Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Pharmaco > Class 1- pharmacokinetic > Flashcards

Class 1- pharmacokinetic Flashcards

1
Q

Pharmacokinetics include

A

absorption, distribution, metabolism, elimination

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

pharmacokinetics definition

A

«What the body does to the drug »

• All the reactions that occur after the introduction of a drug into the body

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

ABSORPTION definition

A

Transition of the drug from its delivery site to the systemic circulation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

ABSORPTION Influenced by:

A

o Physical-chemical properties of drugs (weight, liposolubility, ionization)
o Pharmaceutical form (e.g. tablets, capsules, solutions)
o Route of administration

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

PO administration absorption

A

intestines=blood=liver=systemic circulation=brain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

2 steps in PO absorption

A
  1. Releasing the active ingredient

2. Absorption of the drug (passive diffusion or active transport)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

PO, RELEASING THE ACTIVE INGREDIENT depends

on the following factors :

A 
o gastric pH
o Drug formulation
• Capsule
• Tablet
• Coated tablet
• Extended/controlled release tablet
• Oral solution
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Other factors that may influence: PO absorption

A

o Gastric emptying
o Time of contact with the intestinal wall
o Bowel perfusion
o Food: Food has an impact on gastric emptying, as well as the speed at which drugs are absorbed (↑, ↓ ou ∅ )
o Formation of non-absorbable complexes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

o Gastric emptying definition

A

Some medications influence intestinal motility, thus altering the rate at which other drugs are absorbed

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

FORMATIONS OF NON-ABSORBABLE COMPLEXES def

A

CHELATION
Calcium/iron/dairy products form complexes not absorbed with certain medications
Examples: - Levothyroxine (SynthroidTM)
need an interval of 2h

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Hepatic first-pass

A

When a drug is taken orally, it is absorbed into the
systemic circulation, which passes through the liver
before going to other sites of action.
Part of the drug is metabolized by the liver before it reaches the blood « LOSS » by hepatic elimination

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

BIOAVAILABILITY

A

Fraction (%) of an administered drug unchanged that reaches the systemic circulation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Parenteral administration bioavailiability

A

100%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

ORAL ADMINISTRATION

EXTENDED-RELEASE DRUGS

A

o Reduces the frequency of
administration
o Less variable plasma concentrations = less side effects, same efficacy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

ORAL ADMINISTRATION PROS

A 
o Simple
o Practical
o Economic
o Safe
o Several formulations available
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

ORAL ADMINISTRATION CONS

A 
o First hepatic pass
o Incomplete bioavailability
o Delay of action
o Gastrointestinal side effects
o Adhesion monitoring more difficult
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

ABSORPTION OF PSYCHOTROPIC DRUGS – ORAL

ADMINISTRATION, generally

A

o Good absorption through the gastrointestinal tract
o Maximum concentrations reached in about 1 to 6 hours
o Variable bioavailability
o Fast-dissolving drugs: still need to be absorbed through the gastrointestinal tract

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

SUBLINGUAL ADMINISTRATION

A

doesn’t go through gut
o Thin and highly vascularized epithelium
o Promotes absorption if sufficient contact time

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

SUBLINGUAL ADMINISTRATION

PROS

A

o Faster absorption
o Avoids the hepatic first-pass
o Not modified by the gastrointestinal system

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

SUBLINGUAL ADMINISTRATION CONS

A

o Substance should be powerful and active at low doses

o Irritating local effect

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

RECTAL ADMINISTRATION

PROS

A

o Useful if nausea, vomiting or patient unable to swallow
o Not modified by the gastrointestinal system
o Decrease in the hepatic first-pass

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

RECTAL ADMINISTRATION CONS

A

o Erratic absorption
o Irritation of the mucous membranes
o Absorption sometimes uncomfortable for patients

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

PARENTERAL ADMINISTRATION PROS

A

o Faster action
o Avoids the hepatic first-pass
o Useful if substance not absorbed by other routes
o Useful if the patient is not able to swallow or unconscious

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

PARENTERAL ADMINISTRATION CONS

A

o Requires sterile material
o Usually requires a third party
o Possible pain at the injection site
o Risks of infections or complications

