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Psychosis
Two subdivisions
Organic (known case): toxic, metabolic or
neurophatological changes like drug abuse. SYMPTOMS:
confusion, disorientation, memory disturbance, and
behavioural disorganization
Functional (unknown) --> retention of orientation iin
memory, disordered thought, resigning, emotion and
behaviour
TERM 2
Schizophrenia
DEFINITION 2 From of Functional Psychoses neurodevelopment disorder with presumed structural and functional changes in CNS throughout life 1/100 people develop schizophrenia (genetics too) chronically disorder thinking and emotional withdrawal positive symptoms --> hallucinations, delusions and disorganized thought negative symptoms --> lack of emotion, poor speed and mental thought, loss of motivation TERM 3
Hypothesis of Schizophrenia (1)
DEFINITION 3 Serotonin Hypothesis serotonin receptors modulate the release of dopamine, norepinephrine, glutamate, and GABA LSD causes hallucinations and is a serotonin receptors; no endogenous hallucinogens were found in patients Glutamate Hypothesis majorexcitatoryneurotransmitter in the brain many hallucinogens are inhibitors of a subset of glutamatereceptors and show cognitive impairment and psychosis TERM 4
Hypothesis of Schizophrenia (2)
DEFINITION 4 Dopamine Hypothesis (most develop theory) most typical antipsychotic drugs block postsynaptic dopamine receptors in CNS drugs can increase dopaminergic activity, levodopa, amphetamines, or apomorphine can aggrevate or induce schizophrenia in some individuals dopamine receptor density is increased in schizophrenic patients TERM 5
Antipsychotic Drugs (1)
DEFINITION 5 Blockage of Dopamine Receptors:Therapeutic --> antagonism of dopamine receptor in the mesolimbic and mesofrontal systems of the brain (system that controls behaviours)Adverse --> extrapyramidal movement disorders (parkinson's, dystonia, akathesia), Endorcrine effects --> antagonizing dopamine receptors results in excess release in pro lactinBlockage of Cholinergic (muscarininc receptors)Therapeutic --> reduction of extrapyramidal adverse effectsAdverse --> blurred vision, dry mouth, constipation, difficulty pee
Antipsychotic Drugs (2)
Blockage of Histamine Receptors:Adverse effects --> sedation, drowsiness, weight gainBlockage of alpha adrenoceptorsAdverse effects --> hypotension, dizziness, reflex tachycardiaHaloperidol blocks dopamine receptors sedative and hypotensive actions less observed alternative for patients who cannot tolerate phenothiazines high propensity for producing extrapryamidal movements TERM 7
Antipsychotic Drugs (3)
DEFINITION 7 Phenothiazine: antagonists at dopamine receptors class is not highly specific therefore some effects are therapeutic and adverse - can activate other system 2nd Generation Antipsychotics help pos (efficacy for pos is the same as phenothiazine) and neg symptoms and have less extrapyramidal side effects - improvement is negative is partly due to decrease inside effectsdual action for blockade of dopamine and serotonin receptors EX --> Clozapine weight gain (diabetes,) cardiac death TERM 8
Bipolar Disorder
DEFINITION 8
Occurs in 1-3 % percent of population and include a manic
and depressive phase. Symptoms in manic phase are:
Excitement, hyperactivity, disinhibition, agression,
psychosis
Symptoms in depressive phase are:
similar to depression
sleep disturbances
anxiety
high suicide risk
TERM 9
Lithium Carbonate
DEFINITION 9 mood stabilizing agent that prevents mood swings in patents with bipolar disorder. by action on: electrolytes and ion trasports second messengers that mediate transmission Requires a 204 week period for full therapeutic effect and many require temporary treatment with anti psychosis and anti depressive drug. concentrations should be made approximately 12 hours after the last doseAdverse Effects, nausea fatigue, tremor, thirst, edema, weight gain, confusion, toxic effects, acne, confusion, loss of muscle TERM 10
