Pharmacology101 Midterm Review

Drugs barely altered, instead “me-too” drugs created to benefit large companies instead of moving drugs forward (Over 57$ billion used in marketing) MDs enticed to prescribe drugs; an example where Pfizer had to pay a fine of 2 billion because they promoted drugs where they were not approved through wining and dining with physicians. Ethics: Doctors prescribe medicine and consumer has little to no say in what they must take.

Therefore, the healthcare professional should make informed, correct decisions. Advertising techniques: catch attention, authorities to endorse product, fear, easy solution to problem, before/after techniques “Miracle drugs” showing they can solve any problems – perhaps problems that may not even exist (problem child for example) Drug Trials

Two experiences led to improved regulations: Sulfonamide with toxic solvent which led to deaths and Thalidomide which was found to be a teratogenic later on but given during pregnancy For a trial: submit proof of efficacy and safety, methods to be used in trial, drug given to investigators, preclinical testing to show efficacy of drugs and show results on rodent species + in-vitro, in-vivo toxicology screening also required to do (in animals) – takes years for drug to complete – then inserted into humans and monitored Phase I – One or two doses in healthy volunteers (Absorption, distribution, elimination and adverse effects (limited) Phase II – Short-term efficacy study. Determine dose for phase III. Safety. Proof of concept. Phase III – Long-term study for efficacy and safety. Randomized controlled trials. Phase IV – Often referred to as post-market surveillance – look for possible rare toxicities. Phase III: comparator (placebo/standard of care), patient selection, randomization, blinding, outcome measure, all parameters are controlled Placebo: an inert substance masquerading as a drug. Placebos can have side effects.

Beecher found in his studies that 35% of patients were effected by placebo if they had angina pectoris, cold, anxiety, cough or moodiness along with asthma Designing a trial: study population, comparator, randomization (patients allocated by computer or double-blind), outcome (what is being measured? Is it the appropriate outcome? ) Cross-over designs: compare drug A and drug B. Group A gets A and while Group B gets B for three weeks and then they switch and get the other drug.

Each patient is their own control standard. Can be used for stable chronic diseases (short term) such as infections. Drug Response and Selective Toxicity Potency: amount of drug that must be given to obtain a particular response Efficacy: maximal response that can be obtained with the drug As dose increases, so does the response. There can be variability between individuals as well as between drugs. Therapeutic dose < toxic dose.

Therapeutic index = Lethal or Toxic Dose/Median Effective Dose where the higher the number, the less chance of adverse effect Selective Toxicity: harm to one organism without harming another kind (example: weed killer that doesn’t harm the crop or killing a parasite without harming the host [bacterial infections, cancel cells]) Herbicides can accumulate, for example sulfuric acid Chemotherapy: in early theories, people believed the body was overcome by evil spirits.

Pasteur and Koch believed that some diseases caused by microbes where some agents were selectively toxic to a specific micro-organism. Paul Ehrlich argued that dyes buildup in tissues and the right drug would bind to a specific parasite where human cells would not be harmed.

“Bodies do not act unless fixed” Critics believed that drugs work by strengthening defense mechanisms of body by Ehrlich thought that drugs must bind to organism before it can kill it. Example atoxyl (antibacterial) which worked inside the body but not in vitro. Ehrlich said it was because atoxyl is converted to active form inside the body.

Organo-arsenicals were first selectively-toxic drug for treatment of syphilis. “Money, patience, cleverness, luck” components of success in Science – Ehrlich Sulfonamides: Domagk found that prontosil effective against streptococcal infections. It was converted to sulfanilamide in the body. Selectively toxic because all organisms require folic acid and organisms must make their own.

This acid is made from p-aminobenzoic acid and since sulfanilamide resembles this, it can block the enzyme for making folic acid. Antimetabolites: design of anticancer drugs where the fundamental difference between cancer cells and normal cells can be taken advantage of. Cancer cells divide continuously so by blocking DNA synthesis, it would have a larger effect on the cancer cell than the normal cell. Penicillin: bacteria have cell walls whereas human cells do not.

