Clinical pharmacology connects medical practice and laboratory science by promoting drug safety, maximizing therapeutic effects, and minimizing side effects through rigorous evaluation of evidence and clinical studies. Clinical pharmacologists are trained in medicine and science to analyze various aspects of drug action including therapeutics, toxicology, cardiovascular risks, and drug interactions. Clinical pharmacology applies scientific principles to understand how drugs are administered, distributed, metabolized, and excreted in the body and how they act at molecular, cellular, organ system and whole body levels.
2. Clinical pharmacology
• Clinical pharmacology connects the gap between
medical practice and laboratory science.
• The main objective is to promote the safety of
prescription, maximise the drug effects and
minimise the side effects.
• It is important that there be association with
pharmacists skilled in areas of drug information,
medication safety and other aspects of pharmacy
practice related to clinical pharmacology.
3. Clinical pharmacology
• Clinical pharmacologists usually have a rigorous
medical and scientific training which enables
them to evaluate evidence and produce new data
through well designed studies
• Their responsibilities to patients include, but are
not limited to, analyzing
– Drug therapeutics, toxicology (including reproductive
toxicology), cardiovascular risks, perioperative drug
management (those used in operations),
psychopharmacology, and Iatrogenic effects (adverse
drug effects)
4. Clinical Pharmacology
• Clinical Pharmacology is the subject of the
application of drugs to the body in the
medicinal sense
• Drugs can function either by action through
receptors, or by altering the functions of the
target cell/tissue
6. Receptors
• One facet of drug action is receptors
– Agonist: do have a stimulatory effect
• They produce a response
– Antagonist: do not have a stimulatory effect
• They do not produce a response, or have an overall blocking action
for a parallel stimulation
• Types:
– Agonist: have a central pore
– G – Protein: usually linked by secondary messengers to
physiological (cellular) processes
– Nuclear receptors for steroid hormones: in cell nucleus
and regulate protein translation and thus synthesis
– Kinase – linked receptors: usually process intrinsic tyrosine
activity (insulin, cytokines, growth factors)
7. Neurotransmitters
• These are substances released from the end of
nerve axons, at synapses, and bind to receptors.
They activate the receptors, by changing their
configuration, and trigger a response in the post-
synaptic membrane. If it is an agonist, it may
stimulate a muscle contraction or gland
secretion.
• After they have produced their effect, they are
inactivated by:
– Postsynaptic enzymic degradation
– Reabsorption into the pre-synaptic bulb
8. Hormones
• These are chemicals that are released into the bloodstream, then
they act on tissues that have receptors for them (see videos):
– Cells a long way away (steroids)
– Cells locally
– Themselves
• Drug Hormone Actions:
– Inhibiting hormone release:
• Antithyroid drugs
– Increasing hormone release:
• Antidiabetic drugs
– Interact with hormone receptors:
• Activating: steroidal anti-inflammatory drugs (NSAI)
• Blocking: oestrogen antagonists
– Local hormones (released in pathological processes):
• Histamine - antihistamine
• 5-HT, kinins
• Prostaglandins – aspirin (NSAI)
10. Drug-receptor interactions
• A drug that has a stimulatory effect is an agonist
• A drug that blocks this activity, or has an inhibitory effect is
an antagonist (a term used in relation to the agonist)
• Antagonists can bind in two ways:
– Competitive antagonists bind reversibly with receptors; tissue
response can be normalised/increased by increasing the dose of
agonist
– Irreversible antagonists bind irreversibly with receptors; their
effect cannot be reversed by increasing agonist dose
– Others:
– Calcium-channel blockers do not via receptors, but further along to
prevent the action of an agonist
– Chemical antagonists bind to the active drug, inactivating it e.g.