Alternatives to Lithium as Mood Stabilizers
DEFINITION 10
patients are often given an antidepressant and an
antipsychotic to control the manic and depressive phase
separately
more rapid onset than lithium
2nd generation anti psychotics
EX --> valporic acid, carbamzepine, and clonazepam
mechanism of action of barbiturates
For epilepsy the drugs are consumed orally, anesthesia does route via intravenous, recreational is oral but some inject to obtain the rush effectmechanism: potentiates the effect of GABA at its receptors by enhancing the inhibitory effect of GABA bind GABA receptor at distinct site from GABA and modulate the chloride channel through this TERM 17
Effects of Barbiturates
DEFINITION 17 Short Term --> mild tranquility, mild euphoria, reduced interest in one surroundings, dizziness and impairment of motor coordiation, pleasurable stable intoxication and euphoria, aggressive and hostile, sleepy, cardiovascular system and respiratory is depressed Long Term --> chronic inebriation, impaired thinking, mood swings, hostility and depressionLethality: common with combined with alcohol no specific antidotes for poisoning death can result from withdrawal TERM 18
Potential for Abuse of Barbiturates
DEFINITION 18
equal or greater than alcohol because of pleasurable
effects
inherent harmfulness and risk of death is very high
Drug is much less prescribed that 40 years ago but illicit use
is still a problem, often combined with heroin to obtain and
high or combined with methamphetamine.
TERM 19
Tolerance of Barbiturates
DEFINITION 19
Tolerance
can develop to sleep induction and mood effects within a
few weeks but more slowly to motor coordination and
reaction time
tolerance to anticonvulsant develops much more slowly
cross tolerance is high
TERM 20
Dependence/ Addiction of Barbiturates
DEFINITION 20 Dependence: present as sleep disturbances serve withdrawal symptoms follow chronic use symptoms after 12-24 hours of withdrawal: tremor. anxiety, weakness, insomnia, hypotension, weakness, blink symptoms after 24-72 hours: seizure, delirium, hallucinations high body temp Addiction: results for regular use, crave the drug and feelings of panic occur if they cannot get supply
Benzodiazepines Pharmacological
Properties
These drugs give relief from anxiety, decrease aggression, produce sedation and amnesia, effective hypnotics, produce minimal suppression of REM, skeletal muscle relaxation and anticonvulsant action. They also have high therapeutic indexThe duration of action of determined by the rate of liver formation (or lack of formation) of pharmaxoligcally active metabolism. Individual benzodiazepines have similar pharmacological but are all used for different purposes TERM 22
Mechanism of Action of Benzodiazepines
DEFINITION 22 These drugs have specific receptors in nervous system, in the cerebral cortex and brain they: increase synaptic inhibition which dampens neuronal response and activate benzodiazepine receptors that enhance GABA. act on same receptor throughout the brain binding causes an increase in efficiency in GABA and mediates opening of chloride channel leading to GABA mediated neural inhibition usually taken orally but can be for IV use TERM 23
Effects of Benzodiazepines
DEFINITION 23 Short Term: CNS --> relief from anxiety, relaxation, cal mess, mild/moderate impairment of motor coordination, drowsiness, lethargy, fatigue, impaired thinking and memoryLung --> respiratory depression. GI --> neasuea, constipation, dry mouth, and abdominal discomfort. Motor Coordination --> moderator doses are impaired motor coordinationLong Term: impaired thinking, poor memory and judgement, disorientation, slurred speech, incoordiatnion, weak muscles, cognitive dysfunction, over sedation in elderlyPregnancy --> can cause placenta resulting in effects to fetus TERM 24
Potential for Abuse of Benzodiazepines