Penicillin blocks cell wall synthesis with no effect on the human cell which means it has a wide margin of safety. Newer antibiotics have less of a difference between the microbe and human cells which makes them more toxic. Drug Toxicity and Routes of Administration Acute and chronic drug toxicity

Poisoning: ASA and Acetaminophen, Iron tablets for children, Barbiturates, Benzodiazepines (often with alcohol) Adverse effects: dose, individual (genetics), age, disease state Types of Adverse Effects Extension of therapeutic effect: over sedation with barbiturates or benzodiazepines Unrelated to main drug: such as digitalis and nausea or NSAID with its GI erosions Idiosyncrasy: usually genetic where body can lack and enzyme which leads to the body behaving a certain way with the drug Drug allergy: need prior exposure to form antibodies to the drug (example penicillin) Toxicity Toxicity is rare and not always detected in tests or in animal testing (headache, insomnia, depression), sometimes showing up years later. Usual dose can sometimes have effect in some individuals but be toxic in others.

Wide differences in response to drugs. After absorption however, good relationship between blood concentration and effect. However, relationship between dose and concentration in blood can vary. Absorption and elimination factors:

Genetics, environmental factors, disease, presence of other drugs Therapeutic monitoring needed for some drugs such as phenytoin Routes of Administration Enteral routes: oral/swallowed which is most drugs and can be self-administered; rectal administration when one if vomiting or is unconscious; under the tongue such as nitroglycerin Inhalation: used directly to lungs such as asthma or for systemic effect .

Intranasal: nose sprays; oxytocin to induce labor; peptides or proteins such as insulin Parenteral Routes: intramuscular, subcutaneous(just beneath skin/fat), intravenous, intrathecal (spinal), transdermal (patches) Intravenous: no delay for absorption, large volumes, diffusion continuously, less pain than other methods; however, drug can’t be recovered if given by mistake, meaning immediate toxicity, rate of infusion must be controlled, infection can happen because of unsterile needles or pyrogens (fever causing) can be found on needle Intramuscular: drugs rapidly absorbed because deep muscle, drugs can be stored within tissue.

Subcutaneous: into fat, poorer blood flow so slower effect after injection, can also be “reposites/stored” such as insulin Transdermal: skin provides some barrier, lipid soluble compounds absorbed (nicotine, estrogen, insecticides, nitroglycerin) Drug Absorption, Distribution, Metabolism and Excretion Receptors: binding sites where specific macromolecules play a role in body’s biological processes Sometimes drugs are non-specific in their interaction such as osmotic diuretics or general anesthetics Agonist, competitive inhibitor, allosteric activator (makes more effective), allosteric inhibitor (less effective, worse than competitive).

Drug effect relative to concentration of drug at receptor/action site. But concentration here can’t be measured, so concentration in plasma is measured instead. Drug has to cross various membranes in the GI system to reach the blood. The drug can exist in two forms: the free form or as bound to a protein. If it is bound to a big protein, it won’t be able to cross membranes.

But the free drug can easily reach the site of action. However, the body does not always cooperate, and the free drug will go to unwanted sites of action, it could cause sedation or upset stomach. If it is fat soluble, it will distribute throughout the body and will reach tissue or muscle fat. If pregnant, it can even reach the fetus.

The body has two mechanisms to rid itself of drug: biotransformation (metabolism) done 90% in liver where drug is made more water soluble and changed so it can be moved back to blood and kidney filters the water soluble drug which is excreted in the urine. Some drugs can be excreted unchanged, but they must be water soluble.

The rate of absorption is important, and is different for all individuals (how much fat there is to store, how actively it can be metabolized or excreted, how fast it is distributed).

All these factors alter the amount of drug at the site of action. Concentration at action site factors: amount to be given, extent and rate of absorption, redistribution to other tissues, biotransformation, excretion Membrane transport: filtration via pores, passive diffusion, active transport, pinocytosis Absorption by the lungs: some anesthetics administered this way because they are transferred from lung to the blood and carried to the brain until the concentration is high enough for anesthesia to work.

Also a route for pollutants in the air. Used for asthma as well where the drug needs to reach the bronchi and alveoli and must cross membranes in the process. For enteral route, rectum is not very well absorbing.

By mouth however, tablets disintegrate, dissolute, and get absorbed usually through passive diffusion. To exert effect, oral drug must: be taken, released from dose, dissolve in G. I fluids, then absorbed. To work, tablets must have stated amount of active ingredient, and tablet must disintegrate in a test tube. Generic: the revamped versions of the innovator product. Sometimes these drugs would not work because right dosage was not released.

