The document discusses different branches and topics related to pharmacology: 1. It outlines three main branches of pharmacology - pharmacotherapeutics, pharmacodynamics, and pharmacokinetics. 2. It provides information on oral transmucosal drug administration and how it can lead to rapid drug effects. 3. It defines first-order and zero-order reactions and discusses how drug reactions can change order. This high-level summary captures the key topics and structure discussed in the document in under 3 sentences.

1. Branches of pharmacology
1-Pharmacotherapeutic: ( clinical pharmacology)
It deals with relative effect of drugs in the human system for
various disorders
“The study of drug action in man”.
2- Pharmacodynamic:
“What the drug does to the body” (the relationship between
drug concentration in the body ).
3-Pharmacokinetics:
“what the body does to the drug.” ( the time course of drug
concentration in the body ).
pharmacology

2. Oral Transmucosal Administration
The sublingual or buccal route of
administration permits a rapid onset
of drug effect, because it bypasses
the liver and thus prevents the first-
pass hepatic effect on the initial
plasma concentration of drug.

3. First-order reaction
A reaction whose rate depends upon the
concentration of the reacting components.
This is an exponential process.
Zero-order reaction
A reaction whose rate is independent of the
concentration of reacting components
and is, therefore, constant. A first-order
reaction may become zero order when the
enzyme system is saturated.

4. EVENTS RESPONSIBLE FOR
VARIATIONS IN DRUG RESPONSES
BETWEEN INDIVIDUALSPharmacokinetics
Bioavailability
Renal function
Hepatic function
Cardiac function
Patient age
Pharmacodynamics
Enzyme activity
Genetic differences
Drug Interactions

5. Organs or body tissues
responsible for metabolism:
– Liver (mainly)
– Skeletal muscle
– Kidneys
– Lungs
– Plasma
– Intestinal mucosa

6. Excretion
Removal of drugs from body
• Kidneys (main organ) Whether the
drug is an original compound (parent
compound), an active or an inactive
metabolite----
• Liver
• Bowel
– Biliary excretion
– Enterohepatic recirculation

7. Half-life
How do pharmaceutical companies
determine how often a drug needs
to be given to remain in a
therapeutic range?

8. • The time it takes for one half of
the original amount of a drug in the
body to be removed
• A measure of the rate at which
drugs are removed from the body
• Most drugs are considered to be
effectively removed after about
five half-lives

9. Adrenergic Agents
Drugs that stimulate the
sympathetic nervous
system (SNS)

10. Catecholamines
Substances that can produce
a sympathomimetic response
Endogenous:
• epinephrine, norepinephrine,dopamine
Synthetic:
• isoproterenol, dobutamine

11. Adrenergic Agents
Mechanism of Action
Direct-acting sympathomimetic:
Binds directly to the receptor and causes a
physiologic response

12. Adrenergic Agents
Mechanism of Action
Indirect-acting sympathomimetic:
Causes the release of catecholamine
from the storage sites (vesicles) in the
nerve endings
The catecholamine then binds to the
receptors and causes a physiologic
response

13. Adrenaline
Presentation & uses
Clear solution containing 0.1–1 mg/ml
IV bolus in asystole or anaphylaxis
IV infusion (0.01–0.5 μg/kg/min) in critically ill
with circulatory failure
Nebulized into upper airway → edematous
obstruction
1% ophthalmic solution → open-angle
glaucoma
In combination with LA (1 in 80 000–200 000)

14. Effects
Exerts effects via α- & β-adrenoceptors
Cardiovascular – vary according to dose
•Low-dose IVI → ↑CO, ↑myocardial oxygen
consumption & coronary artery dilatation
•High doses IVI or 1 mg bolus in cardiac arrest
→ ↑SVR
•If infiltrated into areas supplied by end arteries
→ vascular supply become compromised
•Extravasation → tissue necrosis

15. Effects
Respiratory
Bronchodilator
↑PVR
Metabolic
↑Basal metabolic rate
↑Plasma glucose by stimulating glycogenolysis (liver &
skeletal muscle), lipolysis & gluconeogenesis
Central nervous system
↑MAC and increases the peripheral pain threshold.
Renal
↓Renal blood flow
↑Bladder sphincter tone → difficulty micturition

16. Side effects
1-Fatal ventricular fibrillation
2-Cerebral hemorrhage
3- Urinary retention
4- Headache
5- Necrosis at injection side
6-Blurring of vision, photophobia
Volatile anesthetics (halothane) potentiate
dysrhythmic effects of epinephrine

17. Norepinephrine
Direct α1 stimulation in
absence of β2 activity induces
intense vasoconstriction of
arterial & venous vessels

18. ↑Myocardial contractility from
β1 effects contribute to ↑ABP,
↑afterload & reflex bradycardia
prevent elevation in CO

19. ↓Renal blood flow & ↑myocardial
oxygen requirements limit its
usefulness to treatment of refractory
shock, which requires potent
vasoconstriction to maintain tissue
perfusion pressure.
Extravasation at site of administration
cause tissue necrosis

20. Dopamine
Presentation & uses
Clear solution containing 200 mg in
5 ml
Used to improve hemodynamic
parameters & urine output

21. Action
Direct stimulation of β1 receptors →
↑myocardial contraction, ↑CO,
↑renal blood flow & ↑sodium
excretion
In higher doses it stimulates α
receptors → peripheral
vasoconstriction

22. Indications
Cardiogenic, septic shock
Hypotension due to poor CO
Renal failure
In lower doses (1-5μg/kg/min)
used in renal failure???

