Drug Metabolism and Excretion

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Questions and Answers

What role do receptors play in biological processes?

They are involved in chemical signaling between and within cells. (correct)

They activate metabolic pathways directly.

They bind only endogenous ligands.

They serve exclusively as antagonists.

What is a ligand in pharmacology?

Any protein that can mediate a biological effect.

Only hormones that are produced in the body.

A substance that only activates receptors.

Any substance that binds to a receptor, regardless of activation. (correct)

Which of the following is an example of an endogenous ligand?

GABA (correct)

Insulin injected from an external source

Antibiotics

Morphine

What initiates the intracellular signaling cascade upon receptor activation?

The binding of a ligand to a GPCR. Signup and view all the answers

What are effectors responsible for in the intracellular signaling cascade?

Changing second messenger levels. Signup and view all the answers

What is the primary concern during Phase I trials?

Safety and side effects Signup and view all the answers

What is the primary aim of Phase II trials?

Screen out ineffective drugs Signup and view all the answers

Which of the following best describes the primary aims of Phase III trials?

Investigate side effects and collect efficacy data Signup and view all the answers

What is a common pitfall in Phase I trials?

Missed chronic toxicities Signup and view all the answers

In Phase III trials, why is blinding essential?

To prevent biases in treatment assignments Signup and view all the answers

What is the primary function of CYPs 1A2, 3A4, 2D6, and 2C19?

They are responsible for over 50% of small-molecule drug metabolism. Signup and view all the answers

Which of the following best describes the phase 2 reactions in drug metabolism?

They are synthetic anabolic reactions that increase hydrophilicity. Signup and view all the answers

Which of the following factors can influence drug metabolism?

Genetic factors and individual diet. Signup and view all the answers

What process allows for the passive reabsorption of drugs in the kidneys?

Passive tubular reabsorption. Signup and view all the answers

Which excretion route is primarily responsible for drug elimination through breast milk?

Non-specific systemic circulation. Signup and view all the answers

What role do p-glycoproteins play in drug metabolism?

They transport drugs from plasma to bile. Signup and view all the answers

Which statement about the P450 Monooxygenase system is correct?

CYPs vary in sensitivity to inhibitors and inducers. Signup and view all the answers

Which factor affects glomerular filtration of drugs?

Binding to plasma proteins. Signup and view all the answers

What is one potential harmful effect of ingesting red bloodwood oil?

It can cause harm and even be fatal. Signup and view all the answers

Which essential properties are attributed to the red bloodwood's oil?

Antiseptic, astringent, and parasiticide. Signup and view all the answers

How is emu oil traditionally used?

For conditions such as dry skin, wound healing, and sore muscles. Signup and view all the answers

What is the Kakadu Plum recognized for?

Being the highest known source of natural vitamin C. Signup and view all the answers

What happens to emus in Tasmania and other islands?

They were exterminated soon after Europeans arrived. Signup and view all the answers

Which of the following is a contemporary use of emu oil?

In capsules labeled as 'Omega 3'. Signup and view all the answers

What is a property of the dry resin and gum from the red bloodwood?

It contains tannin and is astringent. Signup and view all the answers

In which habitats are emus primarily found?

Sclerophyll forests, open woodland, and savannah woodland. Signup and view all the answers

Which of the following active substances is a COX-2 selective drug?

Celecoxib Signup and view all the answers

What is the primary mechanism by which NSAIDs reduce pain?

Inhibition of prostaglandins synthesis Signup and view all the answers

What is the effect of COX-2 inhibition on inflammatory responses?

Reduces oedema and vasodilation Signup and view all the answers

How do NSAIDs exert their antipyretic effect?

They prevent interleukin-1 from elevating the hypothalamic set point. Signup and view all the answers

What is a characteristic of semi-selective NSAIDs?

They maintain some activity on COX-1 while showing affinity for COX-2. Signup and view all the answers

Which of the following routes of administration is NOT considered enteral?

Topical Signup and view all the answers

What factor can delay the absorption of NSAIDs in the body?

Presence of food and antacids Signup and view all the answers

Which statement regarding cardiovascular risk and NSAIDs is correct?

Non-selective NSAIDs are associated with increased cardiovascular events. Signup and view all the answers

Study Notes

Drug Metabolism

Cytochrome P450 (CYP) enzymes are a large family of enzymes responsible for drug metabolism.
CYP 1A2, 3A4, 2D6 and 2C19 are responsible for over 50% of small-molecule drug metabolism.
Phase 2 reactions are conjugation reactions which involve the attachment of an endogenous molecule to a drug molecule increasing the hydrophilicity of the drug.
Most common phase 2 reaction is glucuronidation.
Enzymes involved in phase 2 reactions are transferases.
Phase 1 and 2 reactions can be sequential or occur simultaneously.