Now, drugs are tested and only released after the proper concentration in blood is found to match the innovator drug. Bioavailability: measure the rate and extent of release of the drug (amount in the blood) after taking a tablet or capsule. This is used to compare a generic with the original product – bioequivalence.

Claims that some products have better release properties. Ontario Drug Formulary lists drugs are considered equivalent because they are closely evaluated and standardized. The Medical Letter is expert opinion that tests drugs in large trials and gives you the bottom line is two pages. Mechanism of Termination of Drug Action Redistribution, excretion, biotransformation Redistribution: does not eliminate drug.

Thiopental (barbiturate) used as an anesthetic where once given, patient falls asleep quickly and wakes after 30 minutes. This is because blood takes thiopental to the brain and gets high concentration there – anesthesia. As the blood then begins to reach other tissue over time, the concentration in the brain decreases and the patient wakes up. Excretion: Kidney plays a major role.

Must be water soluble for renal excretion. Fat soluble are slowly and rarely excreted. Feces are also a way of excretion, along with limited milk, saliva or sweat. Biotransformation: liver contains enzymes that convert drugs to water soluble products which are released in urine.

Everyone handles drugs differently and the enzymes present in the body determine the way in which biotransformation will occur. Main enzyme system Cytochromes P450 because many drugs work on this receptor.

Biotransformation leads to inactivation. Drug Interaction: one drug changes the response of another drug Most patients that take various drugs – they alter the response of each other Mechanisms: absorption, where one drug may prevent absorption of both drugs by binding in the G. I tract or drugs that cause diarrhea which don’t allow enough time for absorption Displacement: many drugs are bound to plasma protein and only the free drug can reach action site.

One drug can displace another from the binding site so more free drug present, leading to larger effect. For example, anticoagulants. Liver handling of drug: Enzymes such as CYP 450 (inactivates drug) can be increased so one drug may stimulate synthesis of this enzyme, and the second drug is then removed at a faster rate.

A drug could also inhibit this enzyme which reduces rate of removal of second drug. Excretion: drugs can enhance or decrease the renal excretion of drugs Toxic substances in food Substances in food can affect drug response; for example, Tyramine found in old cheese is broken down by an enzyme -monoamine oxidase. There is a class of drugs used to treat depression which inhibit MAO as part of their mechanism of action.

If give MAO inhibitor with old cheese may get increased levels of tyramine and tyramine toxicity (high blood pressure). Physiological and Pharmacological Aspects of the Central Nervous System Cerebral cortex: largest part of the brain. Divided into two parts. 4 lobes: vision, hearing, sensory perception and higher-level cognitive functions. Thalamus: relay station for sensory information to cerebral cortex Hypothalamus: autonomic nervous system (sleeping, body temp); controls hormonal output of the pituitary gland Pituitary gland: hormone secretion Brainstem: connected to spinal cord. Three parts: midbrain, pons, medulla. All impulses between brain and spinal cord pass through brainstem.

Regulates vital body functions: blood pressure, heart rate, respiration. Behavioural responses also, such as attention or arousal. Cerebellum: connected to brainstem. Responsible for integration of movement and posture. Alcohol depressed cerebellum leading to loss of balance. Glial cells provide metabolic and structural support Neurotransmission Major neurotransmitters in CNS: Acetylcholine – excitatory in the brain. Drugs that block this produce amnesia (Alzheimer’s). Norepinephrine/epinephrine – usually excitatory. Some antidepressants enhance this system. Dopamine – one excitatory and one inhibitory. Involved with motor coordination, motivation and reward. (Parkinson’s, schizophrenia).

Serotonin – excitatory. Hyperactivity and hypoactivty so responsible for anxiety and depression. Glutamate – major excitatory in brain. Found in almost all neurons, involved in learning. GABA – major inhibitory in brain. CNS depressants such as benzodiazepines bind to GABA receptors. Opioid – both inhibitory and excitatory. Pain regulation, motivation and reward. Termination of Synaptic Transmission: enzymatic degradation – break down transmitter in cleft. Example acetycholine broken down by acetylcholinesterase. Reuptake into presynaptic neuron – transporter proteins take transmitter back into neuron followed by degradation. Example norepinephrine.

Drugs can: mimic neurotransmission (occupy receptor sites and cause effect), block receptor, actively release or block neurotransmitter from presynaptic neuron, block reuptake or breakdown of neurotransmitters Physiological and Pharmacological Aspects of the Autonomic Nervous System (Peripheral Nervous).