23. Phenylephrine
Direct α1-agonist
Peripheral vasoconstriction → ↑SVR &
↑ABP
Reflex bradycardia → ↓CO
IV boluses of 50–100 μg (0.5–1 μg/kg)
rapidly reverse reductions in BP caused by
peripheral vasodilation (spinal anesthesia)
A continuous infusion (100 μg/mL at rate
of (0.25–1 μg/kg/min) maintain ABP but at
expense of renal blood flow

24. Ephedrine
Non-catecholamine direct & indirect
acting
Cardiovascular effects are similar to
epinephrine ↑BP, ↑HR, ↑contractility &
↑CO
Bronchodilator
Stimulates CNS
Does not ↓uterine blood flow (preferred
vasopressor for obstetric???)

25. Uses
Hypotension following spinal
anesthesia
Bronchial asthma
Topically as a nasal decongestant
vasopressor during anesthesia as
temporizing measure while cause
of hypotension is determined &
fixed

26. Side effects
1-Urinary Retention
2-Painful Urination
3-Dry Mouth
4-Drowsiness
5-Blurring Of Vision

27. Dobutamine
Relatively selective β1 agonist
Its primary cardiovascular effect ↑CO
as a result of ↑myocardial
contractility.
Heart rate increases are less marked
than with other β agonists
Favorable effects on myocardial oxygen
balance make it a good choice for
patients with congestive heart failure &

28. Albuterol / Salbutamol /
Ventolin
Sympathomimetic agent
Stimulate β2 receptors of
bronchi leading to
bronchodilation

29. Uses
1-Bronchial asthma
2-Bronchospasm due to
bronchitis or emphysema

30. Side effects
1-Tachycardia, arrhythmias,
anginal pain
2-Nausea, vomiting
3-Dizziness, sweating, flushing
4-Headache, weakness, vertigo &
insomnia

31. Adrenergic Antagonists
Bind but do not activate adrenoceptors
Preventing adrenergic agonist activity
Different spectrum of receptor interaction

32. Receptor selectivity of adrenergic
antagonists
β2β1α2α1Drug
000+Prazosin
00++Phenoxybenzamine
00++Phentolamine
++0+Labetalol
++00Metoprolol
++00Esmolol
++00Propranolol

33. MIXED ANTAGONISTS

34. Labetalol
Labetalol blocks α1, β1 & β2-
receptors

35. Clinical Considerations
↓PVR & ↓BP
HR & CO slightly depressed or
unchanged
↓BP without reflex tachycardia
because of its combination of α & β
effects
Peak effect occurs within 5 min after
IV dose

36. β-BLOCKERS

37. β-Blockers
•Variable degrees of selectivity
for β1 receptors
•Β1 selective have less influence
on bronchopulmonary &
vascular β2-receptors

38. Esmolol
Ultra-short acting selective
β1-antagonist → ↓HR &
↓BP (lesser extent)

39. Clinical Considerations
Prevent tachycardia & hypertension
in response to intubation, surgical
stimulation & emergence
Control ventricular rate of AF or
flutter
Short duration of due to rapid
redistribution & hydrolysis by red
blood cell esterase

40. Side effects
* Reversed within minutes by
discontinuing its infusion
* Avoided in patients
_Sinus bradycardia
_Heart block greater than first
degree
_Cardiogenic shock
_Heart failure

41. Propranolol
Non-selectively blocks β1 &
β2-receptors

42. Clinical Considerations
↓BP by several mechanisms
↓Myocardial contractility
↓HR
↓CO
↓Myocardial oxygen demand
(Myocardial ischemia)

43. Clinical Considerations
↓Atrioventricular conduction
↓Ventricular response to SVT
Controls recurrent VT or VF
Blocks adrenergic effects of
_thyrotoxicosis
_pheochromocytoma

44. Side effects
_Bronchospasm
_Congestive heart failure
_Bradycardia
_Atrioventricular heart block
_Worsen myocardial depression of
volatile anesthetics (halothane)

45. Side effects
_Concomitant administration with
verapamil (Calcium channel blocker) →
↓HR, ↓contractility & ↓AV node
conduction
_Discontinuation of β-blocker for 24–
48 h trigger withdrawal Rebound
1-Hypertension 2-Tachycardia
3-Angina pectoris

46. Atenolol
Β1-adrenoreceptor blocking
drug (cardioselective)
Hypertension, angina pectoris

47. Angiotensin-converting
enzyme inhibitors
Angiotensin-converting enzyme
inhibitors (ACE inhibitors) inhibit
the conversion of angiotensin I to
angiotensin II.

