Week 1: Introduction + Some Basic Pharmacology Flashcards
Smoke and Solids
Burning a dry material will release a drug into the air in smoke which can be absorbed in the lungs
- eg. tobacco, opium, marijuana
Drugs ingested in this way canot be exhaled and must be eliminated through other means
There is risk to damaging the tissues of the respiratory system with this method as many other substances in smoke beyond the drug (eg. tars and hydrocarbons) cause harm like respiratory disease and cancer
Therefore, vapourising a drug is safer
Rate of elimination
Half life = the amount of time it takes to eliminate half of a given blood level of a drug
The exception to this general rule is alcohol
- there is a fixed amount of per unit of time excreted
How do Non-lipid soluble substances cross the blood brain barrier
- There are passive and active transport mechanisms to accomplish this
- Most are accomplished via transmembrane proteins
so, Passive transport (diffusion) - for lipid soluble substances
and facilitated/active transport - for non-lipid soluble or against a concentration gradient
History of Drugs in NZ - Before the arrival of Europeans
- Maori were one of the few societies that didn’t use intoxicants recreationally
- They used psychoactive substances as medicine
eg. Kawakawa - used to treat bladder issues, bruises, as an analgesic and diuretic
eg. Pukatea - used as an analgesic and to treat tuberculosis
eg. Redula Marginata (acts like a cannabinoid)
Vaporising
Refined drugs can be heated until they vaporise and the vapours can be inhaled
This is better than smoking, but not a perfect method as moisture, warmth and sugar (from vape syrups for example) can promote bacterial infection in the lungs.
Transdermal administration
- Transdermal
= absorbed through the skin
Drug Antagonism
= When one drug dimishes the effect of the other
- can decrease potency and effectiveness
shifts the dose-response curve to the right
History of Alcohol in Nz
- Brought into NZ by europoean settlers
- began to be used in trade
- referred to as stinking/strong water (waipiro)
- by the 1850s was incorporated into Maori life although leaders were concerned about its harm on their communities. As such, dry areas were established and some Maori joined the prohibition movement
- It wasn’t until the 1890s when Maori began to match european settlers in alcohol related convictions (prior to this point they hadn’t been as heavy drinkers as Maori).
- The first Maori Doctors described drinking as a major social porblem
- Over time numerous alcohol regulations were passed in NZ with sexist and racist policy;
eg. 1847 Sale of Spirits to Natives Ordinance; prohibited the sale of spirits to Maori
eg. 1870 Outlying Districts Sale of Spirits Act; enabled the createion of a licensing system
eg. 1878 Native Licensing Act; allowed the establishment of dry districts
eg. 1895 Alcoholic Liquors Sale Control Amendment Act; Prevented Maori Women from Buying Alochol unless married to a european man
eg. 1904 Licensing Amendment Act Prevented Maori men from Buying Take-away alochol in most of the north island
After WW2 most of these regulations were repealed and with increased urbanisation, drinking became the norm for many maori through to present day
Inhalation
Gases
- are absorbed quickly through the capillaries of the lungs and move into the blood
- drugs in the form of vapours, gases or fine mists get into the blood very rapidly by the lungs
The blood goes directly from the lungs to the heart and one of the arteries goes directly to the brain, so inhaled drugs can pass into the brian wihtout being metabolised by the liver first (in first pass metabolism)
Intrathecal administration (parenteral)
Experimental Research with non-humans also may involve injecting a drug directly into the central nervous system (Brain/Spinal Cord) to increase experimental control
eg.
1. intrathecal - the needle is inserted between the base of the skull and the first vertebra. The drug gets left in the CSF
2. Intracerebroventricular - the needle is inserted directly in the brain’s ventricles to diffuse out into brain tissue
3. Intracerebral - needle is inserted directly into brain tissue - often using a canula.
For example, an antagonist could be injected into the hippocampus directly to put this area offline for a given study
Inhalation Administration
- inhalation
= Breathed into the lungs
Intramuscular parenteral administration
Intramuscular (i.m.) - a needle is inserted into the muscle
Kidneys role in metabolism
Functions;
- fluid balance
- detection and excretion of waste from the blood
- balance of vitamins, minerals and hormones
All occurs via filtration in the kidneys (generally after metabolism first in the liver)
Factors that influence/alter drug metabolism
- Stimulation of enzyme systems
- excess alcohol dehydrogenase has been found in the liver of heavy drinkers as the body prepares for the higher than average alcohol intake by increase the amount of enzyme required to break down the alcohol - Depression of enzyme systems
- disulfiram (antabuse) is a medication which blocks aldehyde dehydrogenase(used in alcohol metabolism). This means there is a built up of acetaldehyde as there isn’t the enzyme to break this down further to acetyl co-enzyme A. This buildup makes people feel very very sick - Age
- enzyme production and function (and therefore metabolism) changes with age
- liver function is less efficient in elderly people - Species
- levels of certain enzymes differ between species
Pharmacology
= the study of what a drug does to the body
Considers ingestion, digestion and excretion processes
Subcutaneous Parenteral Injection
Subcutaneous (s.c.)- a needle is inserted under the skin or in cutaneous tissue
Potency and Effectiveness
Primary Effect = intended result in a treatment
Side effect - unintended effect of a drug (anything other than the primary effect, may be harmful or not)
This is an arbitrary construct though, as it depends on why you’re taking the drug as to what is the primary and side effects
Class B
Deemed very high risk of harm and available on prescription
- Cannabis (hasish and Cannabis oil)
- Morphine
- Amphetamine
- MDMA
Orals administration
> When drugs are taken into the mouth and swallowed
- sometimes called ‘per oral’ (p.o.)
- the drug is then absorbed in the digestive system
Drugs may also be taken into the mouth but not swallowed
- technically still oral but absorbed through the buccal membranes
- eg. tobacco being held in the gums
Also can be taken as suppositories
- enter the digestive system through the other end (intrarectal)
- not as reliable as oral, but useful if oral is not possible
eg. for small kids if they can’t swallow the tablet
Smoking Rates in Maori and Pakeha and how this has changed with time
in 1962;
- Maori
Men; 58%
Women; 70%
- gen pop
Men; 38%
Women; 31%
In 1990;
over 50% of Maori were smokers
In 2009
Maori women aged 20 - 24 had the highest smoking rate in NZ (61%)
In 2011-2012
Rates of smoking in Maori declined to 41% compared to 18% in all NZ adults
Multiple programmes were intro’d to try and reduce smoking in the younger population (eg. age restrictions)
In 2021/2022
Maori 19.9%
rest of NZ adults 8%
Intravenous Parenteral administration
Intravenous (i.v.) - a needle is inserted into the vein
- is the fastest administration method
Hard Drugs in NZ
NZ has an unusual pattern of taking hard drugs. this is likely due to;
- geographic isolation
- strict border controls and good implementation of thiose controls
Resultingly, high profile drugs (cocaine and heroin) are much less common.
- Heroin use did see a peak in the 1970s as a result of the ‘Mr Asia’ syndicate an organisation that imported Heroin straight from asia
Optiate use is low (traditionally confided to ‘homebake) but prescription optiate use is on the rise
Cocaine use in NZ is extremely low
NZ is about 10 - 15 years behind global drug use trends. Hence only being hit by the opoid crisis
Synthetic drugs (amphetamines, ecstasy) are used more often. The rates of ecstasy and amphetamine (p) are high internaitonally, but are starting to be reduced due to crackdowns on clandestine labs and tighter border controls.
Hallucinogens
- we have low rates of LSD, Mushcroom and ketamine use
Party used
- used to be widely used by were banned in 2007
Active Transport
Transport method to move particles up against the concentration gradient using ATP/energy
Passive Transport
Is the most basic transport mechanism
- is diffusion ; whereby particles move from a high to low concentration
- doesn’t require energy expenditure
- is a slow transport mechanism
- This is mostly used by lipid soluble substances, but even non-lipid soluble substances can enter the intracellular space if there is a strong enough concentration gradient
The differing pattern of drinking between Maori and Non-Maori
Although on average, Maori and Europeans drink about the same amount in total, Maori tend to drink less frequently but consume twice as much per drinking session (aka binge drinking; which is by far the worst way to drink)
Maori are twice as likely to suffer severse alcohol related problems and four times as likely to die of a condition caused or made worse by alcohol (eg. Exacerabating existing health conditions
Superadditive responses/effects (potentiation)
Syngergistic effect of taking two drugs
shifts the curve left
Class A drugs
Are deemed to pose a very high risk of harm and are illegal
- LSD
- Heroin
- Cocaine
- Methamphetamine
- Psilocin and Psilocybin
Organs involved in Metabolism and Excretion
Most of this process is handled by the liver and kidneys
Substances won’t cross the BBB if they are
- Too highly charged (ionised) eg. metabolites
- Too large (as won’t fit through the tight junctions)
- Not lipid soluble (can’t cross phospholipid bilayer)
Drug interactions - Additive effect (potentiation)
Shifts the dose-response curve to the left
- increases potency (less needed to cause an effect)
Additivity: when the effect of two drugs given in combination equals the mathematical summation of their effects when given alone
LD50
Median Lethal Dose
- The drug dose that is lethal in 50% of subjects tested
What are the three processes in Pharmokinetics
- Absorption ; how a drug gets into the blood
- Distribution ; where it goes in the body
- Elimination ; How the drug leaves the body
Parenteral Route of Drug Administration
aka injecting
vehicle - before a drug can be injected it must be liquid
Subcutaneous (s.c.)- a needle is inserted under the skin or in cutaneous tissue
Intramuscular (i.m.) - a needle is inserted into the muscle
Intraperitoneal (i.p.) - a needle is inserted into the peritoneal cavity
- this is not common in humans but is good for animal research
- involved in slow drug release/effect
Intravenous (i.v.) - a needle is inserted into the vein
- is the fastest administration method
Experimental Research with non-humans also may involve injecting a drug directly into the central nervous system (Brain/Spinal Cord) to increase experimental control
eg.
1. intrathecal - the needle is inserted between the base of the skull and the first vertebra. The drug gets left in the CSF
2. Intracerebroventricular - the needle is inserted directly in the brain’s ventricles to diffuse out into brain tissue
3. Intracerebral - needle is inserted directly into brain tissue - often using a canula.
For example, an antagonist could be injected into the hippocampus directly to put this area offline for a given study
Oral Administration
- Oral
= Ingested into the digestive system
Purpose of the drug class system
With Class A, Class B and Class C drugs, the idea is that the penalty for use and possesion through the criminal justice system is staggered based on drug class.
Therefore there is a lot of importance on getting the drug class correct scientifically rather than just politically
Parenteral Drug Administration
= Injection under the skin (aka subcutaneous)
Intraperitoneal parenteral administration
Intraperitoneal (i.p.) - a needle is inserted into the peritoneal cavity
- this is not common in humans but is good for animal research
- involved in slow drug release/effect
Lipid Solubility and Absorption
- All tissue in the body is composed of cells that form membranes
- In order to get inside the cell, drugs have to cross the phospholipid (fat) bilayer, two layers of fat molecules
- Drugs that can dissolve in fat (lipid soluble are more readily absorbed) . This indicates timeframe for drugs to produce effects
Facilitated Transport
Uses channels and carrier proteins to transport materials across a membrane down a diffusion gradient. This is a mode of passive transport which is faster than simple diffusion
The kidneys
Function as a complex filtering system that physically removes certain substances from the blood into urine
- it filters everything out of the blood and then selectively reabsorbs what is needed by the body
Metabolites (from the liver) are generally more likely to ionize, amking them more difficult to be absorbed back into the bloodstream.
- chemical reactions between enzymes and drugs often produce products that are more likely to ionise and less likely to pass the BBB
Combining Absorption and Excretion Functions shows
How the effect of a drug changes over time.
Absoprtion = an acellerating curve (where concentration increases per unit over time)
Excretion = a decellerating curve (where concentration decreases per unit over time)
The resultant = the sum of the absorption and excretion curve in order to show the overall change in concentration over time
The type of administration will influence this drug profile as this will influence the spike and decay of the drug.
IV > IP > IM > PO
Placental Barrier
Is a method to protect a foetus from certain compounds - is similar to the blood brain barrier but much more permissive (less selective)
- Drug concentration in the blood of a fetus reaches 75-100% of that in the mother in about 5 mins. So drugs are passed on to the baby when consumed by the mother
- There is little protection for the fetus likely due to drugs mimicking endogenous chemicals and compounds
First-Pass Metabolism
Drugs that are absorbed through the digestive system pass through the liver first - which is effective in drug metabolism
Some metabolism takes place in this time via liver enzymes
- likely responsible for a significant amount of drug metabolism
The Therapeutic Window
To be effective, the right level of a drug must be maintained in the blood for an extended period of time.
Because of pharmokinetics there’s always some varying amount of absorption and excretion and we need to titrate the levels of the drug in the body to have drug concentration remain in an effective but non-toxic level
Too much of a drug will produce negative side effects
Too little will not produce the wanted therapeutic effect
Intracerebral parenteral administration
Experimental Research with non-humans also may involve injecting a drug directly into the central nervous system (Brain/Spinal Cord) to increase experimental control
eg.
1. intrathecal - the needle is inserted between the base of the skull and the first vertebra. The drug gets left in the CSF
2. Intracerebroventricular - the needle is inserted directly in the brain’s ventricles to diffuse out into brain tissue
3. Intracerebral - needle is inserted directly into brain tissue - often using a canula.
For example, an antagonist could be injected into the hippocampus directly to put this area offline for a given study
Dose- Response Curve
Is a way to establish the true picture of the effects of a drug
- seen lots in animal research
Historically, one would give one dose of a drug to an animal for example and assess the effects to draw conclusions on the drugs effects (eg. Meth makes rats run around so it must be a stimulant)
However, drugs have a dose-dependant relationship, so need to assess the effect of the drug at different doses (dose-response curve will plot this)
Eg. the effect of caffeience on the rate of responding by a mouse measured in relation to it’s response rate at baseline (with a Saline injection)
However, not all drugs can be measured in a response rate type task, sometimes the reaction to a drug isn’t easily measured on a graded metric (eg. anaesthesia - where you’re either awake or asleep)
Intracerebroventricular administration (parenteral)
Experimental Research with non-humans also may involve injecting a drug directly into the central nervous system (Brain/Spinal Cord) to increase experimental control
eg.
1. intrathecal - the needle is inserted between the base of the skull and the first vertebra. The drug gets left in the CSF
2. Intracerebroventricular - the needle is inserted directly in the brain’s ventricles to diffuse out into brain tissue
3. Intracerebral - needle is inserted directly into brain tissue - often using a canula.
For example, an antagonist could be injected into the hippocampus directly to put this area offline for a given study
History on Drugs - Upon European Arrival
In the late 1700’s Europeans brought alcohol and tobacco to NZ
Some Maori leaders discouraged the use of both, but they soon were used as currency in trade, thus pushing it into acceptance
Eg. Alcohol and Tobacco (more info on other cards on this)
Use of the LD50 and ED50
It is important to assess the ED50 and LD50 are important in informing a safety index when it comes to drugs.
A safer drug will have a larger difference between the ED50 and LD50
as a low ED50 means it is effective at low doses and a high LD50 means it’s lethal only at high doses
The therapeutic index = an objective way to decribe the safety of a drug
Ti = LD50/ED50
The higher the Ti, the safer the drug
Class C
Have a moderate risk of harm
- cannabis (plant, leaf, fruit or seeds)
- barbituates
- benzodiazepines
Depot Injection
A drug injection whereby the drug is given such that it slowly dissolves into the body over a long period of time.
So you formulate a drug and inject it into fat for example to prevent a spike of the drug effect and promote slow release/effects
The therapeutic Index
The therapeutic index = an objective way to decribe the safety of a drug
Ti = LD50/ED50
The higher the Ti, the safer the drug
ED50
Is the median effective dose
- the dose that is effective in 50% of the subjects tested
- This is the anaesthetic dose that puts 50% of people to sleep
Pharmokinetics
= the branch of pharmacology concerned with the movement of drugs within the body.
History of Tobacco Use in NZ
Tobacco;
- Cook smoked a pipe, and on arrival to NZ the Ngai Tahu Chief threw water on him to see if his head was burning. He said to Maori that if the water put the fire out then the white chief was human and if not he was an atua (a demon) and should be killed. As the water put the pipe out, cook was deemed a human
- Maori men and women began to use tobacco widely in the early 1800s. But this was and still is frowned upon in women
- There is evidence of a sociocultural and gender inequality with tobacco use from NZ. With quotes from 1899 suggesting “smoke products are used strongly by men women and youth. The rule for Pakeha is that only older men smoke tobacco and it is only at an appropriate age that men start to smoke, women and young women don’t smoke at all”
- The use of tobacco was still opposed among Maori into the early 20th century with some leaders banning it from their communities. Eg. The Moari Councils act of 1900 let Maori councils prohibit the use of tobacco by children and to fine suppliers
- By the time tobacco and smoking dangers were identified in the mid 1900s, smoking was deeply integrated into maori culture and seen at higher rates than in non-maori
How are Drugs named?
Chemical Name = The chemical composition
Generic Name = the drug stem (end of the name) which lets you know what type of drug it is
- ie. diazepam (azepams indicates it is an antianxiety drug)
Trade name = the renaming of the drug by a drug company one it is patented
- ie. valium
Street name - has wide cariation
- eg. V’s, Benzos etc
Routes of Drug Administration
- Parenteral
= Injection under the skin (aka subcutaneous) - inhalation
= Breathed into the lungs - Oral
= Ingested into the digestive system - Transdermal
= absorbed through the skin
Each of these methods have different kinetics - some administration methods (or ways into the blood) are faster than others and resultingly influences the effect of the drug
Cannabis use in NZ over the Years
There wasn’t much Cannabis use in NZ until the 60’s
- the Baby boomers, Vietnam war and psychedelic ‘hippie’ movement/music lead to a strong cultural influnece towards marajuana use
- This led to a huge increase in cannabis use which has continued through to today
NZ currently has one of the highest rates of cannabis use in the world
Factors to consider about the vehicle in parenteral administration
aka injecting
vehicle - before a drug can be injected it must be liquid
Metabolism
= the process of restructuring molecules so they can be filtered out of the blood into the kidneys
- requires enzymes
- catalysts that control chemical reactions
Enzyme products can be recycled or excreted
Where drugs are involves, sometimes metabolism is called detoxification
What is a Drug?
Broadly defined as –> Any substance that alters the physiology of the body
- this however would include food and nutrients which aren’t usually considered drugs
So.. the 330 definition = a substance that alters the physiology of the body but is not a food or nutrient
Drug Dose
Always states in milligrams (1/1000 of a gram)
The impact of a drug is related to its concentration in the body, not the absolute amount of the drug. Therefore dose is monitored by the dose according to body weight (mg/kg)
The same metic intake will therefore produce different effects based on body weight
The same dose however, is generally comparable in different subjects or species
Other Drugs in NZ and Their History
- Chinese miners brought opium smoking to NZ in the 1860s
- Patent medications (that could be ordered in a mail catalogue and used in a non-regulated non-propietary manner) were common and often contained cannabis, morphine or cocaine
- Cannabis cigarettes were widely advertised in the 19th century as a cure of asthma and insomnia - medical authorities promoted smoking which made it more widely acceptable
Absorption from Parenteral Sites
To be effective, drugs must be absorbed into the bloodstream.