Peripheral nervous system has motor neurons and sensory neurons Sensory recognize change in the environment and carry signals to the CNS Motor respond to the changes and carry signals from the CNS to control centres of muscles and glands Somatic Nervous System controls voluntary movement, whereas Autonomic controls involuntary movement. Somatic controls skeletal muscle by stimulating release of Acetylcholine. Ach interacts with nicotinic receptors on skeletal muscle and this synapse is called neuromuscular junction.

This is used in surgical procedures to paralyze muscles or to reduce spasticity through use of muscle relaxants. Autonomic controls responses by influencing organs, glands to regulate breathing, heart rate etc to maintain stable internal environment Autonomic consists of Parasympathetic(rest and digest, conserves energy) and Sympathetic(fight or flight, burns energy) divisions Parasympathetic Neurotransmitter: Acetylcholine.

Receptor: Cholinergic receptors – muscarinic and nicotinic Muscarinic: heart/smooth muscle, glands – decreased heart rate, smooth muscle contraction Nicotinic: skeletal muscle/ganglia – skeletal muscle contraction, impulse taken to postganglionic neuron Long preganglionic fibers release Ach, binds to Nicotinic receptors Short postganglionic fibers release Ach at the target organ and binds to Muscarinic receptors.

All autonomic ganglia have nicotinic receptors All target organs of parasympathetic have muscarinic receptors Cholinergic drugs stimulate parasympathetic nervous system and exert effect on ACh receptors in skeletal muscle or CNS (example toxic nerve gas) Anticholinergic drugs inhibit parasympathetic by blocking muscarinic receptors Sympathetic Nervous System Neurotransmitters: Norepinephrine, Epinephrine.

Receptor: Adrenergic Receptors Activity terminated by reuptake, then degradation by Monoamine Oxidase and Catchol-O-methyltransferase Receptors – Alpha and Beta, subdivided into Beta 1 and 2 located in specific target organs Alpha found in smooth muscle, leads to contraction of the muscle. Beta found in heart, Beta 2 in lungs, vessels, increase heart rate and beta 2 relaxes smooth muscle Short preganglionic fibers release ACh and binds to Nicotinic receptors Long postganglionic fibers release NE at target organ which binds to alpha or beta receptors Adrenergic drugs stimulate nervous system with primary effects on heart, bronchial tree and nasal passages Similar effect to anticholinergics Alpha: phenylephrine used for nasal congestion.

Beta: dobutamine used for heart failure. Beta2: sulbutamol/ventolin used for asthma. Adrenergic blocker drugs inhibit sympathetic nervous system, most widely prescribed to decrease blood pressure and slow heart rate. Non-selective beta blockers used for hypertension and cardiac rhythm abnormalities Summary Drugs that mimic effect of sympathetic: epinephrine Drugs that block sympathetic: propranolol Drugs that mimic parasympathetic: acetylcholine Drugs that block parasympathetic: atropine Sedative-Hypnotics: Reference Chapter 7 Sedative-hypnotic agents are drugs that produce a dose-dependent depression of the CNS Low dose = anti-anxiety ? sedation ? hypnosis ?

High dose = anesthesia Produce a graded depression of the reticular activating system (regulates arousal and sleep/wake cycle) Types: Benzodiazepines (example valium), Barbiturates (barbitals), Ethanol, Chloral hydrate, Over the counter agents such as Antihistamines Barbiturates widely used for 100 years, gold standard for treating anxiety and insomnia but high dependence liability with adverse side effects Benzodiazepines synthesized later on.

Some are more sedative while others are more hypnotic, and speed of action also differs Rohypnol: used as a party drug with alcohol, highest illicit used in 1995 Routes of Administration Readily absorbed from digestive tracts, where rapid effects require IV injection but can be given orally for long term-use Highly lipid soluble agents enter cell more readily Alcohol increases absorption of drug because of the additive effect GABA GABA has two receptors:

A and B Barbiturates and Benzodiazepines bind to GABA(A) on specific sites different from GABA bind sites Interaction with the receptor leads to opening of chloride channel and more Cl- ions flowing into the neuron ? the inside becomes more negative and action potential is unable to form Benzodiazepines can easily pass through the placenta and found in breast milk Alcohol inhibits BDZ metabolism which increases BDZ half-life ? body takes longer to produce effects. Bodies have enzymes that break down the drug, but sometimes breakdown products (metabolites) have drug effects + additional effects.

