7. Drugs used in Mania ¨C Mood Stabilizers
Drugs used in Mania ¨C Mood Stabilizers
? Lithium Carbonate
Lithium Carbonate
? Alternative Drugs:
Alternative Drugs:
¨C Carbamazepine
Carbamazepine
¨C Sodium Valproate
Sodium Valproate
¨C Lamotrigine
Lamotrigine
¨C Topiramate
Topiramate
¨C Atypical anyipsychotics ¨C Olanzapine, risperidone
Atypical anyipsychotics ¨C Olanzapine, risperidone
8. Lithium Carbonate ¨C Pharmacological actions
Lithium Carbonate ¨C Pharmacological actions
? CNS:
CNS:
¨C No discernible psychotropic effect in normal individuals
No discernible psychotropic effect in normal individuals
¨C Similarly, no effect on Manic-depressive patients
Similarly, no effect on Manic-depressive patients
¨C On prolonged administration ¨C acts as mood stabilizer
On prolonged administration ¨C acts as mood stabilizer
¨C Suppresses the episodes af attack
Suppresses the episodes af attack
10. Lithium Carbonate ¨C Mechanism of action
Lithium Carbonate ¨C Mechanism of action
1.
1. Effect on Electrolyte and ion transport:
Effect on Electrolyte and ion transport:
¨C Li is the lightest of the alkali metal atoms
Li is the lightest of the alkali metal atoms
¨C Na+ and K+ are important in this family
Na+ and K+ are important in this family
¨C Li distributes evenly in extracellular and intracellular fluids (contrast to Na+ and
Li distributes evenly in extracellular and intracellular fluids (contrast to Na+ and
K+)
K+)
¨C Build up a small concentration gradient across cell membrane
Build up a small concentration gradient across cell membrane
¨C But, cannot be transported via Na+/K+ ATPase
But, cannot be transported via Na+/K+ ATPase
¨C Interfere with transuducer mechanism of cell membrane
Interfere with transuducer mechanism of cell membrane
11. Lithium Carbonate ¨C Mechanism of action
Lithium Carbonate ¨C Mechanism of action
2.
2. Effects on 2
Effects on 2nd
nd
Messenger
Messenger
¨C IP
IP3
3 and DAG are important 2
and DAG are important 2nd
nd
messenger for alpha and Muscarinic transmission
messenger for alpha and Muscarinic transmission
¨C Lithium inhibits several enzymes in the normal recycling of Phosphoinositide
Lithium inhibits several enzymes in the normal recycling of Phosphoinositide
¨C These include IP
These include IP2
2 to IP
to IP1
1 and IP to Inositol
and IP to Inositol
¨C These leads to depletion of PIP
These leads to depletion of PIP2
2, the membrane precursor of IP
, the membrane precursor of IP3
3 and DAG
and DAG
¨C Ultimate effect may be in G-protein receptors ¨C may uncouple receptors from G-
Ultimate effect may be in G-protein receptors ¨C may uncouple receptors from G-
protein
protein
13. Lithium Carbonate, Mechanism ¨C contd.
Lithium Carbonate, Mechanism ¨C contd.
3.
3. Neurotransmitters:
Neurotransmitters:
¨C Enhances the action of Serotonin
Enhances the action of Serotonin
¨C Decrease the noradrenaline and dopamine turnover ¨C antimanic
Decrease the noradrenaline and dopamine turnover ¨C antimanic
action
action
¨C Augment synthesis of Acetylcholine
Augment synthesis of Acetylcholine
14. Lithium Carbonate - Pharmacokinetics
Lithium Carbonate - Pharmacokinetics
?Initial Dose is 600 mg/day and gradually increased (600
to 1200 mg/day
? Well absorbed orally, but slowly
Well absorbed orally, but slowly
? Not metabolized and not protein bound
Not metabolized and not protein bound
? Attains uniform distribution in total body water
Attains uniform distribution in total body water
? Apparent Vd ¨C 0.8L/kg at steady state
Apparent Vd ¨C 0.8L/kg at steady state
15. Lithium, Pharmacokinetics ¨C contd.
Lithium, Pharmacokinetics ¨C contd.
? Li is actively reabsorbed from proximal tubule in the kidney similar to Na+
Li is actively reabsorbed from proximal tubule in the kidney similar to Na+
? When Na+ is restricted larger portion of Na+ is reabsorbed - similar is in
When Na+ is restricted larger portion of Na+ is reabsorbed - similar is in
case of Li
case of Li
? Initially rapid excretion, then slower in later phase.