DEFINITION 24
Patterns of use:
among most widely prescribed drugs in the world
10% of Canadians use it once per year
abuse does occur
30-76% abuse with alcohol commonly with diazepam and
lorazepam
Potential for Abuse
low abuse liability
inherent harmfulness is low
margin of safety is high
TERM 25
Dependence and Addiction of
Benzodiazepines
DEFINITION 25 Dependence/Withdrawal: risk for dependece is slow sudden discontinuation may lead to withdrawal symptoms that vary in severity depending on dose, duration and abruptness symptoms are: agitation, paranoia, seizures, delirium, headache, insomnia, can't concentrate, fatigue Addiction may develop characterized by persistent craving
Metabolism and Excretion of
Ethanol
95% of ethanol is eliminated by biotransformation in the liver, the other 5% in breath urine and sweatADH converts ehtanol to acetaldehyde and aldehyde dehydrogenase converts that to acidic acid which can then be metabolized by a number of tissues. Alcohol dehydrogenase is the rate limiting stepAcetaldehye produces the flush seen after a few drinks and MEOS contributes to the removal of a dose of ethanol especially at high doses when alcohol is saturatedADH becomes saturated at 20 mg of alcohol per 100 mL of blood TERM 32
Medical Uses of Ethanol
DEFINITION 32 Ethanol is a general CNS depressant where acute ethanol affects CNS, cardiovascular, GI and liver. Chronic material use of high dose ethanol can affect the fetus. Few medicals uses exist including acute sponges to treat fever skin disinfectants low dose to improve appetite and digestion antidote in treatment of methanol poisoning hand sanitizer TERM 33
Mechanism of Neuronal Action of Alcohol
DEFINITION 33 alcohol binds GABA receptor and augments GABA mediated neuronal transmission alcohol binds to different site of GABA receptor complex thereby enhancing the neural depressant of GABA effect of alcohol on GABA receptors in not selective so the influence of GABA receptor activity on other transmitter systems can be enhanced by alcohol Interaction of alcohol with GABA on dopamine cell bodies in reward areas of the brain may explain reinforcing effects of the drug TERM 34
Effects of short term use of ethanol
DEFINITION 34 CNS: depressant, relaxed and more self confident, impaired motor functions, take risks, think they function better, exaggerated emotional response, coma or death can occur, few feel depressed or sleepyCardio: flushing of vessels to skin, depress system (high doses)GI: gastric secretion, ulcers and irritation of stomach lining (high dose)Liver: binge will inhibit glucose production and lead to hypoglycaemiaAdverse Effects: Black out, depression, negative mood, drinking and driving (1250- Canadians die each year - blood alcohol over 0.08 is 8x as likely to crash and 0.05 is 2x as likely), violence, coma, death, respiratory depression, increased sexual performance in men TERM 35
Effect of Chronic High Dose Use of Ethanol
DEFINITION 35 CNS: damages axons in the brain. dementiaCardio: alcoholic cardiomyopathy, hypertension and strokeLiver: There are three stages: Fatty liver: liver cells accumulate causing liver to enlarge Alcoholic Heptatis: liver cells damages and inflamed Cirrhosis: damaged cells are replaced with scar tissue which modifies blood flow ( NOT REVERSIBLE) Vitamin B1: Wernickle's encephalopathy (drowsy confused and cannot work), Korsakoff's psychosis (dementia severe)PNS: damages axons causing gin feet, difficulty in walking
Effects of Ethanol on Fetus (Fetal Alcohol
Syndrome)
Principle Features: CNS dysfunction impairment in attention, learning, memory, problem solving, management pre natal and post natal growth deficiency cluster of facial abnormalities Features of FAS: variable major and minor malformations. 9/1000 livebirthsand a safe dose of ethanol is not established TERM 37
Ethanol Abuse and Dependence
