Pharmacology Flashcards
What is pharmacokinetics?
What the body does to the drug
What is pharmacodynamics?
What the drug does to the body
What is the pathway of the drug?
Drug at the site of administration
Absorption
Distribution
Metabolism
Elimination
What are the routes of drug administration?
Intravascular (directly into the blood)
Extravascular (oral, sublingual, subcutaneous, intramuscular, rectal)
Other (inhalation, intranasal, topical, transdermal)
Which drugs act systematically?
Those given extravascularly
What are the advantages of giving drugs orally?
Easy, practical, reliable (most lily to be complied to by patients)
Why are most drugs absorbed in the small intestine?
Large surface area due to microvilli so easier absorption especially compared to stomach.
Where are oral drugs dissolved?
In the GI tract, by GI fluids, absorbed through epithelial lining and enters blood vessels
What happens if the time in the GI tract changes?
Any condition that changes the passage time of the drug in the GI tract will change the quantity of absorption
Which conditions change the quantity of absorption of oral drugs?
Diarrhea and vomiting will cause drugs to be excreted much faster, so absorption and the effect will be less.
What is the first-pass metabolism?
Some drugs may be extensively metabolised in the liver or in the intestinal mucosa before reaching the system circulation
What is the effect of first-pass metabolism?
Reduced concentration or activity of the drug
When a drug is absorbed in the GI tract where does it go to next?
Portal circulation
What is the sublingual method of administration usually for?
Usually anginatic conditions
What kind of drugs are taken sublingually?
Drugs that would be broken down by the acid of the stomach
What are the advantages of sublingual drugs?
Good absorption through capillary bed under tongue
Self-administered
Why do intravenous drugs have a rapid onset of action?
The drug is injected directly into the bloodstream, avoids GI tract and first-pass metabolism by liver
In which cases are intravenous drugs useful?
Emergencies or when patients are unconscious
What other administration also has a rapid onset of action? Why?
Inhalation Rapid delivery of drug across a large surface area of the mucous membrane of the respiratory tract and pulmonary epithelia
What drugs are given through inhalation?
Gases (aesthetics) or those dispersed in an aerosol (asthma drugs)
Why is the inhalation route effective?
Drug is delivered directly to site of action and system side effects are minimised
What are the advantages of rectal administration?
Partially bypasses the first-pass effect
Bypass destruction by stomach acid
Ideal if the drug causes vomiting
What are some membranes that drugs need to pass in order to reach their target?
Gastrointestinal mucosa (orally)
Lung mucose (inhalation)
Lymphatic or capillary walls
Cell membrane (intracellular targets)
How do most drugs pass across membranes?
Passive diffusion
What are some factors influencing absorption?
pH (unionized drugs pass more readily)
Blood flow
Total surface area
Contact time (if drug moves too fast, it cannot by absorbed)
Expression of P-glycoproteins
What are P-glycoproteins?
Transmembrane transporter protein, responsible for transporting molecules across membranes
What happens if there is a high expression of p-glycoproteins ?
Efflux pump
Which form of acidic drugs is unionised?
Protonated
Are protonated forms of basic drugs unionised or ionised?
Ionised
Which kind of molecules can diffuse across membrane, ionised or non?
Unionised, they are lipid soluble
Why can’t ionised molecules pass through the membrane?
Low lipid solubility
What is the Henderson - Hasselbalch equation?
pH = pKa + log10 (A- / HA)
What is the Henderson - Hasselbalch equation used for?
Determine the ratio of unionized to ionised
Determine degree of ionisation at specific pH
What does a lower pKa value indicate?
Stronger acid
If pH = pKa ?
pH = pKa then 50% ionised and 50% unionised
What happens if pH < pKa ?
Higher degree of ionisation for weak bases so weak acids will be absorbed more readily
What happens if pH > pKa?
Higher degree of ionisation for weak acids so weak bases would be absorbed more readily
What is bioavailability?
Extent to which administered drug reaches the system circulation intact
How to calculate bioavailability?
Compare plasma levels of drug after a particular route to levels achieved by intravenous administration of the same dose (which is 100%)
What are factors that are affecting bioavailability?
First passage elimination in the liver
Chemical stability and solubility of drug that determine extent of GI absorption
What is bioequivalence?
If two drugs have comparable bioavailability and similar times to achieve peak blood concentrations.
What is therapeutic equivalence?
Two drug formulations have the same dosage with the same active ingredient at the same strength and same route of administration
What is distribution and when does it occur?
The process by which a drug reversibly leaves the bloodstream and enters the interstitial and the tissues. It occurs after absorption
What are the phases of distribution?
Initial phase,
Delivery of drug,
Third phase
What is the initial phase of distribution?
Well-perfused organs like the heart, liver, kidney, and brain receive most of the drug during the first few minutes after absorption.
What is the second phase of distribution?
Delivery of drug to muscle, skin, fat, and tissues. This may take several minutes or hours before reaching steady state
What is the third phase of distribution?
Drug slowly accumulates in some tissues, like fat tissue.
What are some factors that affect drug distribution?
Membrane permeability
Blood flow
Plasma protein binding
pH
Capillary permeability
What is volume of distribution?
The extend to which drug partitions between plasma and tissue compartments
What does it mean is Vd is high?
Greater distribution to tissues
What drugs have low Vd value?
Drugs that are highly bound to proteins (heparin)
What is the equation for Volume distribution?
Vd = Dose/ C
C = drug concentration
What is the effect if the drug binds to plasma proteins?
Slower transfer out of vascular compartment
What are some properties of the unbound or free drug?
Cross membranes and undergoes distribution
Exerts pharmacological or toxicological effect
It can be eliminated from the body
What happens when multiple drugs are taken together?
Drugs with greater affinity for binding can displace other drugs with lower affinity. It would also cause a rise in unbound form of drug which can change pharmaceutical effect.
What is the elimination of a drug?
Irreversible removal of the drug from the body, metabolism and excretion
What kind of drugs are metabolised?
Lipophilic
What happens to the drug after metabolism?
Excretion, either major (urine and bile) or minor (saliva, sweat, milk, breath)
How is the activity of the drug terminated?
By elimination
What kind of drugs undergo renal excretion?
Small molecular weight drugs
Fully or nearly fully ionised at physiological pH
NOT protein bound
What are the properties of most pharmacologically active molecules?
Lipophilic
Remain unionised or only partially ionised at physiological pH
Bound strongly to plasma proteins
Where are lipophilic drugs eliminated?
In the liver
Where are many drug metabolising enzymes found?
In the endoplasmic reticulum of the hepatocytes
What happens to drugs absorbed from the GI tract?
Transported to the liver via portal vein
How does the liver convert a lipophilic drug into hydrophilic water-soluble metabolites that can be excreted?
Biotransformation reactions by liver enzymes:
Phase I: create small polar groups in drugs via oxidation, reaction or hydrolysis reactions.
Phase II: conjugation, addition, of large polar groups such as glucuronic acid, glutathione or sulphate to small reactive groups
What utilises phase I?
P450 system
What s CYP450 and what is its function?
Heme-containing isozymes are located in most cells, mainly the liver and GI tract. Important for the metabolism of many endogenous compounds such as steroids and the biotransformation of exogenous substances such as drugs.
When does phase II of metabolism take place?
If phase I metabolism still too lipophilic to be excreted by the kidneys.
What happens if the substance is highly polar?
Rapidly excreted in urine and feces
What are prodrugs?
chemicals that are converted into pharmacologically active substances by metabolic reactions
What is an example of a prodrug?
Codeine is a prodrug of morphine
What happens if active drugs are metabolised?
May lead to active metabolites that have longer duration of action
What are inducers of metabolism?
Enhance the rate of CYP450 enzyme synthesis and or reduce enzyme degradation.
What are the consequences of inducers of metabolism?
Enhance metabolism of other drugs too, may need to increase dose of affected drugs to exert desired effect
What are inhibitors of metabolism?
Bind to CYP450 enzymes and therefore inhibit metabolism of other drugs
What are the consequences of inhibitors of metabolism?
Reduced drug metabolism may require reduction of dose for affected drugs to avoid adverse drug reaction for effects.
What happens to renal elimination if ionisation increases?
Ionised and nonionised forms are filtered, only ionised form is “trapped” in filtrate and excreted in urine
How is nonionised form reabsorbed?
It passively is secreted (diffusion) in proximal tubules or distal tubules
Which fraction of drug is filtered out by glomerulus?
Free, non-protein bound (unionised)
What is the formula for excreted drug?
Excreted drug = Filtered + secreted - reabsorbed
What happens if urine acidifies?
Increases ionisation of weakly basic drugs and increase their renal elimination
What happens if urine alkalises?
Increases ionisation and elimination of weak acid drugs
What is zero order elimination?
A constant amount of drug is eliminated every time
Rate is independent of drug concentration
Variable half-life
What drugs undergo zero order elimination?
Ethanol, salicylates, phenytoin
What is first order elimination?
A constant fraction of the drug is eliminated every time (i.e. 50%)
Rate is directly proportional to drug concentration in plasma
Constant half life
What is the concept of clearance?
Volume of blood cleared of drug per unit of time
Where does clearance mainly occur?
Liver and kidneys
When is clearance constant?
First order kinetics
In kidney when is clearance = GFR?
If there is no secretion, reabsorption, or protein binding of drug
What is the equation for clearance?
CL = 0.693 x (Vd/half-life)
Why is clearance important?
For determining the half life and calculating doses needed to maintain effective or therapeutic effect
What is the elimination half-life?
The time for the drug concentration to reach half of its value
What happens to the half-life if the clearance is high?
Shorter half-life
What is half-life useful for?
Determining the time taken to reach the steady state plasma levels
How long does it usually take to reach steady state?
4 to 5 half-lives
What happens if you increase the drug infusion?
Concentration of drug in plasma increases but time it takes to reach steady stat is the same
What is the goal of drug therapy?
Achieve and maintain concentrations within a therapeutic response while minimising toxicity and side effects
What is the concept of a loading dose?
A single high dose of drug is given initially to obtain desired plasma steady state levels quickly. Followed by slower maintenance dose to maintain steady state
What is the equation for loading dose?
Loading dose = (Vd) x (Desired steady state/bioavailability)