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
DISTRIBUTION
Shifting of the drug in the body and distribution to tissues or organs
26
DISTRIBUTION | Influenced by :
o Blood perfusion of the organ: The best perfused organs will have more medication Heart, brain, lungs, kidneys, liver > skin > muscles, bones, tendons o Physical and chemical characteristics of the drug: Hydrophilic (blood) vs. lipophilic drugs (fat stores and organs) Lipophilic drugs have more ease to pass through the membranes ** ** Blood-brain barrier o Plasma protein binding o Drug tissue affinity
27
BLOOD-BRAIN BARRIER
o Endothelial cells with tight junctions o Limits the passage of molecules (drugs, toxins) o Only lipophilic molecules can pass (most psychotropic drugs)
28
DISTRIBUTION – 2 types of binding
o Bounded to plasma proteins - Binding to proteins serves as transport or storage for the drug o Free (unbound) - Only the unbound drug is available to spread to tissues where pharmacological effects take place - Unbound concentration in the bloodstream reflects the concentration of the drug at the site of action
29
DISTRIBUTION – BINDING TO PLASMA PROTEINS | Influenced by a number of factors, including
1. Amount of available proteins o Possible decrease in albumine under certain conditions - Aging - Undernutrition - Alcohol use disorder (lowers albumin= more free Rx = toxicity) 2. Drug interactions
30
Lab results of medication give us free + bound, true or false
true
31
DISTRIBUTION OF PSYCHOTROPIC DRUGS | Generally
o Quick blood distribution àbrain o Brain concentration > blood ( 10 to 40 x ) o Low steady-state drug concentration in blood o Strong bonding to plasma proteins o Apparent high distribution volume
32
Psychotropic drugs are removed from the body by two processes :
1. Metabolism: mainly in the liver, The majority of psychotropic drugs are fat-soluble and must be metabolized to the liver to create less fat-soluble metabolites and allow elimination. Drug turns into metabolite 2. Elimination: mainly to the kidney
33
METABOLISM | PHASE I and PHASE II reactions
o PHASE I: involvement of cytochromes P450 | o PHASE II: conjugation reactions
34
METABOLISM – PHASE I REACTIONS | Possible results of this biotransformation
1. Drug metabolized into an inactive metabolite | 2. Drug metabolized into an active metabolite
35
METABOLISM – PHASE I REACTIONS | 3 types of active metabolites
A. Drug metabolized into an active metabolite (another existing drug) that may contribute to the therapeutic (or toxic) effect : amitriptyline into nortriptyline B. Drug metabolized into an active metabolite (non-existent drug) that may contribute to therapeutic (or toxic) effect: clozapine to norclozapine C.3. Inactive drug requiring liver metabolism to become active (pro-drug): lisdexamfetamine is the pro-drug of dexamphetamine
36
CYTOCHROMES P450 (CYP)
Enzymes involved in the biotransformation of the drug o Significant variability between people o Genetic polymorphisms o Responsible for many drug interactions
37
``` CYTOCHROMES P450 (CYP) Drugs can be : ```
I. Substrates of CYP II. Inhibitors of CYP III. Inductors of CYP
38
``` CYTOCHROMES P450 (CYP) SUBSTRATE ```
Which is modified by an enzyme o The majority of psychotropic drugs are substrates of CYP2D6, CYP3A4, CYP1A2 or CYP2C19 o Some drugs are substrates of several enzymes They become active/ inactive because of the enzyme
39
``` CYTOCHROMES P450 (CYP) INHIBITORS ```
o Inteferes with the ability of an enzyme to perform metabolism • ↓ CYP activity • ↓ metabolism of drugs that are substrates of this enzyme § ↑ plasma concentrations of the drug * § ↑ toxicity or side effects * * In the event that the metabolite is inactive, as in example 1
40
MAIN CYP INHIBITORS
* Fluoxetine * Fluvoxamine * Paroxetine * Ciprofloxacin * Fluconazole * Grapefruit juice
41
``` CYTOCHROMES P450 (CYP) INDUCTORS ```
o Accelerates enzyme activity • ↑ CYP activity • ↑ metabolism of drugs that are substrates of this enzyme § ↓ plasma concentrations of the drug * § ↓ drug effectiveness * * In the event that the metabolite is inactive, as in example 1
42
MAIN INDUCTORS OF THE CYP
``` • Carbamazepine • St John’s Wort (natural product): increases metabolism of oral contraceptives • Phenobarbital • Phenytoin • Hydrocarbons contained in cigarette or cannabis smoke ```
43
GENETIC POLYMORPHISMS, CYP2D6 POLYMORPHISMS
o 7% of the Caucasian population are «slow metabolizers » of CYP2D6 Ø Intolerance to a normal dose of a CYP2D6 substrate drug Ø Generally require lower doses Ø It is possible to identify these patients using genotyping (not routinely in practice) o > 20% of North Africa's population are « fast metabolizers » of CYP2D6 Ø Ineffective at a normal dose of a CYP2D6 substrate drug Ø Generally require higher doses
44
METABOLISM OF PSYCHOTROPICS DRUGS | Generally
o Important liver metabolism : Ø CYP Ø UGT o Genetic polymorphisms of CYP2D6
45
ELIMINATION
Allows definitive elimination of the drug o Clearance = fully filtered blood volume of a drug per unit of time o Expressed in mL/min o Total clairance = renal clearance + liver clearance + other clearances
46
Elimination routes :
o The kidney is the main excretion organ | o Other: liver, digestive tract, saliva, lungs, sweat, tears, etc.
47
RENAL ELIMINATION