Protamine abolishes effect of heparin
– Physiological antagonists are two agents with opposite effects that
tend to cancel each other out e.g. Prostacyclin and thromboxane- A2
on platelet aggregation
14. NMJ blockers
• Presynaptic exocytosis (block released of
acetylcholine):
– Botulinum toxin (Botox): blepharospasm,
hemifacial spasm (can produce paralysis for about 12 weeks),
wrinkles
– Baclofen (Lioresal) inhibit calcium influx necessary for exocytosis –
usually only NMJ blockers
– Aminoglycoside antibiotics: inhibit calcium influx necessary for
exocytosis – usually only NMJ blockers
– Dantrolene (Dantrium) -Chronic spasticity
15. Competitive NMJ blockers
• Block nicotinic receptors: used by anaesthetists to relax skeletal
muscle during ECT; usually given IV and don’t pass BBB or placenta.
The drug of choice depends upon the side-effects
– Includes:
• Histamine release
• Vagal blockade
• Ganglion blockade
• Sympathomimetic
• Curare (introd 1942; not longer used)
• Gallamine – doesn’t block ganglia, or releases histamine, but causes tachycardia
• Pancuronium – an aminosteroid and blocks muscarinic receptors, causing
atropine-like tachycardia
• Vecuronium and atracurium – commonly used without CVS effect (only
stable when kept cold at low pH, so in body its breakdown does not depend upon
renal/hepatic function, so good for patients with those problems
16. Depolarising NMJ blocking drugs
• Suxamethonium (Anectine)– depolarises the
post-synaptic membrane; initiates brief
contractions, then the block occurs because:
– Inactivation of the voltage sensitive Na channels
– Transforms activated receptors to a ‘desensitised
state’ and unresponsive to ACh.
• Disadvantages:
– Initial muscle RXN may cause damage - pain
– Damage causes K release
– Repeated doses may cause bradycardia in absence
of atropine
17. Potentiating drugs of NMJ
• Neuromuscular transmission can be increased by
anticholinesterases
• They block the break down of acetylcholine and
thus maintain, or potentiate, the effects of nerve
stimulation
• Effective in conditions like myasthenia gravis; an
autoimmune condition with antibodies
competing for receptors
– Neostigmine
– Pyridostigmine (Mestinon)
• Dosage needs to be accurate; overdose can cause xs Ach and a
depolarising block of the NMJ
18. Acetylcholinesterase Inhibitors
e.g. Donepezil (Aricept), Side Effects
Rivastigmine (Excelon),
Pyridostigmine (Mestinon),
• As Cholinergic Agonists
Neostigmine, Galantamine
Uses Interactions with other
• Cognitive Deficit conditions
– Alzheimers
• Constipation
• Attention Deficit (impaired
memory)
– ADHD
• Muscular weakness
– Myasthenia Gravis
25. Adrenaline Effects Biological advantage Sensation
High heart beat Sends more glucose & oxygen to Thumping heart
the muscles
High respiratory rate Increased oxygenation of the Panting
blood; rapid removal of carbon
dioxide
Arteriole constriction Blood diverted from skin & Person turns pale
digestive system to muscles
Muscle tension Ready for immediate action Tense feeling; Shivering; Erect
body hair
Glycogen is converted to Glucose available for energy
glucose production
Fats are converted to Muscles contraction
fatty acids
26.
27.
28. ANS- Adrenoceptors
• Adrenoceptors: - two main types: α, β
– α: 2 types:
• α1 – vasoconstriction
• α2 –
– inhibition of insulin release in pancreas
– induction of glucagon release from pancreas.
– contraction of sphincters of the gastrointestinal tract
– negative feedback in the neuronal synapses
– platelet aggregation
37. Managing hypertension
• Usually done with a combination of factors;
– Blood pressure reduction
– Diuretics
– Cholesterol
– Anxiety
38. Blood pressure
Drug groups used to control blood pressure:
• β Blockers
• Diuretics
• Calcium channel blockers
• Angiotensin converting enzyme (ACE) inhibitors
• Angiotensin II receptor blockers (ARBS)
There is no reliable/consistent evidence indicating
substantive differences between drugs classes in the
effects on BP, but side effects profiles of each drug
class differ.