Initially rapid excretion, then slower in later phase.
? T1/2 is 16 to 30 Hrs
T1/2 is 16 to 30 Hrs
? Clearance is 20% of creatinine
Clearance is 20% of creatinine
? Steady state is attained in 5-7 days
Steady state is attained in 5-7 days
? Available as 300 and 400 mg tablets
Available as 300 and 400 mg tablets
16. Lithium ¨C Monitoring of Treatment
Lithium ¨C Monitoring of Treatment
? Individual variation in the rate of excretion
Individual variation in the rate of excretion
? Narrow margin of safety
Narrow margin of safety
? Done 5 days after the start of treatment
Done 5 days after the start of treatment
? Measurement is done 12 Hrs after the last dose
Measurement is done 12 Hrs after the last dose
? If no therapeutic improvement, chnge the dose
If no therapeutic improvement, chnge the dose
? New dose = desired plasma level/present level
New dose = desired plasma level/present level
? Monitor the new dose level after 5 days again
Monitor the new dose level after 5 days again
? If steady state (0.5 to 0.8 mEq/L ¨C increase the interval of monitoring
If steady state (0.5 to 0.8 mEq/L ¨C increase the interval of monitoring
17. Lithium ¨C Adverse Effects
Lithium ¨C Adverse Effects
1.
1. CNS:
CNS:
¨C Tremor is frequent
Tremor is frequent
¨C Coarse tremor, giddiness, ataxia, motor incoordination, nystagmus etc. ¨C delirium, coma
Coarse tremor, giddiness, ataxia, motor incoordination, nystagmus etc. ¨C delirium, coma
¨C Occurs mainly when plasma level is high (2mEq/L)
Occurs mainly when plasma level is high (2mEq/L)
¨C Treat with propranolol, atenolol etc.
Treat with propranolol, atenolol etc.
¨C If required ¨C Osmotic diuretics for Li excretion
If required ¨C Osmotic diuretics for Li excretion
2.
2. Renal: Polyuria and Polydipsia
Renal: Polyuria and Polydipsia
¨C Loss of ability of collecting tubules to conserve water by influence of ADH (G protein)
Loss of ability of collecting tubules to conserve water by influence of ADH (G protein)
¨C Excessive free water clearance
Excessive free water clearance
¨C Nephrogenic Diabetes Insipidus
Nephrogenic Diabetes Insipidus
18. Lithium, Adverse Effects ¨C contd.
Lithium, Adverse Effects ¨C contd.
3.
3. Cardiac Effects:
Cardiac Effects: Sick-sinus syndrome ¨C contraindicated ¨C
Sick-sinus syndrome ¨C contraindicated ¨C
flattening of T wave
flattening of T wave
4.
4. Thyroid Function:
Thyroid Function: Decrease in thyroid Function ¨C goitre (G
Decrease in thyroid Function ¨C goitre (G
protein)
protein)
5.
5. Pregnancy
Pregnancy ¨C contraindicated
¨C contraindicated
¨C Foetal goitre, congenital abnormalities (cardiac)
Foetal goitre, congenital abnormalities (cardiac)
19. Lithium ¨C Drug Interactions
Lithium ¨C Drug Interactions
? Diuretics: Renal clearance of Lithium is reduced by 25% with Diuretic
Diuretics: Renal clearance of Lithium is reduced by 25% with Diuretic
e.g. furosemide, Thiazides
e.g. furosemide, Thiazides
? NSAIDS: Renal clearance of Lithium is reduced by 25%
NSAIDS: Renal clearance of Lithium is reduced by 25%
? All Neuroleptics, except clozapine ¨C increased EPS
All Neuroleptics, except clozapine ¨C increased EPS
? Insulin and oral hypoglycaemics: enhance hypoglycaemia
Insulin and oral hypoglycaemics: enhance hypoglycaemia
20. Antimanic ¨C Other Drugs
? Carbamazepine:
¨C Prolong remission
¨C Relapse with Li+ therapy and rapid cycling of Mood ¨C Li + CBZ
? Sodium Valproate:
¨C Ist line in acute mania
¨C Lithium resistance cases
¨C Lithium + Valproate ¨C resistance to monotherapy
21. Antimanic Drugs - contd.
? Lamotrigine:
¨C Not for acute cases but Bipolar disorders
¨C Used as monotherapy as well as with Lithium
? Atypical antipsychotics:
¨C 1st line in acute mania in combination with BZD except patient
requiring parenteral therapy
¨C Olanzapine in maintenance therapy and prophylaxis
23. ANTIDEPRESSANTS
1. Tricyclic antidepressants (TCAs) :Imipramine, Amitryptiline, Doxepin, Dothiepin and Clomipramine
2. Serotonin Noradrenaline Reuptake Inhibitors (SNRI)¨C venlafaxine, duloxetine
and milnacipran.