o Glomerular filtration àgoes into the urine o Tubular secretion àgoes into the urine o Tubular reabsorption àreturns to blood
48
Serum creatinine:
Estimating kidney function using glomerular filtration rate (GFR) from muscle metabolism (↑ men / black; ↓ women / elderly) high creat = low creat clearence = eliminate drug less well good creat clearence: 100mL / min below 60: make adjustment bewlo 15: need dialysis
49
Kidney failure
o Cretinine’s clairance decreased | o ↓ renal elimination of the drug à↑ plasma concentrations à↑ effectiveness and toxicity of the drug
50
FACTORS THAT MAY INFLUENCE PHARMACOKINETICS
``` AGE - Pediatrics - Geriatrics SEX Women (vs men) : - ↓ BMI - ↓ muscle mass - ↑ fat mass PREGNANCY COMORBIDITIES Examples : - Kidney failure - Liver failure - Heart failure GENETIC Differences between individuals OBESITY - ↑ fat mass - ↑ elimination - choice of ideal or dosage weight (vs real) ```
51
HALF-LIFE
«The time required for a given drug's blood concentration to be reduced by 50 % » o Expressed in minutes, hours or days o Reflects the speed at which a drug is eliminated o Important for judging the interval of administration between doses Generally : o Approximate half-life of 12 to 36 hours o Some exceptions, e.g. : Ø Long half-life: aripiprazole, fluoxetine Ø Short half-life: quetiapine, ziprasidone
52
Complete elimination of the drug =
about 5 x its half-life
53
STEADY STATE
When the drug concentration in blood is stable | when we repeat the dose and arrive at a plateau
54
Time to reach the steady state is determined by :
1. Half-life (5 x half-life) | 2. Dosage / administration schedule
55
LOADING DOSE
o Quickly achieves the desired drug concentration in blood at steady state o Subsequently: maintenance doses keep the drug's concentrations at steady state
56
True or false: concentration of the drug is lower in the brain than in the blood
false
57
THERAPEUTIC INDEX
«Gap between effective plasma concentration and toxic plasma concentration of a drug » o Indication of «margin of safety » of a drug Ø Narrow therapeutic index: higher risk of toxicity Ø Broad Therapeutic Index: Safer
58
OTHER INDICATIONS OF TDM
o Suspicion of non-compliance o Lack of efficacy/adverse effects at a recommended dose o Relapse under maintenance therapy o Determining optimal plasma concentration when the patient has achieved the intended therapeutic goal o Drug interaction o Change in the formulation o Genetic polymorphisms o Abnormally low or high BMI o Pregnancy/breastfeeding o Pediatrics / Geriatrics o Comorbidities having an effect on pharmacokinetics (e.g. kidney failure, liver failure, inflammatory disease, bariatric surgery)
59
Metoclopramide (MaxeranTM) is a drug that increases gastrointestinal motility and gastric emptying. What phase of pharmacokinetics would be influenced by taking this drug?
Absorption
60
Taking antacid medications (e.g. TumsTM or MaaloxTM) reduces stomach pain by decreasing stomach acidity. How can this affect the absorption of drugs?
Alter pH of stomach = alter absorption, releasing the active ingredient It contains calcium: formation of non absorbable complexes
61
Some medications should not be taken at the same time as calcium or magnesium supplements. What's the reason?
FORMATIONS OF NON-ABSORBABLE COMPLEXES Calcium/iron/dairy products form complexes not absorbed with certain medications
62
Explain the phenomenon of first liver passage according to the different routes of administration.
PO: loses some of it's active ingredients by going through the liver Parenteral: no first liver passage SL: no hepatic first pass
63
What property of psychotropic drugs allow them to pass through the blood-brain barrier?
They are liposoluble
64
Diazepam is a drug that is strongly bounded (about 98%) to plasma proteins. What happens if a second drug is given that has a stronger affinity for plasma proteins? Would the effect be the same if diazepam was 5% bounded to plasma proteins?
It may become toxic. Unbound part will increase. | If it's 5%, if you have 95% unbound, the clinical effect from 95% too 100% doesn't change much.
65
A patient has been taking clozapine for several months. He has been smoking about 20 cigarettes a day for several years. If he decides to quit smoking, what will happen to serum clozapine levels?
Smoking is an inductor of CYP, therefore if he decides to quit, the metabolism of drugs can be decreased = increase dose in blood = toxicity Less norclazapine = less side effects
66
The half-life of olanzapine is about 30 hours. A patient has been receiving 15 mg die olanzapine for about two weeks, but decides to stop treatment because he feels very drowsy during the day. How soon will the drug be completely removed from its blood?
150 h
67
Name 5 clinical situations where it would be appropriate to do a therapeutic monitoring of a drug.
o Suspicion of non-compliance o Lack of efficacy/adverse effects at a recommended dose o Relapse under maintenance therapy o Determining optimal plasma concentration when the patient has achieved the intended therapeutic goal o Drug interaction
68
What factors can affect the kidney elimination of a drug?
``` Age Sex Ethnicity (black, increased) Kidney failure High creat ```

Pharmaco (11 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions