Pharmacokinetics and Drug Administration Quiz

Podcast

Play an AI-generated podcast conversation about this lesson

Questions and Answers

What is the primary factor influencing drug absorption according to pharmacokinetics?

Drug concentration

Lipid solubility (correct)

Volume of administration

Drug form

Which route allows for titration of medication?

Subcutaneous route

Intravenous route (correct)

Intramuscular route

Oral route

What is a disadvantage of the intravenous route of drug administration?

It is less effective than intramuscular injections

No sterile precautions are needed

Requires specialized personnel for administration (correct)

It is the least costly option

Based on the Henderson-Hasselbalch equation, what is the relationship between pH and the form of a drug?

Higher pH favors non-ionized form for acidic drugs Signup and view all the answers

What is bioavailability in pharmacokinetics?

The fraction of a drug dose reaching circulation unchanged Signup and view all the answers

Why are most drugs absorbed more in the intestine than in the stomach?

Intestine has a larger surface area Signup and view all the answers

If a drug has high bioavailability, what does this imply about the dose required?

A low dose is sufficient Signup and view all the answers

Which substance is predominantly absorbed from the stomach due to its acidic nature?

Aspirin Signup and view all the answers

What is the effect of an increase in absorption on bioavailability?

Increases bioavailability Signup and view all the answers

Which route of administration has the highest percentage of bioavailability?

Intravenous Signup and view all the answers

How does an increase in first pass metabolism affect bioavailability?

Decreases bioavailability Signup and view all the answers

What is a significant advantage of the sublingual route for drug administration?

It eliminates first pass metabolism Signup and view all the answers

What does Cmax represent in a plasma concentration versus time graph?

Maximum concentration obtained by a particular dose Signup and view all the answers

What defines two brands of the same drug as bioequivalent?

They demonstrate similar pharmacokinetic properties Signup and view all the answers

What is the primary factor affecting drug distribution in tissues?

Lipid solubility Signup and view all the answers

How is bioavailability calculated for a drug given by the oral route in comparison to intravenous administration?

By plotting the area under the curve of a plasma concentration versus time graph Signup and view all the answers

What effect does competitive inhibition have on Km?

Increases Km Signup and view all the answers

In which type of inhibition does Vmax decrease?

Non-competitive inhibition Signup and view all the answers

Which receptor type corresponds with GABAA and NMDA?

Ionotropic receptors Signup and view all the answers

Which type of drug has no intrinsic activity but can interfere with the action of other drugs?

Antagonist Signup and view all the answers

What describes intrinsic activity in pharmacodynamics?

Ability of a drug to produce action after binding Signup and view all the answers

Where do lines intersect in a Lineweaver-Burke plot for non-competitive inhibition?

X-axis Signup and view all the answers

Partial agonists have what kind of intrinsic activity?

Submaximum intrinsic activity Signup and view all the answers

Which type of receptor is associated with cytokines and insulin?

Enzymatic receptors Signup and view all the answers

Which drug class is known as the first choice for migraine prophylaxis?

Beta Blockers Signup and view all the answers

What is the primary mechanism of action for triptans in migraine treatment?

Stimulating 5HT1B/1D receptors Signup and view all the answers

Which of the following is a DITAN that is effective for acute migraine attacks?

Lasmiditan Signup and view all the answers

What potential adverse effect is associated with methysergide, used for migraine prophylaxis?

Pulmonary fibrosis Signup and view all the answers

Which lipids are associated with bronchoconstriction and are relevant in bronchial asthma?

LEukotrienes Signup and view all the answers

Which class of drugs is categorized as CGRP antagonists used for acute migraine attacks?

Gepants Signup and view all the answers

Which neurotransmitter release is inhibited by triptans to help alleviate migraine symptoms?

CGRP Signup and view all the answers

What is the primary action of monoclonal antibodies against CGRP in migraine management?

Preventing CGRP action Signup and view all the answers

What is the primary clinical use of Latanoprost in eye care?

To manage Primary Open Angle Glaucoma Signup and view all the answers

Which adverse effect is NOT associated with Latanoprost?

Intraocular hemorrhage Signup and view all the answers

What is a significant risk of using Non-Selective COX Inhibitors?

Peptic Ulcer Disease Signup and view all the answers

Which of the following NSAIDs is known for having less risk of Peptic Ulcer Disease compared to Non-Selective COX Inhibitors?

Celecoxib Signup and view all the answers

Paracetamol is mainly considered the analgesic of choice in which scenario?

In patients with renal disease Signup and view all the answers

What theory explains the analgesic effect of Paracetamol in the CNS?

COX-3 inhibition Signup and view all the answers

Which of the following is not a common use for NSAIDs?

Treating bacterial infections Signup and view all the answers

Which condition can lead to Paracetamol toxicity?

Overdosage Signup and view all the answers

Study Notes

Titration Routes

Intravenous (IV) route is possible for titration.
Disadvantages of IV route:
- Requires sterile precautions.
- Requires expert personnel for administration.
- Costly.
Intramuscular (IM) route allows a maximum volume of 5-10 ml.

Pharmacokinetics: Absorption

Pharmacokinetics: Study of ADME (Absorption, Distribution, Metabolism, Excretion)
Absorption: Movement of drug from administration site to the bloodstream.
Lipid solubility is crucial for absorption.
For drugs with the same medium:
- Non-ionized form is lipid-soluble and crosses membranes.
- Ionized form is water-soluble and does not cross membranes.

How Drugs Cross Membranes

Example:
- Drug with pKa = 6.0
- pH | Lipid soluble | Water soluble
- --------- | -------- | --------
- 3.0 | 99.9% | 0.1%
- 4.0 | 99% | 1%
- 5.0 | 90% | 10%
- 6.0 | 50% | 50%
- 7.0 | 10% | 90%
- 8.0 | 1% | 99%
- 9.0 | 0.1% | 99.9%
Henderson-Hasselbalch Equation: pH = pKa + log [X-]/[HX]
Acidic drugs (like Aspirin) are primarily absorbed from the stomach.
Basic drugs (like Morphine) are mainly absorbed from the intestine.
Intestine generally absorbs drugs better than the stomach due to:
- Larger surface area.
- Longer drug retention time.

Bioavailability

Bioavailability: Fraction of the administered dose reaching systemic circulation unchanged.
Bioavailability determines the dose:
- High bioavailability → Low dose
- Low bioavailability → High dose

Factors Affecting Bioavailability

Factors that increase absorption:
- Increase bioavailability
Factors that decrease absorption:
- Decrease bioavailability

Routes of Administration and Bioavailability

Route | % Bioavailability | Fractional Bioavailability
:-------- | --------: | --------:
Oral | 5-100 | 0.05 < F < 1
IM | 75-100 | 0.75 < F < 1
SC | 75-100 | 0.75 < F < 1
IV | 100 | 1

First Pass Metabolism

First Pass Metabolism (Pre-systemic metabolism): Metabolism of a drug before reaching systemic circulation.
Increased first pass metabolism: Decreases bioavailability.
Decreased first pass metabolism: Increases bioavailability.
Example: Nitroglycerine (NTG)
- Has high first pass metabolism.
- Sublingual route is preferred.
Advantages of sublingual route:
- Fast acting (for emergencies).
- No first pass metabolism.
- Self-administration is possible.
- Excess dose can be spit out or ingested.

Bioavailability Calculation

To determine the bioavailability of a drug (Drug A) by oral route:
1. Give Drug A (100 mg) IV.
2. Plot a graph (Plasma Concentration vs Time).
3. Administer the same dose (100 mg) orally and plot the same graph.
4. Bioavailability = (AUC oral) / (AUC IV)

Bioequivalence

Two brands of the same drug are considered bioequivalent if they have similar bioavailability (e.g., 20%).
Most drugs are bioequivalent except for phenytoin.

Plasma Concentration vs Time Graph

Cmax: Maximum concentration reached by a particular dose. Should lie between Minimum Toxic Concentration (MTC) and Minimum Effective Concentration (MEC).
Tmax: Time at which plasma concentration reaches maximum. Indicates the rate of absorption.
AUC: Total area under the graph. Indicates the extent of absorption.

Pharmacokinetics: Distribution

Distribution: Measure of drug amount in tissues after absorption into the systemic circulation.

Factors Affecting Drug Distribution

1. Lipid Solubility: Most important factor.
- Lipid soluble drugs have higher distribution.
- Water soluble drugs have lower distribution.
2. Protein Binding:
- Drugs can bind to plasma proteins (mainly Albumin).
- Only unbound drugs can distribute to tissues.
- Disease states (like hypoalbuminemia) can affect protein binding and distribution.

Competitive vs. Non-Competitive Inhibition

Property	Competitive Inhibition	Non-Competitive Inhibition
Structure	Same as substrate	Different
Binding site	Active site	Allosteric site
Reversibility	Surmountable	Unsurmountable
Km	Increases	Does not change
Vmax	Does not change	Decreases

Lineweaver-Burke Plot

A double reciprocal plot.
Graph: 1/S (X-axis) vs. 1/V (Y-axis).
X-axis: Indicates Km.
Y-axis: Indicates Vmax.
Intersections:
- Intersect at X-axis: Non-competitive inhibition
- Intersect at Y-axis: Competitive inhibition.

Pharmacodynamics: Receptors

Affinity: Ability of a drug to bind to a receptor.
Intrinsic Activity: Ability of a drug to produce action after binding to a receptor.
A drug cannot produce action if it does not bind to a receptor.

Classification of Drugs Based on Intrinsic Activity

Agonist: Maximum intrinsic activity (+1).
Partial Agonist: Submaximum intrinsic activity (0 to +1).
Inverse Agonist: Opposite action to agonist (-ve).
Antagonist: No action of itself but interferes with the action of other drugs.

Classification of Receptors Based on Signal Transduction Mechanism

Receptor	Examples
1. Ionotropic	GABAA, NMDA, NN, NM, 5HT3
2. Enzymatic	Cytokines, Prolactin, Insulin, GH
3. Intracellular
- Cytoplasmic	Vit D, Glucocorticoids, Mineralocorticoids
- Nuclear	Vit A, Thyroid hormones, Sex hormones
4. G-protein coupled

Migraine

Triptans: Sumatriptan, Naratriptan, Rizatriptan, Eletriptan, Frovatriptan.
Mechanism of action: Stimulate 5HT1B/1D receptors, causing vasoconstriction and inhibiting CGRP release.
Adverse Effects:
- Vasoconstriction can cause coronary artery spasm, so avoid in patients with coronary artery disease.
Prophylaxis of Migraine:
- Antidepressants: Imipramine.
- Beta Blockers: Propranolol (DOC).
- Calcium Channel Blockers: Flunarizine.
- Ergot derivative: Methysergide.
- Antiepileptics: Valproate, Topiramate.
- CGRP Antagonists: (Risk of pulmonary fibrosis)
  - Erenumab
  - Fremanezumab
  - Galcanezumab
  - Eptinezumab

New Drugs for Migraine

1. Lasmiditan (DITANS):
- Stimulates 5HT1F receptor and decreases CGRP release.
- Prevents vasodilation and neuronal inflammation.
- Effective orally.
- Approved for acute migraine attacks.
- Advantage over triptans: Does not induce peripheral vasoconstriction.
2. Monoclonal Antibodies Against CGRP:
- Approved for prophylaxis of migraine.
- Injectable route.
  - Erenumab
  - Fremanezumab
  - Galcanezumab
  - Eptinezumab
3. CGRP Antagonist (GEPANTS):
- Used for acute attacks.
- Effective orally.
- Drugs:
  - Olcegapant
  - Rimegepant
  - Ubrogepant

Lipid Autacoids

Leukotrienes:
- LTB4: Chemotaxis.
- LTC4, LTD4, LTE4: Bronchoconstrictors (contribute to bronchial asthma).

Prostaglandins

General effects:
- Fever
- Pain
- Inflammation
Eye:
- PGF2α: Increases uveo-scleral outflow (latanoprost - DOC for Primary Open Angle Glaucoma).
- Adverse Effects of Latanoprost:
  - Pigmentation of iris (heterochromia iridis).
  - Growth of eyelashes (hypertrichosis).
  - Fluid in macula (macular edema).

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)

COX enzymes:
- COX-1: Constitutive enzyme (present normally in most places).
- COX-2: Inducible enzyme (normally present in kidney, endothelium, CNS).
NSAIDs act by inhibiting COX enzymes.
Non-selective COX inhibitors:
- Increase risk of peptic ulcer disease (PUD).
- Drugs: Aspirin, Paracetamol (acetaminophen), Ibuprofen, Diclofenac, Indomethacin, Mefenamic acid, Piroxicam, Nimesulide, Ketorolac.
Selective COX-2 inhibitors:
- Less risk of PUD.

Paracetamol (Acetaminophen)

Unique: Only NSAID with no anti-inflammatory activity.
Less risk of PUD.
COX-3 Inhibition Theory: Paracetamol may inhibit COX-3 in the CNS.
Analgesic of choice in renal disease.
Approved for fever and pain in children.

Paracetamol Toxicity

Occurs due to:
- Overdosage.
- Liver disease.
- Other unknown factors.

Studying That Suits You

Use AI to generate personalized quizzes and flashcards to suit your learning preferences.

Description

Test your knowledge on pharmacokinetics, focusing on drug absorption and the advantages and disadvantages of various drug administration routes, including IV and IM. This quiz will assess your understanding of how drugs cross membranes and the importance of lipid solubility.