39. Beta Blockers
Atenolol (Antipressan, Beta Adalat, Side Effects
Tenormin, Tenoret), Betaxolol, Bisoprolol, • Heart Palpitations – Bradycardia
Celiprolol, Esmolol, Metoprolol (Betaloc, • Hypoglycaemia (reduced glycogenolysis)
Lopresor), Nebivolol (Nebilet), Acebutolol,
Carvedilol, Labetalol, Nadolol, Pindolol, • Bronchoconstriction
Propranolol (Cardinol,Inderal), Sotalol • Insomnia
(BetaCardone,Sotacor), Timolol (Betim, • Nightmares
Prestim, Timoptol) • Depression, Fatigue
Action - Cardiac Selective and Non Cardiac • Cold Extremities
Selective. • Peripheral Vascular Disease
• Beta blockers counteract the action of • Reynaud's Syndrome
noradrenalin, and reduce the force and
speed of the heart beat. Non Cardiac • Decreased Libido and Ejaculation
Selective drugs also prevent dilation of Problems
blood vessels in the head and extremities. Contraindications
Uses • Bradycardia
• Hypertension • Hypotension
• Migraines • Metabolic acidosis
• Hyperthyroidism • Peripheral arterial disease
• Angina • Heart block/failure
• Myocardial Infarction • Phaeochromocytosis
• Bronchial asthma
48. Cholesterol reducing drugs (Statins)
• Atorvastatin (Lipitor), Fluvastatin, Side Effects
• Muscle Cramps
Lovastatin, Pravastatin (Lipostat),
• Abnormal Liver Function Tests
Rosuvastatin (Crestor), • Steatosis (Fatty Liver)
Simvastatin (Vytorin, Zocor) • Pancreatitis, Hepatitis, Jaundice
Action • NAFLD (Non Alcoholic Fatty Liver Disease)
• NASH (Non Alcoholic Steatotic Hepititis)
• Reduce LDL and VLDL Cholesterol • Cirrhosis
by inhibiting HMG-CoA enzyme • Muscle Wastage – Rhabdomylosis (raised serum
used to produce cholesterol in creatine ->urine)
• Acute Kidney Failure (peripheral oedema,
the Liver, and so reduce release weight gain, poor appetite,
into the Bloodstream. • weakness, nausea)
Uses Precautions
• Not to be used with concurrent Liver Disease or
• Hyperlipidemia (High Cholesterol) the Oral contraceptive. Liver function tests
must be performed before administration and
Also repeated regularly during treatment. Creatine
• Cholesterol absorption inhibition Phosphokinase (CPK) levels should be
performed in anyone with kidney impairment,
– Ezetimibe (Ezetrol)- used in hypothyroid disorder, inherited muscle
combination with statins disorders, previous muscle toxicity in
conjunction with statin use or alchohol abuse
49. Fibrates/Bile Sequestrants/Lipase Inhibitors
• (Questran), Colestipol, Ezetimibe Ezetimibe inhibits cholesterol absorption
(Vytorin, Zetia), Niacin (Advicor, from the gut. Again the Liver
Niacor,Niaspan), Omega 3 Acid responds by increasing LDL uptake
from the blood.
Ethyl Esters (Omacor), Orlistat
(Zenical) Niacin acts on adipose tissue and blocks
formation of fatty acids to circulate in
Bile Acid Sequestrants bind with bile the blood to the Liver for repackaging
acids and salts from the into LDL.