This means that the drug continues to dose, and now new drugs attempt to remove the possibility of active metabolites. BAR and BDZ increase GABA’s tendency to bind to its receptor and open Cl- channels BAR increases the duration of the channel opening BDZ increases the frequency of the channel opening BAR & BDZ Barbiturates: at low doses can only make GABA more effective and doesn’t alter operation of CL-channels; at higher dose, it can open Cl- channels.

High enough dose can cause death/suicide Benzodiazepines: at low and high doses, makes GABA more effective and cannot open Cl- channels directly. They have more appeal in medicine because it can’t lead to heart attacks or death by overdose.

BAR: low therapeutic index, but can treat full spectrum of CNS depression. Suppresses REM-type sleep (dreams) so when you stop taking it, you get vivid rebound REMs. Long-acting bar such as valproic acid can work as anticonvulsant. High abuse potential BDZ: very high therapeutic index, produces relief from anxiety, sedation, amnesia, some effective hypnotics, skeletal muscle relaxation.

Also suppresses REM-sleep so you wake up feeling not very rested. Low abuse potential but it can be abused BDZ: effects of memory with anterograde amnesia which is loss of memory for events while on the drug and memory problems can last months after drug is discontinued (such as rohypnol where victims have little memory of assault).

BDZ given to make “conscious sedation” where patient is awake but does not remember medical procedure Tolerance Acute tolerance: can occur during single use Chronic: repeated exposure decreases effectiveness to modulate the effects of GABA Cross-tolerance: between BDZ and other depressants, where drowsiness from high doses of BDZ not seen in patients that abuse alcohol or barbiturate Withdrawal Both BAR and BDZ cause dependence BAR withdrawal: different among individuals according to their patterns of use, such as mild sleep disturbances for low doses or anxiety, insomnia, nausea, seizures for high doses BDZ: high doses produce physical symptoms like BAR/alcohol.

Studies now show that this occurs at low doses also BDZ withdrawal – two types: sedative-hypnotic type where if taken more than recommended for a month, tremors, delirium, cramps and convulsions can occur; low-dose withdrawal where after taking low doses for more than 6 months, anxiety, panic, irregular heartbeat or distortions of reality can emerge slowly Harmful effects of BDZ: can cause birth defects where reaction to stressors is effected; BDZ safer than BAR and its overdoses are not as dangerous because no respiratory depression.

Individuals can tolerate high doses. Other depressants intensify effect. BDZ also have antagonists that can counteract, which makes it safer also. Discontinuation needs supervision, where gradual reduction of daily dose along with group support/counselling and monitoring. Alcohol: Reference Chapter 13 Isopropyl: rubbing alcohol, methyl alcohol: wood alcohol, ethanol: consumable alcohol Fermentation ? sugar + water + yeast = ethanol + CO2 Pharmacokinetics Taken orally, rapid absorption by passive diffusion.

Alcohol distributes evenly through body as soluble in both water and fat and can pass through placental barrier (teratogen) Alcohol dehydrogenase is rate-limiting (due to coenzyme nicotinamide adenine dinucleotide – NAD) which leads to Acetaldehyd which is then broken down by aldehyde dehydrogenase. Final product is acetate which is broken down to CO2 and H2O.

Average adult metabolizes 10-14 mL of 100% alcohol/hour 95% alcohol removed by biotransformation (metabolism) primarily in the liver. 5% excreted through breath, urine, sweat Women have 50% less gastric (liver) metabolism and concentrate alcohol in plasma more than men Low dose (1-2 drinks) ? disinhibition: relaxed, talkative, risk-taking, lower ability to concentrate High dose (>2 drinks) ? sedation, hypnosis, anesthesia, coma, death (respiratory depression) Mechanism of Action.

CNS depressant which disrupts glutaminergic neurotransmission but indirectly increases dopaminergic activity (positive reinforcing effect) Long term effects: mental disorders: memory loss, psychosis, cerebral atrophy; nutritional deficiencies, poor diet, GI dysfunction Wernicke’s encephalophathy: lack of coordination, confusion, short term memory loss due to lack of intake of thiamine Korsakoff’s psychosis:

Anterograde amnesia, memory loss, lack of insight and apathy, confabulation due to deficiency of thiamine Tolerance Regular use decreases intensity of action and shortens duration of action CNS adapts to effects of ethanol and ethanol metabolisms also increases Depends on individual, dose of ethanol, frequency of ethanol administration Does not develop to the lethal dose of ethanol however.