Factors Affecting Drug Metabolism

Genetic variation of liver enzymes can affect drug levels in the body.
Induction and inhibition of CYP enzymes can affect drug metabolism.
Concentration-dependent biotransformation can vary drug metabolism.
Disease-induced factors can affect drug metabolism.

Drug Excretion

Most drugs are excreted through the kidneys either unchanged or as polar metabolites.
25-30% of drugs are excreted in their active form.
Renal impairment can cause drug accumulation.
Other routes of excretion include hepatobiliary system, pulmonary system, sweat, saliva, tears, and breast milk.

Renal Excretion

Glomerular filtration filters drugs freely unless highly bound to plasma proteins.
Active tubular secretion transports basic drugs (protonated form) via organic cation transporters (OCTs) and acidic drugs via organic anion transporters (OATs).
Passive tubular reabsorption allows lipid-soluble drugs to diffuse back across the tubular barrier, reducing excretion.

Hepatobiliary Excretion

Similar to renal tubule, drugs are transported from the plasma to the bile via OCTs, OATs, and p-glycoproteins.
Drugs in the small intestine can be reabsorbed and recirculated until excreted in the urine or feces.

Receptors

Receptors are protein molecules that mediate a biological effect when activated by transmitters, hormones, or drugs.
A ligand is any substance that binds to a receptor forming a complex.
Endogenous ligands are substances produced by the body, such as hormones, neurotransmitters, and growth factors.

Intracellular Signaling Cascade

A ligand (first messenger) binds to a G protein-coupled receptor (GPCR).
GPCRs activate G proteins (transducers).
G proteins activate effectors (enzymes and ion channels).
Effectors alter second messenger levels (calcium, cAMP).
Signalling cascade leads to cellular physiological changes.

Clinical Trial Phases

Phase I: Safety, side effects, best dose and formulation.
Phase I: Maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), recommended phase II dose (RPTD).
Phase II: Efficacy testing, toxicity profile refinement.
Phase III: Randomized, controlled, double-blind, large scale to compare efficacy with control or standard care, and monitor adverse effects.

Red Bloodwood

Native to coastal areas of New South Wales and Queensland.
Leaves, resin, and oil used as traditional Aboriginal medicine.
Essential oil is antiseptic, astringent, and parasiticide.
Oil can be used for coughs, colds, sore throats, and infections.
Resin is astringent and used for diarrhea and bladder inflammation.
Leaves can be burnt to kill airborne bacteria.
Ingesting large doses can be harmful, even fatal.

Emu

Australia's tallest flightless bird.
Found in sclerophyll forests, open woodland, and savannah woodland habitats across Australia.
Emu oil is derived from emu fat.
Emu fat is rich in omega-3, omega-6, and omega-9 fatty acids.
Traditionally used for dry skin, wound healing, and sore muscles.
Comercially produced from emu farms, used in capsules, topical anti-inflammatory treatments, and as a skin moisturizer.

Kakadu Plum

Highest known source of natural vitamin C.
Bio-piracy: US companies have patented extracts of the Kakadu Plum.

COX1 vs COX2

COX2 selective drugs (e.g., Celecoxib) have been developed due to a side pocket in the COX2 enzyme.
COX-1 inhibition: impaired gastric protection, antiplatelet effects
COX-2 inhibition: anti-inflammatory, analgesic, reduction in glomerular filtration rate, reduction in renal flow.

Analgesic Effect

Decreased prostaglandin production, leading to less sensitization of nociceptive nerve endings to inflammatory mediators (bradykinin, 5-hydroxytryptamine).

Anti-inflammatory Effect

Reduced vasodilation and oedema by decreasing prostaglandin E2 and prostacyclin synthesis.

Antipyretic Effect

NSAIDs prevent prostaglandin release from interleukin-1 in the CNS, preventing temperature elevation.

Cardiovascular Risk Associated With NSAIDs and COX-2 Inhibitors

Selective COX-2 inhibitors have a lower risk of cardiovascular events and gastrointestinal side effects.
Semiselective NSAIDs have some selectivity for COX-2 but retain activity against COX-1. Use with caution due to increased cardiovascular risk.
Nonselective NSAIDs have increased risk of gastrointestinal side effects.

Pharmacokinetics

Route of administration: Topical, enteral, parenteral.
Site of absorption: Stomach and small intestine (absorption can be delayed by food and antacids).
Distribution: Highly bound to plasma protein.

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Description

This quiz covers key concepts related to drug metabolism, focusing on Cytochrome P450 enzymes and the roles of Phase 1 and Phase 2 reactions in drug biotransformation. Additionally, it explores factors influencing drug metabolism and the processes involved in drug excretion. Test your knowledge on these essential pharmacokinetic topics!