GallBladder in the SI and cause Uses
their excretion. The Liver then • Hyperlipidemia (High Cholesterol)
takes up more LDL from the blood
Side Effects
to compensate for lack of dietary
• BAS – Nausea, Flatulence,
input, and also causes increased
Constipation, interferes with
bile acid production to take more absorption of fat soluble vitamins A D
cholesterol from the gut. E and K
Fibrates cause an increase in • Fibrates – cholelithiasis, muscle
lipoprotein lipase which breaks inflammation and pain and muscular
down VLDL and promotes storage weakness
of fatty acids in adipose and other • Niacin – skin flushing, burning and
tissues. itching, nausea, abdominal pain,
hyperuricemia, and gout
54. Agents used in anaemia
• Fe preparation (increases Fe available)
– Oral:
• Ferrous sulphate
• Ferrous gluconate
• Ferrous fumarate
– Parenteral
• Iron dextran (ferric hydroxide)
• Iron sucrose (ferric hydroxide)
• Vitamins (important for normal blood production)
– B12, B9 (folate)
• Erythropoietin (produced by the peritubular capillary
endothelial cells in the kidney; stimulates
erythropoiesis in bone marrow - If renal failure)
64. Diarrhoea
• Diphenoxylate (Lomotil), Kaolin, Side Effects
Loperamide (Diocalm, Imodium, • Abdominal Distension and
Diareze, Arret), Methylcellulose Cramps
(Celevac) • Flatulence
Actions • Bloating
• Opioid drugs to decrease muscle • Constipation
propulsion in the bowel by
working on local opioid receptors • Fatigue
in the bowel and slow the • Drowsiness
intestines. Bulk forming agents • Dizziness
absorb water and irritants in the • Itching
bowel and produce larger and • Rashes
firmer stools.
• Dry Mouth
Uses
Precautions
• Diarrhoea
• Not to used in cases of colitis
• Can affect absorption of other
drugs
65. Constipation
Also
• Bisacodyl, Glycerol, Senna, Sodium • Bulk
Picosulfate, Lactulose (Duphalac, – Bran
Regulose), Magnesium Citrate, – Ispaghula (Fibrogel)
• Osmotic
Magnesium Hydroxide (Milk of
– MgSO4
Magnesia, Maalox, Mucogel), – Lactulose
Magnesium Sulphate, Polyethylene • Stimulant
Glycol (Liquid Paraffin) (Glycolax) – Senna
– Bisacodyl (Dulcolax)
Actions – Co-Danthromer (Codalax)
• Stimulants irritate the GI tract and – Glycerol (suppositories)
• Faecal softeners
increase peristalsis for directly
– Docusate
stimulate colon activity. Softening – Arachis oil (enema)
agents emulsify the stool. Osmotic Side Effects
laxatives cause water to stay in the • Flatulence
• Belching
intestines
• Stomach and Abdominal Cramps
Uses • Diarrhoea
• Nausea
• Constipation
• Abdominal Distension
• Osmotic laxatives can cause electrolyte imbalances
66. Irritable bowel disease/syndrome
• Aminosalicylates : Balsalazide, Side Effects
• Nausea and Vomiting
Mesalazine (Asacol, Pentasa,
• Malaise
Salofalk), Olsalazine (Dipentum), • Poor Appetite
Sulfasalazine (Salazopyrin, • Diarrhoea
Sulazine, Ucine) • Headaches
• Abdominal Pain
Actions
• Joint Pain
• These drugs block production of • Tinnitis
prostaglandins and other • Insomnia
chemicals that promote • Fatigue
• Fever
inflammation in the bowel
• Rash
Uses • Sore Throat
• Ulcerative Colitis • Haemmorhage
• Erythema Nodosum
• Crohn’s disease • Hypertension
• Palpitations
• Pancreatitis
• Liver problems
89. Lithium
• Camcolit, Priadel Side Effects
Actions • Nausea, Diarrhoea, Drowsiness,
Frequent Urination (polyuria),
• Largely unknown. Thought Frequent Thirst (polydypsia),
to work by decreasing Weight Gain, Hand Tremors, Acne
release of NE and DA while Toxic effects
stabilising or even • Should have regular checks of
increasing release of 5HT (in kidney function, urine analysis,
serum urea and creatinine,
animal studies).