Cross tolerance between ethanol, sedative-hypnotics and anesthetics Dependence Withdrawal leads to excitability of CNS Tremors, irritability, nausea, confusion, sleep disorders, hallucinations, increased heart rate which can lead to convulsions, coma or death Psychological dependence: compulsion that requires continuous use of drug to produce pleasure or prevent discomfort. Can be treated by substitution of BDZ or with naltrexone which diminishes craving for alcohol Alcohol and Pregnancy Fetal Alcohol Syndrome:

Growth deficiencies (retardation), facial dysmorphology, CNS dysfunction leading to cognitive and behavioural deficits ? most persistent issue No safe level of alcohol to be taken during pregnancy Fetal Alcohol Spectrum Disorder: all prenatal exposure to alcohol Sandy’s Law: all establishments in Ontario that serve alcohol must have signs cautioning women that alcohol during pregnancy can cause FASD Opioids, Reference Chapter 10 Pain: unpleasant sensory/emotional experience associated with actual/potential tissue damage Opiates/opioids: natural or synthetic drug that has similar effects of morphine.

Endorphin: endogenous substance that has pharmacological properties of morphine Analgesia: pain relief Acute pain: short term, short, fast pain ? biologically desirable because functions as a warning signal Chronic pain: long term, dull throbbing pain ? no useful purpose Pain Relievers Natural: main source is poppy and opium is the sap from seed pods.

Contains morphine and codeine. Morphine is legal, needs prescription; codeine can be purchased over the counter Semisynthetic: heroin made by adding two acetyl groups to morphine (diacetylmorphine). It is 10 times more lipid soluble and is illegal. Synthetic: little chemical resemblance to morphine but similar effects. Demerol is short acting, Methadone (dolophine) have longer duration than morphine and more effective orally. Antagonists: Naloxone blocks action of opioids Morphine became the “soldier’s disease” during civil war as they self-administered via injection Heroin invented by Heinrich Dreser who also invented aspirin Pain Transmission.

Painful stimuli reaches brain due to nociceptive neurotransmitters such as Substance P, L-Glutamate, and CGRP (calcitonin gene-related peptide) Drugs mimic analgesic actions and then inhibit release of pain-inducing transmitters in the dorsal horn of the spinal cord Neuromodulators: interefere with release of neurotransmitters Opioid receptors also found in intestines (constipation).

Three types of receptors: mu (? ): all types of pain, kappa (? ): low intensity thermal and mechanical pain, delta (? ): thermal and mechanical pain (modulate mu activity) Spinal cord has all three receptors Mu agonists are strongest and have highest abuse potential, and delta and kappa have little to no additive potential Morphine is basic and is not rapidly absorbed from the digestive tract (which is acidic).

Antagonists are poorly absorbed by the digestive system and are usually injected. Intravenous is typical, but heroin can also be sniffed (intranasal), Heroin can be burned and the smoke inhaled to achieve the same “rush” Often administered directly into the spinal cord: Avoid CNS effects (drowsiness, respiratory depression), Avoid PNS effects (constipation) Pharmacokinetics Readily passes placental barrier.

Morphine: active metabolite exists and is 2 times more potent than morphine, with a longer half-life Heroin: concentrates in the brain faster, although itself is inactive in the brain. Active metabolite: morphine and monoacetylmorphine Codeine: active metabolite is morphine Morphine: 2 hours half-life, Demerol: 3.

5 hours half-life, Methadone: 10-25 hours half-life Mechanism of Action Opioids depress three centres of brain stem: respiratory centre, vomiting centre, cough centre Two actions: prevent neurotransmitter release from presynaptic terminal; hyperpolarize postsynaptic neuron and prevent signal transmission Pharmacological Effects Pain relief, vomiting after first use because of activation of chemoreceptors, can be used for diarrhea, decreased sex drive and fertility (can stop menstruation), constrict pupils Opioid overdose = pin prick pupils, no dilation Euphoria: opioids inhibit GABA which increases the amount of dopamine produced and amount of pleasure felt Tolerance and Dependence.

