IMS1 TBL5 Pharmacology (High Yield Flashcards GPT)

Pharmacokinetics

Study of what the body does to a drug including absorption, distribution, metabolism and excretion

Pharmacodynamics

Study of what the drug does to the body including physiological responses relative to drug concentration

ADME

Acronym for absorption distribution metabolism and excretion the four stages of drug handling

Absorption

Process by which a drug enters the body from the site of administration

Distribution

Movement of drug throughout body compartments including to target tissues

Metabolism

Chemical modification of drugs usually in the liver to increase water solubility

Excretion

Removal of drugs or metabolites from the body usually by renal or biliary routes

Bioavailability

Fraction of administered drug that reaches systemic circulation and can act

First pass metabolism

Metabolism of orally administered drugs by liver or gut before reaching systemic circulation resulting in reduced bioavailability

Routes of drug administration

Examples include oral inhaled rectal topical transdermal intravenous intramuscular and subcutaneous

Parenteral administration

Delivery by injection bypassing gastrointestinal tract with high bioavailability

Factors affecting absorption

Includes route drug form lipid solubility pH gastric motility and food interactions

Protein binding

Reversible binding of drugs to plasma proteins that reduces free active drug concentration

Acidic drug protein binding

Acidic drugs primarily bind to albumin

Basic drug protein binding

Basic drugs primarily bind to globulins and lipoproteins

Effect of protein binding on activity

Only unbound drug is active distributed and excreted

Drug displacement interaction

Competition for protein binding sites leading to increased free drug and potential toxicity

Blood brain barrier

Selective barrier allowing lipid soluble drugs to enter CNS while restricting water soluble drugs

Zero order kinetics

Elimination of a constant amount of drug per unit time due to saturated pathways

First order kinetics

Elimination of a constant proportion of drug per unit time producing predictable half life

Phase I metabolism

Simple chemical modification including oxidation reduction and hydrolysis to introduce or expose polar groups

CYP450 enzymes

Liver enzyme family responsible for most oxidative Phase I metabolism

Phase II metabolism

Conjugation reactions that attach polar groups to drugs increasing water solubility

Common Phase II reactions

Includes glucuronidation acetylation sulfation and glutathione conjugation

Slow acetylators

Individuals with reduced acetylation capacity leading to slower metabolism and increased toxicity risk

Paracetamol metabolism

Primarily conjugated but overdose depletes glutathione leading to toxic metabolite accumulation and liver failure

Enzyme induction

Increased metabolic enzyme activity resulting in faster drug breakdown and reduced effect

CYP450 inducers

Includes rifampicin phenytoin carbamazepine phenobarbital chronic alcohol smoking St Johns Wort and griseofulvin

Enzyme inhibition

Reduction in enzyme activity resulting in slower breakdown and increased drug levels

Grapefruit juice effect

Inhibits metabolism of drugs such as simvastatin increasing toxicity risk

Renal excretion

Drug elimination by kidneys depending on glomerular filtration rate

GFR

Glomerular filtration rate indicator of renal function used to adjust dosing

Therapeutic range

Concentration range between minimum effective and minimum toxic levels

Therapeutic index

Ratio between toxic dose and effective dose higher is safer

Narrow therapeutic index drugs

Examples include digoxin lithium phenytoin carbamazepine theophylline and vancomycin

Half life

Time required for plasma drug concentration to decrease by fifty percent

Importance of half life

Determines dosing frequency and time to reach steady state or washout

Steady state

Achieved after approximately five half lives of repeated dosing

Washout period

Time required for drug elimination usually five half lives

Nuclear receptor

Intracellular receptor activated by lipid soluble hormones that then alter gene transcription

Ligand gated ion channel

Receptor that opens in response to ligand binding producing rapid responses

GPCR

Receptor family with seven transmembrane helices producing slower responses via G proteins

Ion channel blocker

Drug that inhibits ion flow through a channel such as nifedipine blocking calcium channels

Ion channel modulator

Drug that alters channel activity such as benzodiazepines enhancing GABA channel opening

Carrier molecule

Protein that transports substances across membranes such as SERT for serotonin

SSRI mechanism

Blocks serotonin transporter reducing reuptake and increasing serotonin in synaptic cleft

Enzyme target drugs

Drugs that act on enzymes such as ACE inhibitors

Competitive inhibition

Inhibitor binds active site competing with substrate reversible by increasing substrate concentration

Non competitive inhibition

Inhibitor binds allosteric site altering enzyme shape cannot be overcome by more substrate

Affinity

Strength of binding between a drug and its receptor

Efficacy

Ability of a drug receptor complex to produce a biological response

Full agonist

Drug with high efficacy producing maximal receptor activation

Partial agonist

Drug producing submaximal activation even at full receptor occupancy

Antagonist

Drug that binds receptor without activating it preventing agonist binding

Competitive antagonist

Reversible antagonist displaced by increasing agonist concentration

Non competitive antagonist

Antagonist that binds irreversibly or allosterically preventing agonist effect

Opioid full agonist

Methadone

Opioid partial agonist

Buprenorphine

Opioid antagonist

Naloxone