3. Selective Serotonin reuptake inhibitors:
¨C Fluoxetine, Fluvoxamine, Sertraline and Citalopram
4. MAO inhibitors:
¨C Irreversible/ nonselective: Isocarboxazid, Phenelzine and Tranylcypromine
¨C Reversible/ selective (MAO-A) : Moclobemide and Clorgyline
5. Atypical antidepressants:
¨C Trazodone, Mianserin, Mirtazapine, Venlafaxine, Duloxetine, Bupropion and Tianeptine
24. Causes of Depression and Mechanism of
antidepressants
? In DEPRESSION ¨C Deficiency of NA or 5 HT or BOTH
? Till date, the best hypothesis assumed is that the depression results due to decreased
monoaminergic (5-HT and NA) activity in the brain, therefore drugs increasing their activity are
called typical anti-depressants. Drugs acting by other mechanisms are called atypical anti-
depressants.
? According to latest research, depression is associated with decreased levels of brain
derived neurotrophic factor (BDNF) which is critical for regulation of neural plasticity and
neurogenesis. Chronic activation of monoamine receptors (5HT and NA receptors) by
antidepressants result in increase in BDNF transcription. Another method for treatment of
depression is to inhibit the metabolism of BDNF by inhibiting the enzyme glycogen synthase
kinase3 (GSK-3). This action is produced by lithium.
25. Mechanism of antidepressants ¨C contd.
? Drugs act by increasing the local availability of NA or 5 HT
? MAO Inhibitors: MAO is a Mitochondrial Enzyme involved in Oxidative
deamination of these amines
? MAO-A: Peripheral nerve endings, Intestine and Placenta (5-HT and
NA)
? MAO-B: Brain and in Platelets and Mainly Serotonergic
(Phenylalanine)
? Selective MAO-A inhibitors (RIMA) have antidepressant property
26. Mechanism of antidepressants ¨C contd.
? TCAs:
¨C NA, 5 HT and Dopamine are present in Nerve endings
¨C Normally, there are reuptake mechanism and termination of action
¨C TCAs inhibit reuptake and make more monoamines available for action
? SSRIs:
¨C Serotonins also reuptaken by Nerve terminals
¨C SSRIs inhibit the reuptake mechanism and make more 5 HT available for action
28. MAO inhibitors
? Drugs: Irreversible: Isocarboxazid, Iproniazid, Phenelzine and Tranylcypromine, Reversible:
Moclobemide and Clorgyline
? Not popular now except irreversible selective MAO-A inhibitors:
¨C Strict dietary restrictions
¨C Irreversible action
¨C Drug-drug interactions
¨C Safer drugs are available now
? Major drawbacks:
¨C Manic state or hypertensive crisis
¨C Cheese reactions
¨C Other drug interactions
29. MAO inhibitors (Drawbacks) ¨C contd.
? Drug Interactions:
¨C Ephedrine (drugs of cold and cough): hypertensive reaction
¨C Reserpine, guanethidine: excitement and rise in BP
¨C Levodopa: excitement and rise in BP (delayed degradation of NA and DA)
¨C Antiparkinsonian anticholinergics: Hallucinations and symptoms of atropine
poisoning
¨C MAOI and SSRI: Serotonin Syndrome (Mental confusion, hallucinations, sweating,
hyperthermia, twitching of muscle, clonus and convulsion)
30. MAO inhibitors ¨C contd.
? Moclobomide: Advantages
¨C Reversible action (1-2 days after stoppage)