Rapid development of tolerance, doses increase, pupil dilation only partially disappears, constipation never goes away Even in severe opioid withdrawal, never as dangerous as alcohol or barbiturates withdrawal (which can be fatal) It is over within a week (starts 6-12 hours after discontinuation – cramps, vomiting, diarrhea, twitching) Resembles the flu and stops if you reuse an opioid Harmful Effects Acute effects: can produce comatose state at very high doses Chronic effects: constipation, most effects due to poor life style of addicts Reproduction: reduces testosterone in males, in women there are menstrual irregularities.

Maintenance therapies: transfer dependence, or wean off of a drug through substitute such as methadone Mental Illness: Antipsychotics, Reference chapter 4 Accidently discovered in 1950 to relieve anxiety. First developed antihistamines, where patients became sleepy but did not lose consciousness. This was introduced to psychiatrists to treat schizophrenia.

Schizophrenia: “to split mind” onset as youth mature into adulthood Premorbid phase: subtle motor, cognitive, social impairments Prodromal phase: mood, cognitive symptoms, social withdrawal, OCD Full syndrome: substantial functional deterioration in self-care, work and relationships Symptoms: hallucinations/delusions, paranoia, irrational beliefs, unconnected thoughts, blunting of emotional expression (unresponsive face), alogia which is brief and uncommunicative speech, avolition: inability to engage in goal-directed activities, anhedonia: inability to experience pleasure.

Dopamine theory: excessive dopamine activity in brain because of dysregulation of dopaminergic brain pathways Two main observations: drugs that cause dopamine function (cocaine, amphetamines) can cause a similar state to schizophrenia; antipsychotic drugs block dopamine receptor Extrapyramidal symptoms: mostly first generation antipsychotics, symptoms similar to Parkinson’s due to antagonism in basal ganglia Serotonin (5-HT) theory: based on psychedelic drugs which produce hallucinations. LSD works by activating 5-HT receptors.

However, when antagonists were used, no improvement in symptoms and therefore, serotonin theory was ruled out as cause of schizophrenia Glutamate theory: other psychedelic drugs also produce schiz-like symptoms such as PCP or ketamine. NMDA receptor antagonists lead to excessive release of glutamate which leads to cortical damage (creating schizo symptoms) Typical and atypical antipsychotics First generation (typical): block D2 receptors which led to parkinsonian syndrome Second generation (atypical): no parkinsonian symptoms because high affinity for D3 and D4 receptors but not D2.

D3,D4 receptor antagonism depressed dopamine activity in the mesolimbic system (treat psychoses without affecting basal ganglia, preventing side-effects) Atypical also used for non-psychotic disorders: bipolar, unipolar, dementia, agitation and aggression; PTSD, OCD for patients who no longer respond to antidepressants, personality disorder, Parkinson’s disease (reduce psychotic reactions).

Antipsychotic drugs Chlorpromazine (typical): block D2, ACh = dry mouth, blurred vision, NE = hypotension, sedation, Histamine= sedations and antiemetic Clozapine (atypical): developed to address side effects of typical antipsychotics, effective in 1/3 unresponsive patients to conventional medications, no extrapyramidal side effects Side effects: sedation, weight g.

Canadian Drug Legislation: Food and Drugs Act & regulation ? Health Canada ? Health Canada Products & Food branch ? Classification of therapeutics: Drugs (therapeutic products) Traditional drugs (chemical agents): Pills and tablets etc… Biologics & Genetic therapies Antibodies, Hormones …

1. pharmacology Pharmacology is defined as the study of the interaction of chemical substances with living systems. 2.Drug A chemical substance that acts on living systems through chemical processes, which is utilized for diagnosis, prevention and cure of an unwanted …

* Difference in Somatic and Autonomic Nervous System * The somatic nervous system consists of nerves that provide VOLUNTARY control over skeletal muscles * The autonomic nervous system exerts INVOLUNTARY control over the contraction of smooth muscle, cardiac muscle, and …

Homework on Drug Mechanisms 1. Release and degradation of the neurotransmitter inside the axon terminal. Drug: Reserpine Pharmacology: Most often used to treat mild to moderate hypertension. Mode of action: Reserpine inhibits the ATP/MG2+ pump responsible for packaging neurotransmitters into …

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