thyroid and heart function
Uses • Vomiting, Diarrhoea, Ataxia,
• Mania in bipolar disorders Tremors, Convulsions, Coma,
Confusion, Hyper reflexes,
• Prophylaxis of depression Seizures, Nerve Damage,
• Cluster headaches Hypotension, Albuminuria,
Cardiac Arrhythmias
90. Epileptics/anticonvulsants
• Acetazolamide, Carbamazepine (Tegretol, Teril, Side Effects
Timonil), Clonazepam (Rivotril), Clobazam,
Diazepam (Rimapam, Tensium, Valclair, Valium), • Common are : Nausea and Vomiting,
Gabapentin (Neurontin), Levetiracetam, Headache, Confusion, Hallucinations,
Lamotrignine (Lamictal), Lorazepam (Ativan),
Phenobarbital (Gardenal), Phenytoin (Epanutin), • Also
Piracetam, Primidone (Mysoline), (Sodium) • Sedation, Ataxia
Valproate (Convulex – valproic acid, Epilim, • Penytoin – megaloblastic anemia,
Orlept), Tiagabine, Topiramate, Vigabatrin
hyperglycemia
Actions
• Carbamazapine – stupor, comia,
• Anticonvulsants – bind with sodium or chlorine
channels to slow action potentials. respiratory depression, blurred vision,
• Some antipsychotics also bind with sodium
rashes, liver toxicity, hyponatremia –
channels (Carbamazepine, Lamotrignine) needs frequent blood and liver function
• Some anxiolytics (benzodiazepines – tests when on drug
clonazepam, clorazepate, diazepam, lorazepam) • Phenobartital, Primidone – vertigo,
and barbiturates (Phenobarbital) bind with psychosis, rashes, agitation, confusion
chorine channels
• Valproate – tremors, rashes, alopecia,
• Some drugs increase GABA release – which then
thrombocytopenia, inhibition of platelets,
binds with chlorine channels (Gabapentin) or
interfere with its breakdown (valproate) liver failure
Uses • Lamotrignine – rashes, internal bleeding
• Sedative, anticonvulsant and muscle relaxant • Levetiracetam – insomnia
• Topiramate – somnolence, anxiety, weight
loss
103. Posterior pituitary drugs
• Desmopressin (Desmotabs, Side effects
Nocutil), Vasopressin (ADH),
Bromocriptine (Parlodel) • Desmopressin – headache,
Actions nausea, vomiting,
• Desmopressin metabolities nosebleeds, stomach pain,
replace Vasopressin and convulsions, thrombosis,
encourage water conservation myocardial infarction
and release of blood coagulation
• Bromocriptine – confusion,
factors. Bromocriptine inhibits
secretion of prolactin from the dizziness, nausea, vomiting,
pituitary gland. headache, constipation,
Uses dyskinesias
• Diabetes Insipidus (Type 1) –
polyuria, and nocturnal enuresis
• High Prolactin levels – infertility
and impotence
104. Sex hormones and drugs
Infertility • Side effects
• Anti-oestrogen
• Headache
– Clomifene (Clomid)
Action • Oedema
• Selective Estrogen Receptor Modulator • Hypertension
(SERM), increasing production of • Nausea and Vomiting
gonadotropins by inhibiting negative
feedback on the hypothalamus • Post menopausal Uterine
• Gonadotrophins Bleeding
– Choriogonadotropin alfa (Ovitrelle) Long term use
– Follitropin alfa, Lutotropin Alfa
(Pergoveris)
• Thromboembolisms
Actions • Myocardial infarction,
• Causes ovulation • Breast/Uterine Cancer
• Androgens
• Raloxifene – hot flushes, leg
– Testosterone (Andropatch) cramps, swollen ankles, leg pain
• Actions swelling and ulcers
• Stimulates leydig cells to synthesize
testosterone
Uses
• Infertility in men
105. Sex hormones and drugs