- Drugs move through capillarilies into the blood through diffusion and the capillaries permeate most body tissues
- Veins then carry blood to the heart
- Arteries carry blood away from the heart to the rest of the body and brain
Distribution of drugs in the central nervous system - the blood brain barrier
In order to get into the brain, drugs have to cross the blood brain barrier
The blood brain barrier is a complex which surrounds most of the blood vessels of the brain (excluding regions around the circumventricular organs). It acts as a barrier between the bloodstream and the extracellular space in the brain.
Allows entry of;
- water
- O2
- Lipid Soluble Substances
Blocks entry of;
- Toxins
- Pathogens
- & dangerous substances
Components of the BBB;
- Tight junctions of the endothelial cells
- Astrocytic end feet to signal the formation of tight junction and maintain/regulate the BBB
Powdered Inhalation
Powdered drugs can also be inhaled (aka snorted)
Cocaine, heroin and tobacco
- not as efficient in getting drug to the blood but does the job - this works due to the high number of capillaries in nostrils
DALY = Disability Adjusted Life Years;
Is a measure of overall disease burden, expressed as the cumulative number of years lost due to ill-health, disability or early death
- Is a metric that can be used to assess drug impact.
- is used widely but often in a medical context to assess the number of years lost due to the use of a given disease or drug etc
- asks how much healthy life is lost
- One DALY is one year of healthy life lost
What has been found is that even though we have a lower use of drugs people tend to lose more life as a result of substance abuse in NZ
- It is one of the leading causes of disease burden in NZ.
- In NZ, 13.7% of all DALYS are linked to substance abuse versus 4% in the US
- Projected DALYs for 2016 are 1.085 million - with 150,700 DALYs due to drug abuse
Misuse of Drugs Act 1975
Is the current official drugs policy in NZ
Was heavily influenced by President Nixon’s war on drugs which fostered a hard on drugs approach which was prohibition and punihsment driven
This Act was an initiative to bring NZ into line with the general international consensus on drugs
- it established a schedule for drugs
- it underwent revisions in 1978 and 1992
- Lists drugs as being Class A, B or C
Since it’s estblishment, this Act has been widely criticized, undergone several revisions and amendments and yet people feel it likely isn’t comprehensive enough
Measures to Control Drugs in NZ over the years
A few measures were taken to control drugs between 1866 and 1965, even though they weren’t much of a problem
These regulations were brought into place to protect people from the harms identified by drugs (eg. date rape etc)
1866 - Sale of Poisons Act ; Required opium to be labelled as a poison
1871 - An act which required vendors of opium to be registered
1901 - Opium Prohibition Act; Prohibited the smoking and importation of opium
1908 - Quakery Prevention Act; Tried to restrict patent medicines - (quackery = term for medically dubius peddling of medications)
But drugs remained relatively unrestricted until the early 1900s when international pressure forced NZ to severely restrict drugs.
- NZ is most heavily influenced by the US and Uk when it comes to drug laws as they can strong arm the country in to making changes by trading restrictions etc
This lead to the Dangerous Drugs Act 1927
- this brought drugs into line internationally
- Established a list of dangerous drugs, including cannabis
- They could be imported and manufactured only under license and only purchased from a licensed doctor or chemist
- This brought us into the transition to medical regulation over social drug use
Still a lot of drug use however for medical reasons;
- eg. in the 1940s it was discovered that NZ had one of the world’s highest heroin use rates. Due to prescription of the drug by doctors (used to treat mild cough) - this was lowered by 1955
Transdermal Administration
When drugs are absorbed through the skin
- this is a very slow process (unless there is a break in the skin)
eg. nicotine patches
- this is a slow, stable administration