48. Indications
1- Heart failure :ACE inhibitors are used in
all grades of heart failure, usually combined
with a beta-blocker
2- Hypertension :An ACE inhibitor may be
the most appropriate initial drug for
hypertension in younger patients
3- Prophylaxis of cardiovascular events
ACE inhibitors are used in the early and
long-term management of patients who
have had a myocardial infarction

49. Duration
of Effect
(hrs)
Time of
Peak
((hrs
Onset of
Effect
(min)
Dose
(mg)
Drug
6-101-215-30100Captopril
18-304-860-12020Enalapril
18-302-46010Lisinopril
24-603-830-6020Ramipril

50. Side-effects
•profound hypotension
•renal impairment
•persistent dry cough.
•hyperkalemia

51. DIRECT VASODILATORS

52. Within the category of direct vasodilators,
1-sodium nitroprusside 2- nitroglycerin and
3-hydralazine are the three drugs most
commonly employed .
All three produce direct vasodilation.
Sodium nitroprusside produces arterial and
venous relaxation
Nitroglycerin has a greater effect on venous
than arterial relaxation
Hydralazine produces primarily arterial
relaxation.

53. The mechanism of action of all
three agents is believed to be
primarily an induced increase in
the concentration of vascular
nitric oxide

54. SODIUM NITROPRUSSIDE

55. Mechanism of Action
Sodium nitroprusside relaxes
both arteriolar and venous
smooth muscle.

56. Its rapid onset (within seconds) and
its short duration of action (1-3 min)
make it unique among agents for the
rapid control of blood pressure.
Sodium nitroprusside reduces both
afterload and preload

57. Nitroglycerin

58. Nitroglycerin is used in the
treatment of angina pectoris and
ischemia under anesthesia and also
can be used for lowering blood
pressure.
It has a rapid onset and short
duration so it is easily titratable.

59. Nitroglycerin causes venodilation,
with an increase in venous
capacitance and a resultant
decrease in preload.

60. Hydralazine

61. Hydralazine causes direct relaxation
of arterial smooth muscle.
It can be administered intravenously
for the control of hypertension in
doses ranging from 2.5 to 20 mg.
Tachycardia frequently accompanies
the decrease in blood pressure
secondary to the preferential
reduction in afterload.

62. Hydralazine undergoes hepatic
metabolism with renal excretion.
Acetylation is partly responsible for
the metabolism of hydralazine.
Slow acetylators may be more prone
to a drug-induced lupus syndrome
that can result from high serum
concentrations of hydralazine during
chronic treatment.

63. CALCIUM CHANNEL BLOCKERS

64. Calcium channel blockers reduce the flow
of Ca2+ into the cell and cause a much
smaller release of Ca2+ from the
sarcoplasmic reticulum.
All calcium channel blockers produce
vasodilation and reduce arterial pressure,
which leads to a reduction in left
ventricular afterload.

65. Calcium antagonists are used to
reduce peripheral resistance in the
management of
1-
hypertension
2- to treat cerebral vasospasm after
SAH They also
slow conduction and impulse
formation in areas of the heart and
can be used as antiarrhythmic

66. The various calcium channel
blockers show differences in their
affinity for vascular smooth
muscle and cardiac muscle cells.

67. Nifedipine and Nicardipine are much
more effective vasodilators than
myocardial depressants
Verapamil is used for its ability to slow
conduction through the heart and has
little effect on vascular muscle tone.
Diltiazem has vasodilator action as well
as antiarrhythmic effects.

68. Verapamil: Ikacor

69. Class: calcium channel blocking agent
(anti-angina, antihypertensive).
Uses:
P.O:
-angina pectoris.
-arrhythmia (atrial fibrillation,
and flutter).
-Essential hypertension.
IV: supraventricular tachycardia.

70. Contraindications:
hypotension, cardiac shock, and MI.
Side effects: AV block,
bradycardia, headache, dizziness,
abdominal cramps, blurring of
vision, and edema. .
Dosage: Initial 80-120 mg tid
then 240-480 mg /day.

71. Nifedipine: Adalat

72. Class: calcium channel
blocking agent (anti-angina,
antihypertensive).
Uses: vasospastic angina,
essential hypertension.

73. Contraindications: hypersensitivity,
lactation.
Side effects: pulmonary and
peripheral edema, MI, hypotension,
headache, muscle cramps.
Dosage: 10- 30 mg tid.
In hypertensive emergencies: 10-20 mg
given orally or sublingually by
puncturing the capsule and squeezing
contents under the tongue.

74. Nimodipine

75. Its use is confined to
prevention and treatment of
vascular spasm following
aneurysmal subarachnoid
haemorrhage.

76. Diltiazem

77. Diltiazemtsom ni evitceffe si
fo smrofangina
Class: calcium channel blocking
agent (anti-angina, antihypertensive).
Uses: vasospastic angina,
essential hypertension.

78. Contraindications: hypotension,
pulmonary congestion, and MI.
Side effects: AV block, bradycardia,
CHF. Hypotension.
Dosage: 30 mg qid before meals
and at bedtime.

79. Dr.Ismail Mohamed Ismail
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Any Questions