid metabolizer - < therapeutic effect. I.e: Codeine
Slow metabolizer - > toxicity
Examples of CYP450 inducers
Rifampicin
Phenytoin
Carbamazepine
Chronic alcohol
If taken w/Warfarin - > risk of clotting
Examples of CYP450 inhibitors
Grapefruit juice
Ketoconazole (all azoles)
Cimetidine (heartburn)
Acute alcohol
If taken w/Warfarin - risk of bleeding
Where does Phase II rx occurs and kind of rx?
Liver and kidney
Rx: Conjugation rx like:
Glucuronidation - glucuronide
Acetylation
Sulfation
Sites for drug of elimination
Kidneys and liver
Also lungs - Halothane, N2O , bile - cat ionic, anionic, steroid-like , feces
Factors affecting renal excretion
GFR - plasma protein bound drug isn’t filtered
Kidney tubular reabsorption - pH. I.e: ASA (weak acid) easily reabsorbed in acid conditions
Active secretion
Changes: [plasma protein/binding]
Blood flow
#functional nephrons, renal disease
Volume of distribution
Types of drug clearance/elimination
Zero-order
1st-order
How is the elimination in each type?
(Zero/1st order)
Zero order - linear. I.e: alcohol, phenytoin, ASA (toxic)
1st order - exponential. Most drugs
What’s a drug half life and how many does it take to eliminate it from the body
Time required [drug] to decrease by 50%
4-5 half lives
What’s therapeutic index
How safe a drug is
Comparison Therapeutic & toxic effect
Lethal dose for 50% of animals to the effective dose for 50% of animals
Formula for Therapeutic index
Ti = LD50 / ED50
LD - lethal dose
ED - effective dose
What’s the therapeutic window
Range Desired/ adverse response
Narrow therapeutic window >monitoring >risk of side effects
What are the intrinsic activities in pharmacodynamics
Agonist
Antagonist
Agonist-antagonist
What’s pharmacodynamics?
What the drug does to the body
Types of Agonist intrinsic activities
Full Agonist - full response
Partial Agonist - partial response
What’s an agonist drug? And examples
Drug bonds yo receptor and mímica effect of agent/neurotransmitter
NE, EPi, Ventolin, Albuterol
What’s an antagonist drug? Examples
Drug binds to receptor and prevents effect to happen
Atropine, Benadryl
Type of antagonist
Competitive - binds are weak. >agonist = response
Non-competitive - binds too strong. > agonist = No response
What’s an agonist-antagonist
Acts as both. I.e: Opiods
What’s efficacy
receptors for max response
What affects the efficacy of a drug?
Affinity - how strong drug binds to receptor
Intrinsic activity - how strong it can produce desire effect
Drug w/both has high efficacy
What’s potency?
Strength
Important factors determining appropriate dosage of a drug?
MH
Age
Weight
<EC50>Potency >Affinity
T/F
</EC50>
True
Drug effects?
Additive - combination 2 drugs = No enhancement
Cumulative - >drug = > [drug] achieved
Synergistic - combination 2 drugs = > effect
Drugs adverse rx
Toxicity- excessive dosage of drug for pt
Allergy - immune rx
Side effect - rx within therapeutic window
Idiosyncratic- unusual, unpredictable rx
Teratogenicity- fetal abnormalities
Drug abuse
Can result in addiction
Tolerance
Chronic response
>dose <response/effect
Physical/psychological dependence
Physical - continued use of drug to avoid withdrawals
Psychological - repeated use of a drug w/o increase dosage
Perception of acute and chronic pain involves the dame regions of the brain (CNS) T/F
True
Dimensions of pain
Sensory - location, intensity, quality
Affective - emotions
Categories of pain
Somatic - periodontal, alveolar
Visceral - pulpal
Criteria when selecting analgesic
Severity of pain
Age
Current meds
Pregnancy
Which intensity of pain rx Acetaminophen
Mild- mod
Mechanism of action acetaminophen
Inhibits CNS cyclooxygenase
Action of acetaminophen
Analgesic
Antipyretic
Acetaminophen antidote
NAC - N-acetylcysteine
Reason acetaminophen is rx to pt w/ hx ulcers and bleeding disorders
Doesn’t affect inflammatory response
Platelets function
Coagulation pathway
Max dose for adult and kids /day
Adult - 4gr/day
* in alcoholics 2gr/day
Kids - 2.6gr/day (75mg/kg)
What condition can increase risk of hepatotoxicity and lead to renal toxicity
Pt w/liver dysfunction (cirrhosis, chronic alcoholism)
Is not a contraindication is this pt
Contraindications of Acetaminophen
Allergy
Relative contraindications:
- hepatic/renal dysfunction
- alcohol abuse
- warfarin
Side effects of Acetaminophen
Headache
Sweating
Nausea/vomiting
Rash
Abdominal pan
Dark urine