DEFINITION 37 Potential for Abuse: dependence liability is moderate available social and legal acceptance contributes to ethanol's abuse potential Dependence: withdrawal from ethanol produces excitability in the CNS hyper excitability leads to tremors, irritability, restlessness, anxiety, sweating, sleepiness, agitation, nausea, tension, hyperthermia, and increase heart rate convulsion, coma and death can occur if severe TERM 38
Tolerance to Ethanol
DEFINITION 38 Tolerance user becomes tolerant and there is decreased intensity of ethanol action or a shortened duration of a cation larger doses are needed to produce original pharmacologic events - tolerance develops more readily to ethanol induced impairment performance increase dose of ethanol occurs Cross tolerance occurs with ethanol end sedative hypnotic general anesthetics TERM 39
Drugs used to treat alcoholism
DEFINITION 39
therapy is to maintain fluid and electrolyte balance to
prevent seizures.Diazepam:
severe alcohol withdrawal syndrome
benzodiazepine type sedative hypnotic drug
Disulfiram:
inhibits hepatic aldehyde dehydrogenase making ethanol
undesirable to drink
cardio and respiratory changes are adverse
TERM 40
Drugs used to treat alcoholism
DEFINITION 40
Naltrexone:
for alcohol addiction
eliminates craving for ethanol by blocking activation of
dopaminergic reward pathway in the brain
Acomnrosate:
ethanol substitute that affects receptor systems
act as a GABA activator
preventing of relapse to alcohol has not been
overwhelming
Effects of Short Term Use of Cannabis
CNS: relaxation, drowsiness, well being, euphoria, perception of time distance body image, touch, smell taste are enhanced. balance and motor cooridation is impaired. spontaneous laughter, confusion, impairment of short term memory and concentration. fear, anxiety, and paranoia, flashbacks (especially if hallucinogens were abused prior)Cardio: increased heart rate and blood flow, hypotensionRespiratory: irritates mucous membrane in respiratory system, bronchodilationGI: increase appetite, dryness of mouth and throatOther: reduced sex drive, can distribute ovarious cycle, hangover TERM 47
Effects of Long Term Use of Cannabis
DEFINITION 47 Psychological: antimotivational syndrome, loss of short term memory and concentration, inability to think abstract.Cardio: changes in blood pressure and increased heart rateRespiratory: bronchitis, asthma, sore throat, chronic irritation, damage to membrane, cancer risk as more tars and carcinogens are exposedOther: decreased sperm count, reduced follicle stimulating hormone and luteinizing hormone, cycles may be an- ovulatoryFetus: THC freely crosses, developmental delays, cognitive defects, impulsiveness, inattention, hyperactivity TERM 48
Abuse and Dependence of Cannabis
DEFINITION 48 Potential of Abuse: dependence liability is low/moderate inherent harmfulness is low Dependence: can occur with high dose use mild withdrawal syndrome with termination including: sleep disturbances, irritability, loss of appetite, nervousness, agitation, upset stomach and sweating Treatment of Abuse and Dependence: no approved treatment existsDropabinol (synthetic cannaboid) has shown some progress TERM 49
Cannabis Tolerance and Addiction
DEFINITION 49
Tolerance:
long term use
occurs to psychoactive properties and effects on
cardiovascular system and performance
Addiction
develops with regular use
persistant craving from the drug and the drug is the most
important component in their life
TERM 50
Medical Use of Marijuana
DEFINITION 50 Dronabinal and Nabilone (two THC derivatives) are commonly used to prevent nausea associated with anti cancer drugs. Also for given with anti-AIDS drugs to stimulate appetite inhaler containing THC has been approved for treatment of neuropathic pain Sativex Buccal is a mixture of two cannabinoids /\9 THC and cannabidiol. which is approved foradjectivetherapyand to control neuropathic pain and musclespamsassociated with MS