• Female sex hormones (HRT) Side effects
– Oestradiol (Climera, Evorel) • Headache
– Estradiol, Medroxyprogesterone • Upset stomach, stomach cramps or
(Indivina) bloating
– Medroxyprogesterone (for • Diarrhoea
endometriosis) (Provera) • Appetite and weight changes
– Levonogestrel (emergency • Changes in sex drive or performance
contraception) (Levonelle) • Nervousness
Actions • Brown or black patches on the skin
• Replaces hormones • Acne
Uses • Swelling of hands, feet, or lower legs
• Osteoporosis due to fluid retention
• Menopause symptoms • Changes in menstrual flow
– hot flashes, vaginal dryness, • Breast tenderness, enlargement, or
urinary stress incontinence, chilly discharge
sensations, dizziness, fatigue, • Sudden difficulty wearing contact
irritability, and sweating lenses
108. Type 2 Antidiabetic drugs
• Sulphonylureas
– Glibenclamide (Daonil)
Side effects
– Glicazide (Daimicron) • Hypoglycaemia: fatigue,
– Glimepiride (Amaryl) tremors, hunger, headache,
– Glipizide (Glibenese)
Actions
palpitations, blurred vision,
– Act on the pancreas and block ATP confusion, cold sweats,
potassium channels which causes influx of convulsions, coma
calcium and insulin release. Also reduce
glucagon levels and stimulate binding of • Weight gain
insulin to target tissues.
• Glucosidase inhibitors • HyperInsulinemia
– Acarbose (Glucobay) • Acarbose and Metformin –
• Biguanides
– Metformin (Glucophage)
GI disturbances: flatulence,
Actions diarrhoea, cramping. Rarely
– Inhibits glucogenesis in the liver reducing lactic acidosis
the output of glucose from the Liver and
blood sugar levels
127. Drugs used in cancer
Inhibit DNA synthesis Side effects
– Cytarabine (inhibits DNA • Nausea
polymerase)
• Antimetabolites • Vomiting
– Methotrexate • heart arrhythmias
• lymphocytic leukaemia, • Neutropenia
choriocarcinoma, Burkitt's
lymphoma, breast • Hair loss
– Capecitabine (Xeloda)
• colorectalcancer and breast cancer
– Fluorouracil
– Raltitrexed
– Mercaptopurine
– lymphocytic leukemia
• Vinca alkaloids -antimicrotubule
– Vinblastine
– Hodgkin’s lymphoma, cancer of
lung/breast/testicles, head and neck
– Vincristine
– Non-Hodgkin’s lymphoma,
lymphoblastic leukaemia,
• Taxanes
– Paclitaxel
128. Drugs used in cancer
Inactivate DNA • Alkylating agents are
• Alkylating agents carcinogenic and can cause
– Chlorambucil (Endoxana)
treatment induced
– multiple myeloma and
lymphocytic leukemia neoplasms many years after
– Ifosfamide (Mitozana) treatment
– Estramustine - prostate cancer • Common:
– Cyclophosphamide (Endoxana)
• Vomiting
– Burkitts lymphoma, breast
cancer • Stomatitis
– Melphalan (Alkaran) • poor appetite, diarrhoea
– multiple myeloma and
lymphocytic leukaemia • hair loss
– Bulsulfan (Busulfex, Myleran) • bone marrow suppression
– Granulocytic leukaemia
129. Drugs used in cancer
• Antibiotics (cytotoxics) Side effects
– Doxorubicin
– Hodgkin’s lymphoma, lung,
• Nausea
breast, bladder, stomach,
thyroid and uterine cancer,
• Vomiting
Kaposi’s sarcoma
• heart arrhythmias
– Actinomycin D (inhibits
transcription) • Neutropenia
– gestational trophoblastic
neoplasia, Wilms' tumour and • Hair loss
rhabdomyosarcoma
• Steroid hormones
– Glucocorticoids
– Oestrogens
– Anti-oestrogens
– Androgens
• Monoclonal antibodies
– Rituximab (B-Cell lymphoma)
(Mabthera)