¨C Potentiation of pressor response to dietary amines is weak
¨C Dietary restriction not required
¨C Lack of anticholinergic, sedative,, cognitive and CVS adverse effects
¨C Used in elderly patients and with heart diseases
¨C Mild to moderate depression - alternative to TCAs
31. Tricyclic Antidepressants - Imipramine
? NA and 5 HT reuptake inhibitors ¨C Imipramine, Amitryptiline,
Doxepin, Dothiepin and Clomipramine; NA reuptake inhibitors
¨C Desimipramine, Nortryptyline, Amoxapine
? Analogue of CPZ
? Inhibit NET and SERT
? Interacts with variety of receptors ¨C alpha, H1, 5HT1, 5HT2 and D2
32. Imipramine ¨C contd.
? Early effects ¨C sedation, no other CNS effect
? After 2-4 wks:
¨C Elevation of mood, more communicative
¨C REM sleep suppressed and no night awakening
¨C More sedative ones are for agitated and anxiety patients
(amitriptyline, doxepin)
¨C Withdrawn patients ¨C less sedative Imipramine, Nortriptyline
¨C Induce seizure (Clomipramine, bupropion)
33. Imipramine - Mechanism of action
? Inhibit uptake of Biogenic amines ¨C NA and 5-HT
? No inhibition of DA uptake except Bupropion
? Cocaine and amphetamines are inhibitors of DA uptake ¨C strong CNS
stimulant
? May facilitate DA transmission in forebrain ¨C elevation of MOOD
? Reuptake inhibition causes ¨C increase amines in synaptic cleft
? Inhibition of DA ¨C stimulant action
? Inhibition of NA and 5-HT ¨C antidepressant action
34. Imipramine - Mechanism of action ¨C contd.
? But, antidepressant action starts after few weeks, whereas blockade starts
immediately
? Inhibition of uptake is an early step but cascade of events that follow are important
? Initially, auto receptors - ¦Á2 and 5-HT1 are activated by excess of NA/5HT ¨C negative
feed back
? Limiting of synaptic availability of NA - homeostasis
? On repeated exposure ¨C ¦Á2 receptor response diminishes - desensitization of these
pre-synaptic receptors
? Adaptive changes ¨C in number and sensitivity of pre and postsynaptic pre-synaptic
production and release of NA - normal or more
? No reuptake and no negative feed back
35. Imipramine ¨C Pharmacological actions
? ANS: Dry mouth, blurring of vision, constipation and urinary
hesitancy
? CVS: Tachycardia ¨C
¨C NA and anticholinergic action
¨C Postural hypotension
¨C ECG ¨C T wave suppression
¨C Arrhythmia
37. Imipramine - Pharmacokinetics
? Good oral absorption but undergo 1st pass effect ¨C variable
bioavailablity
? Highly bound to plasma protein and high Vd
? Metabolized in Liver: Active metaboites: Imipramine ¨C desipramine and
amitriptyline ¨C nortriptyline
? Excreted via urine, t1/2 ¨C 16 to 24 Hrs
? One daily dose ¨C because of active metabolites
? Therapeutic window phenomenon: Optimal effect at 50-200 ng/ml
? Doses to be individualized and titrated
38. Imipramine ¨C Adverse effects
1. Anticholinergic effects: Dry mouth, bad taste, constipaton, urinary
retention etc.
2. Dysphoric state or mania - suicide
3. CVS:
? Postural hypotension ¨C older patient and overdose
? Arrhythmia ¨C with IHD
4. Weight gain ¨C not with bupropion and SSRI
5. Seizure ¨C in children
6. Sedation, mental confusion etc. ¨C more with amitriptyline
7. Sweating and fine tremor
39. Imipramine ¨C Drug Interactions
1. TCAs and Sympathomimetics (Cough and cold)
2. TCAs and MAO inhibitors ¨C Hypertensive crisis
3. TCAs and SSRIs ¨C SSRIs inhibit metabolism of TCAs
4. Anticholinergic property ¨C delay absorption of other drugs
40. Imipramine - Drawbacks
? Low safety margin
? Anticholinergic, CVS and neurological side effects
? Therapeutic lag (2-4 wks)
? Variable patient response
41. SELECTIVE SEROTONIN REUPTAKE INHIBITORS
? Drugs: Fluoxetine, Fluvoxamine, Sertraline and Citalopram
? Similar antidepressant action
? Relatively safe and better patient acceptability
? Some patients not responding to TCAs may respond with SSRIs
? Because of absence of psychomotor and cognitive impairment -
Preferred in prophylaxis of recurrent depression
42. SELECTIVE SEROTONIN REUPTAKE INHIBITORS
? Relative advantages:
¨C No sedation, so no cognitive or
psychomotor function interference
¨C No anicholinergic effects
¨C No alpha-blocking action, so no postural
hypotension and suits for elderly
¨C No seizure induction
¨C No arrhythmia
? Drawbacks:
¨C Nausea is common
¨C Interfere with ejaculation
¨C Insomnia, dyskinesia, headache and
diarrhoea
¨C Impairment of platelet function ¨C
epistaxis
¨C Serotonin Syndrome: Mental confusion,
hallucinations, sweating, hyperthermia,
twitching of muscle, clonus and
convulsion.
43. SELECTIVE SEROTONIN REUPTAKE INHIBITORS
? Fluoxetine:
¨C Prototype of SSRIs
¨C Slow action and not used for rapid effects
¨C Longest acting ¨C 2 days, t1/2 = 2 days
¨C Used in depression and OCDs in adult and children
44. SSRIs ¨C Pharmacokinetic comparison
Dose
mg/day
Drug
interaction
Half life Steady
state
(Days)
Fluoxetine 5-20 high 2-4 days 30-60
Sertraline 50 low 26 Hrs 7-14
Paroxetime 20 high 20 Hrs 10-14
Citalopram 20-40 low 35 Hrs 7
45. Atypical Antidepressants
1. Trazodone:
? Weak 5-HT uptake block, ¦Á ¨C block, 5-HT2 antagonist
? No anticholinergic action
? No arrhythmia
? No seizure
? ADRs: Priapism, Postural Hypotension
2. Venlafaxine:
? SNRI (Serotonin and NA uptake inhibitor)
? Fast in action
? No cholinergic, adrenergic and histaminic interference
? Raising of BP
46. Atypical Antidepressants ¨C contd.
3. Mirtazapine:
? NaSSA action (Noradrenaergic and specific serotonergic antidepressant) ¨C
enhancement of NA release and specific 5-HT1 receptor action
? Blockade of 5-HT2 and 5-HT3
? No anticholinergic or antidopaminergic action
4. Bupropion:
? Inhibitor of DA and NA uptake (NDRI)
? Non-sedative but excitant property
? Used in depression and cessation of smoking
? Seizure may precipitated
47. Antidepressants - Uses
1. Endogenous Major Depression:
? Aim: Relieve symptoms of depression and restore Normal social Behavior
? 1st
choice ¨C SSRI (atypical ones also may be considered)
? TCAs ¨C in non-responsive cases
(TCAs have to be used in severe depression in adults)
? MAO ¨CA inhibitors in mild and moderate cases
? Maintenance ¨C by TCAs (Imipramine 100 mg)
? Combined with Lithium in Bipolar disorder
? Newer ones are not recommended in children ¨C suicide chance
48. Antidepressants (Uses) ¨C contd.
2. Obsessive Compulsive Disorder (OCD) and Phobic states:
(SSRIs are useful)
¨C Compulsive eating in Bulimia
¨C Body dysmorphic disorder
¨C Compulsive buying
¨C Kleptomania
3. Anxiety Disorders: BZD
4. Neuropathic pain: Imipramine, Amitriptyline ¨C post herpetic neuralgia
4. Attention Deficit Hyperactivity Disorder: TCAs
5. Enuresis
6. Migraine: Amitryptiline as prophylactic
50. What is anxiety?
? Anxiety is a normal reaction to stress
? It helps one deal with a tense situation in the office, study
harder for an exam, keep focused on an important speech
? In general, it helps one cope
? But when anxiety becomes an excessive, irrational dread of
everyday situations, it has become a disabling disorder
51. Antianxiety Drugs ¨C contd.
? Five major types of anxiety disorders are:
¨C Generalized Anxiety Disorder (GAD)
¨C Obsessive-Compulsive Disorder (OCD)
¨C Panic Disorder
¨C Post-Traumatic Stress Disorder (PTSD)
¨C Social Phobia (or Social Anxiety Disorder)
? GAD:
¨C Excessive, exaggerated anxiety and worry about everyday life events with no obvious
reasons for worry
¨C always expect disaster and can't stop worrying about health, money, family, work, or school
¨C interferes with daily functioning, including work, school, social activities, and relationships.
53. What are the Drugs?
? Benzodiazepines: Alprazolam, Diazepam, Chlordiazepoxide,
Oxazepam and Lorazepam
? Older Drugs: Barbiturates, Chloral hydrate and Meprobamate
? Azapirones: Buspirone, Gepirone and Isapirone
? Others: Propranolol, Imipramine Fluoxetine and Zolpidem etc.