History of Opioids
Drugs obtained from papaya somaiferum have been used for millennia but recently has been purified to produce drugs like morphine and cocaine - second most abused drugs in North AmericaUsed for thousands of years for social and medicinal purposes - analgesia sleep and relief from diarrhea. Opoium contains 20 different chemical compounds1900s --> 4% of population dependent on opoidspast century --> most nations passed laws attempting to control use of opoids by society TERM 52
Opioid Receptors (MOP)
DEFINITION 52 endogenous substances called endorphins interact with these receptors. they act as neurotransmitters affecting the perception of pain and emotional response to pain, also influences mood. Three families: Enkephalines, Dynorphins, and Beta- EndorphinsMOP (mu): present in all structures of brain and spinal cord, mediate analgesia, mediate depression and respiration in brain stems, involve compulsive abuse behaviour seen in opiate users.Use beta endorphins TERM 53
Opioid Receptors (KOP and DOP)
DEFINITION 53
KOP (kappa)
analgesia, dysphoria and miosis
mixed agonist/antagonists act on these receptors
dynorphins are the endogenous ligands
DOP (formerly delta)
analgesia at the spinal cord and brain
modulate emotional response to opoids
endogenous ligands and enkephalins
TERM 54
Classification of Opiates/Opioids (agonists,
mixed, antagonists)
DEFINITION 54 Agonists: bind to receptor to produce a full response includes natural compounds and semi synthetic compounds Mixed Agonists/Antagonists: illicit responds when given alone - pentazoeine can block receptor thereby blocking response of some ligands Antagonists: block response of opiates at respective receptor administration will cause withdrawal Naloxone is an example TERM 55
Morphine and Heroine
DEFINITION 55 Morphine: usually taken alone but can be in combination with cocaine and methampethamine can be taken orally, smoked, sniffed, and injected Heroin: more potent that morphine but not more efficacious than morphine - can be injected, sniffed, or smoked concentration of heroin on a street sample can range from 3- 90%
Prescription Opioid Abuse
narcotic analgesics are problematic in terms of drug
pendence when prescribed clinically
oxcodone --> long acting and incorporated into tablet.
abusers grind tablet and inject. Today drug is in a tamper
resistant tablet which is difficult to crush and grind
thereby making it more difficult to abuse
TERM 62
Effects of Opioid Abuse
DEFINITION 62 deleterious effects of chronic needle use like abscesses and infections at site of admin concern over spread of disease crime or prostitution for drug money little nutrition because money spent on drugs do not seek medical help often in poor health and can abandon friends and family OVERDOSE: respiratory depression that causes death treatment include antagonists naloxone and support of vital functions TERM 63
Opioid Tolerance and Addiction
DEFINITION 63 tolerance to most (not all) pharmacological effects occurs reversible in a few days cross tolerance between all narcotic analgesics occur Addiction: craving and compulsion for analgesics can develop use of analgesics with psychoactive drugs can occur basics for addiction is euphoric action TERM 64
Opioid Dependence
DEFINITION 64 Withdrawal Symptoms include: restlessness, anxiety, insomnia, sweating, fever, chills, increased respiratory rate, retching and vomiting, cramping, diarrhea Neonatal Drug Dependence: dependence of ovoid analgesics during pregnancy increases risk of premature delivery infact undergoes termination of drug resulting in withdrawal reaction TERM 65
Treatment of Opioid Dependence
DEFINITION 65
Methaodone is the drug used to treat opioid dependence in
Canada
cessation of drug use --> replaced drug and dose slowly
decreases over time. other agents may be added
metahdone maintenance --> replaces drug of dependence
but dose is not reduced.
Angina Pectoris
chocking pain in the chest due to lipid deposits in the coronary arteries hindering blood flow. This results in dimished oxygen supply to an area of the heart. Pain is reduced by decreasing oxygen requirements of the heart and/or increase the oxygen supply to oxygen deficient area of the heart muscle. Precipitated by: eating,exercise,excitement,exposure to the cold oxygen requirement increases with heart rate, force of contraction, arterial pressure, and volume of the blood pumped (all increased during exercise) therapy aims on reducing this TERM 67
Organic Nitrates
Mechanism
DEFINITION 67 Relax the smooth muscle around the blood vessels and exert their therapeutic effects via two mechanisms: relaxation of large capacitance vessels leading to vasodilation, which results in decrease in venous blood returning to heart Dilation of large coronary arteries - blood is diverted to areas of the heart with low blood flow thereby enhancing oxygen supply to areas of the heart that are oxygen deficient NOS catalyzes conversion of arginine to citrulline and nitric oxide. NO passes into smooth muscle where it actives gyanyl cyclase which relaxes blood vessels. Nitroglycerine is converted to NO in body TERM 68
Organic Nitrate Preparation
DEFINITION 68 Nitroglycerine (GTN) is also the active component in dynamite.GTN is a key drug in the treatment against angina pectoris and are much more intense when given by sublingual route then when given orally as it is not well absorbed with the GI tract so it can be destroyed because it can be absorbed. When placed under tongue GTN is absorbed into blood vessels under tongue very rapidly so onset is rapid with peak at 5 min but termination within 20 - 30 minTransdermal GTN system --> needs to be administered every 30 min. GTN is put into a polymer which is bonded to a membrane that is attached to adhesive bandage placed under skin. 12- 16 hours of use TERM 69
Toleranace to GTN
DEFINITION 69 When GTN is taken sublingually several times a day we have pharmacological effects but no tolerance.Tolernace is observed to GTN in explosive industry. After weeks workers are no longer bothered by headache, flushing, dizziness - effects can reappear after vacationSince GRN patch is removed for a 12 hour period - tolerance does not develop and patients can recover sensitivity TERM 70
Therapeutic Uses for GTN
DEFINITION 70 termination of individuals attacks - acts in 2 min to relieve pain prevention of individual attacks - can allow for increased exertion tolerated by patient before pain is experienced. Effects last for 30 min Chronic Prophylaxis - physician may prescribe long action organic nitrate preparation with the aim of cutting down the number of angina attacks. This is a preparation of isosorbide denigrate which when given orally (2-3 times) daily will cut down on the number of angina tracks and the need to take GTN sublingually
Types of
Lipids
Cholesterol: waxy, fat like ring structure in all cells in the body in cell membranes, synthesis of hormones, bile and bit D 400-500 mg of cholesterol per day in diet, body synthesizes 1000 mg. can infiltrate arterial wall thereby decreasing blood flow when the concentration in the blood is elevated Cholesterol Esters organic compounds containing cholesterol and fatty acids Triglycerides dietary carbs converted to triglycerides - 90% of total lipids TERM 77
Lipoproteins
DEFINITION 77 Fats are packaged for transport in the body in lipoproteinsChylomicrons - -> largest and formed in intestine to carry triglyceride of dietary origin and some cholesterol/choseterol estersVery Low Density Lipoprotein (VLDL) --> secreted by liver to carry triglycerides to peripheral tissues - derived from dietary carbsLow Density Lipoprotein (LDL) --> bad cholesterol because taken up by macrophages and plays a role in dressing fatty deposits inside the arteries and thickening blood vesselsHigh Density Lipoporteins (HDL) --> good lipoprotein because it transporters cholesterol away to arteries to the liver TERM 78
Primary and Secondary Hyperlipoproteinmias
DEFINITION 78 Primary may arise from gene defect inherited in Mendellian fashion can be caused by combination of subtle genetic factors acting together with environmental factors Secondary: arise as complications for more generalized metabolic disturbances like diabetes, hypothyroidism, or chronic ingestion of large amounts of alcohol TERM 79