54. Antianxiety Drugs ¨C BZDs
? High potency BZDs are useful
? Slow and Long duration of action
? Relieve anxiety at low doses ¨C no generalized CNS depression
? Prescribed for short period ¨C especially for alcohol and drug abuse persons
? Less cognitive impairment
? At low dose ¨C CVS and Respiratory side effects are less
? Withdrawal syndrome ¨C tapering of Doses
? Clonazepam - social phobia and GAD
? Lorazepam - panic disorder
? Alprazolam - panic disorder and GAD
? Diazepam ¨C acute panic state and organic disease anxiety
55. Antianxiety Drugs ¨C Buspirone
? No marked sedation and euphoria
? No direct effect on GABA or BZD receptors
? No physical dependence or tolerance
? No muscle relaxant, no anticonvulsant or no extra pyramidal
effects
? No functional and cognitive impairment
? No cross tolerance to other anxiolytics and little abuse
potential
56. Buspirone ¨C contd.
? Partial agonist action on presynaptic auto receptor 5-HT1A ¨C reduces
serotonergic activity in dorsal raphe
? Antagonist of certain 5-HT1A post synaptic receptors
? Weak D2 action but no antipsychotic effect
? Adaptive changes after chronic treatment ¨C reduction in 5-HT2
receptors in cortex
? Given orally, absorbed rapidly ¨C high 1st
pass metabolism, active
metabolite ¨C urine and faeces
? Dose: 5-15 mg dose
57. Antianxiety Drugs - Propranolol
? Reduces symptoms of anxiety
? Symptoms: Sympathetic overactivity ¨C palpitation,
tachycardia, rise in BP, sweating, tremor, GIT hurrying etc
? No action on psychological symptoms ¨C fear, tension etc.
? Useful in examination fear, public appearance etc.
58. Pharmacotherapy of Anxiety
? Anxiety is a Physiological phenomenon
? Start medication only when marked impairment of performance
? Start with a BZD according to the type of disorder at smallest
dose possible
? Doses are found out by titrating with the symptoms
? Usually start with ? or 2/3rd
of the normal dose at bed time
? If required the rest of the doses be given at day time
? Simultaneously treat the primary cause ¨C hypertension, Peptic
ulcer etc.
? SSRIs and Buspirone may be used in severe cases but not in
acute cases
59. Pharmacotherapy of Anxiety ¨C contd.
? Beta-blockers may be given as adjuncts
? Withdraw anxiolytics, if required in tapering doses
? Lifelong therapy may be required for some patients but avoid short
acting drugs for long therapy
? Monitor for Drug interactions
? In GAD ¨C counseling, mental relaxations and Behavioural therapy
? Avoid:
¨C Excess of Cola or Coffee (stimulants)
¨C Combination of alcohol, antihistamines, anticholinergics
#4: Affective disorders are the diseases of mind. They affect the state of mind of the sufferers. It may be from mild disorder to life threatening one. There is serious biological, social, psychological and behavioural factors invilved.
One of the common disorder is MANIA where a person is in hyperactivity, irritable mood, reuced sleep, uncontrolled speech and thought
#7: Bipolar disorders are special category of disorders which where there is mood swing from depression to mania. This special category is treated by Mood stabilizers. Lithium ¨C instead of NaCl in cardiac patient caused severe intoxication.
#26: NA neruones mostly arise from locus ceruleus (pons) and lateral tegmentum in Midbrain
Serotonergic neurones arise from raphe nucleus of pons
#28: MAO degrades some of NA within the neurones even after uptake. Inhibition of this MAO enzyme may accumulate NA in excess and may cause hypertensive crisis and manic state
Cheese reactioon ¨C Indirectly acting sympathomimetic amines escape degradation by MAO, reaches systemic circulation and displace large amount of NA from nerve endings leading to hypertensive crisis. Treated with phentolamine and prazosin
#34: Continued stimulation of cells with agonist results in desensitization (adaptation/refractoriness/down-regulation) such that the effect followed on subsequent exposure is diminished
#42: Serotonin syndrome?is a potentially life-threatening?adverse drug reaction?that may occur following therapeutic drug use, inadvertent interactions between drugs,?overdose?of particular drugs, or the recreational use of certain drugs.
#48: Obsessions?are involuntary, seemingly uncontrollable thoughts, images, or impulses that occur over and over again in your mind.
Fear of being contaminated by germs or dirt or contaminating others
Fear of causing harm to yourself or others
Compulsions?are behaviors or rituals that you feel driven to act out again and again. Usually, compulsions are performed in an attempt to make obsessions go away.
Phobia - ,specific phobia and social phobia