Cholesterol in Blood and in Heart Disease
DEFINITION 79 desirable levels are less that 200 mg/dL borderline high levels are 200-239 mg/dL high levels are those greater than 240 mg/dL not sufficient to measure alone - most measure LDL/HDL rationpopulation studies have shown that elevation of total blood LDL-cholesterol is a major risk factor for atheroscholotic effects so individuals with blood cholesterol greater that 220-250 mg/dL will have 3x risk of heart attack with individuals with less that 195 mg/mL. Elevated tirglycerides (<150mg/dL) are also associated with CAD TERM 80
Therapeutic Measures of Lowering Cholesterol
DEFINITION 80 eliminates aggravating factors via dietary measures, if these fail drug therapy is instituted. Therapeutic measures include: Elimination of aggravation factors - must be down in connection with lowering of lipids. (exercise, no smoking, no alcohol, control blood glucose...) Diet (maintaining a normal body weight low in cholesterol and saturated fats) - reducing sauturated fats intake is considered more effective way to lower blood cholesterol
Bile acid binding resins, fabric acid
derivatives
Binding Acid Binding Resins: cholestyramine is a large insoluble positively charged resin that binds bile acids in intestine and prevents reabsorption liver cholesterol is metabolized to bile acids which are then excreted to intestine - most bile acids are normal reabsorbed with the intestine. enhanced excretion of cholestyramine results in enhanced transformation of bile acids to the liver Fabric Acid Dervaitves: gembibrozil decreases levels of VLDL by enhancing breakdown of triglycerides - used when VLDL predominates TERM 82
Niacin and Stains
DEFINITION 82 Niacin: inhibits secretion of VLDL from liver since LDL is a product of VLDL it also decreases production of LDL and in turn increases concentrations of HDL Adverse effects: vasodilation, itching, skin rash The Statins (most effective) simvastatin, fluvastain, atrovastin inhibit HMG-CoA in liver which is the rate limiting step in cholesterol biosynthesis - employed alone or with other drugs adverse effects: myopathy and elevated liver enzymes TERM 83
Inhibitors of Sterol (cholesterol
absorption)
DEFINITION 83 eztimibe is a selective inhibitor of intestinal absorption of cholesterol and plant sterols inhibits a transportor in the GI tract responsible for absorption of cholesterol and other sterols also blocks reabsorption of bile salts reduction in reabsorption of bile salts leads to conversion of cholesterol to bile salts in liver resulting in a net reduction of cholesterol levels used in combo TERM 84
Normal vs High Blood Pressure
DEFINITION 84
In young adult normal BP is around 120/80. The lower figure
corresponds to the pressure between
contractionsHypertension is silent and a wide scale screening
and ongoing process is used to diagnose the condition as it
leads to increased vascular disease, increase in heart
attacks, increase in stroke, and an increase in renal disease
TERM 85
Regulation of Normal BP
DEFINITION 85 Arterial blood pressure is the product of the amount of blood pumped by the heart and resistance in the peripheral arteriolesBP = CO (cardiac output) x PVR (peripheral vascular resistance) - these are both controlled by the sympathetic nervous system1) Resistance in Arterioles - increases SNS activity results in more norepinephrine onto arterioles thereby resulting in constriction2) Capacitance of Venules - dilated reduces cardiac output and BP3) The Heart - SNS controls heart rate thereby controlling blood pump4) Volume Control - increasing volume of fluid in blood increases BP, this is controlled by kidneys and renin-angiotensin system
Drugs Modifying Renin Angiotensin System
ACE inhibitors (captopril) inhibits conversion of angiotension 1 to 2 to result in less constriction of blood vessels can be used in patents with diabetes 5-20% of patents develop cough and cause fetal injury or death when used in 2nd./3rd trimester most effective in reducing incidence of heart disease Africans Africans and Elderly and more resistant Angiotension Receptor blocking drugs (lorastin) --> block ANG 2 receptor thereby preventing vasoconstriction. no cough TERM 92
Compliance with Therapy
DEFINITION 92
Most individuals find complacence hard because it
includes exercise diet and drugs treatment
can be expensive
adverse effects makecomplacencehard
therapy is required for longperiods
develop of new and more selective antihypertensive drugs
may be anticipated - developing rapidly
TERM 93
Blood Coagulation Cascade
DEFINITION 93 When injury to the vessel occurs the vessel goes into spams restricting blood loss platelets become sticks and will adhere to injury site formation of fibrin occurs Coagulation cascade damaged tissue releases tissue factor which binds to factor VIIa
- this activates factors X and IX to Xa and IXa factor Xa and factor Va converts factor 2 (prothrombin) to factor 2a (thrombin) thrombin coverts fibrinogen to fibrin which completes clot TERM 94
Fibrinolytic System
DEFINITION 94 tissues plasminogen activator (t-Pa) activates plasminogen to plasmid which breaks down fibrin clot plasminogen activator and plasmin are inhibited once the fibrin clot is dissolved antithrombin 3 functions as an endogenous anticoagulant that neutralizes a number of active cofactors in clotting (IIa, IXa, Xa, Xia, and XIIa) to keep balance between bleeding and formation of intravascular clots TERM 95
Pharmacological Targeting of Blood
Coagulation
DEFINITION 95 Many conditions result in an intravascular clot including: genetic factors (primary), infection, cancer or trauma (secondary),drugs.Drugs can prevent clot formation or dissolve already formed clots. Allanticoagulantshave bleeding as a major adverse effect. Thesedrugsdo not alter existing thrombi but preventfurtherformation of thrombiTwo types of ThrombiArterial Thrombi --> made up of mainly platelets (white thrombi) and form in high flow areas Venous thrombi --> clots contain more fibrin (red thrombi) and form in largevessels, clot can move to other areas of body and may be trapped in arteries of other organs
Thrombin Inhibitors
Heparins, Low Molecular Weight Heaprins, and Fondaparinux: natural substances in mammalian species (extracted from pig) LMWH contain more active portion of the molecule all 3 agents must be given by injection all drugs bind to antithrombin 3 thereby enhancing the ability to inhibit the clotting factors Xa and IIa (for fondaparinux only Xa is inhibited, Heaprins accelerate inhibition of Xa and IIa by antithrombin III 1000x - response in immediate) Adverse Effects: Bleeding, thrombocytopenia (heparins) - so should have platelet counts periodically TERM 97
Oral Factor Xa Inhibitors and Direct Thrombin
Inhibitors
DEFINITION 97 Factor Xa Inhibitors: rivaroxaban is approved for prevention of venous thromboembolism following hip and knee surgery drug is as effective as heparins Direct Thrombin Inhibitors leeches have been used as a form of blood letting saliva of leech contains inhibitor of thrombin Lepirudin does not require antithrombin 3 for activity but inhibits the thrombin action directly TERM 98
Warfarin
DEFINITION 98 derivative of original courmarin isolated from spoiled clover widely prescribed drug as can be administered orally inexpensive and effective inhibition of vitamin K clotting facotrs VII, IX X and II it is a vitamin K antagonist and decreases rate of synthesis of these clotting cofactors which reduces ability of blood to clot structure of warfarin is very similar to that of vitamin K warfarin can freely cross placenta onset of response is delayed for 24+ hours response is modified by many other drugs, herbals and food TERM 99
Clinical Use of
Anticoagulants
DEFINITION 99
for inherited disorders of coagulation where natural
anticoagulant system has some form of deficit
acquired disease
prophylactic use during hip and knee replacement
surgeries to prevent thrombotic complications
treats overt thromboembolic diseases
TERM 100
Anti platelet Drugs
DEFINITION 100 Platelet aggregation is the initial step to arrest bleeding after injury to vessel occurs - also participations in heart attack, stoke, and peripheral vascular disease. Three triggers for platelet aggregation: Membrane Receptors (glycoprotein IIB/IIA) --> respond to norepinpehrine, thrombin, some prostaglandins to iniate palatelet aggregation ADP and prostaglandin that can interact with receptors on the surface of the plater thromboxane A2, cAMP and calcium ions that act inside platelet to promote adherence
